USITC Publication 5254•Certain Human Milk Oligosaccharides and Methods of Producing The Same, Inv. 337-TA-1120
Certain Human Milk Oligosaccharides and Methods of Producing The Same, Inv. 337-TA-1120
USITC Publication 5254Itc
Gesamter Gesetzestext
U.S. International Trade Commission Publication 5254 February 2022 Washington, DC 20436 In the Matter of 337-TA-1120 CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME
U.S. International Trade Commission COMMISSIONERS David S. Johanson, Chairman Rhonda K. Schmidtlein, Commissioner Jason E. Kearns, Commissioner Randolph J. Stayin, Commissioner Amy A. Karpel, Commissioner Address all communications to Secretary to the Commission United States International Trade Commission Washington, DC 20436
U.S. International Trade Commission Washington, DC 20436 www.usitc.gov Publication 5254 February 2022 In the Matter of 337-TA-1120 CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME
1 UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. In the Matter of CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Inv. No. 337-TA-1120 COMMISSION ORDER On May 19, 2020, the Commission issued a final determination finding a violation of section 337 of the Tariff Act of 1930, as amended (19 U.S.C. § 1337) (“section 337”), based on the importation into the United States, the sale for importation, and the sale within the United States after importation of certain bacterial strains and 2’-fucosyllactose oligosaccharides produced therefrom that infringe certain claims of U.S. Patent No. 9,970,018 (“the ’018 patent”). See 85 Fed. Reg. 31549 (May 26, 2020); see also 83 Fed. Reg. 28865 (June 21, 2018) (defining the scope of the investigation as “2’-fucosyllactose oligosaccharides”). The Commission also adjudicated infringement with respect to a TTFL12 bacterial strain imported by the named respondent and determined that it does not infringe the ’018 patent. See id. The Commission issued a limited exclusion order (“LEO”) barring entry of 2’-fucosyllactose (“2’-FL”) oligosaccharides that infringe the asserted patent claims but also including an explicit carve-out for 2’-fucosyllactose oligosaccharides made with the non-infringing TTFL12 bacterial strain. On June 2, 2020, complainant Glycosyn LLC (“Glycosyn”) filed a petition for Commission reconsideration of part III(B) of the Commission Opinion (i.e., “Adjudication of Infringement with Respect to the TTFL12 Strain”). Having considered Glycosyn’s petition, the responses thereto, and the record in this investigation, the Commission has determined to deny Glycosyn’s petition for reconsideration.
2 I. BACKGROUND A. Procedural Background The Commission instituted this investigation on June 21, 2018, based on a complaint, as amended and supplemented, filed by Glycosyn of Waltham, Massachusetts. See 83 Fed. Reg. 28865 (June 21, 2018). The complaint alleged violations of section 337 based upon the importation into the United States, the sale for importation, and the sale within the United States after importation of certain human milk oligosaccharides, by reason of infringement of certain claims of U.S. Patent No. 9,453,230 (“the ’230 patent”) and the ’018 patent. See id. The notice of investigation named Jennewein of Rheinbreitbach, Germany as respondent in this investigation. See id. The Office of Unfair Import Investigations was also a party to this investigation. See id. The Commission partially terminated the investigation as to certain claims of the ’018 patent and all asserted claims of the ’230 patent based on the withdrawal of the allegations pertaining to those patent claims. See Order No. 5 (Aug. 9, 2018), unreviewed, Comm’n Notice (Aug. 29, 2018); Order No. 15 (Oct. 30, 2018), unreviewed, Comm’n Notice (Nov. 29, 2018); Order No. 17 (Nov. 19, 2018), unreviewed, Comm’n Notice (Dec. 12, 2018); Order No. 25 (Feb. 8, 2019), unreviewed, Comm’n Notice (Feb. 28, 2019). Claims 1-3, 5, 8, 10, 12, 18, and 23-28 of the ’018 patent remained pending in this investigation. On September 9, 2019, the administrative law judge (“ALJ”) issued a final initial determination (“FID”) finding a violation of section 337 based on the infringement of claims 1-3, 5, 8, 10, 12, 18, and 24-28, but not claim 23 of the ’018 patent based on non-infringement of that claim. See FID at 35. On May 19, 2020, the Commission affirmed the FID’s finding of infringement and issued a final determination finding a violation by certain bacterial strains.
3 See 85 Fed. Reg. 31549 (May 26, 2020). In particular, the Commission reversed the FID’s decision not to adjudicate the TTFL12 bacterial strain and determined that it does not infringe any of the asserted claims. See id. The Commission issued an LEO barring entry of 2’-FL oligosaccharides that infringe the Asserted Claims but also including an explicit carve-out for 2’- FL oligosaccharides made with the non-infringing TTFL12 bacterial strain.1 The Commission also set a bond in the amount of five (5) percent of the entered value of Jennewein’s 2’-FL product during the period of Presidential review. On June 2, 2020, pursuant to Commission Rule 210.47 (19 C.F.R. § 210.47), Glycosyn petitioned for reconsideration of part III(B) of the Commission Opinion (i.e., “Adjudication of Infringement with Respect to the TTFL12 Strain”).2 On June 8 and 9, 2020, respectively, Jennewein and the Commission’s Investigative Attorney opposed Glycosyn’s petition.3 II. STANDARD FOR RECONSIDERATION Commission Rule 210.47 governs petitions for reconsideration and provides that: Within 14 days after service of a Commission determination, any party may file with the Commission a petition for reconsideration of such determination or any action ordered to be taken thereunder, setting forth the relief desired and the grounds in support thereof. Any petition filed under this section must be confined to new questions raised by the determination or action ordered to be taken thereunder and upon which the petitioner had no opportunity to submit arguments. . . . See 19 C.F.R. § 210.47. 1 Complainant did not request, and the Commission did not issue, a cease and desist order. 2 See Complainant Glycosyn LLC’s Petition for Reconsideration of Part III(B) of the Commission Opinion (June 2, 2020). 3 See Respondent Jennewein Biotechnologie GmbH’s Opposition to Complainant Glycosyn LLC’s Petition for Reconsideration of Part III(B) of the Commission Opinion (June 8, 2020); Response of the Office of Unfair Import Investigations to Complainant’s Petition for Reconsideration of Part III(B) of the Commission Opinion (June 9, 2020).
4 III. DISCUSSION Glycosyn’s petition for reconsideration does not identify new questions raised by the ALJ’s FID or the Commission’s final determination or present arguments that Glycosyn did not have the opportunity to address in previous filings before either the ALJ or the Commission. As such, the Commission has determined that Glycosyn’s petition for reconsideration does not satisfy the requirements of Commission Rule 210.47.4 IV. CONCLUSION Accordingly, upon consideration of the record and the submissions in this matter, the Commission hereby ORDERS that: 1. Glycosyn’s petition for reconsideration is DENIED. 2. The Secretary will serve this Order on all parties to the investigation. By order of the Commission. Lisa R. Barton Secretary to the Commission Issued: October 1, 2020 4 Commissioner Schmidtlein respectfully dissents. In light of the particular facts (including the new evidence cited by Glycosyn in its petition for reconsideration) and the procedural history of this investigation, and given the rationale provided in her dissent, in her view, Glycosyn’s petition should be granted and Part III(B) of the majority’s opinion should be reconsidered.
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Inv. No. 337-TA-1120 PUBLIC CERTIFICATE OF SERVICE I, Lisa R. Barton, hereby certify that the attached COMMISSION ORDER has been served via EDIS upon the Commission Investigative Attorney, Lisa Murray, Esq., and the following parties as indicated, on October 1, 2020 Lisa R. Barton, Secretary U.S. International Trade Commission 500 E Street, SW, Room 112 Washington, DC 20436 On Behalf of Complainant Glycosyn LLC: Michael C. Newman, Esq. MINTZ LEVIN COHN FERRIS GLOVSKY AND POPEO, PC 1 Financial Center Boston, MA 02111 Email: MCNewman@mintz.com ☐ Via Hand Delivery ☐ Via Express Delivery ☐ Via First Class Mail ☒ Other: Email Notification of Availability to Download On Behalf of Respondent Jennewein Biotechnologie GmbH: Gary M. Hnath MAYER BROWN LLP 1999 K Street, NW Washington, DC 20006 Email: ghnath@mayerbrown.com ☐ Via Hand Delivery ☐ Via Express Delivery ☐ Via First Class Mail ☒ Other: Email Notification of Availability to Download
1 UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. In the Matter of CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Investigation No. 337-TA-1120 NOTICE OF COMMISSION FINAL DETERMINATION FINDING A VIOLATION OF SECTION 337; ISSUANCE OF A LIMITED EXCLUSION ORDER; TERMINATION OF THE INVESTIGATION AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has found a violation of section 337 of the Tariff Act of 1930 (“section 337”), as amended, in this investigation. The Commission has issued a limited exclusion order (“LEO”) prohibiting the importation by respondent Jennewein Biotechnologie GmbH (“Jennewein”) of Rheinbreitbach, Germany of certain human milk oligosaccharides that infringe complainant’s asserted claims. The investigation is terminated. FOR FURTHER INFORMATION CONTACT: Houda Morad, Office of the General Counsel, U.S. International Trade Commission, 500 E Street SW., Washington, DC 20436, telephone (202) 708-4716. Copies of non-confidential documents filed in connection with this investigation are or will be available for inspection during official business hours (8:45 a.m. to 5:15 p.m.) in the Office of the Secretary, U.S. International Trade Commission, 500 E Street SW., Washington, D.C. 20436, telephone (202) 205-2000. General information concerning the Commission may also be obtained by accessing its Internet server at https://www.usitc.gov. The public record for this investigation may be viewed on the Commission’s electronic docket (EDIS) at https://edis.usitc.gov. Hearing-impaired persons are advised that information on this matter can be obtained by contacting the Commission’s TDD terminal on (202) 205-1810. SUPPLEMENTARY INFORMATION: The Commission instituted this investigation on June 21, 2018, based on a complaint, as amended and supplemented, filed on behalf of Glycosyn LLC of Waltham, Massachusetts (“Glycosyn”). See 83 Fed. Reg. 28865 (June 21, 2018). The complaint, as amended and supplemented, alleges violations of section 337 of the Tariff Act of 1930, as amended, 19 U.S.C. 1337 (“section 337”), based upon the importation into the United States, the sale for importation, and the sale within the United States after importation of certain human milk oligosaccharides by reason of infringement of claims 1-40 of U.S. Patent No. 9,453,230 (“the ’230 patent”) and claims 1-28 of U.S. Patent No. 9,970,018 (“the ’018 patent”).
2 See id. The notice of investigation named Jennewein as a respondent in this investigation. See id. The Office of Unfair Import Investigations (“OUII”) is also named as a party to the investigation. See id. The ALJ conducted an evidentiary hearing on May 14-17, 2019, and on September 9, 2019, issued the FID finding a violation of section 337 based on the infringement of claims 1-3, 5, 8, 10, 12, 18, and 24-28 of the ’018 patent (hereinafter, the “Asserted Claims”). In addition, the FID finds that the Asserted Claims are neither invalid under 35 U.S.C. §§ 103 and 112, nor unenforceable for inequitable conduct. Furthermore, the FID finds that the domestic industry requirement is satisfied. All asserted claims in the ’230 patent were withdrawn during the investigation. The FID also contains a recommended determination (“RD”) recommending that the Commission issue an LEO barring entry of articles that infringe the ’018 patent. The RD also recommends that the Commission impose a 5 percent bond during the period of Presidential review. Furthermore, as directed by the Commission, the RD provides findings with respect to the public interest and recommends that the Commission determine that the public interest factors do not preclude entry of the proposed LEO. Glycosyn does not seek and the RD does not recommend issuance of a cease and desist order. On October 9 and 10, 2019, respectively, Glycosyn and Jennewein filed statements on the public interest pursuant to Commission Rule 210.50. On October 23, 2019, non-party DuPont Nutrition & Health filed a public interest submission pursuant to the Commission’s notice requesting public interest comments. See 84 Fed. Reg. 49335 (Sept. 19, 2019). On January 30, 2020, the Commission issued a notice determining to review the FID in part. See 85 Fed. Reg. 6573 (Feb. 5, 2020). The Commission’s notice requested written submissions in response to certain questions relating to issues under review and on issues of remedy, the public interest, and bonding. On February 18, 2020, the parties, including OUII, filed written submissions in response to the notice, and on February 25, 2020, the parties filed responses to each other’s submissions. On February 18, 2020, non-party Abbott Laboratories filed a written submission concerning the public interest. Having examined the record of this investigation, including the FID, the RD, and the parties’ and non-parties’ submissions, the Commission has determined to affirm with modification the FID’s determination of a violation of section 337 with respect to claims 1-3, 5, 8, 10, 12, 18, and 24-28 of the ’018 patent. Specifically, as explained in the Commission Opinion filed concurrently herewith, the Commission has determined to affirm with modification the FID’s findings with respect to infringement by the accused Jennewein bacterial strains and to reverse the FID’s decision not to adjudicate infringement with respect to Jennewein’s TTFL12 bacterial strain. As to the TTFL12 strain, the Commission has determined that it does not infringe the Asserted Claims. All findings in the FID that are not inconsistent with the Commission’s determination are affirmed. The Commission has determined that the appropriate remedy is an LEO against Jennewein’s infringing products. The Commission has also determined that the public interest factors enumerated in subsection 337(d)(1) (19 U.S.C. 1337(d)(1)) do not preclude the issuance of the LEO. The Commission has further determined to set a bond during the period of
3 Presidential review at five (5) percent of the entered value of Jennewein’s infringing products (19 U.S.C. 1337(j)). The Commission’s order and opinion were delivered to the President and to the United States Trade Representative on the day of their issuance. The Commission’s vote for these determinations took place on May 19, 2020. The authority for the Commission’s determination is contained in section 337 of the Tariff Act of 1930, as amended (19 U.S.C. 1337), and in part 210 of the Commission’s Rules of Practice and Procedure (19 CFR part 210). By order of the Commission. Lisa R. Barton Secretary to the Commission Issued: May 19, 2020
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Inv. No. 337-TA-1120 PUBLIC CERTIFICATE OF SERVICE I, Lisa R. Barton, hereby certify that the attached NOTICE has been served via EDIS upon the Commission Investigative Attorney, Lisa Murray, Esq., and the following parties as indicated, on May 19, 2020. Lisa R. Barton, Secretary U.S. International Trade Commission 500 E Street, SW, Room 112 Washington, DC 20436 On Behalf of Complainant Glycosyn LLC: Michael C. Newman, Esq. MINTZ LEVIN COHN FERRIS GLOVSKY AND POPEO, PC 1 Financial Center Boston, MA 02111 Email: MCNewman@mintz.com ☐ Via Hand Delivery ☐ Via Express Delivery ☐ Via First Class Mail ☒ Other: Email Notification of Availability to Download On Behalf of Respondent Jennewein Biotechnologie GmbH: Gary M. Hnath MAYER BROWN LLP 1999 K Street, NW Washington, DC 20006 Email: ghnath@mayerbrown.com ☐ Via Hand Delivery ☐ Via Express Delivery ☐ Via First Class Mail ☒ Other: Email Notification of Availability to Download
1 UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. In the Matter of CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Investigation No. 337-TA-1120 LIMITED EXCLUSION ORDER The United States International Trade Commission (“Commission”) has determined that there is a violation of Section 337 of the Tariff Act of 1930, as amended (19 U.S.C. § 1337), in the unlawful importation, sale for importation, or sale within the United States after importation by Jennewein Biotechnologie GmbH (“Jennewein” or “Respondent”) of certain 2’-fucosyllactose oligosaccharides that infringe one or more of claims 1-3, 5, 8, 10, 12, 18, and 24-28 (“the Asserted Claims”) of U.S. Patent No. 9,970,018 (“the ’018 patent”). Having reviewed the record of this investigation, including the written submissions of the parties, the Commission has made its determination on the issues of remedy, public interest, and bonding. The Commission has determined that the appropriate form of relief includes a limited exclusion order prohibiting the unlicensed entry into the United States of 2’-fucosyllactose oligosaccharides manufactured abroad by or on behalf of, or imported by or on behalf of, Respondent or any of its affiliated companies, parents, subsidiaries, or other related business entities, or its successors or assigns. The exclusion order does not apply to Respondent’s TTFL12 bacterial strain and 2’-fucosyllactose oligosaccharides produced by that strain, which, as the Commission determined, do not infringe the Asserted Claims. The Commission has also determined that the public interest factors enumerated in 19 U.S.C. § 1337(d) do not preclude the issuance of the limited exclusion order, and that the bond
2 during the period of Presidential review shall be in the amount of five (5) percent of the entered value of the covered articles. Accordingly, the Commission hereby ORDERS that: 1. 2’-fucosyllactose oligosaccharides that infringe one or more of the Asserted Claims that are manufactured abroad by or on behalf of, or imported by or on behalf of, Respondent, or its affiliated companies, parents, subsidiaries, or other related business entities, or its successors or assigns (“covered articles”), are excluded from entry for consumption into the United States, entry for consumption from a foreign-trade zone, or withdrawal from a warehouse for consumption, for the remaining term of the ’018 patent, except under license of the patent owner or as provided by law. 2. This Order does not apply to Respondent’s TTFL12 bacterial strain and 2’-fucosyllactose oligosaccharides produced by that strain, which, as the Commission determined, do not infringe the Asserted Claims. 3. Notwithstanding paragraph 1 of this Order, covered articles are entitled to entry into the United States for consumption, entry for consumption from a foreign trade zone, or withdrawal from a warehouse for consumption, under bond in the amount of five (5) percent of the entered value of the infringing products pursuant to subsection (j) of section 337 of the Tariff Act of 1930, as amended (19 U.S.C. § 1337(j)), and the Presidential Memorandum for the United States Trade Representative of July 21, 2005, (70 FR 43251), from the day after this Order is received by the United States Trade Representative, and until such time as the United States Trade representative notifies the Commission that this Order is approved or disapproved but, in any event, not later than sixty (60) days after the date of receipt of this Order. All entries of
3 covered articles made pursuant to this paragraph are to be reported to U.S. Customs and Border Protection (“CBP”), in advance of the date of the entry, pursuant to procedures CBP establishes. 4. At the discretion of CBP and pursuant to the procedures it establishes, persons seeking to import 2’-fucosyllactose oligosaccharides, that are potentially subject to this Order may be required to certify that they are familiar with the terms of this Order, that they have made appropriate inquiry, and thereupon state that, to the best of their knowledge and belief, the products being imported are not excluded from entry under paragraph 1 of this Order. At its discretion, CBP may require persons who have provided the certification described in this paragraph to furnish such records or analyses as are necessary to substantiate this certification. 5. In accordance with 19 U.S.C. § 1337(l), the provisions of this Order shall not apply to 2’-fucosyllactose oligosaccharides that are imported by or for the use of the United States, or imported for and to be used for, the United States with the authorization or consent of the Government. 6. The Commission may modify this Order in accordance with the procedures described in Rule 210.76 of the Commission’s Rules of Practice and Procedure (19 C.F.R. § 210.76). 7. The Secretary shall serve copies of this Order upon each party of record in this Investigation and upon CBP. 8. Notice of this Order shall be published in the Federal Register.
4 By order of the Commission. Lisa R. Barton Secretary to the Commission Issued: May 19, 2020
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Inv. No. 337-TA-1120 PUBLIC CERTIFICATE OF SERVICE I, Lisa R. Barton, hereby certify that the attached ORDER, COMMISION has been served via EDIS upon the Commission Investigative Attorney, Lisa Murray, Esq., and the following parties as indicated, on May 19, 2020. Lisa R. Barton, Secretary U.S. International Trade Commission 500 E Street, SW, Room 112 Washington, DC 20436 On Behalf of Complainant Glycosyn LLC: Michael C. Newman, Esq. MINTZ LEVIN COHN FERRIS GLOVSKY AND POPEO, PC 1 Financial Center Boston, MA 02111 Email: MCNewman@mintz.com ☐ Via Hand Delivery ☐ Via Express Delivery ☐ Via First Class Mail ☒ Other: Email Notification of Availability to Download On Behalf of Respondent Jennewein Biotechnologie GmbH: Gary M. Hnath MAYER BROWN LLP 1999 K Street, NW Washington, DC 20006 Email: ghnath@mayerbrown.com ☐ Via Hand Delivery ☐ Via Express Delivery ☐ Via First Class Mail ☒ Other: Email Notification of Availability to Download
PUBLIC VERSION 1 UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. In the Matter of CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Inv. No. 337-TA-1120 COMMISSION OPINION The Commission has determined that there has been a violation of section 337 of the Tariff Act of 1930, as amended, 19 U.S.C. § 1337 (“section 337”), on review of the final initial determination (“FID”) of the presiding administrative law judge (“ALJ”), based on the infringement of U.S. Patent No. 9,970,018 by respondent’s accused bacterial strains. The Commission has also determined to reverse the FID’s decision declining to adjudicate respondent’s alternative TTFL12 strain and finds no infringement as to that strain. This opinion sets forth the Commission’s reasoning in support of that determination. In addition, the Commission adopts the findings in the FID that are not inconsistent with this opinion. I. BACKGROUND A. Procedural Background The Commission instituted this investigation on June 21, 2018, based on a complaint, as amended and supplemented, filed by Glycosyn LLC (“Glycosyn”) of Waltham, Massachusetts. See 83 Fed. Reg. 28865-66 (June 21, 2018). The complaint alleged violations of section 337 based upon the importation into the United States, the sale for importation, and the sale within the United States after importation of certain human milk oligosaccharides, by reason of infringement of certain claims of U.S. Patent Nos. 9,453,230 (“the ’230 patent”) and 9,970,018 (“the ’018 patent”). See id. The complaint also alleges the existence of a domestic industry.
PUBLIC VERSION 2 The notice of investigation named Jennewein Biotechnologie GmbH of Rheinbreitbach, Germany (“Jennewein”) as respondent in this investigation. See id. The Office of Unfair Import Investigations (“OUII”) is also a party to this investigation. See id. The Commission later terminated the investigation as to all asserted claims of the ’230 patent and certain asserted claims of the ’018 patent based on the withdrawal of the allegations pertaining to those claims. See Order No. 5 (Aug. 9, 2018), unreviewed, Comm’n Notice (Aug. 29, 2018); Order No. 15 (Oct. 30, 2018), unreviewed, Comm’n Notice (Nov. 29, 2018); Order No. 17 (Nov. 19, 2018), unreviewed, Comm’n Notice (Dec. 12, 2018); Order No. 25 (Feb. 8, 2019), unreviewed, Comm’n Notice (Feb. 28, 2019). Claims 1-3, 5, 8, 10, 12, 18, and 23-28 of the ’018 patent remain pending in this investigation. The ALJ conducted an evidentiary hearing on May 14-17, 2019. On September 9, 2019, the ALJ issued the FID finding a violation of section 337 based on the infringement of claims 1- 3, 5, 8, 10, 12, 18, and 24-28 (hereinafter, “the Asserted Claims”) but not claim 23 of the ’018 patent, based on non-infringement of that claim.1 See FID at 35. Furthermore, the FID finds that the domestic industry requirement is satisfied. The FID also contains a Recommended Determination (“RD”) recommending, should a violation of section 337 be found, that the Commission issue a limited exclusion order (“LEO”) barring entry of articles that infringe the Asserted Claims.2 The RD also recommends that the Commission impose a bond in the amount of five (5) percent of the entered value of the infringing articles during the period of Presidential review. Furthermore, as directed by the 1 Glycosyn did not petition for review of the FID’s finding that Jennewein does not infringe claim 23. 2 Glycosyn did not request, and the RD does not recommend, a cease and desist order against Jennewein.
PUBLIC VERSION 3 Commission (see 83 Fed. Reg. at 28865), the RD provides findings with respect to the public interest and recommends that the Commission determine that the public interest factors do not preclude entry of the proposed LEO. On September 23, 2019, Jennewein and the Commission’s Investigative Attorney (“IA”) filed petitions for review of the FID.3 Jennewein petitioned for review of the FID’s findings with respect to claim construction and infringement, and both Jennewein and the IA petitioned for review of the FID’s decision not to adjudicate infringement with respect to Jennewein’s TTFL12 bacterial strain, which Glycosyn did not accuse in its complaint. On October 1, 2019, Glycosyn and the IA filed responses to the various petitions.4 On October 9 and 10, 2019, respectively, Glycosyn and Jennewein filed statements on the public interest pursuant to Commission Rule 210.50(a)(4), 19 C.F.R. 210.50(a)(4).5 On October 23, 2019, non-party DuPont Nutrition & Health (“DuPont”) filed a public interest submission pursuant to the Commission’s notice requesting public interest comments, see 84 Fed. Reg. 49335 (Sept. 19, 2019), supporting the ALJ’s recommended LEO and asserting that it has the capacity to replace the excluded products in a commercially reasonable time.6 3 See Respondent Jennewein Biotechnologie GmbH’s Petition for Commission Review (Sep. 23, 2019) (hereinafter, “Jennewein’s Pet.”); OUII Petition for Review (Sep. 23, 2019) (hereinafter, “IA’s Pet.”). 4 See Complainant Glycosyn LLC’s Consolidated Response to Respondent Jennewein Biotechnologie GmbH’s and Office of Unfair Import Investigations’ Petitions for Commission Review (Oct. 1, 2019) (hereinafter, “Glycosyn’s Pet. Resp.”); Office of Unfair Import Investigations’ Response to Respondent’s Petition for Review (Oct. 1, 2019) (hereinafter, “IA’s Pet. Resp.”). 5 See Complainant Glycosyn LLC’s Statement of Information Relating to the Public Interest (Oct. 9, 2019) (hereinafter, “Glycosyn’s PI Br.”); Public Interest Statement of Respondent Jennewein Biotechnologie GmbH (Oct. 10, 2019) (hereinafter, “Jennewein’s PI Br.”). 6 See Public Interest Submission of DuPont Nutrition & Health (hereinafter, “DuPont PI Br.”).
PUBLIC VERSION 4 On January 30, 2020, the Commission issued a notice determining to review the FID in part. See 85 Fed. Reg. 6573-75 (Feb. 5, 2020) (“the WTR/Remedy Notice”). Specifically, the Commission determined to review: (1) the FID’s infringement findings with respect to Jennewein’s bacterial strains adjudicated in this investigation; and (2) the FID’s decision not to adjudicate infringement as to Jennewein’s alternative bacterial strain, i.e., the TTFL12 strain. See id. The Commission determined not to review the remainder of the FID. See id. The notice invited written submissions from the parties on issues under review, and from the parties, interested government agencies, and any other interested parties on issues of remedy, the public interest, and bonding. See id. On February 18, 2020, the parties, including OUII, filed written submissions in response to the WTR/Remedy Notice,7 and on February 25, 2020, the parties filed responses to each other’s submissions.8 Also on February 18, 2020, non-party Abbott Laboratories (“Abbott”) filed a written submission concerning the public interest in response to the WTR/Remedy Notice, 7 See Complainant Glycosyn LLC’s Response to Questions in the Commission’s Notice of Commission Decision to Review in Part a Final Initial Determination Finding a Violation of Section 337 (Feb. 18, 2020) (hereinafter, “Glycosyn’s Resp.”); Complainant Glycosyn LLC’s Initial Submission on the Form of Remedy, the Public Interest, and Bonding Pursuant to the Commission’s Notice of Commission Decision to Review in Part a Final Initial Determination Finding a Violation of Section 337 (Feb. 18, 2020) (hereinafter, “Glycosyn’s Remedy Br.”); Respondent Jennewein Biotechnologie GmbH’s Responses to Questions Raised by the Commission (Feb. 18, 2020) (hereinafter, “Jennewein’s Resp.”); Brief of the Office of Unfair Import Investigations on Issues under Review and on Remedy, the Public Interest, and Bonding (Feb. 18, 2020) (hereinafter, “IA’s Resp.”). 8 See Complainant Glycosyn LLC’s Reply to Respondent’s and OUII’s Responses to the Commission’s Questions regarding Final Initial Determination Finding a Violation of Section 337 (Feb. 25, 2020) (hereinafter, “Glycosyn’s Reply”); Respondent Jennewein Biotechnologie GmbH’s Reply to Responses by Glycosyn LLC and the Office of Unfair Import Investigations to Questions Raised by the Commission and Responses to Glycosyn’s and OUII’s Submissions on Remedy, the Public Interest, and Bonding (Feb. 25, 2020) (hereinafter, “Respondents’ Reply”); Reply Brief of the Office of Unfair Import Investigations on Issues under Review and on Remedy, the Public Interest, and Bonding (Feb. 25, 2020) (hereinafter, “IA’s Reply”).
PUBLIC VERSION 5 and alleged that “Jennewein is the only supplier whose product has been fully qualified through Abbott’s quality and regulatory processes, raising public interest concerns from remedial relief.”9 B. The Asserted Patent The ’018 patent issued on May 15, 2018. See JX-3, ’018 Patent. The ’018 patent, titled “Biosynthesis of Human Milk Oligosaccharides in Engineered Bacteria,” relates to “compositions and methods for producing fucosylated oligosaccharides” which are “typically found in human milk” and which “serve critical roles in the establishment of a healthy gut microbiome, in the prevention of disease and in immune function.” See id. at 1:27-39. The specification of the ’018 patent states that “the invention . . . makes use of an engineered bacterium E. coli or other bacteria engineered to produce” fucosylated oligosaccharides. See id. at 15:66-16:4. The ’018 patent specification explains that “[b]iosynthesis of fucosylated HMOS10 requires the generation of an enhanced cellular pool of both lactose and GDP11-fucose.” See id. at 16:27-29; see also id. at Figure 3 (requiring both lactose and GDP-fucose for the synthesis of 2’-fucosyllactose). For example, the specification discloses that “[t]he ability of the E. coli host strain to accumulate lactose was . . . engineered by simultaneous deletion of the endogenous β-galactosidase gene (lacZ) and the lactose operon repressor gene (lacI)” while “the lacIq promoter was placed immediately upstream of the lactose permease gene, lacY.” See id. at 16:37-43 (Example 1). The specification states that “[t]he modified strain thus maintains its 9 See Public Interest Submission of Abbott Laboratories (Feb. 18, 2020) (hereinafter “Abbott’s PI Br.”). 10 “HMOS” refers to Human Milk Oligosaccharides. 11 “GDP” refers to guanosine diphosphate. See JX-3, ’018 Patent at 1:61-63.
PUBLIC VERSION 6 ability to transport lactose from the culture medium via LacY” but the lacZ (β-galactosidase) gene responsible for lactose catabolism (i.e., breakdown) is deleted. See id. at 16:43-47 (Example 1). Therefore, the specification continues, “[a]n intracellular lactose pool is . . . created when the modified strain is cultured in the presence of exogenous lactose.” See id. at 16:47-49 (Example 1). The specification also describes “bacterial host cells with the ability to accumulate a[n] intracellular lactose pool while simultaneously possessing low, functional levels of cytoplasmic β-galactosidase activity for example as provided by the introduction of a functional recombinant E. coli lacZ gene or by a β-galactosidase gene from any of a number of other organisms.” See id. at 7:22-28. The specification explains that “low level of cytoplasmic β-galactosidase activity while not high enough to significantly diminish the intracellular lactose pool is nevertheless very useful for tasks such as phenotypic marking of desirable genetic loci during construction of host cell backgrounds, for detection of cell lysis due to undesired bacteriophage contaminations in fermentation processes, or for the facile removal of undesired residual lactose at the end of fermentations.” See id. at 7:37-45. With regard to GDP-fucose production, the specification of the ’018 patent further states that “[o]ne strategy for GDP-fucose production is to enhance the bacterial cell’s natural synthesis capacity,” e.g., “by inactivating enzymes involved in GDP-fucose consumption, and/or by overexpressing a positive regulator protein, RcsA, in the colanic acid (a fucose containing exopolysaccharide) synthesis pathway.” See id. at 17:4-10. The specification explains that “this metabolic engineering strategy redirects the flux of GDP-fucose destined for colanic acid synthesis to oligosaccharide synthesis.” See id. at 17:10-12.
PUBLIC VERSION 7 Still further, the specification of the ’018 patent describes a “bacterium [that] possesses fucosyl transferase activity,” e.g., “an exogenous fucosyltransferase gene.” See id. at 5:28-32. The specification explains that “[a]n exemplary . . . fucosyltransferase gene is the wcfW gene” and that “[p]rior to the present invention, this wcfW gene . . . was not suspected to possess the ability to utilize lactose as an acceptor sugar,” i.e., as a substrate for HMOS synthesis. See id. at 5:28-38; see also id. at Figure 3 (involving α(1,2)FT, i.e., fucosyltransferase, in the synthesis of 2’-fucosyllactose). Claim 1 of the ’018, from which the remaining asserted claims depend, patent recites the following invention (with the disputed claim limitations in bold): A method for producing a fucosylated oligosaccharide in a bacterium, comprising providing an isolated E. coli bacterium comprising, (i) a deletion or functional inactivation of an endogenous β-galactosidase gene; (ii) an exogenous functional β-galactosidase gene comprising a detectable level of β-galactosidase activity that is reduced compared to that of a wild-type E. coli bacterium, wherein the level of β-galactosidase activity comprises between 0.05 and 200 units; (iii) an inactivating mutation in a colanic acid synthesis gene; and (iv) an exogenous lactose-accepting fucosyltransferase gene; culturing said bacterium in the presence of lactose; and retrieving a fucosylated oligosaccharide from said bacterium or from a culture supernatant of said bacterium. See id. at 111:41-57 (claim 1). C. Domestic Industry Product The FID identifies Glycosyn’s E997 bacterial strain and its production of 2’-fucosyllactose (2’-FL) as practicing at least one claim of the ’018 patent. See FID at 7. The FID also determines that Glycosyn satisfies the domestic industry requirement. See id. at 61-67,
PUBLIC VERSION 8 96-113. No party petitioned for review of these findings, and the Commission determined not to review these findings. D. Accused and Redesigned or Alternative Products The accused product in this investigation is Jennewein’s 2’-FL product which was produced using E. coli bacterial strains #1540 and a derivative thereof, known as “the #1540 derivative” or “the #2410 strain” (collectively, “Accused Strains”). See FID at 7. The FID finds that the Accused Strains infringe the Asserted Claims of the ’018 patent. Jennewein also requested adjudication as to its redesigned or alternative TTFL12 bacterial strain in this investigation. Glycosyn did not accuse that strain in this investigation and the FID declined to adjudicate infringement with respect to that strain. See id. at 28-35. The Commission determined to review the FID’s decision not to adjudicate infringement with respect to the TTFL12 strain. See 85 Fed. Reg. at 6574. II. LEGAL STANDARDS A. Standard on Review Commission Rule 210.45(c) provides that “[o]n review, the Commission may affirm, reverse, modify, set aside or remand for further proceedings, in whole or in part, the initial determination of the administrative law judge” and that “[t]he Commission also may make any findings or conclusions that in its judgment are proper based on the record in the proceeding.” See 19 C.F.R. § 210.45(c). In addition, as explained in Certain Polyethylene Terephthalate Yarn and Products Containing Same, “[o]nce the Commission determines to review an initial determination, the Commission reviews the determination under a de novo standard.” Inv. No. 337-TA-457, Comm’n Op., 2002 WL 1349938, *5 (June 18, 2002) (citations omitted). This is “consistent with the Administrative Procedure Act which provides that once an initial agency
PUBLIC VERSION 9 decision is taken up for review, ‘the agency has all the powers which it would have in making the initial decision except as it may limit the issues on notice or by rule.’” Id. (citing 5 U.S.C. § 557(b)). B. Infringement “An infringement analysis entails two steps. The first step is determining the meaning and scope of the patent claims asserted to be infringed. The second step is comparing the properly construed claims to the device accused of infringing.” Markman v. Westview Instruments, Inc., 52 F.3d 967, 976 (Fed. Cir. 1995) (en banc), aff’d, 517 U.S. 370 (1996) (citations omitted). Infringement must be proven by a preponderance of the evidence. See SmithKline Diagnostics, Inc. v. Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988). The preponderance of the evidence standard “requires proving that infringement was more likely than not to have occurred.” Warner-Lambert Co. v. Teva Pharm. USA, Inc., 418 F.3d 1326, 1341 n.15 (Fed. Cir. 2005). Literal infringement requires the patentee to prove that the accused device contains each and every limitation of the asserted claim(s). See Frank’s Casing Crew & Rental Tools, Inc. v. Weatherford Int’l, Inc., 389 F.3d 1370, 1378 (Fed. Cir. 2004). Where literal infringement is not found, infringement can still be found under the doctrine of equivalents. See TIP Sys., LLC v. Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1376 (Fed. Cir. 2008) (“Infringement under the doctrine of equivalents may be found when the accused device contains an ‘insubstantial’ change from the claimed invention.”) (citations omitted). III. DISCUSSION The Commission determined to review: (1) the FID’s infringement findings with respect to Jennewein’s bacterial strains adjudicated in this investigation; and (2) the FID’s decision not
PUBLIC VERSION 10 to adjudicate infringement as to Jennewein’s alternative or redesigned bacterial strain, i.e., the TTFL12 strain. See 85 Fed. Reg. at 6574. A. Infringement as to the Term Exogenous Functional β-Galactosidase Gene The previously presiding ALJ12 construed “functional β-galactosidase gene” to mean “functional sequence of DNA that encodes β-galactosidase.” See Order No. 22 at 29 (Dec. 18, 2018). No party petitioned for review of that construction. The parties also agreed that “exogenous” is properly construed as “originating outside an organism, tissue, or cell.” See id. at 12. The FID finds that the Accused Strains do not literally satisfy the claim term “an exogenous functional β-galactosidase gene,” but that the term is satisfied under the doctrine of equivalents. See FID at 38-45. The FID reasons that Jennewein’s Accused Strains include two distinct DNA sequences, namely, lacZα and lacZΩ, which, together, encode for the β-galactosidase enzyme. See id. at 38-39. The FID concludes that “Jennewein’s Accused Strains do not literally infringe ‘an exogenous functional β-galactosidase gene’ because they lack a single sequence of DNA which functions to create a β-galactosidase gene.” See id. at 39. Nevertheless, the FID finds “no difference between the combination of lacZα and lacZΩ genes on the one hand, and any particular individual ‘functional β-galactosidase gene’ on the other.” See id. at 40. In addition, the FID recognizes that “lacZα in the Accused Strains was not added by Jennewein, but was present in the original BL21 (DE3) strain which Jennewein engineered to achieve the Accused Strains.” See id. at 44-45. The FID finds, however, that “the exogenous 12 At the time of Order No. 22, the investigation was assigned to the Chief ALJ. On April 2, 2019, the investigation was transferred to Judge Elliot.
PUBLIC VERSION 11 nature of lacZΩ is enough to meet the limitation” at issue. Id. The FID explains that “[i]t is the combination of lacZα and lacZΩ which is equivalent to the claimed ‘β-galactosidase gene,’ and this combination does not exist until lacZΩ is inserted into the bacterium’s genome from outside the organism.” See id. at 45. Thus, the FID concludes, “the combination is ‘exogenous’ and satisfies the claim limitation at least under the doctrine of equivalents.” See id. Jennewein petitioned for review of the FID’s infringement findings with respect to the claim term “an exogenous functional β-galactosidase gene.” Jennewein’s Pet. at 30-35. Jennewein did not dispute the FID’s findings that the combination of the lacZα and lacZΩ genes is equivalent to a functional β-galactosidase gene, but Jennewein argued that the combination is not exogenous because only lacZΩ is exogenous while lacZα is endogenous.13 See id. at 31. Jennewein reasoned that the FID “departs from the parties’ agreed-upon construction for ‘exogenous’” and “incorrectly concludes that ‘[i]t is the combination of lacZα and lacZΩ which is equivalent to the claimed ‘β-galactosidase gene,’ and this combination does not exist until lacZΩ is inserted into the bacterium’s genome from outside the organism.’” See id. (citation omitted) (emphasis in original). Jennewein explained that “[t]he claim language does not encompass a combination of gene fragments that did not ‘exist’ until one fragment is inserted into the genome” but “[r]ather, it requires that the combination itself originated outside of Jennewein’s strain.” See id. (citation omitted). The Commission finds that the FID correctly determined that Jennewein’s Accused Strains include a combination that is equivalent to the claimed “exogenous functional β-galactosidase gene.” See FID at 38-45. Jennewein argued that the ID’s finding that the 13 Jennewein explains that “‘endogenous’ genes are those present in the host strain prior to any genetic engineering.” Jennewein’s Pet. at 34 (citing Hr’g Tr. (Prather) at 441:25-442:4).
PUBLIC VERSION 12 combination “does not exist” in the host strain until lacZΩ is inserted into the bacterium’s genome, is incorrect because, in Jennewein’s view, the construction of “exogenous” (i.e., “originating outside an organism, tissue, or cell”) requires that “the combination itself originate[s] outside of Jennewein’s strain.” See Jennewein Pet. at 31. This alleged distinction, however, is unpersuasive. Indeed, as the FID finds, the combination does not exist in the original strain, and therefore the combination itself does not originate from within the organism. See FID at 44-45 (citing CX-213 at Figure 2, 5158). Thus, the Commission agrees with the FID that “the exogenous nature of lacZΩ is enough” to make the combination exogenous and any difference between the claim term “an exogenous functional β-galactosidase gene” and the accused products is insubstantial. See id. at 45; accord Glycosyn’s Pet. Resp. at 28; IA’s Pet. Resp. at 10. In addition, the Commission finds that lacZα, which is present in the genetically- engineered strain, i.e., BL21[DE3], is also exogenous as compared to the wild-type E. coli bacterium. See Glycosyn’s Pet. Resp. at 30-31. As Glycosyn explains, “[i]t is . . . undisputed that the lacZα gene exists in the BL21(DE3) genome only by way of human intervention.” See id. at 30 (citing CX-213 (Jennewein’s GRAS Notice) at CX-213.297 (“Since its isolation in 1818, the E. coli B strain has also undergone multiple rounds of genetic manipulation resulting in the strain BL21 (DE3).”); RX-386C (Parschat14) at Q/As 68-69). In addition, “it is undisputed that the DE3 is derived from a prophage, or in other words, a virus, that infects E. coli. to insert foreign DNA into the E. coli.” See id. at 31 (citing RX-386C (Parschat) at Q/As 133-134 (“We discovered there was actually a lacZ[α] like fragment already present in the DE3 prophage in the 14 Katja Parschat is Jennewein’s Deputy Head of Research and Development.
PUBLIC VERSION 13 genome of strain #1540. . . . A prophage is the genome [of] an E. coli virus or phage or part of that genome that is integrated into the bacterial chromosome replicate.”)). The language of the Asserted Claims and the specification of the ’018 patent make clear that the claimed genetically-engineered bacterium and its “exogenous functional β-galactosidase gene” are to be compared to the native or wild-type E. coli bacterium rather than to a genetically- engineered strain, i.e., BL21[DE3]. See JX-3, ’018 patent at 111:45-49 (claim 1) (“A method for producing a fucosylated oligosaccharide in a bacterium comprising[:] providing an isolated E. coli bacterium comprising . . . an exogenous functional β-galactosidase gene comprising a detectable level of β-galactosidase activity that is reduced compared to that of a wild-type E. coli bacterium.”) (emphasis added); id. at 5:1-5 (“The bacteria used herein to produce HMOS are genetically engineered to comprise an increased intracellular guanosine diphosphate (GDP)- fucose pool, an increased intracellular lactose pool (as compared to wild type) and to comprise fucosyl transferase activity.”) (emphasis added); id. at 6:45-53 (“In the case of lactose and GDP- fucose, endogenous E. coli metabolic pathways and genes are manipulated in ways that result in the generation of increased cytoplasmic concentrations of lactose and/or GDP-fucose, as compared to levels found in wild type E. coli. For example the bacteria contain at least 10%, 20%, 50%, 2x, 5x, 10x or more of the levels in a corresponding wild type bacteria that lacks the genetic modifications described above.”) (emphasis added). There is no dispute that, as compared to the wild-type E. coli bacterium, both lacZα and lacZΩ are exogenous, i.e., they “originat[e] outside an organism, tissue, or cell.” See CX-213 at CX-213.297; RX-386C (Parschat) at Q/As 68-69, 133-34. Thus, the Commission has determined to affirm with modification the FID’s finding that the Accused Strains infringe the
PUBLIC VERSION 14 Asserted Claims under the doctrine of equivalents, and supplements the FID’s analysis as discussed above. B. Adjudication of Infringement with Respect to the TTFL12 Strain During the investigation, Jennewein sought adjudication of infringement with respect to its TTFL12 bacterial strain, which Glycosyn did not accuse in its complaint. Jennewein identified the TTFL12 strain on September 14, 2018, in its Ground Rule 7.2 disclosure15 (CX-226C) and in its interrogatory responses served on November 5, 2018 (CX-237C). Jennewein further provided two documents, RX-320C (a draft article) and RX-382 (European Patent Application No. 14 162 869.3) (both produced on August 21, 2018), to establish the relevant features of the TTFL12 strain. The FID declines Jennewein’s request for adjudication, reasoning that “there can be no dispute that Glycosyn has not accused [the TTFL12 strain] of infringement.” See FID at 28. The FID states that Commission precedent follows “a four-factor test as to whether a respondent has met its burden to show that infringement of a redesigned product should be adjudicated,” namely, whether “[t]he product [is]: (1) within the scope of the investigation, (2) imported, (3) sufficiently fixed in design, and (4) subject to extensive discovery.” See id. at 29 (citing Certain Two-Way Radio Equipment and Systems, Related Software, & Components Thereof, Inv. No. 337-TA-1053, Comm’n Op. at 8, 2018 WL 8648379 (Dec. 18, 2018) (“Two-Way Radio”)). “Of these factors, [the FID] finds Respondents have not met their burden as to the fourth factor, subject to extensive discovery.” See id. Specifically, the FID determines that Jennewein failed to “provide[] ‘extensive’ or ‘sufficient’ discovery on the TTFL12 strain.” See 15 Ground Rule 7.2 relates to the “Disclosure of Products Within the Scope of the [Notice of Investigation].” See Order No. 2 (June 21, 2018).
PUBLIC VERSION 15 id. at 32. The FID reasons that “while Jennewein identified TTFL12 as falling under the scope of the investigation in its Ground Rule 7.2 disclosure [(CX-226C)], and identified the ‘draft’ article, RX-0320C, as evidence of TTFL12’s relevant features, it did not identify the patent application [(RX-382)] such that Glycosyn would have been on notice of it,” because the patent application “does not refer to TTFL12 by name.” See id. at 32-33. The FID further finds that “RX-0320C may provide information on the conception of TTFL12, but it does not sufficiently identify and describe a product that could serve as an accused product.” See id. at 34. The FID also rejects Jennewein’s discovery responses as insufficient because they were served on the last day of discovery, which ended on November 5, 2018. See id. The FID determines that Jennewein’s failure to identify TTFL12 in response to Glycosyn’s request for admission on importation “was more than enough to dissuade Glycosyn from investigating anything other than the #1540 strain during discovery.” See id. at 34-35. The FID further finds that “Glycosyn [was] on notice of just three things: a strain referred to as TTFL12 exists and was described in an unpublished, undated article as lacking a lacZ gene (CX-0226; CX-0320C); at some point the strain was used to create an unspecified amount of 2’-FL (CX-2037C at 1-2); but that 2’-FL had not been imported into the United States (CX-0216C at 5).” See id. at 34. The FID recognizes that “Glycosyn failed to take discovery of its own on [the TTFL12] issue . . . and to respond to Jennewein’s own requests for admission on TTFL12,” but the FID finds that “it is Jennewein’s burden to introduce TTFL12-based 2’-FL into the case.” See id. at 35 (citing Two-Way Radio). Thus, the FID concludes that “adjudication of whether the TTFL12 strain infringes [is not] appropriate at this time because the discovery on TTFL12 was not adequate.” See id.
PUBLIC VERSION 16 Jennewein and the IA petitioned for review of the FID’s alleged failure to adjudicate infringement with respect to Jennewein’s TTFL12 bacterial strain. Jennewein’s Pet. at 35-41; IA’s Pet. at 5-22. Jennewein argued that the FID errs in requiring a heightened burden of “extensive discovery” where Commission precedent requires only that the respondent “provid[e] sufficient information to put the complainant on notice that [the TTFL12 strain] may be at issue.” See Jennewein’s Pet. at 37-38 (citing Certain Television Sets, Television Receivers, Television Tuners, & Components Thereof, Inv. No. 337-TA-910, Order No. 46 at 23 (Nov. 28, 2014), unreviewed, Comm’n Notice (Dec. 3, 2014)); accord IA’s Pet. at 22 (“[T]he [FID’s] conclusion that the disclosure was somehow not ‘sufficient’ was a clearly erroneous finding of material fact that merits review by the Commission.”). Jennewein also argued that the FID should have adjudicated non-infringement because the “TTFL12 strain lacks a functional β-galactosidase gene, and therefore it is incapable of having any β-galactosidase activity as the claim clearly requires.” See Jennewein’s Pet. at 39. Jennewein asserted that “[its] witnesses explained the structure and capabilities of the TTFL12 strain such that a noninfringement opinion would be straightforward.” See id. at 39-40 (citing RX-320C (Jennewein draft manuscript produced August 2018) (“[g]enes encoding proteins involved in pathways that compete with 2’-FL biosynthesis were inactivated or deleted”); RX- 409C (Stephanopoulos16 RWS17) at Q/A 278 (testifying that the lacZ gene has been deleted or inactivated and that TTFL12 was not further engineered to insert a functional exogenous β-galactosidase gene); Hr’g Tr. (Parschat) at 384:10-17 (“The complete lacZ gene as occurs in 16 Gregory Stephanopoulos was Jennewein’s technical expert in this investigation. 17 “RWS” refers to Rebuttal Witness Statement.
PUBLIC VERSION 17 the operon is not present in the TTFL-12 strain.”); RX-387C (Parkot18 Witness Statement (“WS”)) at Q/A 85 (“The TTFL12 strain is a 2’-FL production strain that has no β-galactosidase (lacZ) gene and does not use lactose to synthesize 2’-FL.”); see also IA’s Pet. at 16-17 (“Unlike in the bacterial strain discussed in the ’018 Patent, in the TTFL12 strain the inactivated lacZ gene was not replaced with an exogenous functional β-galactosidase gene.”) (citing RX-320C). Accord IA’s Resp. at 3-7; Jennewein’s Resp. at 2-11. Jennewein further argued that the FID “improperly rewards Glycosyn for its refusal to take discovery on the TTFL12 strain.” See Jennewein’s Pet. at 40. Jennewein reasons that “Glycosyn never tested the TTFL12 strain during its inspection of Jennewein’s facilities in Germany, even though it had every chance to do so” and “never asked its expert, Dr. Prather, to opine on TTFL12.” See id. (citing Hr’g Tr. (Prather19) at 558:11-14 (“Q. . . . So you at least never asked, through Dr. Wheeler or otherwise, to test the TTFL-12 strain; correct? A. That’s correct. We never asked for it.”), 509:17-25); see also id. at 530:17-19 (“Q. So you did not analyze the TTFL-12 strain for the purpose of this investigation? A. I did not.”); accord IA’s Pet. at 14-15 (“A complainant cannot willfully ignore evidence of noninfringement presented in discovery and then expect that any remedy imposed will apply to the products that the complainant declined to investigate.”) (citing Certain Electronic Digital Media Devices & Components Thereof, Inv. No. 337-TA-796, Comm’n Op., 2013 WL 10734395, *71 (Sept. 6, 2013) (“Electronic Digital Media Devices”) (“When confronted with Samsung’s evidence of noninfringement, Apple had an obligation to either present evidence of infringement or withdraw its allegations concerning these products, but it did neither.”)). 18 Julia Parkot is Jennewein’s Head of Quality Management. 19 Kristala L. Jones Prather was Glycosyn’s technical expert in this investigation.
PUBLIC VERSION 18 Glycosyn argued that Jennewein failed to satisfy its burden under Two-Way Radio to establish that the TTFL12 product is fixed in design and that it was imported, and that Jennewein did not provide sufficient discovery on TTFL12. See Glycosyn’s Pet. Resp. at 33-34. Glycosyn reasoned that “Jennewein failed to produce even the most basic common laboratory documents for any of its strains, including its #1540 production strain.” See id. at 34. Glycosyn further argued that “Jennewein and Staff are . . . wrong to suggest that Glycosyn should have done more to obtain discovery regarding Jennewein’s TTFL12 strain” and that “Glycosyn sought, and Jennewein failed to produce, documents sufficient to describe the nature or use of TTFL12.” See id. at 41. The Commission has determined to reverse the FID’s decision not to adjudicate the TTFL12 bacterial strain.20 The Commission previously stated that the test for determining whether a respondent has met its burden for adjudication of a redesigned or alternative product includes four factors: (1) whether the product is within the scope of the investigation; (2) whether it has been imported21; (3) whether it is sufficiently fixed in design; and (4) whether it has been sufficiently disclosed by respondent during discovery. See Two-Way Radio, 2018 WL 8648379 at *13-14. The Commission also reiterates its policy in favor of adjudicating redesigns to prevent subsequent and potentially burdensome proceedings that could have been resolved in the first instance in the original Commission investigation. See, e.g., Certain 20 Commissioner Schmidtlein dissents from Part III(B) of the Commission’s decision and has filed a separate opinion concurring in part and dissenting in part. 21 The Commission notes that while importation may be relevant to the inquiry, actual importation of the redesign is not a mandatory requirement. See, e.g., Certain Multiple Mode Outdoor Grills and Parts Thereof, Inv. No. 337-TA-895, Comm’n Op. at 20 (July 23, 2014); Certain Television Sets, Certain Television Receivers, Television Tuners, and Components Thereof, Inv. No. 337-TA-910, Order No. 46 (Initial Determination) at 29 (Nov. 28, 2014) (Lord, J.) (not reviewed).
PUBLIC VERSION 19 Television Sets, Television Receivers, Television Tuners, & Components Thereof, Inv. No. 337- TA-910, Order No. 46 at 23-24 (Nov. 3, 2014), unreviewed, Comm’n Notice (Dec. 3, 2014) (“As a policy matter, ‘consideration of design around products during the course of the proceedings before the ALJ provides predictability in enforcement of the order by U.S. Customs and Border Protection.”) (quoting Certain Multiple Mode Outdoor Grills & Parts Thereof, Inv. No. 337-TA- 895, Comm’n Op., 2014 WL 12890485, *10 (July 23, 2014)). However, redesigned products are still within the scope of remedial orders that are issued upon the termination of the investigation even if such products were not adjudicated for infringement in the original investigation. See Certain Optical Disk Controller Chips & Chipsets & Prods. Containing Same, Including DVD Players & PC Optical Storage Devices, Inv. No. 337-TA-506, Comm’n Op., 2007 WL 4713920, *64 (Sept. 28, 2005) (“[W]hile individual models may be evaluated to determine importation and infringement, the Commission’s jurisdiction extends to all models of infringing products that are imported at the time of the Commission’s determination and to all such products that will be imported during the life of the remedial orders.”) (internal quotation omitted); cf. IA’s Pet. at 8 (“[A]lthough it refused to identify TTFL12-based 2’-FL as an accused product, Complainant argued that the product should nevertheless be covered by any exclusion order that issues in this investigation.”). To the contrary, once a respondent has been determined to be in violation of the Commission’s remedial orders, such orders extend to all infringing products (e.g., respondent’s redesigned products), whether or not they were adjudicated in the original investigation. The Commission agrees with the FID that the record evidence establishes that the first three factors specified above are satisfied. See FID at 29. With respect to factor (1) (scope of the investigation), there is no dispute that the 2’-FL produced with the TTFL12 strain is within
PUBLIC VERSION 20 the scope of the investigation, which is defined in the notice of investigation as “2’-fucosyllactose oligosaccharides.” See 83 Fed. Reg. at 28865. As to factor (2) (importation), although Jennewein did not identify TTFL12 in its September 20, 2018 response to Glycosyn’s request for admission as to importation (because it had not been imported at the time), see CX-216C at 5, there is ample evidence that the 2’-FL product from that strain was subsequently imported on October 11, 2018, prior to the close of fact discovery. See IA’s Pet. at 10-12 (citing FID at 34; RX-278C (Jennewein shipping invoice); RX-279C (Jennewein 2’-FL material safety data sheet); RX-280C (summary of Jennewein 2’-FL importation); RX-385C (Jennewein WS) at Q/As 135 (“180 g of 2’-FL produced by using the TTFL12 strain were imported into the U.S.”), 171-72; RX-387C (Parkot WS) Q/As 101-110); Hr’g Tr. at 347:6-22, 348:7-25 (Parkot); id. at 215:24-216:7 (Jennewein)). The record evidence also demonstrates that the TTFL12 strain satisfies factor (3) (sufficiently fixed in design). As Jennewein’s witnesses testified, see Hr’g Tr. at 197:12-21 (Jennewein), “[t]he strain has been in development since 2012” and “[a] lot of different fermentation runs have been done since then.” See also id. at 347:6-22 (Parkot) (discussing certain records showing that Jennewein has actually produced 2’-FL using the TTFL12 strain). Lastly, as to factor (4) (sufficient disclosure in discovery), the Commission disagrees with the FID’s conclusion that Jennewein has not met its burden to establish that this factor is satisfied. See FID at 29. Jennewein was required to provide sufficient (not extensive)22 fact and expert discovery to put Glycosyn on notice of that strain and its relevant features. Cf. Two- 22 The FID recites both “sufficient” and “extensive” evidence (see, e.g., FID at 29, 32), but as explained herein, the test for adjudicating redesigns does not require extensive discovery. Rather, the test requires discovery that is sufficient for the complainant to assess the features relevant to the asserted patent claims.
PUBLIC VERSION 21 Way Radio, 2018 WL 8648379 at *14 (“[T]he principal issues on review are (1) whether [respondent] produced discovery that is sufficient to inform [complainant] with respect to the redesigned product features relevant to the asserted . . . patents . . . ; and (2) whether [complainant’s] decision not to assert infringement by the redesigned products with respect to these [asserted] patents constitutes a failure to satisfy its burden to prove infringement.”). The Commission finds that Jennewein presented sufficient documentary evidence as well as fact and expert testimony to put Glycosyn on notice of the relevant features of the TTFL12 strain.23 Specifically, Jennewein identified the TTFL12 strain on September 14, 2018, in its Ground Rule 7.2 disclosure (CX-226C) and in its interrogatory responses served on November 5, 2018 (CX-237C). Jennewein also produced two key documents, RX-320C and RX-382 (both produced on August 21, 2018, well before November 5, 2018, the close of fact discovery), supported by expert and witness testimony, showing the relevant features of the TTFL12 strain and establishing that the strain does not infringe the asserted patent because it lacks an exogenous functional β-galactosidase gene (lacZ). See Jennewein’s Resp. (citing RX-382 at 24 (Eur. App. No. 14 162 869.3) (showing that the TTFL12 strain was engineered to make lactose inside the cell and to lack or inactivate the β-galactosidase gene because the gene otherwise destroys the lactose feedstock needed to make 2’-FL)); see also RX-409C (Stephanopoulos RWS) at Q/As 279-280 (“[RX-382] describes a preferred bacterial host cell lacking expression of lacZ in one embodiment.”); RX-386C (Parschat WS) at Q/As 161 (“The lacZ gene . . . is 23 The Dissent dismisses witness testimony provided after the close of discovery and/or at the hearing but such testimony is based on expert reports or deposition testimony which must be produced during discovery (generally, such reports are not included in the record evidence). See Order No. 24, Ground Rule 11.5.5 (“An expert’s testimony at the trial shall be limited in accordance with the scope of his or her expert report(s), deposition testimony, or within the discretion of the Chief Administrative Law Judge. Direct testimony from an expert that is outside this scope will be excluded.”).
PUBLIC VERSION 22 actually detrimental since it degrades the lactose substrate needed to make 2’-FL. . . . Since no addition of lactose is needed for 2’-FL production using the TTFL12 strain there is no lactose to remove and the lacZ gene is unnecessary.”); Hr’g Tr. (Jennewein) at 226:25-227:7 (testifying that TTFL12 strain lacked a lacZ gene because there is no surplus of lactose which would have required β-galactosidase to eliminate the surplus); RX-385C (Jennewein24) at Q/As 166-174. The FID finds that exhibits RX-320C and RX-382 have low probative value or provide unreliable evidence of an accused product’s features. See FID at 33-34. However, the testimonial (fact and expert) evidence establishes the relevance of the documents to Jennewein’s non-infringement claims. See, e.g., RX-409C (Stephanopoulos RWS) at Q/As 272-86 (discussing RX-320C and Jennewein’s non-infringement theory, i.e., that the lacZ gene has been deleted or inactivated and that TTFL12 was not further engineered to insert a functional exogenous β-galactosidase gene); Hr’g Tr. (Parschat) at 384:10-17 (testifying that “[t]he complete lacZ gene as occurs in the operon is not present in the TTFL-12 strain”); RX-387C (Parkot WS) at Q/A 85 (“The TTFL12 strain is a 2’-FL production strain that has no β- galactosidase (lacZ) gene and does not use lactose to synthesize 2’-FL.”); accord IA’s Pet. at 13- 14, 16-17, 19-22, 19-20 (“[T]he ALJ appears to have overlooked the hearing testimony of . . . Ms. Parkot . . . [which] is sufficient to supply the missing link between the 2’-FL that was ‘actually produced’ and the TTFL12 strain described in the draft Jennewein article, RX-320C.”), 20 (“RX-382 demonstrates that Respondent had developed a ‘total fermentation’ strain by no later than early 2014, when the European patent application was filed.”). With regard to the FID’s comment that “[a]n earnest effort to force TTFL12 into the investigation would have seen Jennewein prove to Glycosyn the nature of TTFL12, and how it 24 Stefan Jennewein is the Managing Director of Jennewein.
PUBLIC VERSION 23 had been used to produce imported 2’-FL, before the very last day of fact discovery,” FID at 35, the Commission notes that the parties do not dispute that Jennewein produced relevant discovery as to TTFL12 within the fact discovery period established by the procedural schedule. If Glycosyn and its expert deemed such evidence to be insufficient, Glycosyn could and should have taken available procedural steps, such as a motion to reopen discovery or to compel further discovery, because the burden of establishing infringement remains with Glycosyn.25 The Commission also finds that Glycosyn failed to satisfy its burden of establishing infringement with respect to Jennewein’s TTFL12 strain. See Medtronic, Inc. v. Mirowski Family Ventures, LLC, 571 U.S. 191, 194 (2014) (holding that the burden of proving infringement remains with the patentee even in a declaratory judgment action to establish non- infringement); Electronic Digital Media Devices, 2013 WL 10734395, *71 (“When confronted with Samsung’s evidence of noninfringement, Apple had an obligation to either present evidence of infringement or withdraw its allegations concerning these products, but it did neither.”). Unlike the accused #1540 strain and its derivative, there is no evidence that a lacZΩ fragment was inserted into the TTFL12 strain or any of its precursors. See RX-320C at 17-18 25 In Glycosyn’s submissions to the Commission in response to the notice of review, Glycosyn does not contend that the testimony of fact witnesses or the opinions of Jennewein’s expert witness provided in discovery were insufficient to apprise it of information relating to the TTFL12 strain or Jennewein’s non-infringement theory. Glycosyn’s Resp. at 35-39, Glycosyn’s Reply at 13-16. Indeed, the IA points out that “Glycosyn failed to question any witnesses about the product during fact discovery, or to test a sample of the TTFL12 strain or 2’-FL made using the TTFL12 strain during its onsite testing at Jennewein’s facility.” IA’s Resp. at 34; see also Jennewein Resp. at 32-33 (“Glycosyn never questioned any of Jennewein’s fact witnesses at their depositions about the properties of the TTFL12 strain. SIB at 71. And when it traveled to Jennewein’s German facility to conduct testing of Jennewein’s other production strains – six weeks after Jennewein had disclosed TTFL12 and its genetic composition – Glycosyn never asked to test it.”). Glycosyn does not deny the IA and Jennewein’s assertions that it chose not to question witnesses or to test the TTFL12 strain or 2’-FL made using the TTFL12 strain during its on-site testing in Germany. Glycosyn’s Reply at 15.
PUBLIC VERSION 24 (Table 1); RX-409C (Stephanopoulos RWS) at Q/As 277-278 (testifying that “the lacZ gene has been deleted or inactivated” and that “TTFL12 was not further engineered to insert a functional exogenous β-galactosidase gene”); see also Hr’g Tr. (Parschat) at 384:10-17 (“The complete lacZ gene as occurs in the operon is not present in the TTFL-12 strain.”); RX-386C (Parschat WS) at Q/As 159-160 (“[T]here is no β-galactosidase gene so the strain cannot produce β-galactosidase.”); RX-387C (Parkot WS) at Q/A 85 (“The TTFL12 strain is a 2’-FL production strain that has no β-galactosidase (lacZ) gene and does not use lactose to synthesize 2’-FL.”); RX-385C (Jennewein) at Q/As 160-62, 176-177 (testifying that “[Jennewein] deleted the lacZ gene and also did not insert any β-galactosidase gene or complementary β-galactosidase gene fragments so there can be no β-galactosidase activity”); Hr’g Tr. (Jennewein) at 227:8-13 (testifying that he wrote the RX-320 article). Thus, based on the record evidence, the Commission finds that the TTFL12 strain does not contain an “exogenous functional β- galactosidase gene comprising a detectable level of β-galactosidase activity” as required by the Asserted Claims. Accord IA’s Resp. at 3-7; Jennewein’s Resp. at 2-11. Unlike Jennewein, Glycosyn presented no expert evidence to establish the presence of a lacZ gene or lacZΩ fragment in the TTFL12 strain, and thereby infringement by that strain, arguing instead that Jennewein presented insufficient discovery. See Glycosyn’s Resp. at 11; see also Centricut, LLC v. Esab Group, Inc., 390 F.3d 1361, 1370 (Fed. Cir. 2004) (finding no infringement where “a patent law plaintiff who presents complex subject matter without inputs from experts qualified on the relevant points in issue when the accused infringer has negated
PUBLIC VERSION 25 infringement with its own expert.”).26 Glycosyn asserts that “TTFL12[] contain[s] a functional lacZα β-galactosidase gene,” but Glycosyn says nothing about lacZΩ. See Glycosyn’s Resp. at 11-14. As the FID finds, “[i]t is the combination of lacZα and lacZΩ which is equivalent to the claimed ‘β-galactosidase gene,’ and this combination does not exist until lacZΩ is inserted into the bacterium’s genome from outside the organism.” See FID at 45; see also Hr’g Tr. (Prather) at 436:1-6 (agreeing that “the alpha fragment[] . . . cannot make beta-galactosidase on its own”). Nor is there any evidence that the lacZΩ was inserted in the TTFL12 strain. Thus, the Commission finds that Glycosyn failed to establish that the TTFL12 strain contains an “exogenous functional β-galactosidase gene comprising a detectable level of β-galactosidase activity” as required by the Asserted Claims. Accordingly, Glycosyn failed to satisfy its burden to establish infringement by the TTFL12 strain.27 Thus, the Commission has determined to reverse the FID’s decision not to adjudicate infringement with respect to the TTFL12 strain and provides its reasoning above as to why such adjudication is warranted. The Commission further finds that the TTFL12 strain does not infringe the Asserted Claims as discussed above. 26 The ALJ determined that “one of ordinary skill in the art would have (1) a Ph.D in molecular biology, biochemistry, or chemical engineering, or an equivalent field, and 1-2 years of experience working with E. coli bacteria or related systems, or (2) a lower level degree (e.g., a M.A.) in a similar field to those listed above, but a greater amount of relevant working experience (e.g., 5-6 years of experience working with E. coli bacteria or related systems).” See Order No. 22 at 7. 27 Glycosyn also argues that 35 U.S.C. § 295 creates a presumption that Jennewein’s product was made by the patented process, and that Jennewein has the burden to establish that the product was not made by the patented process. See Glycosyn’s Resp. at 14-18. Glycosyn waived this argument both before the ALJ and the Commission. See Order No. 38 at 2-3 (June 14, 2019); 19 C.F.R. § 210.43(b)-(c); see Finnigan Corp. v. ITC, 180 F.3d 1354, 1362-63 (Fed. Cir. 1999) (“A party seeking review . . . of a determination by the Commission must specifically assert the error made by the ALJ in its petition for review to the Commission.”). In any event, the record in this investigation shows that any presumption under 35 U.S.C. § 295 is overcome by Jennewein as to the TTFL12 strain.
PUBLIC VERSION 26 IV. REMEDY, PUBLIC INTEREST, AND BONDING The RD recommends that the Commission issue an LEO barring entry of Jennewein’s articles that infringe the asserted patent claims. See RD at 116-18. The RD does not recommend that the Commission issue a CDO against Jennewein.28 The RD further recommends that the Commission impose a five (5) percent bond during the period of Presidential review. See id. at 118-19. Still further, as directed by the Commission, the RD provides findings with respect to the public interest and recommends that the Commission determine that the public interest factors do not preclude entry of the proposed LEO. See id. at 119-20. A. Limited Exclusion Order The Commission has “broad discretion in selecting the form, scope, and extent of the remedy.” Viscofan, S.A. v. US. Int’1 Trade Comm’n, 787 F.2d 544, 548 (Fed. Cir. 1986). Section 337(d)(1) provides that “[i]f the Commission determines, as a result of an investigation under this section, that there is a violation of this section, it shall direct that the articles concerned, imported by any person violating the provision of this section, be excluded from entry into the United States, unless, after considering the [public interest], it finds that such articles should not be excluded from entry.” 19 U.S.C. § 1337(d)(1). See also Spansion, Inc. v. Int’l Trade Comm’n, 629 F.3d 1331, 1358 (Fed. Cir. 2010) (“[T]he Commission is required to issue an exclusion order upon the finding of a Section 337 violation absent a finding that the effects of one of the statutorily-enumerated public interest factors counsel otherwise.”). The RD recommends that the Commission issue an LEO excluding Jennewein’s infringing 2’-FL product. See RD at 117. Consistent with its decision not to adjudicate the 28 Glycosyn does not request a CDO against Jennewein.
PUBLIC VERSION 27 TTFL12 strain, the RD recommends against a carve-out for 2’-FL product made with the TTFL12 strains. See id. The RD, however, recommends “a certification provision, wherein said certification is required to state with particularity the grounds of non-infringement of the imported oligosaccharide and be accompanied by sufficient corroborating evidence of the type provided in discovery in this investigation.” See id. at 118. The Commission has determined to issue an LEO barring importation of 2’-fucosyllactose oligosaccharides that infringe the Asserted Claims. Consistent with its finding that the TTFL12 strain does not infringe the Asserted Claims, the Commission has determined to include an explicit carve-out for 2’-FL product made with the TTFL12 strain. In addition, the Commission has determined that the LEO should include the standard certification provision. The Commission finds that the certification provision is justified because it may not be readily apparent by inspection whether the imported article is covered or exempted by the LEO, i.e., whether the imported 2’-FL product is made by an infringing strain (e.g., bacterial strains #1540 and its derivative) or by a non-infringing strain (i.e., the TTFL12 strain). See Certain Graphics Sys., Components Thereof, & Consumer Prods. Containing the Same, Inv. No. 337-TA-1044, Comm’n Op. at 65-66 (Sept. 18, 2018). To be clear, as the Commission has previously held, “[t]he standard certification ‘does not apply to redesigns that have not been adjudicated as non- infringing.’” See Automated Teller Machines, ATM Modules, Components Thereof, & Prods. Containing the Same, Inv. No. 337-TA-972, Comm’n Op., 2017 WL 11198798, *16-17 (June 12, 2017) (quoting Certain Marine Sonar Imaging Devices, Including Downscan & Sidescan Devices, Prods. Containing the Same, & Components Thereof, Inv. No. 337-TA-921, Commn Op., 2016 WL 10987364, *53 (Jan. 6, 2016)).
PUBLIC VERSION 28 Thus, the Commission has determined to issue an LEO: (1) covering “2’-fucosyllactose oligosaccharides that infringe the Asserted Claims”; (2) including the standard certification provision in the LEO; and (3) including an explicit carve-out for 2’-FL product made with the TTFL12 strain. B. The Public Interest Section 337 requires the Commission, upon finding a violation of section 337, to issue an LEO “unless, after considering the effect of such exclusion upon the public health and welfare, competitive conditions in the United States economy, the production of like or directly competitive articles in the United States, and United States consumers, it finds that such articles should not be excluded from entry.” 19 U.S.C. § 1337(d)(l). The RD “do[es] not find the requested [LEO] would meaningfully impact public health and welfare, competitive conditions, domestic production of articles, or U.S. consumers.” See RD at 120. The RD finds that “the purpose of providing 2’-FL in infant formula is to improve public health, [but] the evidence shows that the otherwise well-established market has only recently begun including 2’-FL into its products, and with amounts that have unclear efficacy levels.” See id. The RD concludes that “[t]he U.S. public is therefore not dependent on such products, as of yet.” See id. 1. Public Health and Welfare Jennewein argues that “2’-FL has important health benefits, including its use in infant formula,” and “at this time, Jennewein is the only company that can supply 2’-FL to the U.S. market in commercial quantities.” See Jennewein’s PI Br. at 1. Jennewein further argues that its product is incorporated as an ingredient in Abbott’s Similac® product which is “the number one selling infant formula” in the U.S. See id. (citing RX-385C (Jennewein WS) at Q/A 187).
PUBLIC VERSION 29 Jennewein faults the RD for stating that the “market has only recently begun including” its 2’-FL product. See id. at 2. To the contrary, Jennewein continues, “Abbott has been adding 2’-FL in its infant formula since 2016” and “there is no reason to doubt that Abbott chooses to include 2’-FL in its Similac® because of the health benefits of 2’-FL.” See id. (citing CX-205); accord Abbott’s PI Br. at 1-3. Glycosyn does not dispute that “HMOs provide health benefits.” See Glycosyn’s Remedy Br. at 2. Glycosyn, however, argues that the proposed LEO will not adversely impact the public health or welfare. See id. at 2-4. Glycosyn reasons that “only a subsection of infant formulas in the United States contain 2’-FL, and that even in those that do, the amounts ‘have unclear efficacy levels.’” See id. at 3 (citing RD at 120); accord IA’s Resp. at 39-40. Glycosyn also explains that there are “many entities that can meet the demand for 2’-FL in the United States.” See Glycosyn’s Remedy Br. at 4; IA’s Resp. at 40-42; DuPont PI Br. at 1-2. The Commission finds no evidence that the LEO would adversely affect the public health and welfare, particularly in view of the Commission’s determination that using the TTFL12 strain does not infringe the Asserted Claims. For example, Jennewein can import its 2’-FL product if it certifies that such product was produced using the TFL12 strain. Thus, the Commission finds that the LEO discussed supra section IV(A) would not have an adverse effect on the public health and welfare. 2. Competitive Conditions in the United States Economy Jennewein argues that “[it] is the only company currently producing 2’-FL for infants in the U.S. market on a commercial scale.” See Jennewein’s PI Br. at 4 (citing Hr’g Tr. (Newburg29) at 57:3-4; RX-385C (Jennewein WS) at Q/A 188). According to Jennewein, “there 29 Howard Newburg is Co-Chief Executive Officer and Chief Financial Officer of Glycosyn.
PUBLIC VERSION 30 is no showing that Glycosyn can offer any product at this time or in the near future, let alone produce quantities sufficient to replace Jennewein’s production.” See id. at 4. Glycosyn disagrees and argues that “[its] licensee, Friesland, and other third-party industry leaders can replace the subject articles in the U.S. in a commercially reasonable time.” See Glycosyn’s Remedy Br. at 4-5; accord IA’s Resp. at 44; DuPont PI Br. at 1-2. The Commission finds no evidence that the LEO would adversely affect the competitive conditions in the United States economy, particularly in view of the Commission’s determination that using the TTFL12 strain does not infringe the Asserted Claims. For example, Jennewein can import its 2’-FL product if it certifies that such product was produced using the TTFL12 strain. Moreover, the evidence indicates alternative suppliers (including Glycosyn, FrieslandCampina, Glycom, and DuPont) can also replace the excluded products within a commercially reasonable time. See IA’s Resp. at 41-42 (citing, inter alia, RX-385C (Jennewein WS) at Q/A 135; CX-3C (Newburg WS) Q/As 76, 79-80). Thus, the Commission finds that the LEO discussed supra section IV(A) would not have an adverse effect on the competitive conditions in the United States economy. 3. The Production of Like or Directly Competitive Articles Jennewein does not address this factor specifically, but its arguments as to this factor appear to be the same as discussed above in connection with competitive conditions in the United States economy. See Jennewein’s PI Br. at 3-4. Both Glycosyn and the IA argue that the proposed LEO will have no effect on this factor because there is no evidence that the 2’-FL product is produced domestically in the United States. See Glycosyn’s Remedy Br. at 7; accord IA’s Resp. at 45. The Commission finds that the presence of alternative suppliers capable of providing alternative non-infringing 2’-FL product (including Glycosyn, DuPont, and Jennewein itself)
PUBLIC VERSION 31 negates any evidence that the LEO would adversely affect the production of like or directly competitive articles, particularly in view of the Commission’s determination that using the TTFL12 strain does not infringe the Asserted Claims. For example, Jennewein can import its 2’-FL product if it certifies that such product was produced using the TTFL12 strain. Thus, the Commission finds that the LEO discussed supra section IV(A) would not have an adverse effect on the production of like or directly competitive articles. 4. United States Consumers Jennewein argues that the requested LEO would have a severely negative impact on U.S. consumers. See Jennewein’s PI Br. at 4-5. Jennewein explains that it is “the only company making GRAS-approved 2’-FL on a commercial scale for the U.S. market.” See id. Glycosyn asserts that “alternative suppliers of biosynthesized 2’-FL by Glycosyn’s licensee Friesland, Glycom, and DuPont can provide ample replacement articles of like or directly competitive products.” See Glycosyn’s Remedy Br. at 8; accord IA’s Resp. at 46. Glycosyn also notes that “Friesland received GRAS approval from the FDA on April 6, 2018, to manufacture 2’-FL.” See Glycosyn’s Remedy Br. at 4. The Commission finds that the presence of alternative suppliers capable of providing non-infringing 2’-FL product (including DuPont and Jennewein itself) negates any evidence that the LEO would adversely affect U.S. consumers, particularly in view of the Commission’s determination that using the TTFL12 strain does not infringe the Asserted Claims. For example, Jennewein can import its 2’-FL product if it certifies that such product was produced using the TTFL12 strain. Thus, the Commission finds that the LEO discussed supra section IV(A) would not have an adverse effect on U.S. consumers.
PUBLIC VERSION 32 5. Conclusion Based on the record evidence, the Commission finds that an LEO directed against Jennewein’s infringing articles, and including a standard certification provision and an explicit carve-out for articles produced using Jennewein’s non-infringing TTFL12 strain, would cause little to no harm to the public health and welfare, the competitive conditions in the United States economy, the production of like or directly competitive products in the United States, and United States consumers. Thus, after considering the parties’ submissions and the effect that remedial orders would have on the public interest, the Commission has determined to issue a limited exclusion order. C. Bonding If the Commission enters an exclusion order or a cease and desist order, a respondent may continue to import and sell its products during the 60-day period of Presidential review under a bond in an amount determined by the Commission to be “sufficient to protect the complainant from any injury.” 19 U.S.C. § 1337(j)(3); see also 19 C.F.R. § 210.50(a)(3). When reliable price information is available in the record, the Commission has often set the bond in an amount that would eliminate the price differential between the domestic product and the imported, infringing product. See Certain Microsphere Adhesives, Processes for Making Same, & Prods. Containing Same, Including Self-stick Repositionable Notes, Inv. No. 337-TA-366, USITC Pub. No. 2949, Comm’n Op. at 24 (Jan. 16, 1996). The Commission also has used a reasonable royalty rate to set the bond amount where a reasonable royalty rate could be ascertained from the evidence in the record. See, e.g., Certain Audio Digital-to-Analog Converters & Prods. Containing Same, Inv. No. 337-TA-499, Comm’n Op. at 25 (Mar. 3, 2005). Where the record establishes that the calculation of a price differential is impractical or there is insufficient evidence in the record to determine a reasonable royalty, the Commission has
PUBLIC VERSION 33 imposed a 100 percent bond. See, e.g., Certain Liquid Crystal Display Modules, Prods. Containing Same, & Methods Using the Same, Inv. No. 337-TA-634, Comm’n Op. at 6-7 (Nov. 24, 2009). The complainant, however, bears the burden of establishing the need for a bond. Certain Rubber Antidegradants, Components Thereof & Prods. Containing Same, Inv. No. 337- TA-533, USITC Pub. No. 3975, Comm’n Op. at 40 (July 21, 2006). As stipulated by the parties, the RD recommends a bond of five (5) percent of the entered value of Jennewein’s 2’-FL product during the period of Presidential review. See RD at 114- 115 (citing JX-7 (stipulation regarding bond)). Consistent with the parties’ agreement and the RD’s recommendation, the Commission has determined that a bond in the amount of five (5) percent of the entered value of the imported products is appropriate for subject imports entered during the period of Presidential review. V. CONCLUSION For the reasons set forth herein, the Commission determines that complainant Glycosyn has established a violation of section 337 by respondent Jennewein based on the infringement of the Asserted Claims of the ՚018 patent. Accordingly, the investigation is terminated with a finding of a violation of section 337. The Commission determines that the appropriate remedy is an LEO directed against Jennewein’s infringing human milk oligosaccharides, that the public interest factors do not weigh against issuing that remedy, and that the bond during the Presidential review period is set in the amount of five (5) percent of the entered value of the infringing articles. By order of the Commission. Lisa R. Barton
PUBLIC VERSION 34 Secretary to the Commission Issued: June 8, 2020
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Inv. No. 337-TA-1120 PUBLIC CERTIFICATE OF SERVICE I, Lisa R. Barton, hereby certify that the attached COMMISSION OPINION has been served via EDIS upon the Commission Investigative Attorney, Lisa Murray, Esq., and the following parties as indicated, on June 8, 2020. Lisa R. Barton, Secretary U.S. International Trade Commission 500 E Street, SW, Room 112 Washington, DC 20436 On Behalf of Complainant Glycosyn LLC: Michael C. Newman, Esq. MINTZ LEVIN COHN FERRIS GLOVSKY AND POPEO, PC 1 Financial Center Boston, MA 02111 Email: MCNewman@mintz.com ☐ Via Hand Delivery ☐ Via Express Delivery ☐ Via First Class Mail ☒ Other: Email Notification of Availability to Download On Behalf of Respondent Jennewein Biotechnologie GmbH: Gary M. Hnath MAYER BROWN LLP 1999 K Street, NW Washington, DC 20006 Email: ghnath@mayerbrown.com ☐ Via Hand Delivery ☐ Via Express Delivery ☐ Via First Class Mail ☒ Other: Email Notification of Availability to Download
PUBLIC VERSION 1 UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. In the Matter of CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Inv. No. 337-TA-1120 SEPARATE VIEWS OF COMMISSIONER SCHMIDTLEIN CONCURRING IN PART AND DISSENTING IN PART I concur with and join Part III(A) of the majority opinion, which affirms the ID’s finding that the Accused Strains include an exogenous functional β-galactosidase gene. I respectfully dissent from Part III(B) of the majority opinion, which concludes that the administrative law judge (“ALJ”) should have adjudicated whether the TTFL12 strain infringes the asserted method claims. Given the parties’ briefing and the evidence and exhibits cited therein, I would affirm the ID’s conclusion that the TTFL12 strain was not subject to sufficient discovery and not reach the question of whether using the TTFL12 strain infringes the asserted claims. In determining whether an alternative or redesigned product identified by a respondent should be adjudicated, the Commission has considered whether there has been sufficient discovery on the product. See, e.g., Certain Electronic Digital Media Devices and Components Thereof, Inv. No. 337-TA-796, Comm’n Op. at 103–05 (Sept. 6, 2013) (“Electronic Digital Media Devices”) (finding that the complainant took substantial discovery on the design-around products, which included product inspections by complainant’s expert, source code production, and depositions of respondent’s witnesses); Certain Multiple Mode Outdoor Grills and Parts Thereof, Inv. No. 337-TA-895, Comm’n Op. at 15–20 (July 23, 2014) (“Outdoor Grills”)
PUBLIC VERSION 2 (finding that the respondent produced photographs and product manuals that were sufficient to show that certain redesigned products did not infringe the asserted claims); Certain Television Sets, Certain Television Receivers, Television Tuners, and Components Thereof, Inv. No. 337- TA-910, Order No. 46 (Initial Determination) at 23–29 (Nov. 28, 2014) (Lord, J.) (“Television Sets”) (not reviewed) (listing 22 facts establishing that respondents had provided sufficient discovery on an alternative product; notably, the respondents identified the alternative product before the investigation was instituted, produced 9,000 pages of technical documents, and submitted an expert report opining on non-infringement). Further, as these decisions show, the Commission’s analysis of the “sufficient discovery” question focuses on the documents and contentions produced before the close of fact and expert discovery. In the present investigation, the majority opinion finds that Jennewein provided sufficient discovery on the TTFL12 strain by combining the limited disclosures and documents produced during discovery with hearing testimony and witness statements provided after the close of discovery. With regard to the information produced during the discovery period, the majority opinion points to (1) the mandatory Ground Rule 7.2 disclosure and interrogatory responses served on the last day of fact discovery that identified the TTFL12 stain and (2) a draft article and patent application that purportedly disclose the TTFL12 strain.1 Maj. Op. at 21–22. Like 1 The majority opinion states that a respondent must present “sufficient documentary evidence as well as fact and expert testimony to put [the complainant] on notice of the relevant features of the [alternative or redesigned product].” Maj. Op. at 21 (emphasis added, footnote omitted). But, as the decisions cited above show, the threshold for demonstrating that the respondent has provided sufficient discovery on a redesigned or alternative product is higher than simply putting the complainant “on notice” of a product or its relevant features. For example, the Commission has considered whether the discovery proffered on the redesigned products was analogous to the information and materials the parties cited in their infringement arguments. See Outdoor Grills, Comm’n Op. at 18 (“the parties premised their infringement positions based on photographs or diagrams, thereby demonstrating that this particular limitation was readily ascertainable from the
PUBLIC VERSION 3 the ALJ, I find this discovery insufficient. A review of Jennewein’s discovery responses show that Jennewein overwhelmingly focused on the #1540 strain and, importantly, repeatedly disavowed importation of 2’-FL product made by any other strain besides the #1540 strain. For instance, during discovery, Jennewein identified the #1540 strain as its only production strain for the U.S. market2 and admitted in response to requests for admissions that the “#1540 is the only strain Jennewein uses to produce the 2’-FL that is imported into the United States.”3 In the mandatory ground rule disclosure cited by the majority opinion, Jennewein identified the TTFL12 strain by referencing just one document, the undated, unpublished draft article (RX-320C).4 Subsequent to this disclosure, on October 20, Jennewein’s founder testified in a deposition that the #1540 strain was “the only strain that Jennewein was using to create” the product that was being imported.5 Four days later, Jennewein provided interrogatory responses stating that Jennewein had imported 2’-FL made with the TTFL12 strain.6 On the last day of discovery, Jennewein provided supplemental responses stating that Jennewein had imported 2’-FL made with the TTFL12 strain on October discovery provided by Respondents at the time the motion was filed.”); Television Sets, Order No. 46 at 21, 27–28; see also Certain Coaxial Cable Connectors, 337-TA-938, Order No. 9 (Initial Determination) at 4 (Aug. 21, 2015) (Lord, J.) (“Cable Connectors”) (not reviewed) (in finding that respondent’s new designs did not infringe, the ALJ noted that the same type of evidence used to show infringement of the legacy designs “applies to all of the new C3 designs, for which [respondent] produced technical drawings and expert [deposition] testimony”). 2 See CX-228C (Interrogatory Responses) at 5. 3 See CX-215C (Responses to Requests for Admission) at 4–5. 4 Because the draft article is undated, it does not show when Jennewein produced 2’-FL with the TTFL12 strain. Thus, the article does not show that the 2’-FL sample Jennewein imported was made with the TTFL12 strain. 5 See Tr. (Jennewein) at 189 (affirming Oct. 20, 2018 deposition testimony). 6 See CX-236C (Interrogatory Responses) at 4–6.
PUBLIC VERSION 4 12.7 In the supplemental responses, Jennewein provided, for the first time, its contentions that using the TTFL12 strain does not infringe the asserted claims.8 Given that Jennewein repeatedly disavowed during discovery that it was producing and importing product made with an alternative strain, I do not consider that the initial ground rule disclosure of an undated, unpublished article, along with Jennewein’s crafty approach to responding to written discovery, to provide a basis for finding that Jennewein provided “sufficient” discovery. Moreover, the absence of the type of discovery that typically informs the “sufficient discovery” inquiry also shows that Jennewein did not provide sufficient discovery on the TTFL12 strain. For example, Jennewein points to no expert report in relation to the TTFL12 strain.9 Indeed, the statement of undisputed material facts from Jennewein’s motion for summary determination lacks an allegation that its expert opined on TTFL12. 10 While the majority opinion relies on witness statements provided after the close of discovery and hearing testimony to buttress the documents produced during discovery, this evidence simply is not discovery.11 As such, that evidence is not germane to the question before the Commission, 7 See CX-236C (Interrogatory Responses) at 4–6; CX-237C (First Amended Interrogatory Responses) at 2, 9, 18–20; RX-278C (delivery slip dated Oct. 12, 2018, indicating 180g of 2’-FL was imported); RX-280C (production summary indicating 180g of 2’-FL made using the TTFL12 strain had been imported). 8 See CX-237C (First Amended Interrogatory Responses) at 2, 9, 18–20. 9 See, e.g., Electronic Digital Media Devices, Television Sets, Cable Connectors, supra. In these investigations, respondents’ experts’ opinions were relied on to conclude the alternative products had been subject to sufficient discovery and that they did not infringe. 10 See Jennewein Mem. in Supp. of Mot. for Summary Det. at 8–10 (EDIS Doc. ID No. 663068, filed Nov. 30, 2018). 11 The majority opinion observes that this opinion “dismisses” witness testimony provided after the close of discovery and finds that the “testimony is based on expert reports or deposition
PUBLIC VERSION 5 which concerns what was provided during the discovery period. Likewise, the total absence of materials similar to what the parties used in their infringement and domestic industry technical prong contentions further shows that the discovery Jennewein provided is insufficient. For instance, Glycosyn’s expert relied on lab notebooks, weekly lab meeting presentations, internal databases and bioreactor run spreadsheets, Glycosyn’s GRAS notice, and analytical testing in formulating her opinion that Glycosyn practices claim 1 of the asserted patent.12 In opining on infringement, Glycosyn’s expert relied on many sources of evidence, including Jennewein’s responses to Glycosyn’s requests for admission, Jennewein’s interrogatory responses, Jennewein’s GRAS notice, photographs of Jennewein’s production equipment, and Jennewein’s in-house analytical testing.13 Jennewein’s expert, in opining on non-infringement, relied on Jennewein’s GRAS notice and analytical testing of the #1540 and #1540 derivative strains.14 In my view, the absence of any of these types of documents further indicates that Jennewein failed to provide sufficient discovery. Accordingly, Glycosyn was not testimony which must be produced during discovery (generally, such reports are not included in the record evidence).” Maj. Op. at 21 n.23. The majority opinion, however, points to no portion of an expert report or deposition transcript addressing the TTFL12 strain, but rather just assumes that Jennewein’s expert’s report and its employees’ deposition testimony pertain to the relevant hearing testimony. Further, this aspect of the majority opinion stands apart from Commission precedent that has explicitly credited expert reports and deposition testimony in concluding that the respondent provided sufficient discovery. See Two-Way Radio, Comm’n Op. at 26 (noting the respondent “produced discovery (including source code, corporate witness depositions, and expert reports), as well as testimonial evidence at the hearing, regarding its non-infringement contentions”); Television Sets, ID at 30 (noting that respondents submitted “an extensive expert report . . . on non-infringement”); Cable Connectors, ID at 2 (noting that respondents “submitted a noninfringement expert report”). Ultimately, the sufficient-discovery factor hinges on what the respondent provided in discovery, not on what evidence may have been introduced at a hearing. 12 See CX-4C (Prather WS) at Q/A 107, 112, 124, 125, and 149. 13 Id. at Q/A 434, 435, 437, 440, 486. 14 See RX-409C (Stephanopoulos RWS) at Q/A 13, 43–46.
PUBLIC VERSION 6 provided sufficient information regarding the TTFL12 strain prior to the close of discovery to allow it to decide whether to assert infringement.15 In sum, while I do not mean to suggest that all or even a substantial number of the types of discovery discussed above must be provided in order to put a redesigned or alternative product at issue, it is my view that the total absence of these types of documents in this case along with Jennewein’s repeated assertions that it was not producing and importing 2’-FL made with the TTFL12 strain demonstrates that Jennewein did not provide sufficient discovery on the TTFL12 strain.16 Consequently, I find no error in the ALJ’s decision and therefore respectfully dissent from Part III(B) of the majority opinion. 15 The majority opinion finds that Glycosyn “does not contend that” the discovery Jennewein did provide was “insufficient to apprise it of information relating to the TTFL12 strain or Jennewein’s non-infringement theory.” Maj. Op. at 23 n.25. This approach, however, obligates a complainant to investigate alternative or redesigned products of dubious viability, including products that a respondent has repeatedly represented were not made altogether, intended for, or imported into the U.S. market. 16 As I find that Jennewein failed to provide sufficient discovery on the TTFL12 strain, I also find that Jennewein failed to show that its process of making 2’-FL with the TTFL12 strain is sufficiently fixed in design. Compare Maj. Op. at 20 (finding the TTFL12 strain fixed in design). For this factor, the majority relies on two citations to the hearing transcript. See id. In the testimony, Dr. Jennewein averred that Jennewein has been developing the strain since 2012 and that it has conducted “[a] lot of different fermentation runs” since 2012. See Tr. (Jennewein) at 197. Dr. Parkot averred that she prepared the TTFL12 sample for importation and that the company could provide “manufacturing documentation” on request. See Tr. (Parkot) at 347. During discovery, however, Jennewein repeatedly disavowed that it was producing and importing product made with the TTFL12 strain. Similarly, although Jennewein apparently can provide manufacturing documents that might substantiate its argument, it did not produce them during discovery. Taken together, this testimony does not establish that the TTFL12 strain and its attendant production process is sufficiently fixed in design. See Certain GPS Chips, Associated Software and Systems, and Prods. Containing Same, Inv. No. 337-TA-596, USITC Pub. No. 4133, Initial Determination at 51–55 (June 13, 2008) (Luckern, J.) (unreviewed) (declining to adjudicate a new product, where, amongst other things, the product was subject to modification in light of subsequent testing); see also Tr. (Jennewein) at 205–206 (describing a lengthy document-finalization process and the need for additional analysis of the TTFL12 strain).
UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. In the Matter of CERTAIN HUMAN MILK _ _ InV€§tlgatl0Il N0. METHODS OF PRODUCING THE SAME NOTICE OF COMMISSION DECISION TO REVIEW IN PART A FINAL INITIAL DETERMINATION FINDING A VIOLATION OF SECTION 337; SCHEDULE FOR FILING WRITTEN SUBMISSIONS ON THE ISSUES UNDER REVIEW AND ON REMEDY, THE PUBLIC INTEREST, AND BONDING AGENCY: U.S. Intemational Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has determined to review in part a final initial determination (“FID”) of the presiding administrative law judge (“ALI”) finding a violation of section 337 of the Tariff Act of 1930, as amended. The Commission requests briefing from the parties on certain issues under review, as set forth in this notice. The Commission also requests briefing from the parties, interested persons, and government agencies on the issues of remedy, the public interest, and bonding. FOR FURTHER INFORMATION CONTACT: Houda Morad, Office of the General Counsel, U.S. International Trade Commission, 500 E Street SW., Washington, DC 20436, telephone (202) 708-4716. Copies of non-confidential documents filed in connection with this investigation are or will be available for inspection during official business hours (8:45 a.m. to 5:15 pm.) in the Office of the Secretary, U.S. International Trade Commission, 500 E Street SW., Washington, D.C. 20436, telephone (202) 205-2000. General information concerning the Commission may also be obtained by accessing its Internet sewer at httgs://www.usitc.gov. The public record for this investigation may be viewed on the Commission’s electronic docket (EDIS) at httgs://edis. usitc.gov. Hearing-impaired persons are advised that information on this matter can be obtained by contacting the Commission’s TDD terminal on (202) 205-1810. SUPPLEMENTARY INFORMATION: The Cormnissioninstituted this investigationon Jtme 21, 2018, based on a complaint, as amended and supplemented, filed on behalf of Glycosyn LLC of Waltham, Massachusetts (“Glycosyn”). See 83 Fed. Reg. 28865 (June 21, 2018). The complaint, as amended and supplemented, alleges violations of section 337 of the Tariff Act of 1930, as amended, 19 U.S.C. 1337 (“section 337”), based upon the importation into the United States, the sale for importation, and the sale within the United States after importation of certain human milk oligosaccharides by reason of infringement of claims l-40 of U.S. Patent No. 9,453,230 (“the ’230 patent”) and claims 1-28 of U.S. Patent No. 9,970,018 (“the ’0l8 patent”). 1
See id. The notice of investigation named Jennewein Biotechnologie GmbH (“Jennewein”) of Rheinbreitbach, Germany as a respondent in this investigation. See id. The Office of Unfair Import Investigations (“OUII”) is also named as a party to the investigation. See id. On August 9, 2018, the ALJ partially terminated the investigation as to claims 4-7, 9-12, 14, 23-26, 28-31, 33, and 39-40 of the ’230 patent and claims 6, 7, 9, ll, 13-17, 19, and 22 of the ’018 patent based on the withdrawal of the allegations pertaining to those claims. See Order No. 5 (Aug. 9, 2018), unreviewed, Comm’n Notice (Aug. 29, 2018). On October 30, 2018, the ALJ partially terminated the investigation as to claims 1-3, 8, 13, and 15-20 of the ’230 patent based on the withdrawal of the allegations pertaining to those claims. See Order No. 15 (Oct. 30, 2018), unreviewed, C0mm’n Notice (Nov. 29, 2018). On November 19, 2018, the ALJ partially terminated the investigation as to claim 27 of the ’230 patent and claims 4, 20, and 21 of the ’018 patent based on the withdrawal of the allegations pertaining to those claims. See Order No. 17 (Nov. 19, 2018), unreviewed, Comm’n Notice (Dec. 12, 2018). On February 8, 2018, the ALJ partially terminated the investigation as to claims 21, 22, 32, and 34-38 of the ’230 patent based on the withdrawal of the allegations pertaining to those claims. See Order No. 25 (Feb. 8, 2019), unreviewed, Comm’n Notice (Feb. 28, 2019). Claims 1-3, 5, 8, 10, 12, 18, and 23-28 ofthe ’018 patent remain pending in this investigation. The ALJ conducted an evidentiary hearing on May 14-17, 2019, and on September 9, 2019, issued the FID finding a violation of section 337 based on the infringement of claims 1-3, 5, 8, 10, 12, 18, and 24-28 of the ’018 patent. In addition, the FID finds that the asserted claims are neither invalid under 35 U.S.C. §§ 103 and 112, nor unenforceable for inequitable conduct. Furthermore, the FID finds that the domestic industry requirement is satisfied. The FID also contains a recommended detennination (“RD”) recommending that the Commission issue a limited exclusion order (“LEO”) barring entry of articles that infringe the ’018 patent. The RD also recommends that the Commission impose a 5% bond during the period of Presidential review. Furthermore, as directed by the Commission, the RD provides findings with respect to the public interest and recommends that the Commission determine that the public interest factors do not preclude entry of the LEO. On September 23, 2019, Jennewein and OUII filed petitions for review of the FID. On October 1, 2019, Glycosyn and OUII filed responses to Jennewein’s and the IA’s petitions. Having examined the record of this investigation, including the FID, the RD, and the parties’ submissions, the Commission has determined to review the FID in part. Specifically, the Commission has determined to review the FID’s infringement findings with respect to Jennewein’s bacterial strains adjudicated in this investigation. In addition, the Commission has determined to review the FID’s decision not to adjudicate infringement as to Jennewein’s alternative bacterial strain, the TTFL12 strain. The Commission has determined not to review the remainder of the FID. In connection with its review, the Commission requests written responses regarding the following inquiries: 2
Assuming that the Commission determines to adjudicate infringement with respect to JenneWein’s TTFL12 bacterial strain, please provide your position, with support from the evidentiary record, as to whether the TTFL12 strain infringes or does not infringe the asserted patent claims. Should the Commission adjudicate infringement with respect to Jennwein’s alternative strain? Is the Commissi0n’s determination of whether to adjudicate an alternative or redesigned product a legal question, a factual question, a mixed question of law or fact, an exercise of discretion, or something else? Is the TTFL12 strain within the scope of the investigation? What criteria and evidence normally informs this analysis? Does a respondent need to import an alternative or redesigned product for the product to be adjudicated? What evidence corroborates Jennewein’s assertion that the products listed in the shipping documents (RX-278C and RX-280C) were produced with the TTFL12 strain? Please provide your answers in a table with citations in one column and a brief explanation in a second column. What is the effect of Jennewein’s responses to Glycosyn’s request for admission? Why has Jennewein failed to amend its responses if they are incorrect or misleading? Is the TTFL12 strain sufficiently fixed in design? What criteria and evidence normally informs this analysis? Is there any declaratory judgment precedent that is relevant? Which party bears the burden of showing that an alternative or redesigned product is fixed in design? Has the TTFL12 strain been subject to sufficient discovery? What criteria and evidence normally informs the “sufficient discovery” analysis? Should the Cormnission issue remedial orders that are directed to the adjudicated strains (the #1540 and #1540 derivative) at this juncture? Responses to the above questions should not exceed 40 pages, and replies should not exceed 20 pages. In addition, in connection with the final disposition of this investigation, the statute authorizes issuance of (1) an order that could result in the exclusion of flie subject articles from 3
entry into the United States, and/or (2) a cease and desist order that could result in the respondent being required to cease and desist from engaging in unfair acts in the importation and sale of such articles. Accordingly, the Commission is interested in receiving written submissions that address the form of remedy, if any, that should be ordered. If a party seeks exclusion of an article from entry into the United States for purposes other than entry for consumption, the party should so indicate and provide information establishing that activities involving other types of entry either are adversely affecting it or likely to do so. For background, see Certain Devicesfor Connecting Computers via Telephone Lines, Inv. No. 337-TA-360, USITC Pub. No. 2843, Comm’n Op. at 7-10 (Dec. 1994). The statute requires the Commission to consider the effects of any remedy upon the public interest. The public interest factors the Commission will consider include the effect that an exclusion order and/or cease and desist orders would have on (l) the public health and welfare, (2) competitive conditions in the U.S. economy, (3) U.S. production of articles that are like or directly competitive with those that are subject to investigation, and (4) U.S. consumers. The Commission is therefore interested in receiving written submissions that address the aforementioned public interest factors in the context of this investigation. If the Commission orders some form of remedy, the U.S. Trade Representative, as delegated by the President, has 60 days to approve, disapprove, or take no action on the Cornmission’s determination. See Presidential Memorandum of July 21, 2005, 70 FR 43251 (July 26, 2005). During this period, the subject articles would be entitled to enter the United States under bond, in an amount determined by the Commission and prescribed by the Secretary ofthe Treasury. The Commission is therefore interested in receiving submissions conceming the amount of the bond that should be imposed if a remedy is ordered. WRITTEN SUBMISSIONS: The parties to the investigation are requested to file written submissions limited to the briefing questions above. Parties to the investigation, interested government agencies, and any other interested parties are encouraged to file written submissions on the issues of remedy, the public interest, and bonding. Such initial written submissions should include views on the recommended determination by the ALJ on remedy, the public interest, and bonding. Complainant and the Commission Investigative Attorney are also requested to identify the form of remedy sought and to submit proposed remedial orders for the Commission’s consideration in their initial written submissions. Complainant is further requested to state the date that the asserted patent expires and the HTSUS numbers under which the accused products are imported, a.ndto supply the names of known importers of the products at issue in this investigation. Initial written submissions and proposed remedial orders must be filed no later than close of business on February 18, 2020. Reply submissions must be filed no later than the close of business on February 25, 2020 and must be limited to issues raised in the initial written submissions. No further submissions on any of these issues will be permitted unless otherwise ordered by the Commission. Persons filing written submissions must file the original document electronically on or before the deadlines stated above and submit eight (8) true paper copies to the Office of the 4
Secretary by noon the next day pursuant to section 21O.4(t) of the C0mmission’s Rules of Practice and Procedure (19 CFR 210.4(t)). Submissions should refer to the investigation number (“Inv. No. 337-TA-1120”) in a prominent place on the cover page and/or the first page. (See Handbook for Electronic Filing Procedures, https://Www.usitc.gov/documents/ handbook_on_filingJ:>rocedures._pdt). Persons with questions regarding filing should contact the Secretary (202-205-2000). Any person desiring to submit a document to the Commission in confidence must request confidential treatment. All such requests should be directed to the Secretary to the Commission and must include a full statement of the reasons why the Commission should grant such treatment. See 19 CFR 201.6. Documents for which confidential treatment by the Commission is properly sought will be treated accordingly. All information, including confidential business information and documents for which confidential treatment is properly sought, submitted to the Commission for purposes of this Investigation may be disclosed to and used: (i) by the Commission, its employees and Offices, and contract personnel (a) for developing or maintaining the records of this or a related proceeding, or (b) in internal investigations, audits, reviews, and evaluations relating to the programs, personnel, and operations of the Commission including under 5 U.S.C. Appendix 3; or (ii) by U.S. govemrnent employees and contract personnelm, solely for cybersecurity purposes. All non-confidential written submissions will be available for public inspection at the Office of the Secretary and on EDIS. The authority for the Commission’s determination is contained in section 337 of the Tariff Act of 1930, as amended (19 U.S.C. 1337), and in part 210 of the Commission’s Rules of Practice and Procedure (19 CFR part 210). By order of the Commission. / C i\\ /‘t I V‘ Lisa.R. Barton ti V Secretary to the Commission Issued: Januaiy 30, 2020 [1]All contract personnel will sign appropriate nondisclosure agreements. 5
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND Inv. N0. 337-TA-1120 METHODS OF PRODUCING THE SAME PUBLIC CERTIFICATE OF SERVICE I, Lisa R. Barton, hereby certify that the attached NOTICE has been sewed by hand upon the Commission Investigative Attorney, Lisa Murray, Esq., and the following parties as indicated, on January 30, 2020. I W%@Lisa R. Barton, Secretary U.S. International Trade Commission 500 E Street, SW, Room 112 Washington, DC 20436 On Behalf of Complainants Glvcosvn LLC: Michael C. Newman, Esq. El Via Hand Delivery MINTZ LEVIN COHN FERRIS GLOVSKY ANDPOPEO, PC |:| Via Express Delivery 1 Financial Center , 1 V‘ ~ - 1 -1 Boston, MA 021 I 1 Via First C ass Mai U Other: On Behalf of Respondent Jennewein Biotechnologie GmbH: Gary M. I-Inath II] Via Hand Delivery MAYER BROWN LLP El Via Express Delivery 1999 K Sire“, NW Via First Class Mail Washington, DC 20006 U other
UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. In the Matter of CERTAIN HUMAN MILK Inv. No. 337-TA-1129 OLIGOSACCHARJDES AND METHODS OF PRODUCING THE SAME INITIAL DETERMINATION ON VIOLATION OF SECTION 337 AND RECOMMENDED DETERMINATION ON REMEDY AND BOND Administrative Law Judge Cameron Elliot (September 9, 2019) Pursuant to the Notice of Investigation and Rule 2i0.42(a) of the Rules of Practice and Procedure of the United States International Trade Commission. this is my Initial Determination in the matter of Certain Human Milk Oligosaccharides and Methods 0_fPr0dt.-cing the Same, Investigation N0. 337-TA-1120.
TABLE OF CONTENTS Page l. INTRODUCTION ............................................................................................................. I A. Procedural Background .......................................................................................... ..l B. The Parties ............................................................................................................. ..3 C. The Asserted Patent and Claims ............................................................................ ..4 D. Products at Issue .................................................................................................... ..6 l. Domestic Industry Products........ 2. Accused Product ........................................................................................ ..7 II. STANDARDS OF LAW ................................................................................................... 7 A. Claim Construction ................................................................................................ ..7 B. Infringement ......................................................................................................... ..l 1 C. Domestic Industry ................................................................................................ ..I2 1. Technical Prong ....................................................................................... .. l2 2. Economic Prong ....................................................................................... ..l3 D. Invalidity.......................................................................................................... ..l5 1. 35 U.S.C. § l02......... ........l5 2. 35 U.S.C. I03 ........................................................................................ ..l6 3. 35 U.S.C. § 112........................................................................................ ..1S E. Unenforceability .................................................................................................. ..20 III. JURISDICTION AND IMPORTATION ..................................................................... 22 IV. U.S. PATENT NO. 9,970,018 ................................................................... ................... 24 A. Level of Ordinary Skill in the Art ........................................................................ .24 B. Claims-at-Issue ........24 C. Claim Construction .............................................................................................. ..26 D. Infringement ......................................................................................................... ..27 l. Regarding the Jenncwein TTFLIZ Strain .................................................28 2. Direct Infringement bytheJcnncwein #1540— _ ...................................................................................................... ..35 a. Undisputed Claim Limitations ..................................................... ..36 b. Disputed Claim I Limitation “an exogenous functional [3 galactosidase gene comprising a detectable level of B~ galactosidase activity that is reduced compared to that of a wild-type E. colt bacterium" .........................................................38 i
c. Disputed Claim I Limitation “wherein the level of [3 galactosidase activity comprises between 0.05 and 200 units” d. Disputed Claim S “the method of claim 1, wherein Said exogenous functional |3-galactosidase gene comprises an E. coir lacZ.gene" ....................................................................... .. e. Disputed Claim 23 “the method ofclaim l, wherein said exogenous functional |3-galaetosidase gene is inserted into an endogenous gene” .................................................................. .. E. Domestic Industry —Technical Prong............................................................ .. 1. 2. 3. 4. Undisputed Claim Limitations ........................................................... .. Disputed Claim I Limitation “wherein the level of [3-galactosidase activity comprises between 0.05 and 200 units" ................................ .. Disputed Claim 9 “the method of claim 8, wherein the lacZ gene is inserted into an endogenous Ion gene” .............................................. .. Disputed Claim 23 “the method of claim I, wherein said exogenous functional Ii-galactosidase gene is inserted into an endogenous gene" ......68 F. Validity and Enforceability ............................................................................ .. I. 2. 3. 4. 5. Asserted Prior Art .............................................................................. .. 35 U.S.C. § I03 (Obviousness) .......................................................... .. 35 U.S.C. § ll2,1l I (Enablement) .................................................... .. 35 U.S.C. § 112,1] I (Written Description) ....................................... .. .....45 ......57 ......60 ......6l ......62 .... ..65 ......67 67 ......68 ......69 ...."82 ......89 Inequitable Conduct ................................................................................. ..9U V. DOMESTIC INDUSTRY - ECONOMIC PRONG .................................................. 96 A. Qualifying Investments ........................................................................................ ..97 B. "Significant" or “Substantial” ......................................................................... ..l l l VI. CONCLUSIONS OF LAW ......................... ............................................................ 114 VII. RECOMMENDED DETERMINATION ON REMEDY AND BOND ................... 114 A. LIMITED EXCLUSION ORDER ..................................................................... ..l I6 ................................................................................................................ ..l I8 C. PUBLIC INTEREST ......................................................................................... ,,l I9 VII]. INITIAL DETERMINATION AND ORDER ........................................................... 121 B. BOND ii
CDX TABLE OF ABBREVIATIONS Complainant’s Demonstrative Exhibit CIB Cornplainanfs Revised Initial Post-Hearing Brief CPB Cornplainant’s Prc-Hearing Brief CPX C-ornplainant‘s Physical Exhibit CRB Comp1ainant’s Reply Post-Hearing Brief CX Cornplainant’s Exhibit Dep. Tr. Deposition Transcript i Hr’g Tr. Hearing Transcript i]X Joint Exhibit RDX Respondents’ Demonstrative Exhibit RIB Respondents’ Initial Post-Hearing Brief RPB Respondents’ Pre-Hearing Brief RPX Respondents’ Physical Exhibit RRB Respondents’ Reply Post-Hearing Brief RX Respondents‘ Exhibit SDX Staffs Demonstrative Exhibit SIB Staff’s Initial Post-Hearing Brief SPB Staff s Pre-Hearing Brief SPX Staffs Physical Exhibit SRB Staffs Reply Post-Hearing Brief SX Staffs Exhibit iii
I. INTRODUCTION
A. Procedural Background
Complainant Glycosyn LLC (“Glycosyn” or “Comp1ainant") filed the complaint
underlying this Investigation on April 2, 2018, and then filed an amended complaint on May 16,
2018. 'I'he complaint alleged respondent Jennewein Biotechnologie GrnbH (“Jennewein” or
“Respondent”) imports certain products that infringe one or more claims of U.S. Patent Nos,
9,453,230 (the ‘"230 patent”) and 9,970,018 {_the ‘"018 patent” also referred to as JX-0003).
By publication of a notice in the Federal Register on June 21, 2018. the U.S. International
Trade Commission ordered that:
Pursuant to subsection (b) of section 337 of the Tariff Act of 1930, as
amended, an investigation be instituted to determine whether there is a
violation of subsection (a)(l)(B) of section 337 in the importation into the
United States, the sale for importation, or the sale within the United States
after importation of products identified in paragraph (2) by reason of
infringement of one or more of claims 1-40 of the ’230 patent; and claims
1-28 of the ‘O18patent; and whether an industry in the United States exists
as required by subsection (a)(2) of section 337[.]
83 Fed. Reg. 23,865 (June 21, 2018). On July 16, 2018, the presiding administrative law judge set
a target date of October 21, 2019 for completion of this investigation and set the evidentiary
hearing for February 22, 2019. (Order No. 4.) On August 20, 2018, the administrative lawjudge
issued the procedural schedule. (Order N0. 6.) On September 4, 2018, and due to the retirement
of the presiding administrative law judge, the investigation was reassigned to the Chief
Administrative Law Judge. (EDIS Doc. ID 654642.)
In accordance with the issued procedural schedule, on October I6, 2018, the Chief
Administrative Law Judge held a technology tutorial and Markman hearing, and on December 18,
2018, issued Order No. 22, construing certain terms of the asserted patents.At times throughout the investigation, Glycosyn moved for the termination of certain asserted claims from those identified in the complaint. Specifically, on July 27, 2018, Glycosyn moved to terminate claims 4-7, 9-12, 14, 23-26, 28-31, 33, and 30-40 ofthe ’230 patent and claims 6, 7, 9, 11, 13-17, 19, and 22 of the ’018 patent. The presiding administrative law judge at the time granted Glycosyn’s motion on August 9, 2018 with Order No. 5. The Commission determined not to review Order No. 5 on August 29. 2018. (EDIS Doc. l.D654274.) On October 18, 2018, Glycosyn moved to terminate claims 1-3, 8, 13, and 15-20 ofthe ’230 patent. The Chief Administrative Law Judge granted G1ycosyn‘s motion on October 30, 2018 with Order No. 15. The Commission determined not to review Order No. 15 on November 29, 2018. (_EDISDoc. ID 662881.) On November 9, 2018, Glycosyn moved to terminate claim 27 of the ’230 patent and claims 4, 20, and 21 ofthe ’0l8 patent. The Chief Administrative Law Judge granted G1ycosyn‘s motion on November 19, 2018 vfitb Order No. 17. The Commission determined not to review Order No. 17 on December 12, 2018. (EDIS Doc. 1D 663942.) Lastly, on January 30, 2019, Glycosyn moved to terminate claims 21, 22, 32, and 34-38 of the ’230 patent. The Chief Administrative Law Judge granted G1ycosyn‘s motion on February 8, 2019 with Order No. 25. The Commission determined not to review Order No. 25 on February 28, 2019. (EDIS Doc. ID 668665.) lmportantly, Order No. 25 terminated the last remaining asserted claims of the ’230 patent, thereby tenninating that patent in its entirety fi'on1 the investigation. Thus, the sole remaining patent in this investigation is the T113patent. Also during the investigation, Jennewein filed two summary determination motions of non infringement with respect to certain of their processes for the manufacture of its accused product. The Chief Administrative Law Judge denied both motions on March 8, 2019 with Order Nos. 27 and 28. 2
With respect to the procedural schedule, the govemment shutdown occurring between December of 2018 and January 0f2019 necessitated an extension of all deadlines and the target date in this investigation. At the completion of the shutdown, on January, 29, 2019, the Chief Administrative Law Judge issued Order No. 23 which moved the start of the evidentiary hearing to May l3, 2019. Accordingly, the Chief Administrative Law Judge set a new procedural schedule for all remaining deadlines on February 7, 2019 with Order No. 24 and also extended the target date of the investigation approximately eleven weeks to January 9, 2020 with Order No. 26, issuing on February 21, 2019. The Commission determined not to review Order No. 26 on March 14, 2019. (EDIS D00. ID 670060.) Finally, on April 2, 2019 the investigation was reassigned a second time from the Chief Administrative Law Judge to me. (EDIS Doc. ID 671950.) I then conducted an evidentiary hearing between May I4, 2019 and May 17, 2019. Following the evidcntiary hearing, and pursuant to the procedural schedule, the parties submitted initial and reply post-hearing briefs on June 3, 2019 and June 17, 2019 respectively, Further, on June 10, 2019, Jertnewein moved to strike certain portions of Glycosyn’s initial post hearing brief-—-amotion which I granted-in-part on June I4, 2019 with Order No. 38. On June l7. 2019, Glycosyn submitted a revised initial post-hearing brief in accordance with that order. As of the date of this initial determination. no motions remain pending. B. The Parties Complainant Glycosyn LLC is organized and exists under the laws of Massachusetts. (SIB at .2.) ll was founded in 2002 to pursue research and development “of commercially-viable methods for synthesizing and producing human milk oligosaccharides, commonly known as HMOs. (CIB at 7.) While Glycosyn conducts its research and development in the United States, 3
it is currently linked with a Dutch production partner, Royal FrieslandCampina N.V., to manufacture and distribute the 2‘-FL HMO for the infant formula market. (Id. at T-3; see RlB at 3 (citing RX-0056).} Respondent Jennewein Biotechnologie GmbH is based in Germany, and founded in 2005 for the similar purpose of researching means of manufacture for HMOs. (CIB at 8.) Jennewein claims it “is the true innovator and market leader for 2‘-FL in the United States" as “[n]o other company, including Glycosyn or its partner, is supplying Z‘-FL to American consumers.” (RIB at 4 (citing Hr’g Tr. at 57:3-4; RX-0385C at Q1813);see SIB at 3.) in this investigation, and as described further below, Glycosyn has alleged Jenncwein‘s methods of producing 2‘-FL imported into the United States infringe the ’018 patent. Ud.) C. The Asserted Patent and Claims The asserted patent relates to compositions and methods for providing engineered bacteria to produce certain HMOs. The following claims remain at issue in this investigation: Patent Number Infringement Claims DomesticIndustry Claims "U18 patent l~3, 5, S, l0, 12, 18, 23—2S l-3, 5, 8-I4, l8, 22~28 (See CIB at l5-16.) The ’O]8 patent is entitled, “Biosynthesis of Human Milk Oligosaccharides in Engineered Bacteria." (JX-0003.) It was tiled on September 2], 2017, and claims priority as a continuation application of an application filed on February 24, 2017, itself a continuation of an application filed on September 23, 2013, which was a division of an application filed on February I6. 2012. 4
(10/.) Through these applications, the ‘U18 patent also claims liirther priority to a provisional application filed on February 16, 2011. (1d.) ' The ‘O18patent issued on May 15, 2018. The ‘O18 patent generally describes “compositions and methods for engineering bacteria to produce fueosylated oligosaeeharides, and the use thereof‘ in the prevention or treatment of infection." (See id. at Abstract.) The patent explains: Human milk contains a diverse and abundant set of neutral and acidic oligosaceharides (human milk oligosaceharides, HMOS). Many of these molecules are not utilized directly by infants for nutrition, but they nevertheless serve critical roles in the establishment of a healthy gut microbiome, in the prevention of disease, and in immune function. Prior to the invention described herein, the ability to produce HMOS inexpensively at large scale was problematic. For example, HMOS production through chemical synthesis was limited by stereo-specificity issues, precursor availability, product impurities, and high overall cost. As such, there is a pressing need for new strategies to inexpensively manufacture large quantities of HMOS for a variety ofeommercial applications. (Id. at 1:34-47.) In some methods disclosed in the patent, an E. colt‘ bacterium is used. The bacterium is engineered in several ways that assist the production and collection of the desired oligosaceharide. For example, the bacterium may be engineered by the addition, deletion, or inactivation of genes to: create the desired oligosaceharide from first and second basic sugar building blocks (ve.g.,fueosyltranslerase gene, GDP-fucose synthesis pathway); improve the ability to intake the sugar building b1ock(s) from an outside medium (e.g., lactose pcrmease gene); inactivate certain pathways that compete with oligosaeeharide production (e.g., colonic acid synthesis gene); and produce certain enzymes which compete with oligosaccharide production but otherwise assist later steps of purification and retrieval of the oligosaccharide (e.g., functional 13 galaetosidase gene). (See id. at 1:51-60, 3:44-50.) ' The effective date of the asserted patents pre-dates the America lnvents Act (“ALA”) enacted by Congress on September 16, 2011. 5
This last purpose, involving [3-galaetosidase activity, is pointedly in dispute in this investigation. The ’0l 8 patent describes one particularly relevant example of E. coli engineering and culturing: Also described herein are bacterial host cells with tl1eability to accumulate a[n] intracellular lactose pool while simultaneously possessing low, functional levels of cytoplasmic B-galactosidase activity, for example as provided by the introduction of a functional rccombinantE. coli laeZ gene, or by a B-galactosidase gene from any of a number of other organisms . . .. Low, functional levels of cytoplasmic B-galactosidase include [3 galactosidase activity levels, of between 0.05 and 200 units, e.g., between 0.05 and 5 units. between 0.05 and 4 units, between 0.05 and 3 units, or between 0.05 and 2 units (for unit definition see: Miller J H, Laboratory CSH. Experiments in molecular genetics. Cold Spring Harbor Laboratory Cold Spring Harbor, N.Y.; I972; incorporated herein by reference). This low level of cytoplasmic B-galactosidase activity, while not high enough to significantly diminish the intracellular lactose pool. is nevertheless very useful for tasks such as . . . the facile removal ofundesired residual lactose at the end of fennentations. (‘O18 patent at 7:22-45.) In this art, and as used throughout this initial determination, genes are normally identified with a starting lower-ease letter and in italics (e._g.,lm;'Z), and the peptide created from that gene starts in upper case with no italics (e.g., LaCZ). (RX-0384C at Q1511;(IX 0004C at Q6l.)2 Glycosyn contends it owns the ‘O18patent, which is reflected in the assignment filed with its prosecution history (CIB at 31 (citing JX-0006 at -4790; ’0l 8 patent)) and neither Jennewein nor the Staffdisputes ownership (see SIB at 3; see generalfiz RIB; RRB). D. Products at Issue I. Domestic Industry Products The domestic industry products in this investigation consist of certain non comn1ercial~ level amounts of 2’-FL produced by Glycosyn within the United States as part of its research and 2 The ‘O18 patent does not itself necessarily follow the italics scheme for genes. (See, e.g., ’0l8 patent at T126.) 6
development efforts. (CIB at 92 (citing CX-0059C; CX-0131C; CX-0064C); CX-0004C at Q124 l25.) Glycosyn identifies its E997 bacterial strain as practicing at least one claim of the ‘O18 patent. and contends many other strains are fairly represented by E997 with respect to this issue. (CIB at 15-16 (citing CX-0004 at Q99, 123), 126 n.8, 9.) Glycosyn claims the following strains, developed since 2015, are represented by its E997 strain as patent practicing: Products at Issue | Representative Product E997 (C-[B at 126 n.9 (citing CXJJOUZC at Q10"/A108; CX~l)06UC; CX~OO5SC;CX~OO59C; CX-0130(1).) 2. Accused Product The accused product in this case is 2‘-FL which Jennewein has imported or sold for importation into the United States (“Accused Product”) using methods claimed in the ‘O18 patent. In this investigation, Glycosyn has accused Jennewein’s 2’-FL production methods based on an E. mam-1 Th==#154@Jenneweinseeksadjudicationof- knownas TTFL]2. For reasonsdiscussedbelow, I do not find adjudication ofTTFL12 is warranted at this time. ll. STANDARDS OF LAW A. Claim Construction “The construction of claims is simply a way of elaborating the normally terse claim language in order to understand and explain, but not to change, the scope of the claims.” Emlirex, Inc. v. Serv. Engjg Corp, 216 F.3d 1343, 1347 (Fed. Cir. 2000). Although most of the disputed 7
claim terms were construed in an earlier order, some of the issues presented below are only resolvable with additional claim construction. (See Order No. 22.) Claim construction focuses on the intrinsic evidence, which consists of the claims themselves, the specification, and the prosecution history. See Pfiillips v. AWH Corp., 415 F.3d I303, I314 (Fed. Cir. 2005) (en bane); see also Marlcrnan v. Westview Instri, Inca, 52 F.3d 967, 979 (Fed. Cir. 1995) (en bane). As the Federal Circuit in Phillips explained, courts must analyze each of these components to determine the “ordinary and customary meaning of a claim term” as understood by a person of ordinary skill in art at the time of the invention. 415 F.3d at 1313. “Such intrinsic evidence is the most significant source of the legally operative meaning of disputed claim language.” Bel! Ail. Network Servs., Inc. v. Comd Coimrtdns Grp., IPILZ,262 F.3d 1253, 1267 (Fed. Cir. 2001). "lt is a ‘bedrock principle’ of patent law that ‘the claims of a patent define the invention to which the patentee is entitled the right to exclude?” Phillips, 41.5 F.3d at 1312 (quoting lrmova/Pure Water. Inc". v. Sajiari Water Filtration S_}’S.,Ina, 38] F.3d llll, lll5 (Fed. Cit‘. 20l)4')). “Quite apart from the written description and the prosecution history, the claims themselves provide substantial guidance as to the meaning ofpaiticular claims terms.” Id. at 1314; see Interactive Gift Fbrpress, Inc. v. Conrpuserve Ina, "256F.3d l323, I331 (Fed. Cir. 2001) (“In construing claims, the analytical focus must begin and remain centered on the language of the claims themselves, for it is that language that the patentee chose to use to ‘particularly point [ ] out and distinctly claim [ ] the subject matter which the patentee regards as his invention.”). The context i.nwhich a term is used in an asserted claim can be “highly instructive.” Phillips, 415 F.3d at l3|4. Additionally, other claims in the same patent, asserted or unasserted, may also provide guidance as to the meaning of a claim term. hi “Courts do not rewrite claims; instead, we give 8
effect to the terms chosen by the patentcc.” K-2 Corp. v. Salomon S.A., 191 F.3d 1356, 1364 (Fed. Cir. 1999). “[T]he specification ‘is always highly relevant to the claim construction analysis. Usually it is dispositive; it is the single best guide to the meaning ofa disputed term.’” Phillips, 415 F.3d at I315 (quoting V.r'rrom'csCorp. 11.Conceptromic, Inc, 90 F.3d 1576, ISSZ (Fed. Cir. 1996)). “[T]he specification may reveal a special definition given to a claim term by the patentee that differs from the meaning it would otherwise possess. In such cases, the inventor‘s lexicography governs.” Id. at I316. “ln other cases, the specification may reveal an intentional disclaimer, or disavowal, of claim scope by the inventor.” Id. As a general rule, however, the particular examples or embodiments discussed in the specification are not to be read into the claims as limitations. Id. at I323. In the end, “[t]he construction that stays true to the claim language and most naturally aligns with the patent’s description ofthe invention will be the correct construction." Id. at 1316 (quoting Renishaw PLC v. Morposs S0ciela'per Azioni, 158 F.3d I243, l25D (Fed. Cir. 1998)). lu addition to the claims and the specification, the prosecution history should be examined, iI'in evidence. Id. at 1317; see Liebe!~FIai'she1‘mC0. 1/.Medrad, Inc, 358 F.3d 893, 913 (Fed. Cir. 2004). The prosecution history can “often inform the meaning of the claim language by demonstrating how the inventor understood the invention and whether the inventor limited the invention in the course of prosecution. making the claim scope narrower than it would otherwise be.” Piwillips,415 F.3d at 1317; see Chimie v. PPG Indus. Int-., 402 F.3d I371, I384 (Fed. Cir. 2005) (“The ptupose of consulting the prosecution history in construing a claim is to exclude any interpretation that was disclaimed during prosecution”). When the intrinsic evidence does not establish the meaning of a claim, then extrinsic evidence (i‘.e., all evidence external to the patent and the prosecution history, including 9
dictionaries, inventor testimony, expert testimony, and learned treatises) may be considered.
Phillips, 4l5 F.3d at I317. Extrinsic evidence is generally viewed as less reliable than the patent
itself and its prosecution history in determining how to define claim tem-ts. Id. “The court may
receive extrinsic evidence to educate itself about the invention and the relevant technology, but the
court may not use extrinsic evidence to arrive at a claim constmction that is clearly at odds with
the construction mandated by the intrinsic evidence.” Elkay Mfg. C0. v. Ebco Mfg. Co., I92 F.3d
973, 977 (Fed. Cir. 1999).
The construction of a claim term is generally guided by its ordinary meaning. However,
courts may deviate from the ordinary meaning when: (1) “the intrinsic evidence shows that the
patentee distinguished that term from prior an on the basis of a particular embodiment, expressly
disclaimed subjeet matter, or described a particular embodiment as important to the invention;” or
(2) “the patentee acted as his own lexieographer and clearly set forth a definition of the disputed
claim term in either the specification or prosecution history.” Edwards LzfesciencesLLC v. Cook
inch, 582 F.3d 1322, i329 (Fed. Cir. 2009); see GE Lighting Sols., LLC v. Agilight, 11:13.,750 F.3d
I304, 1309 (Fed. Cir. 2014) (“the specification and prosecution history only compel departure
from the plain meaning in two instances: lexicography and disavowal”); Omega Eng ‘g, Inc, it
Raytek Corp, 334 F.3d l3l4, 1324 (Fed. Cir. 2003) ("[W]here the patentee has unequivocally
disavowed a certain meaning to obtain his patent, the doctrine ofprosecution disclaimer attaches
and narrows the ordinary meaning of the claim congruent with the scope of the surrenden”); Rheox.
Inc. v. Entact, Inc, 276 F.3d 1319, 1325 (Fed. Cir. 2002) (“The prosecution history limits the
interpretation of claim terms so as to exclude any interpretation that was diselaimed during
prosccution.”). Nevertheless, there is a “heavy presumption that a claim term carries its ordinary
and customary meaning." CCS F itness, Inc. v. Br:-mswickCorp, 288 F.3d 1359, 1366 (Fed. Cir.
I02002) (citations omitted). The standard for deviating from the plain and ordinary meaning is “exacting” and requires “a clear and unmistakable disclaimer.“ Thor-tierv. Sony Computer Emm ‘t Am. LLC, 669 F.3d 1362, 1366-67 (Fed. Cir. 2012); see Epistar Corp. v. In! '1Trade Comm '12,566 F.3d 1321, 1334 (Fed. Cir. 2009) (requiring “expressions of manifest exclusion or restriction, representing a clear disavowal of claim scope” to deviate from the ordinary meaning) (citation omitted). B. Infringement "An infringement analysis entails two steps. The first step is detemiining the meaning and scope of the patent claims asserted to be infringed. The second step is comparing the properly construed claims to the device accused of infringing." Markmari, 52 F.3d at 976. A patentee may prove infiingement either literally or under the doctrine of equivalents. Infringement of either Sort must be proven by a preponderance of the evidence. Smi'thK1ine Diagnostics, Inc. v. Helena Labs. Corp, 859 F.2d S78, 889 (Fed. Cir. 1988). A preponderance of the evidence standard “requires proving 1.l1atinfringement was more likely than not to have occurred.” Warner-Lambert Co. v. Teva Pharm. USA, Inc-.,418 F.3d 1326, 1341 n.l5 (Fed. Cir. 2005) Literal infringement, a form of direct infringement, is a question of fact. Fittisar Corp. 1*. DirecTV Group, [rtc., 523 F.3d 1323, 1332 (Fed. Cir. 2008). “To establish literal infringement, every limitation set forth in a claim must be found in an accused product. exactly." Microsqfi Corp. V. GeoTag, Ina, S17 F.3d I305, 1313 (Fed. Cir. 2016) (quoting Scmtltwal! Techs., Inc. v. Cardina!1G Ct;-.,54 F.3d I570, I575 (Fed. Cir. 1995). If any claim limitation is absent, there is no literal infringement of that claim as a matter of law. Bayer AG v. Elan Piiarm. Research C0rp., 2.12 F.3d 1241, 1247 (Fed. Cir. 2000). ll
Doctrine of equivalents is also a form of direct infringement. One rubric Forevaluating if a claimed feature is not literally, but nonetheless equivalent to, a claimed feature is known as the fimction-way-result test. Under this test, the accused feature is equivalent to the claim limitation when “it performs substantially the same fimction in substantially the same way to Obtain the same result.” Duncan Parking Techs, Inc. v. IPS Grp.. Ina, 914 F.3d 1347, I362 (Fed. Cir. 2019) (quoting Graver Tank & Mfg. Co. v. Linda Afr Prods. Ca, 339 U.S. 605, 608 (1950)). Another test is known as in the insubstantial differences test, where “[a]n element in the accused device is equivalent to a claim limitation if the only differences between the two are insubstantial." Veda v. Gordie Corp, 536 F.3d 131l, l 139 (Fed. Cir. 2003). The Supreme Court has further instructed, "the proper time for evaluating equivalency . . . is at the time of infringement, not at the time the patent was issued." Warner‘-Jenkinson Ca, inc. v. Hilton Davis Chem. C0., 520 U.S. I7, 37 ( I997). C. Domestic Industry ln an investigation based on a claim of patent infringement, Section 337 requires that an industry in the United States, relating to the articles protected by the patent, exist or be in the process of being established. I9 U.S.C. § l337(a)(2). Under Commission precedent, the domestic industry requirement has been divided into (i) a “technical prong” ” (which requires articles covered by the asserted patent) and (ii) an “economic prong” (which requires certain levels of activity with respect to the protected articles or patent itself). See Certain Video Game i511/stems and C0m'r0Ner'.s',lnv. No. 337-TA-743, Co'mm’n Op. at 6-7 (April 14, 2011) (“Video Game Systems“). l. Technical Prong The technical prong of the domestic industry requirement is satisfied when the complainant in a patent-based section 337 investigation establishes that it is practicing or exploiting the patents I2
at issue. See 19 U.S.C. §§ 1337 (a)(2), (3); Certain Mir-rospiiere Adhesives, Pracessjbr Making Same and Prods. Containing Same, Incliiding Sei;'¥.S‘iick Repositionable Notes, lnv. No. 337-TA 366, C0mm’n Op. at 8 (U.S.l.T.C. Jan. 16, 1996). “In order to satisfy the technical prong of the domestic industry requirement, it is sufficient to show that the domestic industry practices any claim of that patent, not necessarily an asserted claim of that patent.” Certain Ammonium Ocfarnuivbdaie isomers, lnv. No. 337-TA-477, Comofn Op. at S5 (U.S.l.T.C. Aug. 28, 2003). The test for claim coverage for the purposes of the technical prong of the domestic industry requirement is the same as that for infiingement. See Certain Doxoriibicin and Preparations Containing Same, Inv. No. 337-TA-300, initial Determination at 109 (U.S.l.T.C. May 21, 1990), affd, Views of the Commission at 22 (U.S.l.T.C. Oct. 31, 1990); Aiioc, Inc. v. Int’! Trade Comm ‘ii, 342 F.3d 1361. 1375 (Fed. Cir. 2003). “First. the claims of the patent are construed. Second, the complainant‘s article or process is examined to determine whether it falls within the scope of the claims.” Certain Doxorabicin and Preparations Containing Same, Inv. N0. 337'-TA 300, Initial Detennination at 109. As with infringement, the technical prong of the domestic industry can be satisfied either literally or under the doctrine of equivalents. Certain Dynamic‘ Sequential Gradient Devices and Component Parts Thereof] Inv. No. 337-TA-335, ID at 44, Pub. No. 2575 (U.S.l.T.C. May 15, 1992). ln short, the patentee must establish by a preponderance of the evidence that the domestic product practices one or more claims of the patent. Z. Economic Prong The “economic prong” of the domestic industry requirement is satisfied when there exists in the United States, in connection with products practicing at least one claim of the patent at issue: (A) significant investment in plant and equipment; (B) significant employment of labor or capital; or (C) substantial investment in its exploitation, including engineering, research and development, and licensing. 19 U.S.C. § l337(a')(3). Establishment of the “economic prong" is not dependent I3
on any “minimum monetary expenditure" and there is no need for complainant “to define the industry itself in absolute mathematical terms.“ Certain Stringed Musical’ Instruments and Components Thereof, lnv. No. 337-TA-586, Comm‘n Op. at 25-26 (May 16. 2008) (“Stringed instrttmems”). However. a complainant must substantiate the significance of its activities with respect to the articles protected by the patent. Certain Printing and imaging Devices and Components Thereof, Inv. No. 337-TA-690, Comnfn Op. at 30 (Feb. 17, 20] I) (“Imaging Devices”). Further, a complainant can show that its activities are significant by showing how those activities are important to the articles protected by the patent in the context of the company’s operations, the marketplace, or the industry in question. Id. at 27-28. That significance, however. must be shown in a quantitative context. Lela inc. v. Int’! Trade Comm 'n, 786 F.3d 879, 886 (Fed. Cir. 20 l5). The Federal Circuit noted that when the ITC first addressed this requirement, it found the word “‘significant‘ denoted ‘an assessment of the relative importance of the domestic activities.” Id. at 883-4 (internal citation omitted) (emphasis added). In general, “[t]he purpose of the domestic industry requirement is to prevent the ITC from becoming a forum for resolving disputes brought by foreign complainants whose only connection with the United States is ownership of a U.S. patent." Certain Battery-Powered Ride-On Toy Vehicles, Inv. No. 337-TA 314, USITC Pub. No. 2420, Initial Determination at 2t (Aug. 1991). The Commission “has long recognized that the ‘its’ in the phrase ‘investment in its exploitation’ in subparagraph (C) refers to the asserted patent or other intellectual-property right being asserted. That conclusion is supported by the clear text of the statute.” Certain Integrated Circuit Chips and Products Containing the Same, lnv. No. 337-TA-S59, Comm’n Op. at 36 (Aug. l l, 2014) (“[m'eg1'a.redCircuit Chips”). This connection between the investment and the patent is known as the “nexus” requirement. Id. at 38. “To the extent that the patented technology arises I4
from endeavors in the United States, such a nexus would ordinarily exist.” Id. at 39. “'Exploitation’ is a generally broad term that encompasses activities such as efforts to improve, develop, or otherwise take advantage of the asserted patent." Id. Similarly, investments in plant and equipment, labor, and capital that may fairly be considered investments in research and development are eligible for consideration under subsections (A) and (B), in addition to subsection (C). See Certain Solid Store Storage Drives, Stocked Electronics Components, and Products Con-raimngSome, lnv. No. 337-TA-1097, Comm’n Op. at l4 (June 29, 2018) (“Solidiitore Storage Drives”). D. Invalidity 1. 35 U.S.C. § 102 Pursuant to 35 U.S.C. § 102, a patent claim is invalid as anticipated if: ta) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant; (b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date ofthe application for patent in the United States; (e) the invention was described in (1) an application for patent, published under section l22(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent;" (g)(2) before such person’s invention thereof, the invention was made in this country by another inventor who had not abandoned. suppressed, or concealed it. 35 U.S.C. § 102 (pre—AlA). “A patent is invalid for anticipation if a single prior art reference discloses each and every limitation of the claimed invention. Moreover, a prior art reference may anticipate without disclosing a feature of the claimed invention if that missing characteristic is 15
necessarily present, or inherent, in the single anticipating reference." Schering Corp. i.-.Geneva Pharm.. 1210.,339 F.3d 1373, 1377 (Fed. Cir. 2003) (citations omitted). 2. 35 u.s.c.§ 103 Section I03 of the Patent Act states: A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior an are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made. 35 U.S.C. § 103(a) (pre-AIA). “Obviousness is a question of law based on underlying questions of fact.” Scar-met‘ Techs. Corp. v. [COS Vision .S:ys.Corp. N.V., 528 F.3d 1365, 1379 (Fed. Cir. 2008). The underlying factual determinations include: “(l) the scope and content of the prior art, (2) the level of ordinary skill in the art, (3) the differences between the claimed invention and the prior art, and (4) Objective indicia of non-obviousness." Id. (citing Graham v. John Deere C0. of Kansas C.iljP,383 U.S. I, I7-I S (l966)). These factual determinations are oflen referred to as the "Graham factors.” The critical inquiry in determining the differences between the claimed invention and the prior art is whether there is a reason to combine the prior art references. KSR In: '1Co. v. Teleflex Iricz,550 U.S. 398, 418-2] (2007). IIJKSR, the Supreme Court rejected the Federal Circuit’s rigid application of the teaching-suggestion-motivation test. While the Court stated that “it cmt be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does,” it described a more flexible analysis: Ofien, it will be necessary for a court to look to interrelated teachings of multiple patents; the effects of demands known to the design community or present in the marketplace; and the background knowledge possessed by a l6
person having ordinary skill in the art, all in order to determine whether there was an apparent reason to combine the known elements in the fashion claimed by the patent at issue . . . . As our precedents make clear, however, the analysis need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ. Id. at 413. Since KSR, the Federal Circuit has announced that, where a patent challenger contends that a patent is invalid for obviousness based on a combination of prior art references, “the burden falls on the patent challenger to show by clear and convincing evidence that a person of ordinary Skill in the art would have had reason to attempt to make the composition or device . . _and would have had a reasonable expectation of success in doing so.” Pr'mrrnaSIem Therapeutics, Inc. v. ViaC'e!t',[nc.. 491 F.3d l342, I360 (Fed. Cir. 2007); see KSR, 550 U.S. at 399 (“The proper question was whether a pedal designer of ordinary skill in the art, facing the wide range of needs created by developments in the field, would have seen an obvious benefit to upgrading Asano with a senson”). In addition to demonstrating that a reason exists to combine prior art references, the challenger must demonstrate that the combination of prior art references discloses all of the limitations Of the claims. Hearing Camp0nem‘s, Inc‘. v. Share I;m:'.,600 F.3d 1357, l3’/'3-4 (Fed. Cir. 2010) (abrogated on other grounds by Nautilus, Inc. v. Biosig Instruments, Ina, I34 S.Ct. 2120 (2014)) (upholding finding of non-obviousness based on the fact that there was substantial evidence that the asserted combination of references failed to disclose a claim limitation); Velander v. Gamer, 348 F.3d l359, i363 (Fed. C‘-ir.2003') (explaining that a requirement for a finding of obviousness is that “all the elements of an invention are found in a combination of prior art references"). “A reference qualifies as prior art for a deter-mirialion under § 103 when it is analogous to the claimed invention.” fmiavenrion Toys, LLC v. MG/1 Erirm‘t_1:16.,637 F.3d l3l4, 132i (Fed. 17
Cir. 201 I) (citing In re Clay, 966 F.2d 656, 658 (Fed. Cir. 1992)). “Two separate tests define the scope of analogous prior art: ( I) whether the art is from the same field of endeavor, regardless of the problem addressed and, (2) if the reference is not within the field of the inventors endeavor, whether the reference still is reasonably pertinent to the particular problem with which the inventor is involved.“ In re Bigio, 33! F.3d 1320, 1325 (Fed. Cir. 2004) (citing In re Deminslci, 796 F.2d 436, 442 (Fed. Cir. 1986]). One way of evaluating whether a reference is reasonably pertinent is to consider if, “logically [it] would have commended itself to an inventor's attention in considering his prolnlern.” K-TEC. Inc. v. Vita-Mix Corp, 696 F.3d 1364, 1375 (Fed. Cir. 2012) (citing hmovenrion, 637 F.3d at 13211). The requirement for prior art to be analogous is “meant to defend against hindsight." In re Khan, 441 F.3d 977, 986-937 (Fed. Cir. 2006). An obviousness determination should also include a consideration of “secondary considerations” such as “commercial success, long felt but unsolved needs, failure of others, etc., might be utilized to give light to the circumstances surrounding the origin of the subject matter sought to be patented.” Graham, 338 U.S. at l7-IS. “For [such] objective evidence to be accorded substantial weight, its proponent must establish a nexus between the evidence and the merits of the claimed invention." In re GPAC Inn, 57 F.3d 1573, 1580 (Fed. Cir. 1995); see Merry’:& Cie v. Gnosis S.P.A., 808 F.3d 829, 837 (Fed. Cir. 2015). “Where the offered secondary consideration actually results from something other than what is both claimed and novel in the claim. there is no nexus to the merits of the claimed invention.” In re Hnaf-Hung Koo, 639 F.3d 1057, I068 (Fed. Cir. 201i). 3. 35 U.S.C. § 112 Pursuant to 35 U.S.C. § 112, a patent claim is invalid for lack of written description ifthe patent’s specification fails to “reasonably c0nvey[] to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Pharm., Inc. v. Eli Lilly & 18
Co., 598 F.3d 1336, I351 (Fed. Cir. 2010) (en bane). “[T]hc test requires an objective inquiry into the four corners of the specification fiom the perspective of a person of ordinary skilled in the art,“ fol, and “the level ofdetail required to Satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology," id. (citing Capon v. Eshnr, 418 F.3d 1349, 1357-58 (Fed. Cir. 2005)). Additionally, under 35 U.S.C. § H2, a patent claim is invalid for indefiniteness if “its claims, read in light of the specification delineating the patent, and the prosecution history, fail to inform, with reasonable certainty, those skilled in the art about the scope of the invention." Nautilus, Inc. v. Biosig Instruments, Ina, 134 S. Ct. 2120, 2124 (2014), lndefiniteness can result from a single claim covering both an apparatus and a method of use of that apparatus, as “a manufacturer or seller of the claimed apparatus would not know from the claim whether it might also be liable for contributory infringement because a buyer or user of the apparatus later performs the claimed method using the apparatus." [PXL Holdings v. Amozoncom, 430 F.3d I377, 1334 (Fed. Cir. 2005); see UIfimorePot'm‘er_L.L.C. v. Nintendo Co., S16 F.3d 816, 326 (Fed. Cir. 2016) (holding these types of claims may make it “unclear whether infringement . . . occurs when one creates an infringing system, or whether infringement occurs when the user actually uses the system in an infringing manner") (citation omitted). “[A]pparatus claims are not necessarily indefinite for using functional language," however, as in, for example, means-plus-function formatted claims. MasterMi'rie Software, Inc. v. Microsoft Corp, 874 F.3d 1307, 1313 (Fed. Cir. 2017) (citing Microprocessor Enhcmcernen! Corp. v. Tex. Instruments Ina, 520 F.3d I367, 1375 (Fed. Cir. 2003)). Another example may be when the claim merely recites “that the system ‘possesses the recited structure which is capable of performing the recited functions.” Id. at 13l 5~ I6 (quoting Microprocessor Enhancemem‘, 520 F.3d at 1375). I9
Further. under 35 U.S.C_.§ 112, a patent specification must contain a description “of the manner and process of making and using” the invention. 35 U.S.C. § ll2. This is referred to as the enabiement requirement, and a patent claim is sufficiently enabled only when the specification teaches “those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. " Genentech, Inc. v. Nova Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997). To determine whether the specification leaves a person of ordinary skill to perform undue experimentation, the Federal Circuit has identified the following factors to consider: (1) the quantity of experimentation necessary; (2) the amount of direction or guidance presented; (3) the presence or absence of working examples; (4) the nature of the invention; (5) the state of the prior art; (6) the relative skill of those in the art; (7) the predictability or unpredictability of the art; and (8) the breadth of the claims. In re Wands, 585 F.2d 731, 737 (Fed. Cir. 1988). “[1]t is not necessary that a court review all the Wands factors to find a disclosure enabling. They are illustrative, not mandatory.“ Amgen, Inc. v. Chugai Pharm. C0., Ltd, 927 F.2d 1200, 1213 (Fed. cit. 1991). E. Unenforeeahility “Each individual associated with the filing and prosecution of a patent application has a duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the Office all information known to that individual to be material to patcntability as defined in this section.“ 37 C.F,R. § l.56(a). Thus, a patent may become unenforceable if “the applicant misrepresented or omitted material information with the specific intent to deceive the PTO.“ Theraserio'e, Inc. v. Bec!o.=i.Dickinson and CCL,649 F.3d 1276, 1287 (Fed. Cir. 2011) (en bane). “Unlike validity defenses, which are claim specific, see 35 U.S.C. § 288, inequitable conduct Ztl
regarding any single claim renders the entire patent unenforceable.“ Id. at 1288 (citing Kingsdown Med. Consultants, Ltd. v. Hollister Inc, S63 F.2d S67, 877 (Fed. Cir. 1988)). “Intent and materiality are separate requirements.” Id. at 1290 (citing Hofinrorr-Lo Roche, Inc. v. Promego Corp., 323 F.3d 1354, 1359 (Fed. Cir. 2003)). With respect to materiality: [T]he materiality required to establish inequitable conduct is but-for materiality. When an applicant fails to disclose prior art to the PTO, that prior art is but-for material if the PTO would not have allowed a claim had it been aware of the undisclosed prior art. Hence, in assessing the materiality of a withheld reference, the court must determine whether the PTO would have allowed the claim if it had been aware of the undisclosed reference. Id. at 1291. With respect to intent: A finding that the misrepresentation or omission amounts to gross negligence or negligence under a "should have known" standard does not satisfir this intent requirement. Kingsdown, 363 F.2d at 876, "In a case involving nondisclosure of information, clear and convincing evidence must show that the applicant mode o deliberate decision to withhold a known material reference." Molina, 48 F.3d at 1181 (emphases added). In other words, the accused infringer must prove by clear and convincing evidence that the applicant knew of the reference, knew that it was material, and made a deliberate decision to withhold it. Id. at 1290. Further, the evidence of specific intent must “require a finding of deceitful intent in the light of all the circumstances“ such that “when there are multiple reasonable inferences that may be drawn, intent to deceive cannot be found.” Id. at 1290-91 (citations omitted). In the context of withheld prior art, “[p]artia1disclosure of material information about the prior art to the PTO cannot absolve a patentee of intent if the disclosure is intentionally selective." Am. Caleor, Inc. v. Am. Honda Motor’ C'o., 768 F.3d 1185, l 190 (Fed. Cir. 2014) (citing Aventis Phorma S./-1. v. Hospiro, Ina, 675 F.3d 1324, 1335-36 (Fed. Cir. 2012)); Semiconolnctorjy Energy Lab. Co. v. Samszmg Elecs. C0,. 204 F.3d 1368, 1376 (Fed. Cir. 2000)). lt is also true that “[a]n inference of intent to deceive is appropriate where the applicant engages in ‘a pattern of lack of candor,’ including where the applicant repeatedly makes factual representations ‘contrary to the true 2|
inforrnation he had in his possession?” Regeneron Pharm, Inc. v. M€t‘llS'N. V., 364 F.3d i343, I351 (Fed. Cir. 2017) (citing Aporex Inc. v. UCB, Inc, 763 F.3d 1354, 1362 (Fed. Cir. 2014)). Nevertheless, “the specific intent to deceive must be ‘the single most reasonable inference able to be drawn fi"omthe evidence.” Theraseivse, 649 F.3d at 1290 (citation omitted). Ill. JURISDICTION AND IMPORTATION Jcnnewein has stipulated to importation, as noted in its own briefing. (See RIB at 10(citing IX-0003C; JX-0D09C').) l therefore find the importation requirement under 19 U.S.C. § l337(a)( 1)(B) satisfied. and find the Commission has in rem jurisdiction over the Accused Product. See S'ea1edAir Corp. v. Int ‘ITrade Comm ‘:1,645 F.2d 976. 935 (C.C.P.A. 198]), One of Jennewein’s fact witnesses, Dr. Stefan Jennewein, testified that an exhibit, RX-0280C, “is a summary of the 2‘-FL we produced and imported into the U.S. according to strain." (RX-0385C at Q132-133.) He explained the information came from Jennewein’s CFO, who “prepared it from our accounting system in response to one ofGlycosyn‘s discovery requests.” (Id. at QI34.) Based on this document, he mludsd tha1— TTFLI-'1— 11¢ at Q135.) The importation record, RX-0280C, is briefand shows the following: 21
(RX-028°C at -284583-> D1 Jelmewees testimony confinns it (RX-0385C at Q135) as docs Jcnncwcin’s final response to Glycosyrfs request for admission on this issue: REQUEST FOR ADMISSION 7: Admit that .Iennewein‘s strain #1540 is the only strain Jennewein uses to produce the 2’-FL that is imported into the United States. AMENDED RESPONSE TO REQUEST NO. 7 Jennewein objects to this Request as vague and ambiguous with respect to the terms “uses” and “produce.” Subject to its objections, Jennewein responds as follows: tcx-0216c at 5). 23
IV. ll.S. PATENT NO. 9,970,018 A. Level of Ordinary Skill in the Art In Order No. 22, the Chief Administrative Law Judge found a person of ordinary skill in the art for the asserted patent at the time of the invention would have (1) a Ph.D in molecular biology, biochemistry, or chemical engineering, or an equivalent field, and 1-2 years of experience working with E. coli bacteria or related systerns, or (2) a lower level degree (tag, a MA.) in a similar field to those listed above, but a greater amount of relevant working experience (e.g., 5-6 years ofexperienee working with E. colt bacteria or related systems). (Order No. 22 at 7.) I find no reason to diverge from this definition and apply it throughout this initial determination. B. Claims-at-Issue Claims l-3, 5, 8-I4. 18, and 22-28 ofthe ’0l 8 patent are at issue in this investigation, either through allegations of infringement or of the domestic industry technical prong: 1. A method for producing a fiicosylated oligosaccharide in a bacterium, comprising providing an isolated E. coir‘bacterium comprising, (i) a deletion or functional inactivation of an endogenous [3 galaetosidase gene; (ii) an exogenous functional B-galactosidase gene comprising a detectable level of B-galaetosidase activity that is reduced compared to that of a wild-type E. coir‘ bacterium, wherein the level of B galactosidase activity comprises between 0.05 and 200 units; (iii) an inactivating mutation in a colanic acid synthesis gene; and (iv) an exogenous lactose-accepting fucosyltransferase gene; culturing said bacterium in the presence of lactose; and retrieving a fucosylated oligosaecharide from said bacterium or from a culture supernatant of said bacterium. 2. The method of claim 1, wherein said colanic acid synthesis gene comprises an E. calf weal, wzxC, weal), wza, wzb, or wzc gene. 24
3. The method of claim 2, wherein said colanic acid synthesis gene
comprises a weal gene.
5. The method of claim 1, wherein said exogenous lactose-accepting
fiscosyltrarisferase gene encodes 041,2) fucosyltransferase and/or oi.(1,3)
fucosyltransferase.
8, The method of claim I. wherein said exogenous functional [3
galactosidase gene comprises an E. cofi 1:102gene.
9. The method of claim 8. wherein the IacZ gene is inserted into an
endogenous Ion gene.
10. The method of claim l, wherein said bacterium further comprises a
functional lactose permease gene.
ll. The method of claim l0, wherein said lactose permease gene is an
endogenous lactose permease gene.
12. The method ofelaim 10, wherein said lactose permease gene comprises
an E. colt lacY gene.
13. The method of claim I, wherein said bacterium further comprises an
exogenous E. coir‘rcsA or E colt resB gene.
14. The method of claim 1, wherein said bacterium funher comprises an
inactivating mutation in a lacA gene.
18. The method of claim l. wherein the level of [3-galactosidase activity
comprises between 0.05 and 5 units.
22. The method ofclaim l, wherein said bacterium comprises the genotype
of
(a) ampC::(PtrpB?tcl+), Placl q {Alacl-lacZ)lacY+. Aweal,
1hyA::Tn10, Alon::(kan, lacZ+); or
(b) ampC'::(PtrpB?tcl+), Placl q (Alacl-lacZ)1acY+, Awca.L
thyA::Tnl0, Alon::(kan, lacZ+), AlacA.
2523. The method of claim l, wherein said exogenous flinctional B galactosidase gene is inserted into an endogenous gene. 24. The method of claim l, wherein said exogenous filnctional B galactosidase gene comprises a recombinant B-galactosidase gene engineered to produce a detectable level of B-galaetosidase activity that is reduced compared to the level of [3-galactosidase activity in a wild-type E. colt bacterium. 25. The method of claim 24. wherein the level of [5-galactosidase activity comprises between 0.05 and 5 units. 26. The method of claim 1, wherein the level of ll-galactosidase activity comprises between 0.05 and 4 units. 27. The method of claim 1, wherein the level of B-galactosidase activity comprises between 0.05 and 3 units. 28. The method of claim 1, wherein the level of [3-galactosidase activity comprises between 0.05 and 2 units. (CIB at I5-16.) C. Claim Construction As pan of the Mar'k)ira:iprocess, the following terms of the ’0l8 patent were construed, either as-agreed between the parties or detennined by Order No. 22: Claim Term CtJ_l18_tllI_Qljlllj______ __ _ 0 “providing” plain and ordinary meaning. i.e., furnishing, supplying, making available, or preparing. “in the presence oflactose” plain and ordinary meaning, i'.e., lactose is available to the bacterium “exogenous” plain and ordinary meaning, 1'.e., originating outside an organism, tissue, or cell “colonic acid synthesis gene” “By ‘colanic acid synthesis gene’ is rneant a gene involved in a sequence of reactions, usually controlled and catalyzed by enzymes that result in the synthesis ofeolanic acid.“ ooh"lacZ gene” plain and ordinary meaning, 1'.e., a structural gene that encodes the [5-galactosidase protein and is part of the lac operon in the DNA of E. colt 26
“[3-galactosidase activity comprises Not indefinite; “fl-galactosidase activity is between 0.05 and [200 units / 5 units / 4 measurable at between exactly 0.05 and exactly units I 3 units / 2 unitsj" [200/5/4/3/2] Miller Units, as defined in Miller, J.l-l., Experiments in Molecular Genetics (Cold Spring Harbor Lab. I972) at 352-355“ “functional . . . [5-galactosidase gene” “a Functional sequence of DNA that encodes EI galactosidase” “wild type“ “the type most commonly found in nature” (See Order No. 22 at I2-I3, 22-35.) None of Glycosyn, Jennewein, or the Staff specifically identify any remaining claim construction issues for this initial determination. (See CIB at 32-33; RIB at 16-17; SIB at 29-30.) D. Infringement According to Glycosyn‘s post-hearing briefing, and not contested by Jennewein or the Staff, the following products are within the scope of the Investigation and accused ofinfringing the following claims ofthe ‘U18patent: Product Claims Jennewein #1540 and I-3, 5, 8, 10, 12, 18, 23-28 [CIB at 15.) As referred to above, Jennewein and the Staff each argue that another of Jennewcin’s E. calf strains is properly within the scope of the investigation and subject to a determination of infi-ingcrncntea strain designated TTFLI 2. Glycosyn disputes that an infiingement determination on TTFLl2 is appropriate given the circumstances. 27
l. Regarding the Jennewein TTFLIZ Strain With respect to Jcnnewein’s 2 ’-FL produced by the TTFLI 2 Strain. there can be no dispute that Glycosyn has not accused it of infringement such that it is an “accused product.” (CPB at 27 (“E. The Accused Process. At the hearing, Glycosyn will demonstrate that [] Jennewein’s method ofmaking 2’-FL using Jennewein’s #1540 z K) infringes the asserted claims of the ’0lS Patent”); SIB at 61 (‘Glycosyn has not alleged that 2'—FLmade using Jennewein’s TTFLIZ strain infringes any claim of the asserted patents, either literally or under the doctrine ofequivalents.").) Nevertheless, Jennewein contends itplaced this strain into the scope ofthe investigation such that an infringement determination is warranted. (RIB at 66 (“Despite being aware of Jennewein‘s TTFLI2 strain since August 21, 2018, Glycosyn failed to accuse 2’-F L made using this strain of infringing any claim of the ‘O18patent.").) The Staff concurs. (SIB at 63.) As noted, Glycosyn disputes that such a determination should he made. tens at 67.) The Commission has recently addressed the circtunstances under which non-accused products nonetheless fall within the scope of an investigation. tn Certain Two-Way Radio Equipment and Syslerm‘, Related Software, and Compotrerifs Thereof (“Two—Way Radio”), the Commission had determined to review “(5) the [final] lD’s finding that insufficient record evidence exists to make a conclusive detennination as to whether any redesigned products infringe the "701 patent and the 1D‘s lack ofan express finding on this issue with respect to the ‘S69 or '99l patenI[s]." lnv. No. 337-TA-1053, Comm’n Op. at S (Dec. 18, 2018) (public version). Contraljl to that [D‘s finding, the Commission held “[respondent] has met its burden to show that the redesigned products are fixed in design, have been imported, and have been sufficiently disclosed by respondents during discovery.” Id. at 23 (citations omitted). The Commission also noted that in a prior opinion, it had affirrned an ID which found that “redesigned products should be 28
adjudicated where ‘the design around products are within the scope of the investigation, have been imported into the United States or sold in the United States, [and] were the subject of extensive discovery as well as testimony during the cvidentiary hearing in this investigation.'” Id. at 24 (citation Omitted);see id. at 27 (“sufficiently fixed, have been subject to extensive discovery, and have been imported“). From these discussions in Twu~Way Radio, I divine a four—factortest as to whether a respondent has rnet its burden to show the infringement of a redesigned product should be adjudicated. The product must be: (I) within the scope of the investigation, (2) imported, (3) sufficiently fixed in design, and (4) subject to extensive discovery. Of these factors, I find Respondents have not met their burden as to the fourth factor, subject to extensive discovery. Technically, the issue of whether TTFLIZ was subject to extensive discovery is not actually disputed, given that when Glycosyn first attempted to argue this in their initial post hearing brief, it was struck upon motion by Order No. 38. (See Order No. 38 at 3-4.) I understand from the parties’ reply briefing that Glycosyn has resurrected this line of argument in its reply brief (CRB at 35-37 (Section II.B.2)), but I disregard this content and do not depend on it in reaching the present finding. Both Jennewein and the Staff contend that Glycosyn either was aware or should have been aware of the TTFLIZ strain on August 21, 2018. (RIB at 66; SIB at 6|.) Jennewein cites no evidence to explain why this is (see RIB at 66), but the Staff states this date is “when Jennewein produced documents describing that product, including the TTFI_.l2 strain‘s genotype and construction.” (SIB at 6|.) To support its assertion, the Staff cites two documents, RX-0320C and RX-0332, which I infer to mean these documents were produced on or before that day. (See SIB at 61.) 29
The first, RX-0320C, is an article authored by certain Jennewein personnel, characterized
by Jcnnewein as a “draft article” (RIB at 67), and which Dr. Jcnnewein tcstified was submitted for
publication but then withdrawn to protect the information disclosed in it (_R){—O385C at Q160-1 65).
The article bears Bates numbers of JENNITCI l20_OO2Ol76-210. The document discusses
Jennewein’s strain engineering activities which resulted in
(RX
oazoc at -20177.)
(id. at -20192, -20207).
The second document, RX-03 82, is described as a European patent application (FLLBat 9
n.2), although it is unclear ifthe particular copy is the EPO publication of that application or a
copy ofa Jennewein submission as part of that application process; Dr. Jennewein offered a third
explanation, that RX-0382 is the issued patent itse|f(RX—0385C at Ql66-167). hi any event, the
document bears Bates numbers of JENN ITC1 l2UA00006729-S5 and discloses a “present invention
re]at[ing] to a method for producing oligosaccharides comprising a terrninal galaetose-91->4}
glucose disaccharide.“ (RX-U382 at -6729.) Importantly, it discloses bacterial strains that
intentionally lack B-galactosidase activity as we-llas bacteria including that activity. (Id. at [0084]~
[[)USS]). The document does not appear to refer to any of its embodiments or strains as TTFLIZ.
In any event, on September 14. ZOIB, Jennewein complied with its Ground Rule 7.2
obligation to identify those of its products it understood to be within the scope of the Investigation.
(See RIB at 9 n.2; SIB at 70.) In this mandatory disclosure. CX-0226C. Jennewein provided, in
relevant pan:
Pursuant to Ground Rule 7.2.I(2), Jennewein identifies the following
processes that are within the scope of the investigation:
30TTFLl2. See, e.g., JENNEITCI lZU_UU2Ul76-JENNITCI l2O_UUZO2lU. (CX-0226C at 2.) Notably! the production numbers listed here correspond only to the draft article. which is RX-0320C, and not RX-0382. Six days later, on September 20, ZOIS, Jerutewein amended a response to one ofGlycosyn’s requests for admission regarding importation (SIB at 3384). On that day. Jennewein provided the following: REQUEST FOR ADMISSION 7: Admit that Jennewein°s strain #1540 is the only strain Jennewein uses to produce the 2’-FL that is imported into the United States. AMENDED RESPONSE TO REQUEST NO. 7 Jennewein objects to this Request as vague and ambiguous with respect to the terms “uses” and “produce.” Subject to its objections, Jennewein responds as follows: (CX-0216C at 5.) Notably, this response does not mention TTFLIZ at all. The last important discovery date is November 5, 2018, the close offact discovery, which saw Jennewein provide a final round of discovery responses, CX-0237C. (RRB at 7; SIB at 70.) According to Jennewein, it “plainly disclosed the TTFLIZ strain to Glycosyn during discovery, first in its [Ground Rule 7.2 disclosure] and again in its discovery responses on November 5, ZOIS." (RRB at 7.) The Staff also characterizes that day as when “Jennewein amended its 31
interrogatory responses to clearly identify the TTFLIZ strain.” (SIB at 70.) In both of their descriptions, Jennewein and the Staff reference page 2 of CX-0237C, where Jennewein provided the following: INTERROGATORY NO. 21 For each version, commercial name, and internal code name or other unique identifier of Jennewein 2’-FL identified in response to [nterrogatory No. l, identify all corresponding bacterial strains used to produce Jennewein 2’-FL. RESPONSE TO INTERROGATORY NO. 2 Jennewein objects to this interrogatory as Dverbroad, unduly burdensome and seeking information not reasonably calculated to lead to the discovery of admissible evidence or not proportional to the needs of this case to the extent that it encompasses products Jennewein does not import commercially into the U.S. or are not the subject of this investigation, or strains used to produce such products. Subject to and without waiving general and specific objections, and subject to Jennewein’s objections to lnterrogatory No. l, Jennewein responds to this interrogatory as follows: Jennewein identifies the production strain it uses to produce Jennewein 2"-FL for commercial importation into the United States as E. colt strain BL2l (DB3) #1540. FIRST SUPPLEMENTAL RESPONSE TO INTERROGATORY NO. 2 [ll/‘S/18!: Subject to Jennewein’s prior objections to Interrogatoiy No. 22 Jennewein incorporates by reference its 1 ' 1 nd hi - TTFLI (CK-0237C at 1-2.) Again, November 5, 20lS was the day fact discovery closed. Thus, on the question of whether Jenncwein provided “extensive” or “sufficient” discovery on the TTFLl2 strain, I find it did not. Only two documents provide any specific information on TTFLI 2; the undated “draft” article which describes the development strain and identifies it by name (see, e.g., RX-0320C at -20191, Fig. 1); and the ZOI4 patent application specification, which 32
does not refer to TTFLIZ by name and simultaneously discusses strains that could be TTFL12 (see SIB at 74 n.23 (discussing RX-0382 at 111][D084], [l]085])) as well as strains that are definitely not rrruz (see rd. (discussingax-03s2 at'll1| [U087], [0OS3])). An accused infringer's own patents (RX-0382 in the case of Jcnnewein) are generally not Considered reliable evidence of an accused product's features in the first place. Sea Forest Labs, Inc. v. Abbot Labs, 239 F.3d 1305, 1313 (Fed. Cir. 2001). Further, while Jennewein identified TTFLIE as falling under the scope of the investigation in its Ground Rule 7.2 disclosure, and identified the “draft” article, RX-0320C, as evidence ofTTFLl2’s relevant features, it did not identify the patent application such that Glycosyn would have been on notice of it. Thus, in an effort to meet its burden on sufficient discovery, Jennewcin has effectively pointed to just one document that Glyeosyn could have used—-theundated article (RX-0320C). Moreover, the probative value of that article is low. While Jennewcin argues it “includes a complete description of the genetic makeup of the TTFL12 strain; no more is required to conclude that the use of this strain cannot infringe the Asserted Claims” [RIB at l4 n.3), it does not show that any 2’-FL which Glycosyn might accuse of infringement was actually produced in this way, l find it perplexing why there were no other documents produced (or at least identified in .lennewein‘s briefing as having been produced) and/or identified to Glycosyn during discovery to confirm this basic fact, especially given: (I) the prevalence of batch or fermentation run records in this industry (see RIB at 145 (“Jennewein can readily determine the strain used to make any particular lot of 2‘~FL. As Dr. Parkot testified, Jermewein can identify the strain used to produce each lot number of2’-FL within Fourhours of a request”) (citing Hr’g Tr. at 34810-21)); (2) the fact that Jennewein seems to have produced its first and only TTPL l2 2’-FL during the discovery period of this investigation (RX-0385C at Q170 (“Qt When did Jermewein start producing 2’-FL 33
using the TTFL12 strain?" Dr. Jennewein himself testified, "[w]e performed a fermentation run in the summer M2018.” (emphasis added))); and (3) .lennewein’s claim that TFFLIZ is so fixed in deem t1(RRB at 4 (citing Hr’g Tr. at 204:] 5720516)). RX»O32OCmay provide information on the conception ofTTFLl2. but it does not sufficiently identify and describe a product that could serve as an accused product. The discovery responses which Jenneweirt and the Staff point to add little. Again, while TTFLIZ was identified on September 14, 2018 as a product alleged to he within the scope ofthc investigation (CX-0226). the earliest interrogatory responses identified as mentioning TTFL l2 are those Jennewein provided on the last day of discovety (CX-0237C at I-2). Perhaps more important are Jenneweirfs responses to Glycosyn’s request for admission on importation. Here. the request asked Jetmewein to admit that #1540 was the only strain they use to produce 2’-FL imported into the U.S. (CX-0216C at 5.) Jermewein had initially answered with reference to just the #1540 strain, but updated that answer toinclude t andthe neverupdatedit ism This was done despite Jennewein‘sfirst ever importation of TTFLI2-based 2’-FL on October 1l, 2018. (PUBat I l (citing, inter alia, RX-0278C; RX-280C; Hr’g Tr. at 347:6-22).) Then, on the very last day of fact discovery, Jennewein added TTFLIZ to its response to an interrogatory asking for simply “all corresponding bacterial strains used to produce Jenneweio 2’-FL.” (CX-0237C at I 2.) In total, these responses put Glycosyn on notice of just three things: a strain referred to as TTFL12existsandwasdescribed inanunpublished, undated article— (CK 0226; CX-0320C); at some point the strain was used to create an unspecified amount of 2‘-FL (CX-2037C at I-2); but that 2’-FL had not been imported into the United States (CX-0216C at 5). 34
It is the burden of the respondent to provide the “extensive” or “sufficient” discovery on the redesigned product, Tw0—WayRadio, Con'im’n Op. at 23, and Jennewein has not met this burden, from either a document production or discovery response perspective. An eamest effort to force TTFL12 into the investigation would have seen Jettnewein prove to Glycosyn the nature of TTFLIZ, and how it had been used to produce imported 2’-FL, before the very last day of fact discovery. This was not done, however. Admittedly, Glycosyn failed to take discovery ofits own on this issue (see Rll-3at 9-1(J. 14. 66; RRB at 2-4) and to respond to Jc11newein's own requests for admission on TTFL12 (see RIB at 68-69 (citing RX-03 17C)). As Jennewein summarizes, “Glycosyn has been hard at work trying to keep this product out of‘this investigation on procedural grounds." (Id. at 9.) Nevertheless, it is Jennewein’s burden to introduce TTFL I2-based 2’»FL into the case, Two-WayRadio, Cornm’n Op. at 23, and Jenneweir1’sinaccurate response to Glycosyn‘s request for admission on importation was more than enough to dissuade Glycosyn from investigating anything other than the #1540 strain during discovery. Accordingly, I do not find adjudication of whether the TTFLl2 strain infringes to be appropriate at this time because the discovery on TTFL 12 was not adequate. 2. DirectInfringement bythe Jennewein #1540and— Strains Glycosyn has shown by a preponderance of the evidence that the Accused Strains (#1540 a meet thelimitations ofasserted claims l-3,5,S,10,I2,18, and 24-23 either literally or under the doctrine of equivalents, and thus, Jennewein directly infringes those claims. Jennewein has not been shown to infringe dependent claim 23. 35
a. Undisputed Claim Limitations The parties do not dispute most of the asserted claim limitations of the ‘O18 patent as compared to Jennewcin‘s Accused Strains. (See, e.g., CIB at 33-34; RIB at 18; SIB at 33-36; RRB at B-41.) Commission Rule 2l0.3l(d) states in relevant part, “[a]ny matter admitted under this section may be conclusively established unless the administrative law judge on motion permits withdrawal or amendment ofthe admission.” I9 C.F.R. § 2l0.3l(d). l agree with Glycosyn that this rule allows me to conclusively find for the purposes of this investigation that the Accused Strains meet each of the claim limitations admitted to in Jenneweirfs responses to requests for admission (CX-0215C; CX-0216C; CX-0217C), and I do so find. (CIB at 34 (citing CX-02l5C at l-2, 4-7, 8, .39-40; CX-0216C at l-2, 4-7, 8, 39-40, 25-33, 63, 69; CX-02l 7C at 72-74).) As to independent claim 1, these limitations include: I. A method for producing a fueosylatcd oligosacchariclc in a bacterium, comprising providing an isolated E. calf bacterium comprising, (_i) a deletion or Functional inactivation of an endogenous B galactosidase gene; (iii) an inactivating mutation in a colanie acid synthesis gene; and (iv) an exogenous lactose-accepting fucosyltransferasc gene; culturing said bacterium in the presence of lactose; and retrieving a fueosylated oligosaccharide Erom said bacterium or from a culture supernatant of said bacterium. PO18 patent at cl. 1.) With respect to the asserted dependent claims, .leru1ewein’smethod of producing 2‘-FL practices the additional elements recited in dependent claims 2, 3, 5, 10, l2, I8, and 24-28. (See CIB at 63-64 (citations omitt-ed').) The Staff agrees these claim elements are met. (See SIB at S7 36
60.) Jennewein does not dispute the claims are practiced either, apart from their dependence on independent claim I. (See RIB at 66; RRB at 8-4| .) a dispute over these claims, I find they are met by Jennewein’s Accused Strains. These claims include In light of the evidence identified by Glycc-synand discussed by the Staff, and the lack of 2. The methed of claim 1, wherein said colanic acid synthesis gene comprises an E. colt weal, wzxC, wcaD, wza, wzb, or wze gene. 3. The method of claim 2, wherein said colanic acid synthesis gene comprises a wcaJ gene. 5. The method of claim 1, wherein said exogenous lactose-accepting fucosyltransferase gene encodes n.(_l,2) fueesyltransferase andfor rx(1,3) fucosyltransferase. 10. The rnethed of claim 1, wherein said bacterium further comprises a Functional lactose permease gene. 12. The method efclaim IO, wherein said lactose permease gene comprises an E. coir‘ lacY gene. 18. The method of claim l, wherein the level of B-galaetosidase activity comprises between 0.05 and 5 units. 24. The method of claim l, wherein said exogenous functional _B galactosidase gene comprises a recombinant B-galactosidase gene engineered to produce a detectable level cf [3-galactosidase activity that is reduced compared to the level of |3-galactosidase activity in a wild-type E. 0011'bacterium. 25. The method of claim 24. wherein the level of B-galaetesidase activity comprises between 0.05 and 5 units. 37
26. The method of claim l. wherein the level of [3-galactosidase activity comprises between 0.05 and 4 units. 27. The method of claim I, wherein the level of B-galactosidase activity comprises between 0.05 and 3 units. 28. The method of claim l,, wherein the level of B-galactosidase activity comprises between 0.05 and 2 units. (’()l8 patent at cls. 2, 3, 5. It], 12, l8, 24-28.) b. Disputed Claim 1 Limitation “an exogenous functional B galactosidase gene comprising a detectable level of [£ galaetosidase activity that is reduced compared to that of a wild-type E. coli bacterium” Lnaddition to those undisputed limitations listed above. claim 1ofthe ’0lS patent requires: (ii) an exogenousfiincrionai B-gaiaciosidase gene comprising a detectable level’0f,B-gaiactosidase activity that is reduced compared to that of a wild iype E. coii bacterium, wherein the level of [3-galactosidase activity comprises between 0.05 and 200 units; (‘0l8 patent at cl. l (emphasis added).) For the emphasized portion of this limitation, Glyeosyn alleges it is met in the Accused Strains both literally and under the doctrine of equivalents through the strains‘ use of lacZa and lricZ.Qgenes. (CIB at 35, 42.) More specifically, Glycosyn contends that lacZ0t encodes the “LacZo. portion" and lat-ZQ encodes the “LacZQ portion” “of the full LacZ B-galactosidase enzyme“ and thus, together, they “literally comprise a sequence of DNA that encodes |3 galactosidase“ under the claim construction ordered by Order No. 22. (See id. at 35-36.) l disagree it is literally met. To repeat, the claim recites “a[] . . . fiinctional [3-galactosidase gene," which Order 22 construed as “a functional sequence of DNA that encodes 0-galactosidase." (Order No. 22 at 29.) This limitation requires “a sequence” of DNA that encodes for the enzyme known as [3-galactosidase. Jcnnewein has put forward persuasive evidence that 11202::and lacZQ arc, in fact, distinct sequences of DNA in which neither by itself comprises the full collection of 38
nucleotides needed for a B-galactosidase enzyme. (See. e.g., RIB at 26-27 (citing l-Ir‘g Tr. at 435:l8-436:6; RX-0386C at Q56, 64-66; RX-0409C at Q329-330; RX-0408C at Q63-64).) The Staff agrees with Jennewein (see SIB at 39) and Glycosyn acknowledges that IacZa and IQCZQare distinct: "[i]n other words, 13-galactosidase can be encoded by either two sequences OTDNA, i.e., IacZa and IacZ.Qgenes together, or by a single sequence ofDNA, 1'.e.,the laeZ gene.” (C-IBat 37.) Nonetheless, Glycosyn disputes that “a sequence,” as used in the ordered construction of “gene,” means “that the ‘functional sequence of DNA’ be a single contiguous sequence within the bacterial genome." (CIB at 38.) Glycosyn offers no evidence in support, however, and I find a plain and ordinary meaning of “sequence” does imply contiguity. Indeed, if “sequence” did not mean a contiguous string of nucleotides (i.e., a contiguous string of DNA), then Glycosyn and its expert would not bother to refer to [acZa and lacZQ as separate genes, as they do in the excerpt above and throughout the record. (See, e.g., CIB at 3, ll, 35, 36, 36 n.3, 38, 39, 43, 44, 64, 117; CX-0004C at Q62, 458, 462, 468, 477. 48!. 578. S95, 596.) Accordingly, .len.newein’s Accused Strains do not literally infringe “an exogenous fimctional B-galactosidase gene” because they lack a single sequence of DNA which fimctions to create a [3-galactosidase gene. As G]ycosyn’s own expert states, Jennewein “uses two shorter, functional sequences of DNA (lac'Z'a and 1'acZ.Q)which, together, encode B-galactosidase.” (CK t)OO4Cat Q475.) The use of such shorter fimctional sequences, which encode for enzyme fragments, is called o.-complemcntation. (RX-0011 at -14798 (“[t]his cornplcmentation involves noncovalent reassociation ofcomplementary fragments of the [1-galactosidasesubunit polypeptide chain, which then reassemble into an enzymatically active tetrameric structurc.”).) Glyeosyn also argues, however, that Jennewein’s IacZa and IHCZQmeet “an exogenous Functional [3-galactosidasegene" under the doctrine of equivalents filnction-way-result test. (CIB 39
.. -‘ at 42.) Its expert testitied that Jennewein's use or ‘ two shorter. functional sequences" as compared to “one long, functional sequence” “is a quintessential example of ‘equivalence,’ because in both cases a functional B-galaetosidase enzyme, with a low level of activity, is obtained.“ (CX-0004C at Q475.) To understand why Ci]ycosyn’s expert is correct, it is llfllpflll to break the analysis into two parts; (1) “a[] . . t functional [3-galactosidase gene”; and (2) “exogenous.” Regarding “a[] . . . fimctional B-galactosidase gene,” the term was construed in Order 22 as “a fiinctional sequence of DNA that encodes [5-galactosidase.” (Order 22 at 29.) As for function and result, there is no difference between the combination of lacZtt and lacZS2 genes on the one hand, and any particular individual “fitnctional ii-galactosidase gene” on the other. The function and result of the “fimctional B-galactosidase gene” are baked right into its name--to provide expressible DNA which, when expressed through understood pathways, results in the creation of a [3-galactosidase enzyme: Also described herein are bacterial host cells with the ability to accumulate a intracellular lactose pool while simultaneously possessing low, ftmetional levels of cytoplasmic B-galactosidase activity, Forexample as provided by the introduction ofa functional recombinant E. coii lacZ gene, or by a B~ galactosidasc gene from any of a number of other organisms (e.g., the lac4 gene of Kluyveromyces lactis (e.g., GenBank Accession Number M84410 (GI: 173304), incorporated herein by reference). (See. é'.g., ’0 18 patent at 7:22-30.) Nowhere in this claim element is there any limit on: the amount or type of DNA; the location of the DNA in the genome; the amount or type of peptides expressed from that DNA; or the nature or way those peptides assemble into [3-galactosidase. Similarly, the function and result of the lncZa and i'acZ.Qgenes is also the provision of DNA which, when expressed, results in the creation of a B-galactosidase enzyme. This function and result are communicated clearly in Jcn11cwein’s submission to the U.S. Food and Drug Administration (the “GRAS notice”) for the #1540 strain. (See CX-0240C at -6804 (describing inseflion of lacZa and iacZ.Q“for the degradation ofexcess lactose”), -6805 (“Verification oflacZ 40
integrations and 13-galactosidaseactivity"), -6806 (“The clones having the !aeZ omega fragment
integrated were analyzed for 2‘-FL productivity and LacZ activity"), -6807 (“Clones showing B
galactosidase activity at 42°C but not at 30°C were selected for further modifications.”); see also
RX-0387C at Q77-78.)
And the way the result is achieved is substantially the same as claimed. Inasmuch as the
"way" analysis focuses on gene expression, that is, the role of the “functional 13-galactosidase
gene," the claim term imposes no limits on the way the result is achieved apart from the basic
process applicable to all DNA*the gene is transcribed and translated, resulting in peptides which.
through folding and/or combination with one another, become the |3-galactosidase enzyme. (See
C-X-0004C at Q53-54, 60 (discussing gene expression basics); RX-0384C at Q 103-1 14 (discussing
same); RX-0386C at Q93-97.) The evidence shows that this universal process also applies to
lacZ-1;:and !acZQ in the Accused Strains such that when these genes are expressed (i.e., transcribed
and translated), the peptides necessary to eventually become the B-galactosidase enzyme are
created. (See, e.g., CX-0004C at Q62, 468, 475-481; CDX-0032; RX-0384C at QI49-151; RDX
0005; RX-0386C‘ at Q90, 94, 98, 102; RX-0387C at Q77-78; RX-0409C at Q21-24. 252; l{r’g Tr.
at 435:5-14, 523:lS-524:l4_, 6l5:l6-25.) Inasmuch as the “way” analysis focuses on genome
structure, because the first step in the method of claim 1 is “providing an isolated E. calf bacterium"
possessing “a . . . functional [3-galactosidasc gene,“ the evidence shows that t1-Complementation
was well-known in the afl. (I-lr’gTr. at 265:5-I6, 664:6-7.) Persons ofordinary skill would have
known that using !acZ'a and MCZQas the relevant structure, instead of a single gene, would have
been effective, albeit “overco1nplicatcd.“ (I-Ir‘gTr. at 265:1"!-266: l, 664:6-7.)
I am not persuaded by Dr. Stephanopoulos‘ (.lenncwcin's expert) testimony on this point.
His witness statement cites three basic differences between the claimed invention and the use of
4llacZ0: and lacZQ: (1) the two gene fragments were inserted at different times and in different
genome locations; (2') assembling a B-galactosidase enzyme using lacZa and Im:ZQ involves a
process with more steps than assembling it after a single gene is expressed; and (3) the two gene
fragments are temperature dependent, that is, there is no expression unless temperature conditions
are satisfied. (RX-0409C at Q332-335.) The first two differences are seemingly foreseeable
aspects of employing t1—COmp lementation, so these differences are not substantial. (See CX-0004C
at Q4’/7.) As for the third difference, Dr. Stephanopoulos points out that “.lermewein’s [lacZ.Q] is
under temperature-sensitive repression C1357,” which allows for temperature control of
expression of the lrrcZ$'2fragment. (See RX~O4U9Cat Q335.) But as Dr. Prather (Glyeosyn’s
expert) explains, C1857 is a protein added to the Accused Strains, and one which is not always
effective. {l-Ir’gTr. at 540:3-18, 543121-23.) That is, when the C1857 is not present, or when it
“leaks,” expression of the lacZa and 1'acZQwill not be temperature-dependent. (Id. at 540115-18.)
And because Cl857 is apparently not a part of either the lacZrx or !acZ.Q gene fragments
themselves, temperature-dependence has nothing to do with “providing . . Aa . . . functional B
galactosidase gene,” and it is therefore not a substantial difference between the way claim l of the
‘U18 patent achieves its result and the way the Accused Strains do. (RX-0407C at Q26-28 (“A
temperature-sensitive repressor is another genetic regulatory element that represses expression of
a gene.").)
Jennewein makes two further arguments against equivalence. First, Jennewein argues its
vrfldustisn Paws is ash 1hfl1
time at 19.)
Jennewein reasons that “[s]ince all parties admit !acZQ is required to produce B~galactosidase,
Jennewein’s process cannot be equivalent to the claims.” Ud.) [do not agree. Claim l covers a
42method Forproducing a fucosylated oligosaccharide in a bacterium, comprising three overall steps: ( I) providing a bacterium having certain characteristics; (2) culturing the bacterium in the presence of lactose; and (3) retrieving, in this case, 2’-FL. (‘O18 patent at cl. 1.) The claim limitation at issue here falls under the first step, requiring that the bacterium have a particular characteristic, namely, a functional [3-galactosidase gene. (ldf) .le11newein’sargument is about how the bacterium is cultured to produce ZKFL, which falls under the second step. (MI) How Jennewein cultures a bacterium has no bearing on whether the bacterium possesses a functional [3-galactosidase gene. The combination of lacZa or1ru."Z.Qis unquestionably functional—thc fragments sewe no other purpose except to produce B-galactosidase. (CX-0004C at Q48l (“That is their only funetion.").) That they can be repressed under certain conditions does not affect whether they are fimctional, and, similarly, does not affect whether an equivalent to the claimed gene is present within the Accused Strains. (Hr'g Tr. at 631:3-6 (“Q ls it Fairto say that in your view, the [!acZ0:and lacZ'.Q]fragments are functional genes, they’re just not beta-galactosidase genes? A. Correct.”).) .Iermewein‘s temperature-induced trigger is lherefore irrelevant Second, Jennewein argues against equivalence because lacZa and !ncZ.Qwere known to the ‘Ol 8 patent inventors, but they "chose not to disclose it in their patent or claim this foreseeable mmmatomww-ga1mdas= _ (RRBat 19(citingH1"g Tr.94:12-l5, 265:1?-266:1, JX-0022C at l22:l l-l-4).] Jennewein reasons “[t]hus, 0.-complementation cannot be equivalent to a normal [5 galactosidase gene." (Id. (citing Forest Labs. , 239 F.3d at 1313).) Again, 1do not agree, primmily because I do not see a connection between this supposed choice of the inventors and the function way-result test. Moreover. to the extent inventor Dr. Massimo Merighi testifiecl U. 43
cornplementation “seems like an overcomplication.” he also testified moments later that “[b]ut alpha complementation [gives you] a iilnctional beta-galactosidase polypeptide. So under that interpretation, yeah, we talk about it because the whole engineering we did was try to make a functional beta-galactosidasc polypeptide inside a strain.” (Hr’g Tr. at 266:5-l 1.) Accordingly, the i'acZn and lacZQ genes in Jcnnewein‘s Accused Strains are equivalent to “a[] . . . functional B-galactosidase gene.” See Ajinomoto C0., Inc. v. 1211'!Trade Comm '11,Nos. 2018-I590. 4629, -- F.3d --, 2019 WL 3558560 at *9-l0 (Fed. Cir. Aug. 6, 2019) (holding substantial evidence supported finding equivalence between two proteins exporting same aromatic compounds, consisting of 85-95% identical structure, and resulting in increased production ot same L-tryptophan). I also find the lncZa and facZ.Q genes are equivalent to “an exogenous fitnctional B galactosidase gene.” Jennewein advances two arguments on this issue, First, it argues that “[n]either lacZ0cnor !acZQ encodes for or can produce a fiinetional 13-galactosidaseenzyme or B galactosidase activity when exogenous, or outside of, the production strain." (RIB at 32 (citing RX-0409C at Q25S).) But in the Markmcm process, the parties agreed to a construction oi “exogenous” as “originating outside an organism, tissue, or cell." (Order 22 at I2.) Whether or not a gene, like [acZa and 1acZ.Qindividually, can produce B-galactosidasc activity outside of the production strain is irrelevant to where a gene “originated.” Jennewein secondly argues that because the lacZa in the Accused Strains was not added by Jennewein, but was present in the original BL2l (DE3) strain which Jennewein engineered to achieve the Accused Strains. the “exogenous” limitation is not literally present in those strains. (RJB at 32-33.) However, lcrcZ.Qwas not originally in strain l54O, but was added during the sti-ain's development, and it is therefore exogenous. (CX-02 l3 at Fig. 2, -5158 (“Strain 1540 was 44 ~
derived from its parental strain I242 by integrating a heat inducible lacZ§l gene fragment . . . .").) Because !cicZa and lat-Z52together are equivalent to “a[] . . . functional |3-galactosidase gene," the exogenous nature of laeZQ is enough to meet the limitation. It is the combination of !acZa and 1acZQ which is equivalent to the claimed “|3-galactosidasc gene," and this combination does not exist until 1aeZ£2is inserted into the bacteriunfs genome from outside the organism. Therefore, the combination is “exogenous” and satisfies the claim limitation at least under the doctrine of equivalents, whether or not the IacZa alone is literally endogenous or exogenous. Accordingly, I find the IacZ0t and IoeZ.Q genes in Jcnnewein’s Accused Strains are equivalent to “an exogenous functional ‘B-galactosidasegene." e. Disputed Claim l Limitation “wherein the level of B galaetosidase activity comprises between 0.05 and 200 units” In addition to those undisputed limitations listed above, claim l of the ‘O18 patent requires; (ii) an exogenous functional B-galactosidase gene comprising a detectable level of B-galactosidase activity that is reduced compared to that of a wild type E. coli bacterium, wherein the level of fl’-galactosfdase acfiviifv comprises between 0.05 and 200 uiiits; (‘0l8 patent at cl. l (emphasis added).) For this limitation, “wherein the level of B—galactosidaseactivity comprises between 0.05 and 200 units,” Order 22 clarified that the term is not indefinite and means “I3-galactosidase activity is measurable at between exactly 0.05 and exactly [200/5/4/3/2] Miller Units, as defined in Miller, _l.H.,Experiments in Molecular Genetics (Cold Spring Harbor Lab. 1972) at 352-355.” (Order 22 at 22-23.) Thus, regardless of whether the Miller protocol is scientifically sound or reliable (see RIB at 41 (citing RX-0003)), it is the test to be used to determine it'a bacterium falls within the scope of the claims. Glycosyn provides a rough surnmary of the Miller protocol as follows: 45
(1) taking a sample from a culture of growing cells, (2) “permeabilizing" the cells, (3) incubating the penneablizecl cells with a chemical compound l-cnownas ONPG (a colorless compound which is specifically recognized and cleaved by [3-galactosidase to yield a yellow product), and (4) measuring with a spectrophotometer the amount of yellow color that develops over a known period of time. The values recorded by the spectrophotometer are then entered into a mathematical equation to yield the level of B-galactosidase activity in “Miller units.“ (CIB at 48-49 (citing CX-0251; Hr’g Tr. at 3:15:19-318:12).) Upon a review of the parties’ testing methods, it is clear .lennewein‘s (both that which it conducted itself and hired third-party Battelle to perform) diverges further from the Miller protocol than Glycosyn‘s. Jennewein‘s methods are therefore less reliable evidence on whether Jennewein “provides” an colt‘ bacterium" which “comprises” Miller Unit activity within the claimed range. (’0l3 patent at cl. 1.) Considering Glycosyn bears the burden on this issue, I begin with its testing and Jennewein’s criticisms thereof. Many of these criticisms are not rooted in a failure to follow the Miller protocol, however, but rather a failure to: (1) perform additional steps Jenncweill deems necessary or appropriate to properly identify exactly that amount of Miller Unit activity is attributable to what would be the “functional B-galaetosidase gene” (z'.e.,the combination of1acZ0i and .l'acZQ) in the strain (see RIB at 38-39; R_R_Bat 20-21, 24-27, 29); or (2) perform testing that reflects .lennewein‘s actual manufacturing process (see RJB at 38, 50, 54-55; RRB at 21-23. 28). Starting with the issue of Jennewein’s manufacturing process, Jennewein alleges Glycosyn improperly:testedwithshakerflasks;didnot culturethe strainsinthe presenceoflactosc; (RIB B15455 (stations omitted); see RRB at 28.) These criticisms are misplaced. The test is not whether Jennewein’s 46
accused strains exhibit the Miller Unit activity level during Jennewein’s production process, but
whether Jennewein “provides” an “E. coir‘bacterium" which “comprises” Miller Unit activity
within the claimed range when put through the procedures outlined in Miller. (’0l 8 patent at cl.
1; Order 22 at 22-23.) In other words, .lennewein’s manufacturing process could involve chilling
the E. coli to 10°C or boiling to 100°C. for 10 minutes or 10 hours, and any other number of
variations, but that would not bear on whether the E. calf which Jennewein "provides" to its process
exhibits Miller Unit activity within the claimed range when put through Miller's protocol.
Jennewein also complains that the Miller protocol is simply unreliable on its face and
“insufficient to prove infringement." (See RIB at 4| (“A paper by Giacomini shows that. even
following Miller's methods. Miller Units varied wildly. . . . This variability means that the Miller
assay is not reliable proof of infringement, particularly at very low levels near the limit of the
assay’s detection"), 53-54 (citing, inter alia, RX-0409C at Ql96; RX-0008; RX-0037); see also
RIB at 19 {citing Aporex. Inc. v. Cephalon, Inc._ No. 2:06-cv-2768, 20l2 WL 1080148 at *1l-12
(ED. Pa. Mar. 28, 20121).) This complaint is beside the point. The U.S. Patent and Trademark
Office issued claims to Glycosyn which expressly define the invention’s scope in terms of Miller
Units customized by the Miller protocol. Thus, reliable or not, it is the test to he used—a point
Jennewein concedes in other portions of its brief. (See RIB at 49 (“Third, Glycosyn failed to
follow Miller in performing its testing, and its test results are thus unreliablc.“).) l also agree with
the Staff that any complaint over unreliability in defining an invention by reference to Miller Units
is effectively an indeflniteness argument that was not included in Jennewein‘s pre-hearing brief
and is therefore waived. (SRB at 3-9 11.3.)
Jennewein makes two other unpersuasive arguments regarding the Millet‘protocol. First,
Jcnnewein argues Glycosyn’s results vary “significantly” (RIB at 53) or “much more . . . than other
47testing” (id. at 55-56) such that they have a lack of reproducibility leading to unreliability. The argument is largely conclusory, however, offering no discussion of Glycosyn’s results or why their variance is “significant[].” (R_lBat 53 (citing Hr’g Tr. at 505: I -I5 (discussing general importance of reproducibility)).) Based on my own review of the data, I do not [ind Glycosyn‘s results vary meaningfully more than Jennewein‘s. (Compare CX-0258C with CX-0292C with CX-0294C.) Second, Jcnnewein argues Glycosyn failed to subtract Miller Unit levels associated with Aim-Zor lacZ“ control strains. (See, e.g., RIB at 50-S2.) This step is indisputably not found in Miller (see gerieraliy CX-0251), and, for reasons discussed further below, I do not find it has been shown to be necessary or even appropriate. Finally, of all the criticisms Jennewein lodges against Glycosyn‘s testing, only two are based in a deviation from the Miller protocol: (I) Glycosyn failed to test with toluene in addition to SDS/chloroform (RIB at 56 (citing RX-0409C at Q2l4-216: RX-0408C at Ql25; RX-0008; Hr’g Tr. at 509:4-16); and (2) Glycosyn failed to test at longer incubation times than 60 and 120 minutes (id. at 56-57 (citing RX-0409C at Q2lS; RX-0408C at Q1 13, 1I4, l39; I-lr‘gTr. at 307:3 308:25, 309;7- 16).) On the first, Miller teaches use oftoluene and SDS/chloroform as alternative techniques. (CX-0251 at -1810, -I B12.) Therefore, using one technique but not the other does not render testing unreliable. On the second, it was not wrong for Glycosyn to fail to test at “extended incubation times,” because Miller does not specify a reaction time. Miller instead states “[s]top the reaction by adding 0.5 ml of a [stop solution] afier sufficient yellow color has developed." (CX-D251 at —l8lt).) Glycosyn's expert persuasively testified that sampling should occur while the reactions are linear (a point reinforced by Miller (CX-0251 at -1809)) and she confirmed that. for her experimental assays, 60-minute incubations gave a sufficient amount of visible yellow color, and times after that no longer represented linear reactions. (CX-0004C at Q502.) 48
Taming now to Glycosyn‘s criticisms of Jennewein’s testing, I find these have more merit, but to varied effect. For example, a primary dispute in this investigation is whether Jem1ewein’s additional step of subtracting a AlacZ or lacZ’ control strain’s Miller Units from each accused sample’s measured Miller Units is necessary—-—a step perfonned in Jenneweitfs own testing and that of third-party Battelle. Jennewein argues this step “is not only appropriate, but necessary” (RIB at 39) to correct for any agent within the strain that causes “enzymatic cleavage of ONPG by other enzymes besides [J-galactosidase" (RX-0409C at Q99)? Jen.newein'S point is seemingly scientifically valid, but the fact of the matter is that the Miller pt‘0tOCOldoes not include this step. (See generally CX-0251.) Further, the record does not identify any such “other enzyme[] besides |3-galactosidase,” let alone one present in Jenncwcin’s 2 and #1540 strains. (See RIB at 41, 43, 45, 52-.54,60, 104; RRB at 21-23, Z3, 30.) Given the supposed importance of this control step, Jennewein‘s expert's immense metabolic engineering experience (RX-0384C at Q9-40), and the well-studied properties of E. colt, I do not understand how this agent was not identified. Indeed, when pressed, both parties’ experts testified they were unaware of such substances. (Hr‘g Tr. at 454:9-23, 680:3-10.) And in many cases, Jennewein‘s subtraction resulted in negative Miller Unit levels for an accused sample. The Staff presents one such instance taken from .lenneweiI1’Sin—housetesting: 3 Other sources of “background noise” .lennewein’s expert identifies (RX-0409C at Q96-99; RDX-0013) are Lutderstood to be controlled for by techniques already disclosed in Miller itself (see CX-0251 at -1810-l l (describing 550 nm optical reading or centrifugation to correct for cell debris affecting 420 nm light reading); -1811 (describing Z buffer with no cells to correct for spontaneous splitting of ONPG)) or otherwise implemented in Jennewt-:in’stesting (RIB at 43 (describing washing for fermentation media), 52 (describing time:O reading for spontaneous ONPG hydrolysis)). 49
(SIB at 51 (showing excerpt of RX-0029C); see RX~OD29C(columns “O” and “P” at various w0rksheets).) There are negative results in Battelle’s data as well: (CX-0294C; see generally CX-0294C (columns “P” and “R"); CX-0292C (columns “P” and ”R”).) These negative values in particular should have put Jennewein on notice that its negative control technique was unreliable on its face, or implemented unreliably, or some other assumption was(MB M5-56— The 50
Staff notes that the Battelle Scientist involved in the testing testified that such negative values “would correspond, correlate to a zero value,“ but, in the Staffs view, it is really “an impossible result." (SIB at Sl n.l6 (citing Hr’g Tr. at 32'/‘:4-19).) [agree with the Staff. I also find the scientist’s explanation unacceptable given other evidence in the record that Jennewein may have chosen its‘ control strain over alternatives because of the effect it would have on infringement testing. The following email was produced during discovery (see Order No. 30) in which testing protocols were discussed between Jemtcwein personnel and a third party in the context ofwhether a “0.05" valuc would be met: It-o_.ztt1'dt11gthe Mullet assm (CX—04'.?.2Cat -0306730-l; see CXYDllO4Cat Q534-538; SIB at 53.) It is likely that the “U115” value is the bottom of the claimed range “0.05 to ZOOunits," that is, Jertrtewein sought a control strain that would minimize the measured Miller Units. (‘DIBpatent at cl. I.) Moreover, of the two testifying experts who offered contrasting opinions on whether negative control strain subtraction is necessary (see, e.g., CX-0004C at Q534, 539; RX-0409C at 92-I0], 196-20]), .lennewein’s expert was shown to have a significant lack of experience and familiarity with Miller testing prior to this litigation (see CIB at 57-59 (citing, inter alia. Hr’g Tr. 51
at 582:8-604:l8)), while G|ycosyn's expert has “performed the Miller assay many times [as] a graduate student [and] was able to reference my notes on those assays, which assisted me in my review of the documents in this investigation“ (CX-0004C at Q86). l therefore assign Jennewein’s expel-t’s testimony less weight on this issue. For at lcast these reasons, subtraction ofa negative control strain was inappropriate for the purposes of determining infringement of “wherein the level of B-galactosidase activity comprises between 0.05 and 200 units.“ Nevertheless, .lennewein‘s data clearly shows the Miller Unit levels prior to the subtraction, so the reliability ofJennewein’s testing can be assessed without reference to the negative control strain. Two of Glycosyrfs other critiques call that reliability into question. The first involves Jennewein’s exclusive reliance on Miller Unit sampling at no less than 120 minute reaction times. (See RX-0333C at Q99 (Battelle testing); RX-0386 at Q22O (Jennewein in-house testing); RX O4-OSCat Q1 13 (Jennewein in-house testing); see, e.g., RX-0292C (Battelle testing): CX-D29-4C (Battelle testing); RX-0029C (Jennewein in-house testing); CX-0275C; see also CIB at 56-57.) Jennewein justifies its choice “because it was authorized by Miller and Jennewein believed it needed to incubate its strains for a minimum of 120 minutes to obtain interpretable results in the Miller assay.” (RRB at 3| (citing RX-0408C at Q1 13).) More specifically, Jennewein states “incubation time should be extended if the yellow color develops slowly, which would be expected for low-level [5-galactosiclase activity, such as near 0.05 Miller Units." (RIB at 56 (citing RX O409C at QZIS; Ht"g Tr. at 307:8-308325, 30917-16).) Yet, testimony from the Battelle scientist who performed the experiments indicates Jennewein instructed her to measure at 120 min without regard to how color was developing in the samples. (Hr‘g Tr. at 318:1"/-320:6 (“Jennewein 52
provided a protocol to me that l followed, and it was consistent with the Miller assay. So yes, that is what I did.").) This is problematic because in Order 22, the presiding ALJ determined that “wherein the level of [3-galactosidase activity comprises between 0.05 and 200 units" was not shown to be indefinite because the patent failed to identify for how long the activity level must be maintained or when it must be measured. (Order 22 at 21-22.) Order 22 concluded, "the claim is not ambiguous as to when the claimed activity range must be met—it need only be met at some point in time." (Id. at 22 (citation omittcd).) Given this flexibility in the temporal scope of the claim, and Millcr’s instruction that the reaction should be stopped “alter sufficient yellow color has developed" (CX~025l at A1810),Jennewein’s justification for its minimum I20 minute sample rings hollow. Moreover, the evidence shows it likely would have made a difference to take a sample at an earlier time. In a chart Jennewein prominently presents as summarizing the highest Miller unit values third-party Baltelle recorded (CX-0291C), a trend of decreasing Miller unit activity levels with respect to time is visible: 53
(CX-0291C at -308410; see RIB at 44.) Given this trend, Miller's instruction to stop the reaction when sufficient color is present, and the breadth of the claim term, it would seem readings at less than I20 minutes are required in order to ascertain ifthe activity falls within the range. (See. e.g., CX-0004C at Q502, 513.) Indeed, the same Battelle scientist acknowledged a time less than I20 minutes would have been advisable: Q. And at your deposition, you testified that you probably should have done an OD420 nanometer reading for a time period less than I20 minutes; correct‘? A. I did, but due to time constraints while I was at their Facility, I did not perform those —those steps, But what I did perform was consistent with what's described in the Miller assay, along with what’s in the Jennewein protocol. Q. But you did testify that you probably should have measured attime point ofless than I20 minutes; correct? A. Yes, I did. 54
(Hr‘g Tr. at 320117-321:3.) Glycosyn’s test results support this conclusion. When it sampled at
both 60 and I20 minutes, Miller Unit levels decreased over time. (See CX-0004C at Q5013-S04;
CX-0258C; CX-0203C at CX-0203C.0004.) Glycosyn has also shown that in an earlier testing
session, when Jennewein did sample at limes less than 120 minutes, Miller Units Within the
claimed range were found. (CIB at S7 (citing CX~024lC; CX-0271C); see RX-0408C at Q10]
IU6.) Unlike the negative control strain subtraction discussed above, the effect on Miller Unit
activity resulting from measuring only at times after I20 minutes cannot be undone. The reliability
of this testing is therefore diminished.
Glycosyn’s second critique of Jerincwein’s testing is that Jennewein improperly took an
initial OD420 inn (yellow light) reading before the ONPG reaction begun, and subtracted that
reading from the OD-420 nm reading taken at the 120 minute or greater sampling time. This is
described in the briefs as the “time=0" or “t=0“ reading. This step is clearly not found in Miller
(seegenera/{)1 CX—025l). yet Jermewein describes its use as “to correct[] for the absorbance before
[3-galactosiclaseactivity could start, which was at the t=0 time point." (RIB at 43 (citing CX-0338C
at Q1 15, 120), 52, 52 n.ll (citing Hr’g Tr. at 592:l8-22, 593:6-1 l; RX-0386C at (1202)). More
specifically, Jeimewein contends it is necessary to account for non-enzymatic hydrolysis of ONPG
(i.e., spontaneous ONPG hydrolysis). (RIB at 52~53 (citing I-lr’g Tr. at 557:3-7), 45 (citing RX
0409C at Q98-99; I-1r’gTr. at 455;?-16, 559:9-13); RRB at 23 (citing, im‘era1i'a, RX-0385C at
Ql8l-l 84).)
Setting aside whether this technique accurately controls for non—enzymatic (i.e.,
spontaneous) hydrolysis ofONPG, it introduced significant effects into the results. Namely, this
subtraction caused negative values of Miller Units in some circumstances even before the negative
control strain values were considered (see CX~U292Cat Column “O”; CX-0294C at Column "O";
55RX-029C at Column “O”), and in other circumstances, greatly diminished the OD420 I1I1'lvalue that serves in the numerator position of the Miller equation: . . _ (.)i.)4*>,) " 71 01);“; .' ‘. 1-‘= l i l C -“ ,_- i i [I11 :> OJJ ‘» I K F R Uijmm [1l)+3,. and UlI)==Uare read from the reaction snireturc. £)I),,,,.-. lellects the cell den.~1il_v_iu.~n before zissav. .1 L lime’ tit‘ the l'¢.‘;!i.lt|L'tI'llfl minutes. 1: —' \’Oll.i1‘tl<3 ofculturc tised to the ussat\, lfl ml. (CX~O25l at —lS1 1; See CX-0292C at Columns “H” and “J”; CX—(l294Cat Columns “H” and “J”; RX-0029C at Columns “I” and "J”.) The effect of this “control” is clear—Miller Unit values will decreaseiancl while .lennewein‘s records make it possible to undo this subtraction, l decline to wade through the dozens of samples to do so. The fact remains this step is not in Miller and greatly affected the results. To the extent Jcnnewein argues its IiI'l'1t.F0subtraction is effectively the same as Miller’s ONPG hydrolysis control (CX-D251 at -I81 l), I find it is not. Miller teaches that correction for ONPG hydrolysis is only needed if the reaction runs for extended periods, like overnight, and should be measured via a blank with no cells. (See CRB at l7-18; CX-O25] at -l8l 1.) Clearly, Jennewein‘s 120 minute Samples and time=O readings on samples with cells do not meet tbcsc criteria. Taken altogether, there is insufficienl reason to discount or view as wholly unreliable G1ycosyn’s testing of the Accused Strains, but there is such reason to discount Jennewein’s. Apart from reliability concerns, Glycosyqfs testing simply hewecl more closely to the Miller protocol, i.e., the terms in which the invention is defined. The Staff takes the position that Glycosyn’s testing is therefore more relevant for infringement analysis purposes (SIB at 56), and I agree. That 56
testing showed a large majority of samples exhibiting Miller Unit activities within the claimed
range. (See CX-0004C at Q504-505; CX-0258C; see afsu CX-0004C at QSI6, 527; CX-0241C.)
It is therefore more likely than not that .lem1cwein‘sAccused Strains meet the limitation “wherein
the level of B-galactosidase activity comprises between 0.05 and 200 units."as in claim 1. It is also
more likely than not that Jertneweit-i’s Accused Strains infringe claim 1 of the ‘O18 patent.
d. Disputed Claim 8 “the method of claim 1, wherein said
exogenous functional B-galactosidase gene comprises an
E. coli lacZ gene”
Dependent claim 8 of the ’0l 8 patent requires;
The method ofclaim l, wherein said exogenous functional B—galactosidase
gene comprises an E. coir‘iar:Z gene.
("O18 patent at cl. 3.)
For this claim, Whichdepends from independent claim l and adds fitrther narrowing detail
to the “exogenous fiinctional B-galactosidase gene“ recited therein, Glycosyn alleges it is met by
Jcnnewein’s Accused Strains both literal1_yand through the doctrine of equivalents. (CIB at 64
65.) Jermewein’s IacZr;tand lacZ!J genes are neither individually nor collectively a “filnctional I3
galactosidase gene” in the literal sense, so they are also not literally “an E. calf lac-Zgene,” despite
.Iennewein’s GRAS notice describing lacZ0t and lacZ.Q as “originating from E. coll [(12 DH5o.“
(CIB at 64 (citing CX-0213) (emphasis removed).) Therefore, claim S is not literally infringed.
Regarding doctrine of equivalents, the function and result of the ‘O18patcnfs “E. colt lacZ
gene" is no different than the fiinction and result of the “firnctional B-galactosidase gene" of claim
l—namcly, to provide expressible DNA which, when expressed through understood pathways.
results in the creation of a B-galactosidase enzyme. (See, e.g.. ’0l8 patent at 7:22-30.) To be sure,
the “way” the shared result is achieved is more specific in the “E. calf t'acZ gene" than the more
generic “filnctional B-galactosidase gene“ of claim l. The parties are in agreement as to the
57technical details of this process, however; and those details are best explained with the following joint demonstrative: . __-V _ 7 t____ _ _ __/ Four larl Monomers Enwme ‘“l""e l.ai:/IQ l\-'lonumi:rs (1 "'39 '9' 7 l - I ~ 8 I V . ‘I X‘ , ___.. t ,2 I _ G‘ .‘ i ' 3 1" “. '§*"—' T' s “T Fnwrnre inm".1iu= Fnryrne ar:lr.Io (CDX-0032; RDX-0005 (excerpted); see CX-0004C at Q62; RX-0384C at Ql49-151; see also SIB at 7-8.) In this figure, and as explained by both experts, the upper box is a depiction of how four LacZ peptides (i.e., monomers), produced from the naturally occurring “E. coll lacZ gene" spontaneously fold and combine into the tetramer (r'.e., four monomers) or homeotetramer (i.e., four identical monomers) which is the [3-galaetosidase enzyme. (CX-0004C at Q54, 62; RX 0384C at Q98, 109, 150.) Similarly agreed to, the lower box is a depiction of how four LacZQ peptides, produced from the [acZ.Q gene, and four LaeZo. peptides, produced from the lacZ0cgene, spontaneously combine into the [3-galactosidasehomeotetratner. (CX-0004C at Q62; RX-0384C at QISO-151.) As shown, the LacZQ and LaeZntpeptides complement each other so as to result in a structure similar to a LacZ peptide, with spontaneous assembly into [3-galaetosidase. Jer1newein’s expert nonetheless asserts that due to nucleotide differences between the combination of ¢'acZaand lacZQ and !acZ, “combining LacZ0tand LaeZQ leads to a heterodimerie enzyme that differs from wild-type LaeZ.” (RX-0384C at QI57; see Hr‘g Tr. at 565:1-3.) In fact, 58
however, four of those heterodimers spontaneously combine to form the complete LacZ. Indeed, an article cited by Jennewein‘s expert (albeit on the written description issue) describes the structure produced by er.-complementation as “tetrameric,” rather than dimeric. (RX~00ll at v 14798 (“[t]his complementation involves noncovalent reassociation of complementary fragments of the [3-galactosidasc subunit polypeptide chain, which then reassemble into an enzytnatically active tetrarneric structure.").) That is, with !acZ the [3-galactosidase result starts with four subunits, and with IacZa and lacZQ the B-galactosidase result starts with eight subunits; this is not a substantial difference. And the various peptides are otherwise created in substantially the same wayeamino acids produced by the two step process of DNA transcription and translation. Jennewein additionally emphasizes how laeZ0.and lac-Z.Qare not simply chopped portions of !acZ, and include their own start codons, stop codons, promoters, and other regulatory elements (RIB at 33-37; RRB at 18, 38-39), as well as how the LacZ.ctand L~acZQpeptide combination are not “contiguous” or bonded in the same way as LacZ monomers are (RRB at 17-I8). These structural differences are undisputed, but all they show is that the limitation is not literally met, as opposed to a substantial difference in function (supply necessary DNA). way (create spontaneously folding and combining proteins), or result ta B-galactosidase enzyme). (See Hr’g Tr. at 221 :20 222:7 (“Q. . . . Why do you use two fragments? A. . . . the fact is that the lacZ gene cannot be completely regulated by itselfin the E. coli —in E. coli, unfortunately. That is [why] we’re talking about the fi.|lllength gene here. And if you cut the gene into several fragments, then this improves its ability to be regulated. . . . that also enhances e lowers the stability of the protein, which is also advantagcous.”).) 59
Accordingly, I find the lacZa and lacZQ genes in .lennewein's Accused Strains are equivalent to the “E. coir‘!acZ gene“ of claim 8. Thus, the Accused Strains infringe claim S of the ‘O18 patent. e. Disputed Claim 23 “the method of claim 1, wherein said exogenous functional B-galactosidase gene is inserted into an endogenous gene” Dependent claim 23 of the ’0l8 patent requires: The method of claim l, wherein said exogenous functional |3-galactosidase gene is inserted into an endogenous gene. (‘O18 patent at cl. 23.) For this claim, Glycosyn alleges it is met in the Accused Strains under the doctrine of equivalents. (CIB at 65.) Specifically. Glycosyn argues that the development of the strains saw Jennewein intentionally insert the Iacza gene into an endogenous gene known as yihQ. (Id. at 66 (citing CX-0240C; CX-U29'7C)._)Glycosyn acknowledges, however, Jcnnewein’s claim that this version of !acZa “simply felt out” and ceased to exist in the strain. (Id. (citing CX-0237C at 7~9; JX-0012C at 29-30, 79:23-806).) Glycosyn argues this makes no difference because it was subsequently discovered that t'acZa nevertheless continued to exist in the strain from a much earlier insertion “into the int gene of the DE3 prophage” by other groups of scientists. (Id. (describing a BL2l host strain convened to BL?.l (DE3).) Glycosyn concludes, “[w}hat is clear, is that the difference between Dr. Parschat inserting the facZo gene into the endogenous gene yihQ gene, and someone else inserting the [acZo: into the DE3 prophage’s inf gene are so insubstantial that Jennewein never even noticed it for years, and only after this investigation began." (Id. at 66-67 (citing Tom C0. v. White Consul. Indus, 266 F.3d 1367, 1370 (Fed. Cir. 200l)).) Glycosyn does not address [£262-Q. 60
The Staffs argument on this point is persuasive: “both the IacZ.Q fragment and the DE3 prophage itself,” into which the la.-:Z'Qfragment was inserted, “were introduced into the original host strain.” (SIB at 60 (citing CX-0004C at Q598 (Prather).) That is, "either both are exogenous to Jennewein’s production strains or both are endogenous.” Ud.) But because claim 23 requires an exogenous gene inserted into an endogenous gene, the Accused Strains cannot literally infringe it. And because this claim limitation cannot be met through the doctrine of equivalents without viliating it entirely, Warner-Jerikinsoii, 520 U.S. at 39 n.8, dependent claim 23 is not infringed. E. Domestic Industry - Technical Prong According to Glycosyifs post-hearing briefing, and not contested by Jennewein or the Staff, the following domestic industry products are alleged to practice the following claims of the ‘O18 patent: Product Claims Glycosyn's E. coir’production strains ofwhich l-3, 5, 8-14, 18, 22-28 E. calf strain E997 is representative (CIB at 15-I6.) With respect to those strains allegedly represented by E997, Glycosyn argues: Glycosyn has developed strain E997 as well as several other E. cnli bacterium strains that practice claims l-3, 5, 8-14, 18, and 22-28 ofthe ’0l8 Patent, and thus are domestic industry strains. See CX-0059C (curated 258 strainsxlsx). Since Fall of 2015, Glycosyn has documented the amounts of 2'-FLproduced bythesedomesticindus strainstobe— 2, with ab being produced by E997. See C-X-0131C (!All Runs Sunimaiyxlsx); CX-0064C (!All Runs Summaiyxlsx). (Id. at 92; see id. at l5 (citing CX-0004C at Q99, I23); see also CX-0004C at QI64.) l do not observe any dispute from Jennewein or the Staff over Glycosyrfs contention of representativeness 6]
of E997. I therefore accept Glyeosyn’s claim of representation for the ptuposes of evaluating domestic industry. Further, for the reasons explained below, I find Glycosyn has shown by a preponderance of the evidence that its production of 2’-FL using its E997 strain practices claims l-3, 5, 8, IO-I4, 18, 22, and 24-28 ofthe “O18patent. Glyeosyn has not shown it practices claims 9 or 23. I. Undisputed Claim Limitations As with infringement by the Accused Strains, discussed above, and as reflected in the parties’ posbhearing briefing, the practice of a large majority of the ’Ol8 patent claim limitations by Gly-::esyn‘s E997 strain is not in dispute. (See, e.g., CIB at 92; RIB at 69-72; SIB at 76-86; RRB at 41-43; SRB at 20-22.) With respect to independent claim I, and in reference to claim limitation identifiers used within the witness statement of Glyeosyn‘s expert (CX-1004(1), Glycosyii asserts “that [it] literally produces 2’-FL, a fucosylated oligosaccharide, in a bacterium using a method that practices claim elements l(pre), 1(a), l(e), l(d), I(e), and I(f)," an assertion supported by its expert's witness statement. (CIB at 92 (citing CX-0004C at Q! IU-126, I27-I34, I69-I 75, I76-I87, 188-192, I93-209).) Glycosyn also demonstrates that, for the remaining limitation, E997 includes “an exogenous fiinctional I5-galactosidase gene comprising a detectable level ofB-galaetosidase activity that is reduced compared to that of a wild-type E. colt bacterium.“ (Id. (citing RPB at 76; CX—O0O4Cat QI27-134).) The Staff agrees these limitations are met. (See SIB at 77-79.) Jennewein does not dispute the limitations are met, either. (See RIB at 69~72; RRB at 4] -43.) In light of the evidence identified by Glycosyn and discussed by the Staff, and the lack of dispute. l find they are practiced by Glycosyrfs E997 strain. These limitations include: 1. A method for producing a fucosylated oligosaccharide in a bacterium, comprising 62
providing an isolated E. calf bacterium comprising, (i) a deletion or Functional inactivation of an endogenous 13 galactosidase gene; (ii) an exogenous functional I3-galactosidase gene comprising a detectable level of I3-galaetosidaseactivity that is reduced compared to that of a wild-type E. coir‘bacterium, (iii) an inactivating mutation in a colanic acid synthesis gene; and (iv) an exogenous laetose~accepting fueosyltransferase gene; culturing Said bacterium in the presence of lactose; and retrieving a fucosylated oligosaccharide from said bacterium or from a culture supernatant of said bacterium. (‘O18 patent at cl. 1.) With respect to the asserted dependent claims, Glycosyn argues it “practices the additional claim elements present in dependent claims 2, 3, 5, 8, 9, ll], l 1, 12, 13, 14, 18, 22, 23, 24, 25, 26, 27, and 23 ofthe ’0l 8 Patent.” (CLBat 96 (citing CX-0004C at Q21!)-294; CX-0065).) Jennewein indeed does not dispute this. (See RIB at 69-72; RRB at 41-43.) The Staffi however, does challenge Glyc0syn’s practice of claims 9 and 23, and I address these below. (SIB at S2-86.) l also address the B-galactosidase activity level of claim 1 below. Otherwise, in light of Glyeosytfs expert evidence, and the lack of a dispute from Jennewein or the Staff, I find the following claims are practiced by Glycosyn’s E997 strain: 2. The method of claim l, wherein said colanic acid synthesis gene comprises an E. cnii weal, wzxC_,wcaD, wza_ wzb, or wzc gene. 3. The method of claim 2, wherein said colanic acid synthesis gene comprises a weal gene. 63
5. The method of claim l, wherein said exogenous lactose-accepting fucosyltransferase gene encodes o(l,2} fucosyltransferase and/or a(_l_.3) fucosyltrarlsferase. 8. The method of claim l, wherein said exogenous functional [5 galactosidase gene comprises an E. calf lacZ gene. IO. The method of claim l, wherein said bacterium fiirther comprises a functional lactose permease gene. ll. The method of claim 10, wherein said lactose pennease gene is an endogenous lactose permease gene. I2. The method of claim 10, wherein said lactose permease gene comprises an E. coli lac‘? gene. 13. The method of claim l, wherein said bacterium further comprises an exogenous E. coli rcsA or E. calf rcsB gene. 14. The method of claim l, wherein said bacterium Further comprises an inactivating mutation in a lacA gene. I8. The method of claim l, wherein the level of [5-galactosidase activity comprises between 0.05 and 5 units. 22. The method of claim 1, wherein said bacterium comprises the genotype of (a) ampC::(PtrpB?tcl+), Placl q (Alacl-lacZ)laeY+. Awcal, thyA::Tn10, A|on::(kan, 1aeZ+);or (b) ampC::(PtrpB7l.cl+), Placl q (Alacl-lacZ)lacY+, Awcal, thyA::Tnl0, Al0n::(kan, lacZ+), AlacA. 24. The method of claim 1, wherein said exogenous filnctional [3 galactosidase gene comprises a recombinant B-galaotosidase gene engineered to produce a detectable level of [3-galactosidase activity that is reduced compared to the level of I3-galactosidase activity in a wild-type E. coli bacterium. 64
25. The method of claim 24, wherein the level of B-galactosidase activity comprises between 0.05 and 5 units. 26. The method of claim l, wherein the level of B-galactosidase activity comprises between 0.05 and 4 units. 27. The method of claim 1. wherein the level of B-galactosidasc activity comprises between 0.05 and 3 units. 28. The method of claim l. wherein the level of B-galactosidase activity comprises between 0.05 and 2 units. (‘O18 patent at cls. 2, 3, 5, 8, l0-14, 18, 22, 24-28.) 2. Disputed Claim 1 Limitation “wherein the level of B galactosidase activity comprises between 0.05 and 200 units” The only claims and limitations in dispute for the domestic industry technical prong are the B-galactosidasc activity level of claim 1, which Jennewein contests, and dependent claims 9 and 23, which the Staffcontests. Claim l of the “O18patent requires: (ii) an exogenous functional B-galactosidase gene comprising a detectable level of [l-galactosidase activity that is reduced compared to that of a wild type E. coli bacterium, wherein the level of fignlactosidase activitfv comprises between 0.05 and 200 units; (’0l8 patent at cl. 1 (emphasis added).) For this limitation, Glycosyn’s evidence shows that “E997. and other Glycosyn strains that contain a re-introduced lacZ gene at the same location and direction. reproducibly exhibit [3 galactosidasc activity between l and 3 Miller units." which is well below the approximately 1000 Miller units exhibited by wild-type E. coir’bacteria. (CIB at 94 (citing CX-0024C; CDX-0070C: CX-0021C; CX-0049C; CX-0050C; CX-0251.) Jennewein, however, complains that “Glycosyn relics solely on its own in-house testing to support the technical prong of the domestic industry requirement“ as specified by an intemal index card of instructions. (RIB at 70 (citing Hr‘g Tr. at 76:5-12, 2'71:19-272:8, 514118-22; RX-0409C at Q349).) Jenncwein repeats its non~infi'ingemeI1t position (discussed and rejected above) that the testing method suffers from no negative controls 65
(id. at 70-7!) and adds, as Glycosyn anticipated, criticisms ofGlycosyn‘s incubation temperature
-we-= as1h@ we
id. at 7!-72.)‘
As noted above, failure to subtract negative control strain Miller Units does not constitute
deficient testing. Jennewein’s remaining criticisms regarding temperature and redundant sample
preparation steps also lack merit. On temperature, Glyco-syn’sresults show that testing was done
— butalsoat 28"Cand30°C-—the tormerofwhichJcnnewcinclaimsisthecorrect
temperature. (RIB at 71; RRB at 4|-42; CX-0004C at Ql65-167; CX-0048C.) As shown below,
Miller Unit levels within the claimed range were met at all temperatures:
0 I
(ox-0043c at -122123.) Regarding Glycosyifs
— whichJcnneweincorrectlyobservedis redundantaccordingto Miller('CX
025l at-I81 I), I am persuaded that use ofj ust one of these preparation steps would have increased
Miller Unit values but not so much as to travel outside of the claimed 0.05 to 200 range. (CK
0251C at-1810-I811 (describing formulae in which 550 nm readings are used to lower Miller Unit
4 While Jennewein and Glycosyn refer to the 28°C as an incubation temperature, it is likely
more accurately described as a reaction temperature. {CX-0251 at -I310 (cells are grown at 37°C
but driven to 23°C right before ONPG is added).)
66calculated amounts); Hr’g Tr. at 536: l-9.) Lndced,Jem1ewein’s argument is limited to an assertion that the Miller Units would simply be “altered”~—apremise that it otherwise provides little support for. (RIB at 72 (citing RX-0409C at Q350 (withdrawn testimony)); RRB at 42 (citing Hr’g Tr. at 305:7-l5; R.X—0409Cat Q2l2 (discussing Jennewein strains and inapplicable)).) Accordingly, I find Glycosytfs E997 strain practices this limitation of independent claim 1, and in light of the other limitations not in dispute, all of independent claim l. 3. Disputed Claim 9 “the method of claim 8, wherein the lacZ gene is inserted into an endogenous lon gene” Dependent claim 9 of the ‘O18patent requires: The method of claim 8, wherein the lacZ gene is inserted into an endogenous Ion gene (‘O18 patent at cl. 9.) Glycosyn‘s own expert interpreted Glycosyn’s GRAS Notice No. 735 as evidence that the ‘loo’ gene was modified with a ‘complete deletion and replacement with a gene cassette . . . .‘ (CX-0004C at Q229; see CX-0065 at Table l.) Clearly, “complete deletion” of a gene precludes insertion into that gene, so claim 9 is not practiced. Glycosyn does not dispute this in their reply brief. (See CRB at 47.) 4. Disputed Claim 23 “the method of claim l, wherein said exogenous functional B-galactosidase gene is inserted into an endogenous gene” Dependent claim 23 of the ‘O18patent requires: The method of claim l, wherein said exogenous functional B-galactosidase gene is inserted into an endogenous gene. (‘O18 patent at cl. 23.) For the same reasons outlined above with respect to claim 9, l agree that claim 23 is not practiced. Glycosyn does not dispute this in their reply brief. (See CRB at 47.) 67
F‘. Validity and Enforceability
Jennewein‘s initial post-hearing brief identifies the following invalidity and
unenforceability theories against the asserted claims of the ‘O18 patent;
Claims Theory
l-3, 5, 8, IO, 12, IS, and 23-28 Rendered obvious under 35 U.S.C. § 103 by Samain
(RX-0002) in view of Kawano (RX-0014) and the
knowledge of one of skill in the art as shown by
Drouillard (RX-0015), Geisser (RX-0016), and Dekany
{RX-0017).
l-3, 5, 8, I0, I2, l8, and 23-28 Indefinite under 35 U.S.C.§ 112, 1]2
(included solely for right ofappeal in light of Order 22)
1-3, 5, s, 10, 12, 1s, 23, and 24 Lack of enablement under 35 U[s.eT§ *1512,-111
1-3, 5,3, 10, 12, 18, 23, and 24 2Lack ofwritten description 35 u.s.c. § 112,11 1
1-3, 5, 3, 10, 12, 13, and 23-28 Unenforceable due to inequitable conduct K
I. Asserted Prior Art
Jennewein alleges the “Samain” reference, U.S. Patent No. 7,521,212 (RX-0002) is prior
art to the ’OlS patent because it issued from an application filed on May Z4, 2002 and further
claims priority from international applications to July 7, L999. (RIB at 75.) Glycosyn does not
contest the prior art status of Samain (see CIB at 96-109; CRB at 47-54), and l find it qualifies as
prior art under pre-AIA 35 U.S.C. § 102(a), (b), and (e).
Jenneweiri alleges the “l(awano" reference, a publication Foundin “Volume 33 ofNucleic
Acids Research“ (RX-0014) is prior art to the ’0I 8 patent because it was published in 2005. (RIB
at 75.) Glycosyn does not contest the prior art status OfKBWfll'lO(see CIB at 96-109; CRB at 47
54), and I find it qualifies as prior art under pre--AIA 35 U.S.C. § lU2(a) and (b). 35 U.S.C. §
68ltl2(e) only applies to patent applications and issued patents, which Kawano is not; Jcn11ewein"s contention to the contrary is not well-taken. (See RIB at 75.) Jennewein alleges the “Drouillard” reference, a publication found in “Volume ll8 of the Angewandte C-hemie(German for ‘Applied Chemistry’) journal" (RX-0015) is prior art to the ’DI8 patent because it was published in 2006. (RIB at 77.) Glycosyn does not contest the prior art status of Drouillard (see CIB at 96-109; CRB at 4'/~54), and l find it qualifies as prior art under pre-ALA 35 U.S.C. § ]O2(a) and (bl. Jennewein alleges the “Geisser“ reference, a publication found in “the Journal of Chromatography A" (RX-D016) is prior art to the ‘O18patent because it was published in 2005. (RIB at 77.) Glycosyn does not contest the prior art status of Geisser (see CIB at 96-109; CRB at 47-54), and I find it qualifies as prior art under pre-ALA 35 U.S.C. § l02(a) and (b). Jennewein alleges the “Dekany” reference, published application number W0 ZOIO/l 15935 (RX-DOl7) is prior 311to the ’0l S patent because it “was filed on April 7, 2010, and claims priority to a Danish application filed on April 7, 2009.” (RIB at 78.) Glycosyn does not contest the prior art status of Dekany (see CIB at 96-109; CRB at 47-54), and l find it qualifies as prior art under pre-AIA 35 U.S.C. § lO2(a). 2. 35 U.S.C. § 103 (Obviousness) Jennewein contends that “claims l-3, S, S, 10, 12, 18, and 23-28 ofthe ’Ol8 patent are each obvious, and thus are invalid, based on Samain [RX-0002] in combination with Kawano [RX OOI4] and optionally one of Drouillard [RX-0015], Geisser [RX-0016], or Dckany [RX-0017]." (lei) More specifically, and with respect to claim l from which all other asserted claims depend, Jennewein°s theory is that Samain teaches all elements of this claim except for “(ii) an exogenous functional 13-galactosidase gene comprising a detectable level of [3-galactosidase activity that is reduced compared to that of a wild-type E. coir"bacterium. wherein the level of [3-galactosidase 69
activity comprises between 0.05 and 200 units.” (See RIB at 7'9(citing RX-0384C at Q20], 202; Hr‘g Tr. at 707:2-7l2:l9).) For this missing element, Jennewein claims it is taught by Kawano, and that a person of ordinary skill in the art would have been motivated to incorporate this teaching ofKawai1o into Samain‘s fiicosylated oligosaccharide-producing strains. (See id. at 79-80 (citing RX-0384C at Q206-209; RX-ODI4 at -2244-45).) .lennewein’s expert testified in support of that motivation in several places, as part of his ‘230 and ’0l8 patent discussions: Ln my opinion, it would have been obvious to use a low lcvcl of $3 galactosidase activity in Samairfs E. cuff strain, less than wild-type activity, to solve the known problem of purifying oligosaccharides from lactose, as taught by Druillard, Geisscr or Dekany, but keeping the level low enough to avoid preventing 2‘-FL production as taught by Sarnain. (RX-0384C at QZO3(citing RX-0015 at *l8lO; RX-0016 at *lS; RX-0017 at *1-5)); Lactose as a feedstock would necessarily be present in Significant amounts in the fermentation medium as l explained above. and would be difficult and impractical to separate from 2’-FL, particularly at large scale, due to these known difficulties in separating 2’-FL from lactose. Keeping the level of lactose inside the cell low also would have been desired to avoid lactose toxicity and degrading the substrate for 2‘-FL production, for which some level of [Lgalactosidase activity would have been an obvious solution. (id. at QZO4); To avoid impacting 2‘-FL production, but still allow excess lactose to be eliminated, a low level of B-galactosidase activity would have been desired, including as low as 0.05 to ZOOunits. (id. at (2206); A POSA would have been motivated to combine Kawano’s low level offi galactosidase activity with Samain to address the known problem of purification of Fucosylalecloligosaccharides like 2“-FL from lactose, while not destroying too much lactose substrate to prevent production of any 21 FL. B-galactosidase was known to destroy lactose. (id. at Q2091; 70
One of ordinary skill would have been motivated to modity Samain with a reasonable expectation of success by introducing a low-level of B galactosidase activity according to Kawano to aid in the purification of the fucosylated oligosaccharidcs produced by eliminating other oligosaccharides present, like lactose. (id. at Q2l9 (citing RX-0015 at *18l0; RXAOUI6at *18; RX-0017 at *1-5); see also id. at Q259, 262 (citing RX-0015 at *lSlO; RX-U016 at *lS; RX-D017 at l-5)). The expert further testified that a person of ordinary skill would have known how to accomplish this given “the teachings of Kawano, which teaches a POSA how to engineer E. cofi to have a low level of B-galactosidase activity, including activity of l30-200 Miller units.” (Id. at Q206 (citing RX-U014at Table 2, Fig. 1); see id. at QZI6, 258.) I find that a person of ordinary skill in the art would not have been motivated to combine the teachings of Sarnain and Kawano, without the benefit of hindsight fiom the ‘O18patent, for two primary reasons. First, a fair reading of Samain shows that it teaches away from the proposed combination. Samain not only fails to teach “(ii) an exogenous functional [3-galactosidase gene comprising a detectable level of [5-galactosidase activity that is reduced compared to that of a wild-type E. cnii bacterium, wherein the level of B-galactosidase activity comprises between 0.05 and 200 units,” but it repeatedly insists that no [3-galactosidaseactivity be present to avoid consuming the lactose “precursor” outside the production pathway of 2’-FL: [S]aid method comprising the steps (i) of obtaining a cell that comprises at least one recombinant gene encoding an enzyme capable of modifying said exogenous precursor or one of the intermediates in the biosynthetic pathway of said oligosaccharide from said exogenous precursor necessary for the synthesis of said oligosacchariden from said precursor, and also the components for expressing said gene in said cell, said cell‘ locking any enzymatic activity Ifabfe to degrade said 0lig0.rac'charfde,said precursor and said intermediares[.] (RX-0002 at 2:38-4'7 (emphasis added)); 7!
According to one preferred embodiment of the invention, the bacterium is Escherichia coli. According to another embodiment of the invention, the cell is a yeast that is preferably Sacclraromyces cerevsae, Saccharomyces pombe or Candida albicaas. The cell according to the irivetitiorzlacks any enzymaticactivity liable to degrade said oligosaccltaride, said precursor or said metabolic intermediates. (Id at 3:35-41 (emphasis added)); The B-galactosides are normally hydrolyzed in the cytoplasm of the bacterium by the B-galactosidase encoded by the LacZ gene. ht order to overcome this problem, a lacZ* bacterial mutant lacking [3-galactosidase activity is used when the precursor used is lactose andlor a B-galactoside. One of the objects of the invention is tlms also to provide the method according to the lnverition that is characterized in that said cell lacks enzymatic activity liable to degrade said precursor or said metabolic intermediates. (id at 7:6-14 (emphasis added)); in the method according to the invention, said cell may be lacking in enzymatic activity liable to degrade said precursor(s). According to one preferred embodiment, the method is characterized in that said cell has 21 genotype chosen from LacZ‘ andtor NanA‘. at 7:25-30 (emphasis added)); FIG. lt . . . Lactose (,5-D—Gal-[1-4]-/3‘-D-Glc)is transported into the cell by lactose permease (Lac permease). The lactose cannot be hydrolyzed in the cell since the strain is a LacZ' mutant. (id at 10:66-1 I :9 (emphasis added); see also id. at l 1:40-51 (emphasis added)); FIG. 9: . . . Lactose and sialic acid (Nemic) are internalized in the cell by lactose permease (lacy) and sialic acid permease (nanT). These two cornpottnds are not degraded in the cell since the strain is a lac? and nan/I‘ mtitant. The expression ofCMP-l\leuA synthase and ofo-2,3-sialyh transferase allows the activation of the sialic acid internalized into CMP~ NeuAc and its transfer onto the intracellular lactose. (id at I l:63-12:3 (emphasis adcled)). Sarnain achieves this lack of B-galactosidase activity by maintaining a LacZ‘ status in multiple disclosed embodiments (through deletion or inactivation): 72
Thus, according to one preferred embodiment . . . it is characterized in that
said cell is a bacterium of LacZ‘, LacY* genotype, said enzyme is [3-1,3-N
acetyl-glucosaminy]»transi'erase, said substrate is glycerol, said inducer is
isopropyl B-D-thiogalactoside (IPTG) and said precursor is lactose.
According to a second preferred embodiment, the method according to the
invention is used for the production of lacto-N-neo-tetraose and
polylactosamine; it is characterized in that said cell is a bacterium of LacZ‘,
LacY* genotype[.]
According to a third preferred embodiment, the method according to the
invention is used for the production of allyl 3-O-(2-acetamido-2-deoxy-{L
D-glucopyranosyl)-|3-D-galactopyranoside, ([3-D-GleNac-[1—>3]-[i-D-Gal
IHO-allyl); it is characterized in that said cell is a bacterium of LacZ',
LacY* genotype[.]
According to a fourth preferred embodiment. the method according to the
invention is used for the production of analogs of lacto-N-nee-tetraose and
of polylactosarnines in which the glucose residue is replaced with an allyl
group; it is characterized in that said cell is a bacterium of LacZ’,
LacY‘ genotype[.]
According to a fifth preferred embodiment, the method according to the
invention is used for the production of allyl-B-D-laetosamine (I3-D-Gab
[l—>4]f:-D-GlcNac-l—>Orallyl); it is characterized in that said cell is a
bacterium of LacZ‘, LacY"genotype[.]
(rd at 7:43-8:19);
Another subject of the invention relates to a method described above for the
production of 3’-sialyllactose (ct-NeuAc-[2—r3]-—>-D-Gal-[ l —>~4]-B-D-Gle)
or 6'-sialyllactose (0.-NeuAc-[2—+6]-fa-D-Gal-[l —+4]'fi»D~Glc),
characterized in that:
said cell is a bacterium of LacZ', LacY*, l‘-lanA_or NanT"genotype[.]
at9:1-12);
According to a seventh preferred embodiment, the method according to the
invention is used for the production of 3'-fucosyllactose (B-D-Gal-[l—>4]
73(tit-L-Fuc-[l—>3]-D-Glc) or 2'-fucosyllactose ([3-D-Gal-[I—>2]-(a-L-Fuo [l—>3]-D-Glc), characterized . . . in that the cell has a wcaj_ Iacfffgenotype and overexpresses the rcsA gene and in that said precursor is lactose. (id. at 9:39-46; see also id. at 16:1-I 5 (“The strain JM I09 is lacZ‘, that is to say that it is incapable of hydrolyzing lactose.”)). Notably, Jennewein’s expert does not squarely address this important aspect of Samain’s disclosure in his direct witness testimony. He responds in conclusory fashion, “Q. What about Glycosyn‘s argument that the prior art teaches away from their invention? A. I do not find that Jenn-=:wein’spatent or Samain ‘teach away’ from the claimed inventions or evidence skepticism relating to the alleged inventions." (RX-0384C at Q31 5; see RIB at 96-97 (citing sarne).) Based on the above excerpts, Sarnain clearly expresses skepticism as to the value of re-introducing LacZ activity into its strains. Similarly, Jennewein is wrong in asserting that the above excerpts amount only to “lacking a limitation” and not “teaching away." (See RRB at 45.) Samain"s consistent emphasis on a LacZ‘ status for its strains is too great to be written off in this way. Jcnnewein cites Sanlorus, Inc. v. PaI'Pharm., Inca, 694 F.3d 1344, l355 (Fed. Cir. Z012) and Galderma Labs., LP. v. Tolmar, Ina, 737 F.3d 731, 739 (Fed. Cir. 2013) to show otherwise (RIB at 45), but I am not persuaded. For one, Samarus actually Supportsteaching away by Samain. In that case, the court held that a reference did not teach away from a drug formulation claim limitation because it advocated for a first version of that fonnulation while also advocating for a second. 694 F.3d at I355 (“Although Pitbrant ‘ruled out’ conventional dosage forms such as tablets, capsules, or granules with non-enteric coated PPIs, it states that a ‘rapidly dissolving suspension of micronized omeprazole is the second best choice as the reference fonnulation.‘“). But it held the reference did teach away from the first version, specifically through a discussion of stomach degradation problems it would encounter. Id. In this case, there is no instance of Samain 74
advocating for LacZ activity, and, like the first version of the formulation in Snnrams, Sarnain discourages LacZ use because of precursor consumption problems. In Gafderma Labs, the court held that the prior art articles only taught an optimal ingredient percentage For a phan-naceutical (0.1%), as opposed to discouraging the patent‘s claimed percentage (0.3%), before disagreeing with the lower court over whether the references taught away. 737 F.3d at 738-9 (“Mort-:over, there is nothing in either of these references to indicate that increasing the concentration to 0.3% would be unproductive . . . ."). In this case, Sarriain actively discourages LacZ activity in its strains, setting it apart from Galderma Labs. And Jetmeweirfs expert agreed under cross-examination that “the teachings of Samain are so compelling that you can’t fathom a reason that someone would use an E. colt strain with a low level of beta-galactosidase activity to produce 2‘-FL, as opposed to using a strain with zero beta galactosidase activity”: Q. And the reason Samain doesn't teach this element is because Samain teaches no beta-galactosidase activity. not a low level of beta-galactosidase activity; correct? A. Yes. Q. And you think that zero beta-galactosidase activity is the ideal situation; correct‘? A. Yes. Q. And, in fact, the teachings of Sarnairi are so compelling that you can‘t fathom a reason that someone would use an E. eoli strain with a low level of betavgalactosidasc activity to produce 2‘-FL, as opposed to using a strain with zero beta-galactosidase activity; correct? A. Correct. Q. Okay. And you can't fathom that they would do that with any low level oi'beta~galactosiclase activity, whether it's .04, .05, .06, or .07 units; correct? A. Correct. 75
(I-lr’g Tr. at 625:1"/—626:2O.) Jennewein also seeks to bolster its motivation to combine theory based on the disclosed use of a certain “JM 109" or “JM 109” bacterial strain. (See RIB at 73-74, 83, 85, 90.) Jennewein argues: But, as Dr. Stephanopoulos explains and Dr. Prather acknowledges, Samain discloses a IMIO9 strain of E. coll, which already possesses a low level of [3-galactosidase activity. RX-0384-C (Stephanopoulos WS) at QIA 218; Tr. (Prather) at 7 12: l 7-7 13:19; see RX-U002 (Samain) at l2:5-22 (Example 1). Dr. Stephanopoulos also testifies that this would not change were the strain to be used for 2’-FL production. RX-0384C (Stephanopoulos WS) at Q/A 218. Indeed, the ordinarily skilled artisan would have been motivated to have used a strain with a low level of |3- galactosidase activity (such as the IM 109 strain described in Example I of Sarnain) in order to avoid destroying the lactose feedstock necessary to produce lactose-containing oligosaccharides like 2'-FL. 1d.; see RX-0002 (Samain) at 7:6-15. (Id. at 73-74 (wherein cited expert testimony further cites RX-0008 (Giacomini) at *88).) In Fact, the JM I09 strain disclosed in Samain has zero [5-galactosidase activity (see RX-0002C at 16:] 15), although the seemingly identical strain disclosed in Giacomini has substantial [3-galactosidase activity (see RX-0008C at -H693). Dr. Prather testified that it was “impossible to believe that those were actually the same strains,” and in any event Giacomini merely malyzes the effects of various parameters on measuring I3-galactosidaseactivity using the Miller assay, and says nothing about 2’-FL production. (Hr’g Tr. at 748114-I5; RX-OUOSC.)So the disclosure of.lM 109 in both Samain and Giacomini would not motivate a skilled artisan to combine their teachings. Nor does Kawano provide a motivation to combine. Although Kawano “teaches inserting a 13-galactosidase gene into a gene construct in E. 0011',producing a low-level [3-galactosidase activity, including 130-220 Miller Units“ (RIB at 76 (citing RX-0014 at -22445, Table 2; Hr‘g Tr. at 462125-4632)), Kawano also teaches insertion ofthe same gene so as to produce much higher levels of B-galactosidase activityfialong the lines of 5.000-12,000 Miller Units (RX-0014 at 76
22443, Table I). In fact, Kawano discloses an extremely wide range of Miller Unit activities resulting from the insertion of a B-galactosidase gene into E. coir‘: Talrir I, .‘\».l|\l|.iL1‘,:|nl :,\'rs>||al. l-.~..m--ru.,e't|;l|al|.>g|!_u.1l> ~rlc:lcd tin ||i;,-In-Mi-lh _ L _ ._ \.l":\i»| ml. M -;:lt:\l‘:'.1.!-aw ~&cw|=m-of |:.|;:ni.-m \'| I ml \r.-wt-~| .‘\-H'/h-Ii M; .'<|| '\ll "~-‘ Kl l ‘Fifi \l l7') \1l '-"F; .‘u’ll'."m .‘$lT5"‘ 'l'.|1JIl~ 2. '1. W l.! ltltl Hi lllil *Ii!lll -'~‘h'm (vim: n_‘:t1) ullltl 4‘-‘H1! I'miI:n||. si/=‘ me uH.r|l.:l|:\r3 lien. illlf-'5 -'. la‘ hp llh rlt: .|..P' ‘H\Il.“i.‘~ I‘-‘i HP .-- um.~u=.:< ‘ \\' 4 I‘!-1%.?! 1 4 In hp :. H-1 has I-5,l‘Hv» = _"~.h;- t\'l1€.'s\ m iH2'11.§-I ~: la‘-|~p lI1i'Jr~|H l-1-1.‘1ii' mm»:-. .; lfnl*[> lh"4r\JI! .-...-"iv 1 5. . .-1. .. _'?o?ui*r: |r..w=,~ J .?-r1:u> H :-1 l. 1, r.~|».= . -1 |'..~\|m-| .xn-san-_w|::|:\arr' 1%?“ < vnl lit: _ -Iluwiir < |~‘s'ra.‘ . ilrrr~IY.(= -1 ll\"*l—lt“il‘- ~'. 3"u'.-ls} i;lt1|=;.> Rn l-nan ..-" l :1! “J -l:1;.‘\\1i 1:0: ifm I 1'11"] 17:. I an-1|!‘-‘r. 1 r.y.-g,=.. tall-ill 5* \ lln ~ 1m-I ;__--ttnln. hlmi--||-. -if ‘<1 ll n\| <1.|i\\ _ I» :1m.\|- \:l\..|\\l -| iinvlulll ‘~|\..-1 III \||.I\i'l \1|.:‘u1 .\‘l|--Hi .\'l| 1'-'-F \1| ""5 ~.1 | 1‘-*1 .\'ll—"l .\1 I »-rvi Ml re: \1 I-tfi fill 1:-3 \1| -Mi .'\H -i‘ \1I-“I \ll-‘*5 \1l.:._v .\1t.~= .‘»lF—I=1 .'\ll--Z< \||-11 =\-c1_.\......_i.|.~.- :»......_...| =:‘;[|\|,‘y4lan ...r; \r. .| rum.-... “as |.-..|..r.m|‘ 1 R. .iL ‘.11 |"~\\||-|.| ~1.r= .n=l u:i\;.-mm.-\ (i;._:r-" 1 K I ll 5 *1 ll‘! ll if qt i-l 1: it‘. 41' 4~. 1-1 1|i '\.‘.=:[| Iwrn .' IIHI 1.‘-ll-ll l lllil \:'1r| "UH hlll 5 ‘ll _".‘|1 mu Flu I"?u Jun 1-an Im |r\ll |‘r] lifl |"l1 fulfil:-~&|i. 1;.;'|,|. l<.1T'.'\:< a e;._=1q> :'~m\*-1 »- re." 1-.,.-w,=.-.. :1.-|»i~ !‘:nu.‘1 L‘-ii !'.\'-‘N4’, t Ho tr-1= -iv? F1 Ix;-. I lit:-E4»- -'. :5‘ l_""lhl <' l‘!!||\ J |= I .‘u.u'~'-‘. 3 if lftll l-la ._ L'!l~ hp lip ills §..|. up .!‘7 -Ii ~' Ell i'|= \"n=J.\‘-2 < Iluhp l‘ I ~|, , |l~‘u< '. I" ... H ., ;.s'.1.|. l I:Tn|i~' 1 iii .il?<:.lIrI ii‘ I_'l}ilI\ l'| ' !h'.1 up -mil“ |:j||= , I l 1.‘ 5111-i I51. I1‘ 1‘l<r|1 NF |5l?=1r\3 .‘ Si)-111:3 ;<;5i;':_-=; 1 s ||]'.u§ ; r'4,1\1r;-‘< .\ §'*IFH Ill-+.%5“'] ‘._‘ Ml 1111 lu-.‘.||=12'-' I 7!|l Q? E‘)in-i il"§'|H.~=| ‘u Hr=.:§.' i iIh'~‘-I ;:7‘1-1*: J l.\'.)-\i.“ l_'lZ")\=>Sl l|§-‘Liln rm?‘-(>3 5119!! :|'|||' ‘..'.'\ c< -- i WEFIH -mu 1,:-...|. =..,, ( air‘! u) ll‘? m|n:=1:'\-d' ml. u:||\.'1r.r-\l’ ._l:-';.|l§ 4 rt" ‘I v.':.'l.' r. an :1pl fr.‘-.-_\ \.-lirl.‘ H42! u--_\ _\| :'-F .-§.!:_-\ Iuwi Are] §_"~ji\liJ ; ,-5;n»R=1 1 |\_‘.~;(,1_ lily" ‘-ll .'.*_-\ ":¢ i|}.;7u . _' - .- Em: lltzzt "‘lII E 7:!“ 1‘-1'1 r ?1rJ$1" ' 25 P-*5 In 1'-4 J“ Tin ; _.f,uryI’\ I“-nl i ‘l\H1"_‘ Eriliit .‘ Ian ;.'\!l J |\$\1' _‘t1'»\ '\.‘~rrm| 1|-H -hf a1-is |"\ NU -NR! -.=' .1 I')\§l -Pi? T) 1 | =.3'-"ml 1) .. :"::i til 2 [I - 2‘.'l!!5t¢== .\. i §;.||l"_I_:. H . s‘=4-»'>|:- n --. _t 'u_§i<_L 5 |||-l.\l_-_-tr: 5 . . a.'“=;us u . » ::>.u|¢=1|,- s I 7l.“JN-in S , l‘l|H.sZ‘ §n| .1 I“l‘l \ . , 2" 19‘ !Ul }t|"I:-| 5”‘ _ 3 | ".*tHo~1 U !’\r|j'I11 ta ,1 I ‘Tl i fifiii (J Zlri 1'1‘ S J I:-Itltiiae .\ l 1 llli \l H U , -r_1~|u.;\ ~, t._ L." lUi'-‘?i.‘i I! |i![$Nl)| 1|] *- (RX-OOI4 at -22443, Table l, Q2445, Table 2 (aI1notated).) As shown in the above combined table, the lowest Miller Unit level reported is 130. While Kawano makes reference to additional strains with promoters causing Miller Unit activities below l30, it does not disclose the details of those strains (see id. at -22444, Figure l) nor does it disclose why any particular activity level would be preferable over any other (see generally id.HKawano is solely directed to “a direct experimental approach for identifying chromosomal sequences with promoter activity” (id. at 22441) and not any particular use for resultant B-galactosidase. 77
This 130 Miller Unit level is important to a motivation to combine because it is the testimony of Jennewein‘s expert, given in the context of enablemcnt, that “beta-galactosidase activity well above 5.8 would be expected to destroy lactose too quickly for the cell to use it to produce 2’-FL”: Q. So you agree that those claims are enabled? A. Up to about 5 Miller units, l think so, yes. Q. It’s your opinion that beta-galactosidase activity well above 5.8 units ivoufd be expected to destroy lactose too quickly for the cell to use it to produce 2’-FL; is that right? A. Correct. (I-Ir’g Tr. at 644:l l~l7 (emphasis added); RX-03 84C at Q1236(stating same); see RX-0384C at QI77-178 (“One better fit would be linear, for example one which shows about zero 2’-FL production at approximately 40 [Miller units]. This would be realistic as it reflects that higher B galactosidase activity would essentially prevent a cell from making a decent amount of 2’-FL.”).) l emphasize “would be” in the above excerpt because enablemcnt, like obviousness, is evaluated from the perspective of one having ordinary skill in the art: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and Shall Set forth the best mode contemplated by the inventor of carrying out his invention. 35 U.S.C. § l 12 (pre-AIA); .S':'rri'ckv. Dreamworks, LLC, 5 l6 F.3d 993, 999 (Fed. Cir. 2003) (“The ‘enablcrncnt requirement is satisfied when one skilled in the art, afier reading the specification, could practice the claimed invention without undue experirnentation.’”) (citation omitted). Thus, Jermewein‘s expert pleads both sides of the same coin: a person of ordinary skill in the art would be motivated to incorporate ](awano’s l30 Miller Unit plasmids into Samairfs 78
processes to help purify the oligosaccharides (RX-0384C at Q25?-258). but would also expect that any Miller Unit activity above 5.8 would degrade lactose faster than it could be used for oligosaecharide production (id at Ql86). This contradictory picture significantly diminishes the persuasiveness of the purported motivation to combine. Nor do the other references cited by Jcnnewein support a motivation to combine. Geisser (RX-0016), for example, is not directed to enzymatic production through modified organisms at all, but instead to “[t]he SLICCE-5Sfi.ll separation of the disaccharide lactose from a complex mixture of human milk oligosaccharides (HMOS) with the continuous chromatography of simulated moving bed (SMB) technique." (RX-0016 at Abstract.) Glycosyn's expett persuasively testified that “to the extent a person of skill in the art could learn anything from Geisser about B» galactosidase activity, they would understand that a high level, not a low level. of B-galactosidase activity would he preferred” to enhance the separation of lactose from other oligosaccharides in the milk. (CX-0487C at Ql57.) Drouillard (RX-0015) discloses synthesis of 2’-FL through metabolically engineered E. colt, but it claims in both of its setups that no leftover lactose remained, that is, it does not address 2‘-FL purification at all, nor does it even reference 13 galactosidase. (RX-0015 at -15184 (“Alter 22 h of incubation, the lactose was completely consumed" and “To produce [2’-FL] without [LNnF-1] . . . . After 25 h incubation, lactose was completely consumed and converted into [2’FL].”).) Lastly. Dekany discloses enzymatic methods for creating oligosaccharides. but only in background and with general discouragement: Either genetically engineered microorganisms or mammals are used in biotechnological methodologies for the synthesis of 2’-O-fucosyllactose. Such technologies use complex enzymatic systems facilitating both the biosynthesis of precursors and the required glycosylations. To date, such approaches face severe regulatory approval hu.rdles due to the use of genetically engineered organisms and potential contaminations of non natural oligosaccharides. (RX-O01’? at -22356-7); 79
Enzymatic methodologies suffer from the low availability of enzymes, extremely high sugar nucleotide donor prices and regulatory difficulties clue to the use of enzymes produced in genetically modified organisms. (id. at -22359). I therefore do not see this reference as useful or related to a motivation to combine I3-galactosidase activity into the enzymatic techniques disclosed in Samain. Apart from the lack of motivation to combine, some secondary considerations of non obviousness further undermine Jennewein‘s case, Jennewein does not dispute the existence of a long felt, but unresolved need. (RRB at 50.) As for teaching away, Samain and three Jennewein patents all disclose the importance of inactivating the facZ gene to preserve lactose for 2’-FL production. (CIB at 107 (citing CX-0487C at Ql9l-198).) The Iennewein patents demonstrate the existence of the conventional outlook: any other lactose-consuming processes should be deleted or inactivated during 2‘-FL production. (See CX-0504 at 6:4-20; CX-0506 at [O0l4].) As the rc-introduction of a filnctional |3-galactosidase enzyme into E. colt during 2'—FLproduction is a central inventive aspect of the ’0l 8 patent, I find the requisite nexus is met here. Merck & Cie, SOS F.3d at 837; In re Hm2i—HzmgKoo, 639 F.3d at H168. And as for unexpected results, Jcnnewein‘s own expert was surprised that using a low level of [3-galactosidaseactivity to produce oligosaccharidcs works, since it is contrary to what he believes even today is the preferable method for producing oligosaccharicles, namely, use of an E. coll strain with no B-galactosidase activity. (Hr‘g Tr. at 625:l2-626:2O.) Moreover, a non-testifying experfs issued patent states that the use of a low level of [3-galactosidase activity had unexpected and surprising results in the production ofoligosaccharides. (CX-0507 at 7:1 l-l5.) For clarity, that reference, filed after the ‘OI8 patent, teaches: Surprisingly, it was determined that microorganisms that produce less B galactosidase activity than a microorganism with a non-defective lacZ gene are the best producers of 2-FL (as compared to microorganisms that express normal levels of [5-galactosidase or express no [3-galactosidase). 80
(Id. at 7:] l-I 5.) So non-obviousness is supported by a long felt, but unresolved need, teaching away, and unexpected results. However, I arn not persuaded that the failure of others supports a finding of non obviousness. To be sure, Glycosyn‘s evidence shows it is not only hard to make 2‘-FL in bioengineered organisms, but also hard to make it in sufficient quantifies for commercial purposes, such as an ingredient in baby formula, so much so that “many have tried and failed.“ (RRB at 50: CIB at 105 (citing CX-0004C at Q52; Hr’g Tr. at 18:3-12; C-X-0001C at Q34-35; RX-0320C at 20] 87).) ln particular, the evidence shows that “there was no prior art solution for manufacturing liueosylated oligosaccharides that did not suffer from either low yields or purification difficulty“ even though others, such as Jennewein, Abbott, and Nestle’, tried. (CIB at 106-107 (citing CX 048'/‘Cat Ql9l-198).) Nonetheless, Jennewein is the only current commercial provider of 2‘-Fl. in the United States. (See id. at 93; RX-0384C at Q3l4.) And the failure of others is readily attributable to the inability to make 2‘-FL in sufficient quantities and with necessary purity required for use in baby formula, while also making it cost-efficient. (See CIB at 105-106; CX 0487C at Ql72, l78~l8l .) None of these goals are recited or necessarily accomplished through the simple practice of the ‘U13 patent claims. (See, e.g., ’Ul8 patent at cls. 1-28 (not reciting amount of fueosylated oligosaccharide produced, cost, or purity leve1).) Based on the stage of Glycosyn’s collaboration with production partner FrieslandCampina, it seems too early to tell if the '01 S patent answers the identified comiirercfal needs. It was confirmed at the hearing that such production has not even begun. (Hr’g Tr. at 45:3-2|, 48:1-17.) l therefore do not find that the failure of others supports a finding of non-obviousness. The other three secondary considerations asserted by Glycosyn do support such a finding, however, and Jennewein has additionally failed to demonstrate a motivation to combine references. On 8]
balance, therefore, neither claim 1 of the ‘O18 patent, nor any of the dependent claims, are invalid for obviousness. 3. 35 U.S.C. § I12, 1l 1 (Enahlement) In its opening brief, Jennewein contends “[c]laims l-3. 5, 8, 10, 12, 18, 23, and 24 are invalid for failing to satisfy the enablement requirement of 35 U.S.C. § 112, 1] l." (RIB at 99.) Jennewein presents two specific arguments that “[t]he '01 8 patent‘s specification does not enable the full range of 15-galactosidase activity" because it only shows fitcosylated oligosaccharide production at an activity level of 1-2 Miller Units, while claim 1 recites a much broader range of 0.05 to 200 Units. (See id. at l00 (citing ’0l 8 patent at 18:23-32).) First, Jennewein contends that “it would require undue experimentation to make a fucosylated oligosaceharide at such higher levels of [3-galactosidase activity.” (RIB at 109; see, e.g., RIB at 101-102 (“[A] person of ordinary skill in the art would need undue experimentation to produce 2’-FL at these high leve|[s] of [3-galactosidaseactivity"), 102 (“A person of ordinary skill in the art would need to conduct periodic experiments over the entire range of 0.05 to 200 . . , to ensure that the B-galaetosidase level at each measurement would both (a) not be so high as to halt production of the fucosylated oligosaccharides and (la) eliminate residual lactose after 2‘-FL production to allow isolation of the 2’-FL product, as claimed by Glyeosyn during prosecution of the '0l8 parent's parent"), I02 (“significant experimentation would be necessary to ensure that the fi.1llscope of values within the claimed range of 0.05 to 200 units would ‘strike a balance between production of desired fucosylatecl oligosaceharides and the level of 13-galactosidase produced“), 106 (“Three data points over a relatively narrow range would be deemed as insufficient to show that strains having activity up to 200 units could in fact make 2‘-FL.").) This position is tied to the claim limitation "retrieving a fucosylated oligosaccharide from said bacterium or from a culture supernatant of said bacterium.” (‘DIS patent at cl. 1.) It revolves S2
around the argument that at higher [3-galactosidase activity levels, the [3-galactosidase "would
destroy intracellular lactose "Fasterthan it could be processed into significant amounts of 2‘-FL”
such that “it would require undue experimentation to make a fucosylated oligosaccharide at such
higher levels of 13-galactosidaseactivity.” (RIB at I09.)
To the extent this argument avers lack of enablement for producing “significant,” useful,
or “commercial levels“ of a fucosylated oligosaccharide (RIB at 100 (citing RX-038-4Cat Ql86)),
it is entirely misplaced. No asserted claim requires any particular amount of fucosylated
oligosaccharide to be produced or “retriev[ed].” (See, e.g., ‘U18patent at cl. 1.)
To the extent this argument avers lack of enablement for producing any fitcvosylated
oligosaccharide whatsoever at high I3-galactosidase activity levels, there is a lack of clear and
convincing evidence on this point. Jennewein relies on the testimony of its expert to make the
claim (see RIB at 108-109 {citing RX-0384C at Ql86))5, but this testimony is contradicted by
.lennewein‘s own obviousness arguments:
Fttrthermore, shottlalthe claims encompass producing any amozmtaf2 '-FL,
2 '-FL would be produced even in the presence offl-galactosidase activity
within the claimed range. This occurs because the [3-galactosidaseenzyme
and the 2‘-FL-producing fucosyltransfcrase enzyme are competing
simultaneously for lactose. See Tr. (Prather) 730:l5-73l:l4, RX-0384
(Stcphanopoulos WS) at Q/A 195. . . . As shown in RDX-0012, should
fttcosyltransferase [be] present, some 2‘-FL will be produced, even though
less 2’-FL would be produced if |3-galactosidase is also present. See id. It
is also worth noting that Jennewein’s fucosyltransferase attaches fucose to
the galactose moiety of lactose.
(RIB at 83-84 (emphasis added).) That is, Jennewein concedes in its discussion of obvtousness
that simultaneous competition between B-galactosidase and fucosyltransferase will still result in
5 Jennewein also cites hearing testimony from Glycosyn‘s expert here, but that testimony
does not support the concept that competition will prevent any 2‘-FL production. (RIB at 108-109
(citing Hr‘g Tr. at 73016-21. 131 ;1-14).)
S3some 2’-FL production, even when that competition is stiff. A person of ordinary skill would know this. (Hr’g Tr. at 730115-731:l4, 743:5-18. 737114-73820.) Even setting aside this concession, I agree with Glycosyn (CIB at I 12) and the Staff (SIB at 98) that Jennewein’s expert testimony on the destruction of 2’-FL at higher [5-galactosidase activity levels is largely conclusoty and thus entitled to little weight. Cephalon, Inc. v. Watson Pharm.v.. Ina, 707 F.3d 1330, 1338 (Fed. Cir. 2013). For example, the expert claims that the data points contained in Dr. McCoy’s declaration submitted during prosecution are better Iit by a linear line than the exponential fit Dr. McCoy employed, but he provides no explanation for why it would be bcttcr—cspecia1ly with regard to the science ofsimultaneous competing enzymatic pathways he acknowledges elsewhere. (Compare RX-0384C at Q178, 195 (discussing RDX-0012) with I-Ir‘gTr. at 743:5-18.) The expert's claim that “[3-galactosidaseactivity well above 5.8 units would be expected to destroy lactose too quickly for the cell to use it to produce 2’-FL” is similarly conclusory. (See RX-0384C at Ql86.) Dr. Stephanopoulos did not perform any experiments or cite any disclosures in connection with his contention that high B-galactosidase activity will prevent any 2’-FL production. (I—lr’gTr. at 644: 13-646:4.) Thus, I find it far from clear and convincing that higher 13-galactosidaseactivity levels (i.e.. higher than ~6 Miller Units) would result in no 2‘-FL production whatsoever. Jennewein does not explicitly address the Wands factors on this point, and, therefore, neither do I. (See RJB at I06 llflj .lennewein’s second enablement contention is that “undue experimentation would be required to modify microorganisms having |3-galactosidase activity for the entire range.” (RIB at 102; see RIB at 100 (“The specification fails to enable the full scope of the claim limitation ‘the level of [5-galactosidase activity comprises between 0.05 and 200 units" of claim 1 of the ‘O18 84
patent“), IO] (“[T]he evidence showed that undue experimentation is required to produce strains
with any specific activity in the claimed range“), I03 (“The specification . . . leav[es] a person of
ordinary skill completely in the dark about how to create modified bacteria that could, taken
together, cover the entire claimed range”), 105 (“The highly complex nature of this invention in
this unpredictable field also contributes to a high level of experimentation necessary to achieve the
claimed range of [5-galactosidase activity/.”).) This position is tied to the claim limitation "(ii) an
exogenous Functional [5-galactosidase gene comprising a detectable level of B-galactosidase
activity that is reduced compared to that of a wild-type E. colt’bacterium, wherein the level oft?
galactosidase acrwity comprt'.re.rbetween (1.05 cmd 200 tmits.” {"018 patent at cl. l (emphasis
added).)
This contention is a closer call. The ‘O18 patent specification only discloses a single
species of‘bacteria which produces between l and 2 Miller units of [5-galactosidase activity:
The lon mutation in E390 increases intracellular levels of RcsA, and
enhances the intracellular GDP-fucose pool. The inserted lacZ+ cassette not
only knocks out lon, but also converts the lacZ—host back to both a lacZ+
genotype and phenotype. The modified strain produces a minimal (albeit
still readily detectable) level of B-galactosidase activity (1-2 units), which
has very little impact on lactose consumption during production runs, but
which is useful in removing residual lactose at the end of runs, is an easily
scorable phenotypic marker for moving the lon mutation into other lacZ—
E. coir‘strains by P1 transduction, and can be used as a convenient test for
cell lysis (e.g. caused by unwanted bacteriophage contamination) during
production runs in the bioreactor.
(‘O18 patent at 18:19-32; see RIB at I03; SIB at 94 (not disputing Examiner’s observation); see
generm"iy CIB at 109-116.) Thus, the issue is whether this limited species disclosure sutficiently
enables a person having ordinary Skill in the art to practice the limitation “(ii) an exogenous
functional [3-galactosidase gene comprising a detectable level of [3-galactosidase activity that is
reduced compared to that of a wild-type E. colt bacterium, wherein the level offl-galactosidase
activity comprises between 0.05 and 200 units," over the full range without undue experimentation.
S5Resolving this issue requires consideration _of the Wands factors: (1) the quantity of experimentation necessary; (2) the amount of direction or guidance presented; (3) the presence or absence of working examples; (4) the nature of the invention; (5) the state of the prior art; (6) the relative skill of those in the art; (7) the predictability or unpredictability of the art; and (8) the breadth of the claims. Wands, 585 F.2d at 737. In reviewing fllese factors, I have avoided relying on the evidence cited in Dr. McCoy’s declarations during prosecution. Declarations submitted during prosecution, while nndisputedly part of the intrinsic record, are not part of the specification, but it is the specification that is the focus of the enablement inquiry. And as for the Wands factors themselves, factor one. “the quantity of experimentation necessary,” outweighs all others in significance, and I consider it last. The second and third Wands factors, “the amount of direction or guidance presented” and “the presence or absence of working examples.” favor Jennewein. The ’0l8 patent specification provides just one example of an engineered bacterium with Miller Units of any amount (l-2 units). (‘O18 patent at 18:9-32.) And although Glycosyn’s expert testified that “[t]he ’0l8 specification and the documents cited therein provide significant guidance on how to modify a bacterium to express different levels offi-galactosidase activity and/or produce different amounts of 2‘-FL," her testimony is conclusory. (CIB at 115 (citing CX-0487C at Q59-64).) She merely cites passages in the ‘O18 patent (CX-0487C at Q61 (citing ’OlS patent at l6:31-35, 18:12-l3)) which mention that an increased cellular pool of lactose and the lon replacement mentioned above were achieved using “Jr Red combineering” or "X Red recombineering.” The expert does not explain what this technique is or how it can be used to achieve varied |3-galactosidase activity levels. The fourth and eighth factors, “the nature ofthe invention" and “the breadth of the claims,” do not favor either side. While the obviousness discussion above identifies “wherein the level of 86
[3-galactosidase activity comprises between 0.05 and 200 tmits” as a key distinguishing feature over the prior art, engineering a bacterium with this level of activity is not by itself an aspect of the invention. (See, e.g., RX-0014 at -22443-S, Table l, Fig. 1, Table 2.) Rather, the benefit of the invention comes from the combined use of a bacteria producing the claimed activity range, alongside those other techniques implemented for increased oligosaccharide production within the bacteria. And the recited 0.05 to 200 Miller unit range is not particularly broad. Prior art references such as Kawano (RX-0014) show that, depending on the promoter used, B-galactosidase activity within an E. colt‘bacterium can run anywhere between 0 and 12,200 Miller units. (See RX-0014 at -22443, Table l. -22445, Table 2.) The filth, sixth, and seventh factors. “the state of the prior art," “the relative skill of those in the art," and “the predictability or unpredictability of the art,” also do not favor either side. There is persuasive evidence in the record that this art is generally unpredictable, in that those skilled in the art understand and expect experimentation to he performed before conclusions on genetic or enzymatic activity can be reached. (See Hr’g Tr. at 676:1?-678:4 (“You would not know the results. You expect results, but you do not know the results until you do the experiment. . . . You have to do the experiment"); CX-0002C at Q36 (“This is how genetic engineering works, you try several different modifications unit you get the result you want”); see‘ generally JX-0002 at -296] -2963 (rejecting claims due to unpredictability in the field); RX-0384C at Q1815, 190; Hr’g Tr. at 296:l3-23, 640:l6-641:5, 505:1-15, 1-47:18-149:t8; CX-0053C at H7388; CX-0483C at QZOQ3, 39.) Yet, there is also evidence showing the person of ordinary skill in the art at the time of invention would have known how to conduct this experimentation and would be aware of various E. cob‘lacZ promoters to try. (See, e.g., JX-0002 at -2934 (citing prior 87
art investigation of promoters); RX-0014; I-lr’g Tr. at 619:4-624:l2; CX-0468; CX-0469; CK
0487C at Q64.)
Turning finally to the first Wands factor, “the quantity of experimentation necessary,” I
find this favors Giycosyn. Again, Kawano is instructive. While Jennewein is correct that Kawano
explicitly teaches bacteria strains for only a portion of the claimed 0.05-200 Miller Unit range
(RIB at 105), it is also true that o:°Kawano‘s 105 randomly selected strains for potential promoter
activity, a vast majority exhibited Miller Unit activity levels within the 0.5-200 range. This is
explained alongside Kawano’s Figure l:
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(RX-0014 at -22444.) This data strongly suggests that when a person of ordinary skill in the art,
and familiar with E. calf gene manipulation techniques, searches for promoters to use with a
functional B-galactosidase gene to accomplish “wherein the level of B-galactosidase activity
comprises between 0.05 and 200 units," they will find one with little trouble, possibly just through
a review of the literature. Kawano shows that the process is not like searching for a needle in a
haystack. “The test is not merely quantitative, since a considerable amount of experimentation is
permissible, if it is merely routine, or if the specification in question provides a reasonable amount
of guidance with respect to the direction in which the experimentation should proceed[.]” Wands,
858 F.2d at 737.
On balance, although several factors are neutral and two factors favor Jennewein, the
weightiest factor, the quantity of experiment necessary, favors Glycosyn, so much so that it
outweighs the factors that favor Jennewein. Therefore, Jennewein has not shown by clear and
convincing evidence that the asserted claims of the ’Ol8 patent are not enabled.
4. 35 U.S.C. § 112, {I1 (Written Description)
l.naddition to lack of enablement, Jennewein argues “[c]laims 1-3, 5, S, 10, 12, 18, 23, and
24 are also invalid for failing to satisfy the written description requirement of 35 U.S.C, § l 12, 1l
891.” (RIB at l I0.) Specifically, Jermewein refers to the tr-eomplementation technique used in its Accused Strains and argues “[i]f interpreted broadly enough (as Glycosyn does) to encompass o. complementation, the patent fails to show possession of the full scope of the term ‘functional . t . 13-galactosidasegene.” (Id. at ll l.) This argument is clearly conditioned on interpretation of the claims as covering Lt-complementation. (See RIB at l l3 (“Glycosyn‘s argument that Jennewein literally infringes the ‘O18 Patent requires the claims to literally encompass not just o. complementation, but also the unique form of at-complementation employed by .lennewein.”); RRB at 58 (“As the written description requirement cannot be applied to equivalents, Jennewein is not conflating the written description requirement with the doctrine of equivalents“); id. (“If interpreted broadly enough . . . to include uacomplernentation, the specification fails to Show possession of the full scope of the term ‘functional . . . B-galactosidase gene . . . .“); SRB at 28-29 l“The Staffagrees with Jennewein that [ct-eomplernentation]does not literally infringe the asserted claims. . . . If the Administrative Law Judge adopts this interpretation of the claim language, then Jenneweirfs written description argument is moot.").) As explained above, Jennewein‘s o cornplementation technique does not fall within the literal scope of “functional . . . B-galactosidase gene." Therefore, Jennewein has failed to prove that the claims in suit fail the written description requirement. S. lnequitable Conduct A patent may become unenforceable it'“the applicant misrepresented or omitted material information with the specific intent to deceive the PTO.” Therasense, 649 F.3d at 1287. According to Jennewein: Glyoosyn intentionally withheld information that was plainly material to patentability and was known to it during prosecution of the ’0] 8 Patent and its parent (the ’23l) Patent). Co-inventor Dr. John McCoy intentionally withheld information that contradicted his affirrnative representations to Examiner Rebecca Prouty, which she relied upon to grant the ‘O18 patent 90
Accordingly, inequitable conduct renders the Asserted Claims unenforceable. (RIB at I 18.) More specifically, Jennewein contends that Dr. McCoy knew of certain Glycosyn testing data that, as characterized by Jennewein, “reveals that bacterial strains having B galactosidase activity within the claimed range of 0.05 to 200 Miller units actually failed to produce 2’-FL. . . . but chose not to disclose any of it to the Examiner." (RIB at 123.) Jennewein has not shown inequitable conduct by clear and convincing evidence, with respect to both materiality and intent. Understanding why requires consideration of the prosecution history. On August 8, 2014, the Examiner rejected the claims of the application that would become the ’23Dpatent “under 35 U.S.C. l l2(a) or 35 U.S.C. I12 [pre-AIA), first paragraph, as failing to comply with the written description requirement.” (JX-0002 at Y2728.) The Examiner explained the rejection as follows: The specification includes no evidence that the presence of any modified lacZ gene wherein the bacterium has between 0.5 and 200 units of [3 galactosidase activity when grown under inducing conditions is not detrimental to producing a fucosylated oligosaccharide as would be expected since [3-galactosidase will degrade the lactose acceptor necessary for the fi.tCOSylEl[i0l1,yet the claims clearly encompass any functional |3 galactosidase gene having up to I00 fold more B-galactosidase activity than the single disclosed species. (Id. at -2730-l.) The Examiner issued a parallel rejection based on the same facts under enablement. (See id. at -2732-34.) On February 9, 2015. Glycosyn amended the claims (IX-0002 at -2916-22) and provided a first declaration from Dr. John McCoy to overcome the written description and enablement rejections (id. at -2924-7). On May 8, 20l5, the Examiner issued the same rejections. (JX-0002 at -2953-68.) With respect to the declaration, the Examiner stated: Applicants argue that the declaration of John McCoy shows that even relatively high levels of 13-galactosidaseproduced by the Lac? bacteria of FIG. 2 did not deplete the lactose pool such that the desired titcosylated 91
(JX-0002 at -2964-5.) The Examiner provided similar commentary in the context of the renewed oligosaccliaride end product was not made by the engineered bacteria. However, this is not persuasive as the declaration does not show that the range of activity of the bacteria of Figure 2 of the declaration encompasses the claimed range of 0.05-200 units claimed. Without any indication of the level of B-gal activity present in the bacteria of Fig. 2 of the declaration, the declaration does not provide evidence that the claimed range of B-gal activities will not deplete the lactose pool such that the desired fiicosylatcd oligosaccharide end product will not be made. enablemcnt rejection. (See id. at -2966-8.) 3|.) With respect to the § 112 rejections, and the previous declaration in particular, Glycosyn On November 9, 2015, Glycosyn responded and amended the claims. (JX-0002 at -3025 argued; Fig. 2 of the Declaration is a photograph of the art-recognized X-GAL colorimetric assay for [5-galactosidase in which low levels of the enzyme appear as light blue colonies/streaks and high levels appear dark blue [,] thus providing an art-recognized and standard indication of B-galactosidase enzyme activity. Applicant's statement (copied above) also addresses the Exarniner‘s concern that the claims may encompass bacteria that do not make the fucosylated oligosaccharide, stating that even relatively high levels of I3-galactosiclase produced by the LacZ+ bacteria (dark blue streaked colonies in Fig. 2) did not deplete the lactose pool such that the desired fiicosylated oligosaccharide end product was not made by the engineered bacteria. In view of the foregoing clarifications and arguments, Applicant respectfully requests withdrawal of this rejection. (JX-OOO2at -3038-9.) Following this, on January 22, 2016, the claims were again rejected on the same written description and enablement grounds. (See JX-0002 at -3044-53.) In the context of the alleged written description problem and the X-GAL assay image above, the Examiner stated However, this is not persuasive as it is not clear how much B-galactosidase activity is necessary to obtain a light blue or dark blue color and a quick intemet search by the examiner did not provide this infonnation such that there is still no indication whether the colonies of Fig. 2 of the declaration span the claimed range or not. 92
(JX-0002 at -305 1.) However, the Examiner invited Glycosyn to submit a declaration stating “that the bacteria of Figure 2 of [a] previous declaration all successfully produced fucosylated oligosaccharides and include strains with B galactosidase activities of about 20 units (or more)," and, if so submitted, “the examiner will withdraw the instant rejection." (JX-D002 at -3051.) LnApril 2016, Dr. McCoy submitted the suggested declaration, containing data for three exemplary 2’-FL producing strains, E997, E890x4l6/pG2l7, and E890x422fpG2l7, and affii-matively stated that “good levels of 2’-FL are produced in all 3 strains.“ (RX-0396 at 3.) These strains had B-galactosidase activities of 1.5, 2.5, and 5.8 Miller Units, respectively. (hi) The declaration also contained an extrapolation of the measured data to 200 Miller Units in graph form, accompanied by a statement that “even strains producing 200 Miller Units of galactosidase would be capable of producing significant levels of 2’-FL in the femienter (>2g/L).” (RX-0396 at 4.) After tiling the declaration, first in the prosecution of the ‘Z30 patent, and then in the prosecution of the ’0l 8 patent, all claims were allowed. (JX-0002 at -1750; JX-0004 at -304-310.) Jemiewein contends, in summary, that: Dr. McCoy withheld material information not once, but at least three times. First, he withheld the fact that the only strain with beta-galactosidase activity of about ZOOMiller Units that Glycosyn had actually tested prior to McCoy’s declaration in fact failed to make 2’-FL. CX-0053C at 7. Second, he withheld the fact that two strains that Dr. McCoy represented as producing 2’-FL actually failed to produce it reliably. Id. at 6. Third, demonstrating a pattem of lack of candor, he also withheld material information from the European Patent Offiee. (RIB at l34-l35.) I consider these points individually. First, Jennewein argues that CX-0053C, a slide deck summarizing certain research and development activities and dated almost a year before Dr. McCoy’s second declaration, shows no 2’-PLby a we — with approximately 200 Miller Units of |3-galactosidase activity. (RIB at 125 (citing CX-0053C).) But 93
these test results were not germaneto the invention,becausethe - strain was not comparable to the strains Dr. McCoy identified in this second declaration, for two reasons. First, t made itapoor candidate For creating 2’-FL, regardless ofits [3—galactosidase activity. As Dr.Merighi,the creatorof the slidedeck,testified,- wasa - so it was not fullyexpressingthe pathwayfor making2’-FL. So it didn’tsurpriseme too much that we were not making it. I was hoping that we would make some.” (_Hr’gTr. at 281:3-25;see CX-0053C at -I 17382 (“Next Make a lon- version"}.) In contrast, each ofthe E997, E390x4]6/pG2l7, and E890x422/pG217 strains used as the basis for Dr. McCoy‘s declaration (andshownin ex-0053c) were- (Id.at 227124-238:5.)Indeed,Dr.Merighi,=1non party,testifiedthatcomparing- and_ isnotmeaningful. (Id.(“Youshowed me the slide, it was the. units. That was not ready for apple to apple comparison, because it was- correct.Sothesestrainsareall- soyoucancomparethern.”).)Second,it is not a mere “technicality” (RRB at 62) that the 2’-FL production rate in a large scale ferrnentor does not match smaller tube-scale runs. (See. e.g., CX-0053C at ~l 17379, -117381, -117388;CX* 0488C at Q9, Q20-22, 39; Hr’g Tr. at 1-47:18-l50:25, 295:20-296:2}, 63920-641:19, ‘[25:14 727:9; RX-0409C at Ql67.) Dr. McCoy, in particular, testified at length about the differences between the two test methods. (Hr‘g Tr. at 147118-l50:25.) The fact that Dr, McCoy’s declaration was in the context ofthc former (JX-0002 at -321 l (“significant levels of2’FL in the fermc11tor")). whereas Dr. Men'ghi’s experiment was the latter (CX-0053C at -1 1'73S2 (“(tube scale)"))__ diminishes therelevance ofthe_ result. Second, Jennewein argues that of the three strains discussed in Dr. McCoy's declaration as producing “good levels of2‘-FL,” CX-0053C shows two, E890x416/pg217 and E890x422/pG2l7, '-)4
actually failed to make Z’FL. [RIB at l32.) Jennewein bases this claim on the following line from CX-0053C: i (RIB at 132 (citing CX-0053C at -117381).) As Dr. McCoy testified, however, this comment could not have referred to testing of ES9(]x4l6/pg2l7 and E89Ox422/pG2l7, because those tests (which are documented a few pages earlier in CX-0053C) did show 21FL production. (Hr‘g Tr. at l 15:1-2 (bullet point 5 is “clearly not referring to the ones that we werejust looking at, because they produced 2’-FL”).) And Dr. Merighi, the bullet p0int‘s author, testified that he was unsure whatit referenced,but thathe thoughtatwastrdistinctstrain,- (Id.at 2s1;19-23.) Third, Jennewein points to other B-galactosidase experimental data that Dr. McCoy did not submit to the USPTO, including one set that was submitted to the European Patent Office for similar prosecution purposes. (See RIB at 131-132 (citing RX-0067C; JX-0019C at 35O:l9-21 (non-designated») Jennewein asserts that Dr. McCoy “demonstrate[ed] a pattern of lack of candor” by withholding information from the European Patent Office. (RIB at 135.) But Jcnnewein makes no effort to demonstrate that he had a duty to disclose such allegedly withheld information to the EPO. (See id. at I34-135.) Moreover, the information pertains to a strain, EH77, that produced 2’-FL with B-galactosidase activity far outside the claimed range, and therefore of little relevance. (RIB at l3l.) And Jcr1newein‘s discussion of the evidence cites principally to a 246-page laboratory notebook of Dr. McCoy, which appears to be admitted as CK 0025C. but without citing to page numbers. (Id. at I3 l-I32.) Nor does it appear that Jermewcin questioned Dr. McCoy about this exhibit during the hearing. On balance, Jertnewein has failed to prove that Dr. McCoy withheld anything from the PTO regarding E1277, and I do not address this argument further. 95
Overall,Dr.McCoy‘sfailuretodisclosethe— tube-runexperiment and WhatDr. Merighibelievedwas the— tube run, as recordedin CX-0053C,was not material to the patentability of the claims. The Federal Circuit has explained, “the materiality required to establish inequitable conduct is but-for materiality. . . . in assessing the materiality of[witl1he1d information], the court must determine whether the PTO would have allowed the claim if it had been aware of the undisclosed [inforrnalion].“ The-rasense,649 F.3d at 1291-92. Admittedly, it was material to patentability whether the claims were enabled at 200 Miller units. But if Dr. McCoy’s second declaration had included the challenged tube runs, and also explained why he subjectively did not consider them relevant, there is every reason to believe the Examiner would have allowed the claims. And because of his subjective views of the two challenged tube runs, the requisite deceptive intent is also lacking. As acknowledged by both parties, a specific intent to deceive must be “the single most reasonable inference able to be drawn from the evidence.“ Tlrerasense, 649 F.3d at 1290 (citation omitted). Dr. McCoy, who testified at the hearing with a confident but otherwise unremarkable demeanor, doesnotviewthe— testresultandthe] tuberuns _ bulletpointin CX-0053Cas contradictingthe statementsmadein his second declaration; Jcnnewein. by contrast, offers only innuendo and case citations in support ofdcceptivc intent. (See generally CX-0488C at Q19-39; RIB at 134-36.) The most reasonable inference to be drawn from the evidence is that Dr. McCoy sincerely believed that the challenged evidence was immaterial. and there is therefore no inequitable conduct. V. DOMESTIC INDUSTRY - ECONOMIC PRONG In a patent-based complaint, a violation of Section 337 can be found “only if an industry in the United States, rclating to the articles protected by the patent concerned, exists or is in the process of being established.” 19 U.S.C. § l337(a)(2). Under Commission precedent, this 96
“domestic industry requirement” of Section 337 consists of an economic prong and a technical prong. StringedInstruments, lnv. No. 337-TA-586, Comm’n Op. at 12-14. The complainant bears the burden of establishing that the domestic industry requirement is satisfied. See Certain Set-Top Boxes and Components Thereofl lnv. No. 337-TA-454, TDat 294 (June 21, 2002) (not reviewed by Commission in relevant part). The economic prong of the domestic industry requirement is defined in subsection (a)(3) of Section 337 as follows: (3) For purposes of paragraph (2), an industry in the United States shall be considered to exist if there is in the United States, with respect to the articles protected by the patent, copyright, trademark or mask work concerned - (A) Significant investment in plant and equipment; (B) Significant employment of labor or capital; or (C) Substantial investment in its exploitation, including engineering, research and development, or licensing. 19 U.S.C. § l337(a)(3). The economic prong of the domestic industry requirement is satisfied by meeting the criteria of any one of the three factors listed above. Importantly, the Commission has clarified that investments in plant and equipment, labor, and capital that may fairly be considered investments in research and development are eligible for consideration lmder Subsections (A) and (B), in addition to subsection (C). See Solid State Storage Drives, Comm’n Op. at I4. Here, Glycosyn alleges a domestic industry exists under all three factors. I agree. A. Qualifying Investments For subsection (A). and investments in plants specifically, the evidence shows Glycosyn conducted engineering, research and development activities related to the production of 2‘-FL by E. coir‘bacteria at two domestic locations in Medford, Massachusetts and Wobum, Massachusetts between 2015 and the filing of the amended complaint in May 2018. (CX-0003C at Q1 I-14, Z3, 97
39-41.) The evidencealso showsGlycosynspent approximately- per month in rent on caeh location,suchthatbetweenJanuaryl, 20!5 and May l6, 2018,Giycosyninvested in these facilities. (Id. at Q44-52; CX-0087C.) Glycosyn acknowledges that, between 2015 and May 2018, however, these locations were used for the development of 2‘-FL as well as other compounds which do not fall under the scope of the asserted claims. (CIB at 128, I30-132; see CX-0003C at Q7, 23, 31-33; EX-0002C at Q93, I I i.) In order to accommodate expenditures unrelated to the ’()l8 patent, Glyeosyn applies an allocation percentage to its facility investments. wherein said percentage is based on the amount of time its scientists at these locations spent on developing 2‘-FL production per the ’Ol8 patent. (See CIB at 129-13] (citing, inter alto, CX— Ot]D3C at Q26, 27, 30-32, 44-53; CX-OOOZC at Q33, 93, 94; CX-0089C; CX-OUS7C].} The resulting claimed investment in facilities directed to the development of 2'-FL produced under the claims ofthe ’0l8 patent is summarized in the below table; The Staff agreeswith this-r figureas the amountin facilitiesexpensesattributableto the ‘DIS patent for purposes ofdomestic industry under subsection (A). (SIB at I I7; SRB at 34.) .!ennewein’s dispute with respect to this investment in facility is that “Glyeosyn attributes all of that rent to its domestic industry expenditures, even though it conducts R&D related to other acti'vities— at thisfacility."(RIBat I39;RRBat 67.) Thispointis notwelltaken; Glycosyn has reasonably apportioned its Facilities expenses based on its labor expenses. In any event, Glycosyn’s witness testimony on this issue (CX-0003C at Q30-53; CX-UOUZCat Q33, 92 98
94) is credible and its documentary records (CX-0089C; CX-0037C) are reliable. Thus, I find the record supportsa facility investmentamountof - for purposesof domesticindustry, subsection (A). With respect to equipment under subsection (A), Glycosyn has presented evidence showing its various investments in equipment used at the Medford and Wobum locations discussed above. (See CIB at I32.) Glycosyn’s witness testified that equipment purchases include “ferrnenter machines, a recirculate chiller/pressure reducer, Visiferm DO optical oxygen sensor, steam generator, sterilizers, a Biosat B plus Fermentation Control System, and a Touch Panel and Conversion Kit for the Biosat B equipment“ as well as other equipment and tools attributable to the development ot‘2’-FL. (CX-ODOBCat Q55 (citing CX~OUS5C).)That witness also categorized each purchase in the year it was incurred (id. at Q56 (citing CX-0085(3)), identified the costs expended with the maintenance of this and previously purchased equipment (id. at Q57 (citing CX-0085(1)), and described depreciation costs incurred in 2017 for that equipment purchased prior to 2015 (id. at Q58 (citing CX-00S6C)). Further, Glycosyn witnesses identified an additional equipment purchase for the two locations made on behalf of Glycosyn in 2016 by an organization called Glycosyn Health lnitiatives, Inc, “an organization that provides funding, donations, and research sponsorship to various institutions in support of 2‘-FL research experiments,” which included “a Synergy H4 M‘Pate Reader. an anaerobic chamber, camera, and freezer.” (Id. at Q56.) Additional testimony elicited at the cvidcntiary hearirigexplained that Glycosyn Health Initiatives, Inc., a non-party, and Glycosyn, the complainant, have “interlocking leadership and board members." (Hr’g Tr. at 28:22-29:23.) In sum, the claimed investments in equipment at Glycosyifs research and development facilities are summarized in the below table: 99
TheStaffessentiallyagreeswithtl1ts_ figureas the amountin equipmentinvestment attributable to the ’Ol S patent tor purposes ofdomestic industry under subsection (A). (SIB at l 18 (calculating_); SRB at34(calculating -) Jemieweiifs dispute with respect to this investment in equipment is that it includes amounts “wholly unrelated to Glycosyrfs 2’-FL R&D efforts” because there is no apportionment between “activities related to 2’-FL and activities related to other molecules unrelated to the claims of the ’O18patent." (RIB at I39; see RRB at 68.) Jennewein provides examples of a security alarm system, certain sterilizers, and a fermentation control system as equipment which a Glyeosyn witness admitted at the hearing may not be solely related to 2’-FL development. (See RIB at I39 (citing Hr’g Tr. at 52: 14421,52:22-27, 53:S—l7).) Jenncwein fitrther argues, inter aim, the timing of Glycosyrfs switch to developmentof the - in mid-2017,£15comparedto Several equipment purchases after this time, shows “Glyeosyn’s equipment expenses are therefore suspect and should be disregarded as unreliable.” (See id. at I39-140.) “ Both Glycosynand the Staff incorrectlyre ort this amountas‘ (CIB at 132 SIB at ll8.i It is understood that this 1s a typo; H would be the correct rounding-Lipof l (ill
Here. l find .lennewein’s criticisms have merit. Of primary importance, Glycosyn directly acknowledges. and the evidence shows. that its concentration on 2‘-FL greatly diminished following July 20l7. (See CX-0089C at -74622 (showing scientist time changing from lO0% to 25%);CX-OOUZC at Q93(“Aroundthe end of 20]’/,ourprojectwith— — started ofGlycosyifs resources went there starting around mid-20177).) It is natural to assume, therefore. that the use of its equipment for 2‘-FL development similarly diminished; yet Glycosyn has not applied any allocation percentage in the way it had done for facility and labor. The Staff agrees that Glycosyn has not done this but contends applying the 2’-FL allocation percentage derived front labor records makes little difference. (SRB at 35.) In its reply brief, Glyeosyn similarly does not dispute that no allocation was applied or that one should have been. (See CRB at 66.) Given the record. and Glycosyrfs application of an allocation to both of its facility and labor expenses, l find the same allocation should be applied to equipment. Glycosyn’s witness does not sufficiently make clear that every item listed in the equipment record, C-X-0085C, has been used solely for 2’-FL development work (see CX-0093C at Q54-59). which is important giventhe clearrecognitionthat only. ofscientists’timein 2017and] in 2018was related to 2’~FL (see CIB at 130-13 I). I do not agree. however, that this failure to allocate means all of the equipment investments are unreliable and should be disregarded. as Jennewein urges. When applied, GlycoSyn’s domestic investment in equipment, for purposes of subsection (A), becomes: lUl
With respect to labor under subsection (B)s, the evidence shows Glycosyn employed several scientists and corporate officers between 2015 and May 2018 to develop and improve manufacturing methods of2‘-F L under the ‘O18 patent. with respect to both bacterium engineering and fermentation procedures. (See CIB at 125-133; CXYODOZCat Q92»l22; CX-0089C.) A Glycosyn witness identified, for each of these employees, “allocated amounts of salaries and benefits per year [] based on the percentage of time each individual employee spent dedicated to 2’-FL“ in each ofthe years 2015 through May 2018. (CX-0003C at Q31-37 (citing CX-0089(1).) That witness, Howard Newburg, explained that the allocation of time for the scientists, as reflected in CX-0089C, was created by one of the scientists, Dr. John McCoy, whereas he generated the allocation for corporate officers. (CX-0003C at Q32; see CIB at 130 (citing, inter cilia, CX-0002C at Q93-94).) The document, CX-0089C. reflecting the allocations of time spent towards 2’-FL showspercentagesof either- dependingon theemployee,priorto July2Ol7;and percentagesof_ oi‘ dependingontheemployee,forJuly2017throughMay2018. (CX-0089C at -74621-2.) The resulting claimed investment in labor directed to the development oF2’~FL produced under the claims ofthe ’Ol8 patent is summarized in the below table: i See FN 6. H As described below, Glycosyn names a fourth category of expenses as “Research and Development” and considers them as subsection (C) expenditures, rather than capital expenditures under subsection (B). (See CIB at 132-133, 138-140.) I02
The Staffagreeswiththis— figureas the amountin laborinvestmentattributableto
the ‘O18patent for purposes ofdomestic industry under subsection (B). {SIB at I20; SRB at 34.)
Jertrtewein’s dispute with respect to this investment in labor is three fold. First, Jenneweirt
criticizesGlycosynForfailingto breakoutlaborassociatedwith— to foreign
corporation FrieslandCampina. (See RIB at 140443.) Jcnncwein claims this assistance cannot be
counted for multiple, disparate, reasons: (l ) because it “rctlect[s] work done outside ofthe U.S..
(2) “because it has not established that FrieslandCarnpi1ta
is practicing any claims ofthe *018 patent”; and (3) because FrieslandCampina did not sufficiently
participate in discovery such that Glycosyn “[did not] request assistance from Fries1andCampina,
Glyeosyn carutot now rely on any activities related to FricslandCampina in support ofits domestic
industry.” {See id.) These arguments lack merit. That Glycosytfs research and development of
2'—FLproduction has some relation. or value, to FrieslandCarnpina does not take away from the
Factthat the investments occurred in the United States and have a connection to the ‘O18 patent.
Similarly, Jennewein cites no authority for discounting the labor costs of a domestic employee
when that employee temporarily travels overseas and does work in a foreign location. Such hyper
particularity is not consistent with Commission precedent. Stringed Insrruntenrs, lnv. No. 337
I03TA-586, Comm’n Op. at 26 (“[a] precise accounting is not necessary; as most people do not document their daily affairs in contemplation of possible litigation"). Even then, the record only supportsfindingthatsuchphysically-overseas— wouldhavebeena fewdays of labor. (See generefiy Hr’g Tr. at 60:18-61:1, 43:1-23, 50:7-5| :23; CX-0003C at Q13-21; CK OUUZCat Q92-94, I20, 122.) Nonetheless, the Staffs “u.nderstand[ing oi] Mr. Ncwburg's testimony to mean that hours worked outside the United States were not included in Glycosyn’s economic prong calculations" (SRB at 36 (citing I-lr‘gTr. at 60: l l—6l:l)) is likely incorrect. CX (JU39Cis a record of gross wages and benefits paid to Glycosyn employees. not hours worked. (See CX-0089C at -74621-2.) Thus. unless employees who traveled and worked overseas were compensated apart from these gross wages, that expense is included in Glycosyn’s economic prong calculations. And the fact that Frieslandtlampina did not participate in discovery and may or may not be practicing the ‘O18patent outside the United States is irrelevant. Jenneweirfs second criticism of the claimed labor investment is that it improperly includes general and administrative expenses. (RIB at 142 (citing Certain Clidfnittnr Bromide & Prods‘. Containing Same, Inv. No. 337-TA-l I09, Order No. l I at 5-6 (July 25, 2018) (public version) (“Clidirzitrm Bromide"); Certain Kinesiorherapy Devices & Components T!rere0j,' Inv. No. 337 TA-823, Comrn’n Op. at 29 n.S (June I7, 2013) (“Kinesior/rerapy Devices"), rev 'd on other gr'0tmds,Le10, 736 F.3d 879).) To make the argument, however, Jennewein eonflates general and administrative expenses in support of domestic engineering with the more commonly prohibited sales and marketing expenses of an importer—and it is the latter which .Iennewein's cited caselaw is concerned with. See, e.g., Ciidiniztm Bromide, lnv. No. 337-TA-llO9, Order No. ll at 5-6 (“Paying wholesalers to distribute pharmaceutical products is a cost oi‘ sale borne by pharmaceutical manufacturers selling to those entities, regardless of whether or not the l (J4
pharmaceutical is imported or rnade domestically. . . . [The] fees are nothing more than standard U.S. expenses of a mere importer, which should not be considered in a domestic industry analysis"). Even then, the Commission has shown latitude in including sales, marketing, or general administrative investments when they are provided in support of other qualifying activities: ln the case at hand, P0pSockets is not relying solely on marketing and sales expenditures to satisfy the economic prong. While PopSockcts has included sales and marketing expenditures. it has also provided evidence of significant expenditures in its employment of labor in other qualifying activities, such as engineering, product development, product assembly, supply chain and operation management, and customer service, as well as capital expenditures for fixtures, furniture, software, and equipment used for design. engineering, and operation management, which are sufficient to establish the existence of a domestic industry under subsection (B). Certmn Collapsible Sockets for Mobile Electronic Devices and Components Thereof; Inv. No. 337-TA-I056, Comm’n Op. at I9-20 (July 9, 2018) (public version). Jennewein’s third criticism of the claimed labor investment is that Glycosyn’s allocation percentage of time spend on 2’-FL is flawed and unreliable, pointing to testimony from Dr. Merighi. an ex-employee of Glycosyn, where he explained that “he did not devote all of his time to 2*-rr:* (RIB at 141 (citing I-lr’g Tr. at 292:1-14).) Jennewein contrasts this with the record of CX-0089C, where 2 of Dr. Merighi"s time is listed as spent on 2‘-FL. (CX-0089C at -74621.) Neither the Staffnor Glycosyn addresses this discrepancy in their post-hearing briefs. (See CIB at 124-140; CRB at 64-68; S[B at I I4-125; SRB at 33-39.) An expanded view ofthe testimony shows there many not necessarily be a conflict. DrrMerighi states that at times he wouldhave been- focusedon 2’-FL or. Q. Just a couple more questions. At Glycosyn you worked on projects other than 2‘-FL, correct‘? I05
A. Yes. Q. So you didn’t spend 100 percent of your time working on 2‘~FL at Glycosyn. correct‘? A. If you did —ifthe time is —what is —the five, six years‘? No. But l had like this big s rin sometime where it would be - percent of my week was on2’-FL“ Q. And then other times you would he devoted to other projects‘? A. Yes, yes. l think at this time if you look at my notebook, it would be like a mix of —because we had to —we were supposed to keep the book in a chronological order, so you will see how much time I was doing one thing or the other. Just count the pages, because it’s pretty much in chronological order. (Hr’g Tr. at 292:]-19.) I therefore do not find this to be a reason to consider Glycosyrfs records tlawedor unreliable,andI detemiinethat_ of laborinvestmentis attributableto the ’UI8 patent for purposes of domestic industry under subsection (B). With respect to research and development under subsection (C), Glycosyn’s claimed investment includes the aforementioned plant, equipment, and labor expenses“ in addition to a fourth category of miscellaneous research and development expenses allegedly attributable to 23 FL development in the relevant time period of 2015 through May 2018. (CIB at 132-133, l3S~ I40.) A Glycosyn witness identified these expenses as: ( l ) “costs for the FDA’s GRAS assessment ol'Glycosyn’s purified 2‘-FL for the U.S. market"; (2) “manufacturing run of a test batch of 2’-FL (3) “lab supplies purchased for use in Glycosyn’s R&D of 2’-FL”; (4) “software subscriptions For its laboratory facilities, for Glycosytt scientists’ use in their research and development efforts”; and (5) domestic travel Q For subsection (C) only, Glycosyn excludes its general and administrative labor costs. I06
=XP¢nS~=S in “mhaical marketing *=t1°°fl$ — (cx-0003catQ61-65(citingcx-0091c;CX-0092C; cx-0093c;cx~0094c;ex 0O95C).) Of these, Glyeosyn’s witness applied the time allocation percentages derived from the labor to only the software subscriptions, to accommodate any usage not attributable to 2‘-FL development. (Id. at Q63.) The resulting amounts of these miscellaneous investments are summarized in the below table: Further, in light of subsection (_C)’srequirement that a complainant must show a nexus between the research and development investment and the invention of the asserted patent. see, e.g., Solid .S't‘a!eStorage Drives, lnv. No. 337-TA-1097, Comm’n Op. at I4, Glycosyn applied a second allocation percentage “according to the proportion ofGlyoosyn‘s 2’-FL fermentation runs of using 2’-FL strains that practice the patented technology, as opposed to other 2“-FL strains." (CIB at 138.) A second Glyeosyn witness testilied that, based on a record of all fermentation runs since August 2015: - ot“2‘-FL runs in 2015 were done with ‘O18 patent practicing bacteria strains;— ot'2‘-FLrunsin2Ol6;- of2'-FLrunsin2017;and- of2’-FLrunsin ‘D The documents reflecting purchases of lab supplies, CX-0093-C through CXAOOQSC,are limited to the years 2015, 2016, and 2017. I O7
2018. (CX-0002C at Ql ll (citing CX-0131C‘); see CX-OOOZCat Q] 13.) Glycosyn further removed the labor costs associated with its general and administrative officers. (CIB at I38.) The resulting table of investments, for all categories Glycosyn alleges qualify Forsubsection (C), is as lbllows: The Stafffinds a — figureas the amountin researchand developmentinvestment attributable to the ‘O18 patent for purposes of domestic industry under subsection (C). (SIB at I22; see SRB at 34, 38.) ln reaching this amount, which is higher than Glyeosyn’s, I understand the Staff either takes the position that general and administrative labor can be included or did not observe that Glycosyn removed this item. Here, .Iennewein’s dispute is a general assertion that “Glycosyn has failed to provide Sufficient evidence on the extent ofany nexus between its investments and the ‘Ul S patent." (RIB at 142 (citing 1m‘t=.gra.tea'Cr'rcz4irChips, Inv. No. 337-TA-S59, Comm’n Op. at 38 (Aug. 22, 2014) (public version)).) Jennewein does not, however, acknowledge Glycosyn’s two-tier application of a 2“~FL»rclatedallocation percentage (based on labor) and then a ‘O18patent-practicing allocation “ See FN 6, :03
percentage (based on termenter runs) to its investments. I find this two-step allocation is probative of the value of investment related to the invention of the ‘O18patent; i.e., the required “nexus.” Integrated Circuit Chips, Con-tm‘nOp. at 42 (holding domestic industry under subsection (c) can ordinarily be infened from investment in a practicing [method] and “[r]equiring an extensive inquiry as to the adequacy of nexus when it is not challenged on the merits by respondents would unduly consume [1 time and resources . . . ."). Again, Jcnnewein does not appear to dispute Glycosyn‘s claim of which strains. and thus which of its fermentation runs, practice the claims of the ‘O18 patent. I also find nexus based on the nature ofGlycosyn’s activities at its Massachusetts locations as compared to the subject matter of the asserted claim limitations. Glycosyn‘s activities, such as “all aspects of continued genetic engineering on our E. colt strains" and “improving the fennentation process for our production strains” (CX-0002C at Q92) relate directly to claim limitations, such as “providing an isolated E. coli bacterium comprising. (i) a deletion or functional inactivation of an endogenous B-galactosidase gene,“ “culturing said bacterium in the presence of lactose,” and “retrieving a fucosylated oligosaccharide form said bacterium or from a culture supernatant of said bacterium" (‘O18patent at cl. l). I therefore find the record supports Glycosyn‘s claimed investment amount in research and development with a nexus to the claims ofthe ‘O13 patent, with certain exceptions. In the same way that Software subscriptions were adjusted using the labor allocation percentages, and equipment investment more reasonably should have been (‘discussed above), l find Glycosyn's laboratory research and development supplies should be as well. Glycosytfs witness does not sufficiently make clear that every item listed in the purchase records, CX-0093C through CK DUQSC,was solely for 2’-FL development work (see CX-0093C at Q62‘),which is important given I09
the clear recognitionthatonly. of scientists’time in 20]’?and] in 2018 was relatedto 2’ FL (see CIB at 130-131). When that allocation is applied, the record supports a research and developmentinvestmentwitha nexusto theclaimsof the ’Ol8patentof_ as in the below tables: ‘Z See FN 10. 1’ See FN 6. llO
Finally, Jennewein makes an overall claim, seemingly against all of Glycosyrfs investments, that “Glycosyn was no longer involved in that research at the time the Amended Complaint was filed, and had already moved to other projects” such that “Glycosyn cannot rely on R&D that was discontinued at the time of filing its Amended Complaint in support of domestic industry.“ (RIB at 143.) Jcnnewcin contends “[p]ast expenditures may only be used to support a domestic industry claim if the complainant ‘is continuing to make qualifying investments at the time the complaint is filed.” (id. (citing Television Sets, Television Receivers, Tefei-isifonTuners, and Comporients The:-eofi lnv. No. 337-TA-910, Comm'n Op. at 68 (Oct. 30. 2015) (“Television Sets"); Marina, LLC v. Mr’! Trade Comm ’n, 716 F.3d 596, 601 n.6 (Fed. Cir. 20l3)).) I do not agree. Jenneweitfs sole support for this alleged cessation of activity is a line from a Glyeosyn witness’s deposition, which does not support the argument. (See R_lBat 143 (citing .lX-0020C at 151:20-1523).) There, the witness testified, “Q. And for the second half 0f2018. whatdo you expectwill be the allocationsof the employeesfor 2~FL-7 A. I think there’s still, at least a (JX-0020C at I51 :20-152:3.) l find additional evidence shows Glycosyn continues to make qualifying investments in2‘-FL. Forexample, thesame witness testified th “to continue the research in 2’-FL" (1-lr’gTr. at 44:20-45: 13), and Glycosyrfs records show it continued with 2’-FL fermentation runs throughout 2018 (see CX-OOOZCat Q1 13). B. “Significant” or “Substantial” The next step in the evaluation of domestic industry is to determine if the investment amounts identified above are “significant,” as in subsections (A) and (B), or “substantial,” as in subsection (C). The most recent precedential decision by the Court of Appeals For the Federal lll
Circuit addressing this determination is Leia, which restated law applicable to a number of issues surrounding the economic prong of domestic industry. See 786 F.3d at S83-85. In particular, the Federal Circuit held that the statutory tenns ‘“significant’ and ‘substantial’ refer to an increase in quantity, or to a benchmark in numbers” and “[a]n ‘investment in plant and equipment’ therefore is characterized quantitatively, r'.e.,by the amount of money invested in the plant and equipment.“ Lela, 786 F.3d at 883. Continuing. the Federal Circuit held that: “[a]ll ofthe foregoing requires a quantitative analysis in order to determine whether there is a ‘significant’ increase or attribution by virtue of the claimant’s asserted commercial activity in the United States.” Id. In short. “Qualitative factors cannot compensate for quantitative data that indicate insignificant investment and employment." Id. at 885. I find GIycosyn’s investments in plant, equipment. and labor are “significant.” Glyeosyn conducts virtually all of its research and development in the United States, and has provided records showingits foreignexpensesconstitutea de minimi.s- in travel costs. (CX-0003C at Q64.) Whencomparedagainstthis- Glycosyn’sdomesticfacility,equipment,and labor investment Of_ 2 ill facilities, - inequipment,_ in labor) must provide a “‘significant’ increase or attribution" of value to its 2’-FL development under the rubric set by Leia. 786 F.3d at 883. There is simply no other source but domestic activity to credit. Moreover, the record shows Glycosyn’s investment with respect to 2’-FL is significant even unto itself. A Glycosyn witness testified, using profit and loss schedules, that its Company wideoperatingexpensesovertherelevanttimeperiodtotal_ (CX-0003Cat Q67,68; CX-0088C.)l havenotroubleconcludingGlycosyn’s_ inZFFLfacility,equipment, and labor cost is a significant portion of this company-wide investment. For the same reasons, I H2
concludeGlycosyn‘s— inresearchanddevelopmentcostswitha nexusto theclaims of the ‘O18patent are "substantial." Jennewein‘s dispute over significance. and substantiality, is mainly that “the roughly. I Glycosyncontends it investedin a domestic industry for the ‘O18patent since 2015 pales in comparisonto the— at least,investmentFrieslandCarnpinahas made for its 2’-FL production facility-” (RIB at 141 (citing l-1r’gTr. at 46:13-16).) Vtfhilcthis may be true, I disagree that this inter-company comparison is more indicative of significance (or lack thereof) than, for example, a comparison of Glyc0syn’s domestic versus foreign expenditures. It is also important to consider that the domestic industry article in question is not the 2’-FL which Frics1andCampina will produce, but the 2’-FL produced by Glycosyn in the United States under the methods of the ’018 patent. (See CIB at I5, 92 (citing CX-0059C; C-X-0131C; CX-0064C).) It cannot be reasonably disputed that G1ycosyn’s investments have significantly contributed, in a quantitative sense, to that production. Jennewein also argues “[e]ven taken in their totality, the whole of Glycosyrfs investments and employmentare _ Any investmentsand employmentthat would relate to exploitationof the ‘O18patentare_ and Glycosynhas not offeredany contextfor concluding that those investments would be ‘significant’ or “substantial,” (Id. at 144.) To the contrary, - isnota trivialamountandGlycosyn offeredeachofthequantitative contexts discussed above—oomparison to its company-wide operating expenses and comparison lo foreign expenditures. (CIB at 135-136, 139-140.) Accordingly, I find Glycosyn satisfies the economic prong of domestic industry under each ofsubsections (A), (B), and (C). 113
VI. CONCLUSIONS OF LAW l. The Commission has in rem jurisdiction over the Accused Product, 2‘-FL. 2. The importation or sale requirement of Section 33'? is satisfied. 3. Glycosyn has been shown to practice claims 1-3, 5, 8, 10-14, 18, 22, and 24-28 of U.S. Patent No. 9,970,013. 4. Glycosyn has not been shown to practice claims 9 or 23 of the ‘O18patent. 5. The domestic industry requirement is satisfied with respect to the ’0l8 patent. 6. Jennewein directly infringes claims 1-3, 5, 8, 10, 12, 18, and 24-28 of the ‘O18 patent. 7. Jennewein does not infringe claim 23 of the ‘O18patent. 3. No claims ofthe ‘0lS patent have been shown to be invalid under 35 U.S.C. § 103. 9. No claims ofthe ‘O18patent have been shown to be invalid under 35 U.S.C. § 1I2. I0. The ‘O18patent has not been shown to be unenforceable. 11. There is a violation of Section 337 with respect to the ’0l 8 patent. VII. RECOMMENDED DETERMINATION ON REMEDY AND BOND The Commission's Rules provide that subsequent to an initial determination on the question of violation of section 337 of the Tariff Act of 1930, as amended, 19 U.S.C. § 1337, the administrative law judge shall issue a recommended determination concerning the appropriate remedy in the event that the Commission finds a violation of section 337, and the amount ofbond to be posted by respondent during Presidential review of the Commission action under section 3375). See 19 C.F.R. § 210.-42(a)(l)(ii). The Commission has broad discretion in selecting the form, scope, and extent of the remedy in a section 337 proceeding. Viscofim, SA. v. In! '1 Trade Comm ’n, 787 F.2d 544, 543 (Fed. Cir. 1986). Under Section 337(d)(l), if the Commission determines as a result of an investigation that there is a violation of section 337, the Commission is authorized to enter either l 14
a limited or a general exclusion order. 19 U.S.C. § 133'?(d)(l). A limited exclusion order instructs the U.S. Customs and Border Protection (“CBP”) to exclude from entry all articles that are covered by the patent at issue and that originate from a named respondent in the investigation. A general exclusion order instructs the CBP to exclude irom entry all articles that are covered by the patent at issue, without regard to source. Certain Purple Protective Gloves, luv. No. 337-TA~5OD, Com1n’n Op. at 5 (Dec. 22, 2004). Under section 337(t')(1), the Commission may issue a cease and desist order in addition to, or instead of, an exclusion order. 19 U.S.C. § 1337(i)(1). The Commission generally issues a cease and desist order directed to a domestic respondent when there is a “commercially significant“ amount of infringing, imported product in the United States that could be Sold, thereby undercutting the remedy provided by an exclusion order. See Certain Crystoflirte Cejodroril Monoliydrote, lnv. No. 337-TA-293, USITC Pub. 2391, Cornm‘n Op. on Remedy, the Public Interest and Bonding at 37-42 (June 1991); Certoin Coiiderisens,Parts Thereof and Prods. Containing Some, IrichzdingAir Conditiorters for Automobiles, Inv. No. 337-TA-334 (Remand), Comm’n Op. at 26-23, 1997 WL 817767, at *1 1-12 (U.S.l.T.C. Sept. 10, 1997). Additionally, during the 60-clay period of Presidential review under 19 U.S.C. § 1337(j), “articles directed to be excluded from entry under subsection (d) . . . shall . . . be.entitled to entry under bond prescribed by the Secretary in an amount determined by the Commission to be sufficient to protect the complainant from any injury." See 19 U.S.C. § 133'/(i)(3). "The Commission typically sets the bond based on the price differential between the imported infringing product and the domestic industry article or based on a reasonable royalty. However, where the available pricing or royalty information is inadequate, the bond may be set at one hundred ( IOU) percent of the entered value of the infringing product." Certain Industrial Automation Systems and Components Thereof Including Control Systems, Controllers, Visuotization Hardware, I15
Motioit and Motor Control Systenis, Networking Equipment, SafetjvDevices, and Power Supplies, lnv. No, 337-TA-1074, Comnftl Op. at 13 (Apr. 23, 2019) (“Azttomation .S:vsterns")(public version) (citation omitted). Section 337 also mandates consideration of the effect of exclusion on (1) public health and welfare; (2) competitive conditions in the U.S. economy; (3) U.S. production of articles that are like or directly competitive with the articles subject to the investigation; and (4) U.S. consumers. 19 U.S.C. § l337(d)(l). By publication in the Federal Register, the Commission has instructed me “to take evidence or other inforrnation and hear arguments from the parties and other interested persons with respect to the public interest in this investigation, as appropriate, and provide the Commission with findings of fact and a recommended determination on this issue, which shall be limited to the statutory public interest factors set forth in 19 U.S.C. 1337(_d)(1),(f)(1), (g)(1).” S3 Fed. Reg. 28.865 (June 21, 2018). A. LIMITED EXCLUSION ORDER Should a violation be found, Glycosyn seeks a limited exclusion order “against the subject article, 2‘-FL.” (CIB at 147.) Glycosyn argues against any carve-out for 2'-FL made by any particular strain number in light of a general reluctance from the Commission to identify model numbers in exclusion orders (id. at 148 (citations omitted)) and the record evidence showing the only strain Jennewein actually uses to create imported 2’-FL is its #1540 strain (id. (citing, inter aha, RX-0337C at Q71, 75, 131-132; CX-0215C at 7)). The Staff agrees with Glycosyn here. (SRB at 40-41.) Similarly, Glycosyn argues against a certification provision based on its view that there is no other strain “that docs not infringe the ‘O18Patent, that is sufficiently fixed in design (and with regulatory approval) for sale to the United States market for foodst|1ffs.“ (Id. at 149 (citing Certain 116
Self-Cleaning Litter Boxes and Components Thereofl lnv. No. 337-TA-625, Cornm’n Op. at 59 [60] (Apr. 28, 2009_)).) Glycosyn also argues Jennewein is most likely incapable of so certifying. (See CRB at 7 I-72.) If a certification is used, Glycosyn insists that Jennewein should nonetheless be prohibited from importing 2’-FL for use in foodstuffs until “all necessary regulatory approval" has been granted (id.), and that Glyeosyn should be afforded rights to audit Jennewein‘s production facilities (id. at 151]). The Staff does not agree with the above proposals. [SRB at 41-42.) Jennewein seeks a carve-out from a limited exclusion order for its TTFL12 strain for reasons of non-infringement, as well as a certification provision. (RIB at 144-145.) Jenneweiri argues that the process nature of the patent at issue, the ’0l8 patent, is not grounds to refuse a certification provision. (Id. at 145 (citing Certain Salinornvciir Biomass & Prepmwtions Containing Same Recommended Determination on Remedy & Bonding, Inv. No. 337-TA-370 (Dec. 13, 1995); Certain Acfd—Washed Denim Garments and Accessories, Including Jeans, Jackets", Bogs and Skirts, lnv. No. 337—TA-324, Cornrn’n Op. at 22-23 (Aug. 14, 1992)).) Jertnewein contends it is capable of providing such information. (Id. (citing Hr"g Tr. at 3148:10 2 1).) Jennewein also challenges G1ycosyn’s premise that any regulatory approval is needed at all before 2’-FL from additional bacterial strains can be imported or sold (RRB at 71-74) and argues the requested audit rights are inappropriate on a number of grounds (id. at 75). As determined above, a violation of Section 337 has taken place, and 1 therefore recommend to the Commission that a limited exclusion should issue according to statute. 19 U.S.C. § l337(d)( 1). As to those positions taken by Glycosyn on additional provisions for the exclusion order, I do not agree. Glycosyn’s requested audit rights are without precedent and its request for prohibitions on importation tmtil regulatory approvals have been met intrudes on the Food and Drug AdIninistration’s authority—in addition to placing an inordinate burden on the 117
Commission. l do not recommend the Commission include either provision in any limited exclusion order. Certification presents a difficult question. The record evidence shows that 2‘-FL produced by a first process is essentially indistinguishable from 2’-FL produced by another. (See, e.g., Hr‘g Tr. at 350120-351:2: RX-0406C at Q60; CX-0002C at Ql2l; JX-0011 at l45:l5-I8 (“Q. Once Jennewein’s 2’-FL is in powder form, is there any way to ~ to determine, using that powder, which strain was used to produce that 2‘-FL? A. No.”).) As the ‘O18patent is strictly a method patent. this creates two problems. First, there is no way for Customs and Border Patrol to discern on their own whether Z‘-FL was rnadc by an infringing process or not. Second, there is likely no way for Glyeosyn to ascertain for itself whether Jennewein violates any exclusion order from importation records alone. (See CPB at 147-l48 (describing knowledge gained through GRAS submission).) And Jennewcin’s ability to import 2‘-FL (or any “fucosylated oligosaccharidc”) made under a non infringing process rnust be maintained as well. Accordingly, l see some son of certification provision necessary, with certain heightened requirements. l therefore recommend the Commission include a certification provision, wherein said certification is required to state with particularity the grounds of non-infringement of the imported oligosaccharide and be accompanied by sufficient corroborating evidence of the type provided in discovery in this investigation. B. BOND Regarding bond during the presidential review period. the parties have stipulated to a 5% bond on Jet1newein's 2’-FL during the 60-day-Presidential review period. (CIB at 150 (citing JX D007);RIB at I45.) This is a reasonable amount to protect Glycosyn from hann during the review H8
period. Accordingly, l recommend the Commission set a bond in the amount of 5% of entered value. C. PUBLIC INTEREST Regarding the statutory public interest factors, Glycosyn contends there is no evidence of any significant adverse effects from an exclusion order. (CIB at 140-147.) Regarding health and welfare, Glycosyn argues “the evidence does not show that any of the infant formula products on the make ed-av — (CIBat 140-141 (citingHr’gTr.at26:23-22:21, 31:5-33121; ex-0001c at Q37-50, 57-58; RX-0406C at Q86).) Thus, as oftoday, Glycosyn adds, .Iennewein’s 2’-FL “is not essential to the health and safety of babies in the United States, or necessary for any important public health or welfare need . . . (Id. at 141.) Regarding competitive conditions, Glycosyn notes that “infant formula supplemented with 2‘-FL [1was introduced to the market only recently" (id. at 143 (citing, inter ufia, JX-0010C at 30:1-23 (“It is very difficult to make any forecasts at this early stage about possible sales figures because it’s a completely new product.”))) and ofthe many infant formula products available, only a few contain small amounts of 2‘-FL (see id. at I43 I44). Glycosyn also identifies “numerous alternative, non-infringing 2'-FL producers that can step in and replace the excluded products, such as GlycosynfFrieslandCampina. DuPont/Inbiose. Glycorn, and eventually, BASF.” (Id. at I46.) The Staff agrees with Glycosyn on these points. (SIB at 127-134.) Jennewein emphasizes 2’-FL‘s “critical role[]" in infant development and the benefits of including it in infant formula, keeping in mind that Jennewein was the first and is the only company selling 2‘-FL in the U.S. (RIB at I36-137 (citing RX-0358C at Q188).) Jennewein asserts that “Glycosyn makes no competitive products that could replace .Iennewein’s 2‘-FL if it were I19
excluded from the US" lid. at 137 (citing, inter cilia, Hr’g Tr. at 57:1-4, 57:22-5813)), and “Glycosyn provided no evidence that alternate suppliers can replace Jeru1ewein‘s 2‘-FL in a commercially reasonable time or in sufficient quantities" (id. at 138). Based on the record, I do not find the requested limited exclusion order would meaningfully impact public health and welfare, competitive conditions, domestic production of articles, or U.S. consumers. While it is clear that the purpose of providing 2’-FL in infant formula is to improve public health, the evidence shows that the otherwise well-established market has only recently begun including 2’-FL into its products, The U.S. public is therefore not dependent on such products, as ofyet. Moreover, assuming Jennewein is the only supplier of 2‘-FL to the U.S. market, then all infant formula manufacturers or vendors in the U.S. will be affected cqually—along with the consumers who purchase those formula products. To the extent these entities wish to continue using 2‘-FL in their formula, the Staff, in particular, has persuasively shown that the demand can be met by competitors. (See SIB at I29 l3l (citing, infer cilia. RX-0327C at 25; CX-0009; CX-OOIl), 132; SRB at 43-44.) Accordingly, it is my recommended determination that issuance of a remedial order in this investigation would not be contrary to the public interest. I20
VIII. INITIAL DETERMINATION AND ORDER Based on the foregoing, Mit is my Initial Determination that there is a violation of Section 337 ofthe Taritt‘ Act of 1930, as amended, I9 U.S.C. § 1337, in the importation into the United States, the sale for importation, or the sale within the United States after importation of certain human milk oligosaccharides and methods of producing the same, in connection with the asserted claims ofU.S. Patent No. 9,970,018. Fnrthefinore, it is my determination that a domestic industry in the United States exists that practices or exploits the asserted patent. The undersigned hereby certifies to the Commission this lnitial Detennmation, together with the Record of the hearing in this investigation consisting of the following: the transcript of the evidentiary hearing, with appropriate corrections as may hereafter be ordered; and the exhibits accepted into evidence in this investigation as listed in the appendices hereto. '5 Pursuant to I9 C.F.R. § 2l0.42(h), this Initial Determination shall become the determination of the Commission unless a party files a petition for review pursuant to 19 C.F.R. § 2 l0.43(a) or the Commission, pursuant to 19 C.F.R. § 210.44, orders on its own motion a review of the Initial Determination or certain issues therein. H The failure to discuss any matter raised by the parties or any portion of the Record herein does not indicate that said matter was not considered. Rather, any such rnalter(s) or portion(s) of the Record has/have been determined to be irrelevant, immaterial or meritless. Arguments made on brief which were otherwise unsupported by Record evidence or legal precedent have been accorded no weight. '5 The pleadings of the parties filed with the Secretary need not be certified as they are already in the C‘ornmission’spossession in accordance with Commission rules. I2l
Confidentialig Notice: This [nitial Determination is being issued as confidential, and a public version will be issued pursuant to Commission Rule 2lO.5(f). Within seven (7) days of the date of this [nitial Determination, the parties shall jointly submit; (1) a proposed public version of this opinion with any proposed rcdactions bracketed in red; and (2) a written justification for any proposed redactions specifically explaining why the piece of information sought to be redacted is confidential and why disclosure of the information would be likely to cause substantial hami or likely to have the effect of impairing the Commissioifs ability to obtain such information as is necessary to perform its statutory functions.“ SO ORDERED. 1?; . L_ D//U tamcron Elliot V if if C Administrative Law Judge 5° Under Commission Rules 210.5 and 20l.6(a)_.confidential business information includes: information which concerns or relates to the trade secrets, processes, operations, style of works, or apparatus, or to the production, sales, shipments, purchases, transfers, identification of customers, inventories, or amount or source of any income, profits, losses, or expenditures of any person, firm, partnership, corporation, or other organization, or other infomiation of commercial value, the disclosure of which is likely to have the effect of either impairing the Commission's ability to obtain such information as is necessary to perform its statutory functions, or causing substantial harm to the competitive position of the person, firm, partnership, corporation. or other organization from which the information was obtained, unless the Commission is required by law to disclose such information. See 19 C-.F.R,§ 20l.6(a). Thus, to constitute confidential business information the disclosure of the infomiation sought to be designated confidential must likely have the effect of either: (I) impairing the Commission’s ability to obtain such infomiation as is necessary to perform its statutory functions; or (2) causing substantial harm to the competitive position of the person, firm, partnership, corporation, or other organization from which the information was obtained. 122
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME INV. NO. 337-TA-1120 PUBLIC CERTIFICATE OF SERVICE l, Lisa R. Barton, hereby certify that the attached INITIAL DETERMINATION has been served by hand upon the Commission Investigative Attorney, Lisa Murray, Esq. and the following parties as indicated, on UET B 3 2919 . Lisa R. Bartdn, Secretary O U.S. lntemational Trade Commission 500 E Street SW, Room 112A Washington, D.C. 20436 FOR COMPLAINANT GLYCOSYN LLC Michael C. Newman, Esq. ( ) Via Hand Delivery MINTZ LEVIN COHN FERRIS GLOVSKY ( /5 ExpressDelivery AND POPEO PC y( ) Via First Class Mail One Financial Center ( ) Other; Boston, MA. 02111 FOR RESPONDENT .]ENNEWEIN BIOTECHNOLOGIE GmbH Gary M. Hnath, Esq. Via Hand Delivery MAYER BROWN, LLP Express Delivery 1999 K Street, NW Via First Class Mail Washington, DC 20006 Other:
UNITED STATES INTERNATIONAL TRADE COMMISSION Washington, D.C. In the Matter of CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME Inv. No. 337-TA-1120 ORDER NO. 22: CONSTRUING THE TERMS OF THE ASSERTED CLAIMS OF THE PATENTS AT ISSUE (December 18, 2018)
TABLE OF CONTENTS I. INTRODUCTION ................................................................................................................. 1 IL IN GENERAL ........................................................................................................................ 1 III. RELEVANT LAW ................................................................................................................2 IV. LEVEL OF ORDINARY SKILL .......................................................................................... 6 V. THE ASSERTED PATENTS ................................................................................................ 7 A. The '230 Patent ..........................................................................................................7 B. The '018 Patent .......................................................................................................... 9 VI. CLAIM CONSTRUCTION ................................................................................................. 12 A. Construction of the Agreed-Upon Claim Terms ...................................................... 12 B. Construction of the Disputed Claim Terms ............................................................. 13 1. "P-galactosidase activity comprises between 0.05 and [200 units I 5 units I 4 units/ 3 units/ 2 units]" ............................................................................... 13 2. "functional . . . p-galactosidase gene" ......................................................... 23 3. "wild type" ................................................................................................... 29
I. INTRODUCTION
This Investigation was instituted by the Commission on June 21, 2018 to determine whether
certain human milk oligosaccharides and methods of producing the same infringe U.S. Patent Nos.
9,453,230 (the "'230 patent") and 9,970,018 (the '"018 patent"). See 83 Fed. Reg. 28865-6 (June
21, 2018). The Complainant is Glycosyn LLC ("Glycosyn"). The Respondent is Jennewein
Biotechnologie GmbH ("Jennewein") (altogether, ''the Parties").
Pursuant to Ground Rule 8, a Markman hearing was held October 16, 2018 regarding the
interpretation of the certain terms of the patents at issue. Prior to the hearing, the Parties and the
Commission Investigative Staff ("Staff') filed initial and amended joint claim construction charts
setting forth a limited set of terms to be construed. The Parties and the Staff also filed initial and
reply claim construction briefs, wherein each party offered its construction for the claim terms in
dispute, along with support for its proposed interpretation. 1 At the beginning of the hearing, the
Parties indicated one of the claim terms in dispute, "promotor-less," would not construction due to
withdrawal of the relevant claims by Glycosyn. See Hr'g Tr. at 4:13-5:3.
Il. IN GENERAL
The claim terms construed in this Order are done so for the purposes of this section 337
Investigation. Those terms not in dispute need not be construed. See Vanderlande Indus. Nederland
1 For convenience, the briefs and amended chart submitted by the Parties are referred to hereafter
as:
CIMB Comolainant's Initial Markman Brief
CRMB Comolainant's Reply Markman Brief
RIMB Respondents' Initial Markman Brief
Resoondents' Reply Markman Brief
SIMB Staffs Initial Markman Brief
SRMB Staffs Reply Markman Brief
JC Amended Joint Claim Construction Chart
Hr'g Tr. Markman hearing transcriptBV v. Int 'l Trade Comm 'n, 366 F.3d 1311, 1323 (Fed. Cir. 2004) (noting that the administrative law judge need only construe disputed claim terms). ID. RELEVANT LAW "An infringement analysis entails two steps. The first step is determining the meaning and scope of the patent claims asserted to be infringed. The second step is comparing the properly construed claims to the device accused of infringing." Markman v. Westview Instruments, Inc., 52 F.3d 967, 976 (Fed. Cir. 1995) (en bane) (internal citations omitted), affd, 517 U.S. 370 (1996). Claim construction is a "matter of law exclusively for the court." Id. at 970-71. "The construction of claims is simply a way of elaborating the normally terse claim language in order to understand and explain, but not to change, the scope of the claims." Embrex, Inc. v. Serv. Eng'g Corp., 216 F.3d 1343, 1347 (Fed. Cir. 2000). Claim construction focuses on the intrinsic evidence, which consists of the claims themselves, the specification, and the prosecution history. See Phillips v. AWH Corp., 415 F.3d 1303, 1314 (Fed. Cir. 2005) (en bane); see also Markman, 52 F.3d at 979. As the Federal Circuit in Phillips explained, courts must analyze each of these components to determine the "ordinary and customary meaning of a claim term" as understood by a person of ordinary skill in art at the time of the invention. 415 F.3d at 1313. "Such intrinsic evidence is the most significant source of the legally operative meaning of disputed claim language." Bell All. Network Servs. , Inc. v. Covad Commc'ns Grp., Inc., 262 F.3d 1258, 1267 (Fed. Cir. 2001). "It is a 'bedrock principle' of patent law that 'the claims of a patent define the invention to which the patentee is entitled the right to exclude."' Phillips, 415 F.3d at 1312 (quotinglnnova/Pure Water, Inc. v. Safari Water Filtration Sys. , Inc., 381 F.3d 1111, 1115 (Fed. Cir. 2004)). "Quite apart from the written description and the prosecution history, the claims themselves provide substantial guidance as to the meaning of particular claims terms." Id. at 1314; see also Interactive Gift 2
Express, Inc. v. Compuserve Inc., 256 F.3d 1323, 1331 (Fed. Cir. 2001) ("In construing claims,the
analytical focus must begin and remain centered on the language of the claims themselves, for it is
that language that the patentee chose to use to 'particularly point [] out and distinctly claim [] the
subject matter which the patentee regards as his invention."). The context in which a term is used
in an asserted claim can be "highly instructive." Phillips, 415 F.3d at 1314. Additionally, other
claims in the same patent, asserted or unasserted, may also provide guidance as to the meaning of a
claim term. Id. "Courts do not rewrite claims; instead, we give effect to the terms chosen by the
patentee." K-2 Corp. v. Salomon SA., 191 F.3d 1356, 1364 (Fed. Cir. 1999).
The specification "is always highly relevant to the claim construction analysis. Usually it is
dispositive; it is the single best guide to the meaning of a disputed term." Id. at 1315 (quoting
Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)). "[T]he specification
may reveal a special definition given to a claim term by the patentee that differs from the meaning
it would otherwise possess. In such cases, the inventor's lexicography governs." Id. at 1316. "In
other cases, the specification may reveal an intentional disclaimer, or disavowal,of claim scope by
the inventor." Id. As a general rule, however, the particular examples or embodiments discussed
in the specification are not to be read into the claims as limitations. Id. at 1323. In the end,"[t]he
construction that stays true to the claim language and most naturally aligns with the patent's
description of the invention will be ... the correct construction." Id. at 1316 (quoting Renishaw PLC
v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998)).
In addition to the claims and the specification, the prosecution history should be examined,
ifin evidence. Id. at 1317; see Liebel-Flarsheim Co. v. Medrad, Inc., 358 F.3d 898,913 (Fed. Cir.
2004). The prosecution history can "often inform the meaning of the claim language by
demonstrating how the inventor understood the invention and whether the inventor limited the
invention in the course of prosecution, making the claim scope narrower than it would otherwise
3be." Phillips, 415 F.3d at 1317; see Chimie v. PPG Indus. Inc. , 402 F.3d 1371, 1384 (Fed. Cir.
2005) ("The purpose of consulting the prosecution history in construing a claim is to exclude any
interpretation that was disclaimed during prosecution.").
When the intrinsic evidence does not establish the meaning of a claim, then extrinsic
evidence (i.e.,all evidence external to the patent and the prosecution history, including dictionaries,
inventor testimony, expert testimony, and learned treatises) may be considered. Phillips, 415 F.3d
at 1317. Extrinsic evidence is generally viewed as less reliable than the patent itself and its
prosecution history in determining how to define claim terms. Id. "The court may receive extrinsic
evidence to educate itself about the invention and the relevant technology,but the court may not use
extrinsic evidence to arrive at a claim construction that is clearly at odds with the construction
mandated by the intrinsic evidence." Elkay Mfg. Co. v. Ebco Mfg. Co., 192 F .3d 973,977 (Fed. Cir.
1999).
If, after a review of the intrinsic and extrinsic evidence, a claim term remains ambiguous,
the claim should be construed so as to maintain its validity. Phillips, 415 F.3d at 1327. Claims,
however,cannot be judicially rewritten in order to fulfill the axiom of preserving their validity. See
Rhine v. Casio, Inc., 183 F.3d 1342, 1345 (Fed. Cir. 1999). Thus,"if the only claim construction
that is consistent with the claim's language and the written description renders the claim invalid,
then the axiom does not apply and the claim is simply invalid." Id.
The construction of a claim term is generally guided by its ordinary meaning. However,
courts may deviate from the ordinary meaning when: (1) "the intrinsic evidence shows that the
patentee distinguished that term from prior art on the basis of a particular embodiment, expressly
disclaimed subject matter, or described a particular embodiment as important to the invention;" or
(2) "the patentee acted as his own lexicographer and clearly set forth a definition of the disputed
claim term in either the specification or prosecution history." Edwards Lifesciences LLC v. Cook
4Inc., 582 F.3d 1322, 1329 (Fed. Cir. 2009); see also GE Lighting Sols., LLC v. AgiLight, Inc., 750
F.3d 1304, 1309 (Fed. Cir. 2014) ("the specification and prosecution history only compel departure
from the plain meaning in two instances: lexicography and disavowal."); Omega Eng'g, Inc, v.
Raytek Corp., 334 F.3d 1314, 1324 (Fed. Cir. 2003) ("[W]here the patentee has unequivocally
disavowed a certain meaning to obtain his patent, the doctrine of prosecution disclaimer attaches
and narrows the ordinary meaning of the claim congruent with the scope of the surrender."); Rheox,
Inc. v. Entact, Inc., 276 F.3d 1319, 1325 (Fed. Cir. 2002) ("The prosecution history limits the
interpretation of claim terms so as to exclude any interpretation that was disclaimed during
prosecution."). Nevertheless, there is a "heavy presumption that a claim term carries its ordinary
and customary meaning." CCS Fitness, Inc. v. Brunswick Corp., 288 F.3d 1359, 1366 (Fed. Cir.
2002) (citations omitted). The standard for deviating from the plain and ordinary meaning is
"exacting" and requires "a clear and unmistakable disclaimer." Thorner v. Sony Computer Entm 't
Am. LLC, 669 F.3d 1362, 1366-67 (Fed. Cir. 2012); see Epistar Corp. v. Int'/ Trade Comm 'n, 566
F.3d 1321, 1334 (Fed. Cir. 2009) (requiring "expressions of manifest exclusion or restriction,
representing a clear disavowal of claim scope" to deviate from the ordinary meaning) ( citation
omitted). As the Federal Circuit has explained, "[w]e do not read limitations from the specification
into claims; we do not redefine words. Only the patentee can do that." Thorner, 669 F.3d at 1366.
A claim must also be definite. Pursuant to 35 U.S.C. § 112, second paragraph: "The
specification shall conclude with one or more claims particularly pointing out and distinctly
claiming the subject matter which the applicant regards as his invention." 35 U.S.C.§ 112, � 2. In
Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120 (2014), the Supreme Court held that§
112, � 2 requires "that a patent's claims, viewed in light of the specification and prosecution history
inform those skilled in the art about the scope of the invention with reasonable certainty." Id. at
2129. A claim is required to "provide objective boundaries for those of skill in the art," and a claim
5term is indefinite if it "might mean several different things and no informed and confident choice is
among the contending definitions." Interval Licensing LLC v. AOL, Inc. , 766 F.3d 1364, 1371 (Fed.
Cir. 2014). A patent claim that is indefinite is invalid 35 U.S.C.§ 282(b)(3)(A).
Courts are not required to construe every claim limitation of an asserted patent. See 02
Micro Intern. Ltd. v. Beyond Innovation Technology Co., 521 F.3d 1351, 1362 (Fed. Cir. 2008)
(citations omitted). Rather, "claim construction is a matter of resolution of disputed meanings and
technical scope, to clarify and when necessary to explain what the patentee covered by the claims,
for use in the determination of infringement." Id. at 1362 (quoting U.S. Surgical Corp. v. Ethicon,
Inc., 103 F.3d 1554, 1568 (Fed. Cir. 1997)); see also Embrex, 216 F.3d at 1347 ("The construction
of claims is simply a way of elaborating the normally terse claim language in order to understand
and explain, but not to change, the scope of the claims.") (citation omitted). In addition, "[a)
determination that a claim term 'needs no construction' or has the 'plain and ordinary meaning' may
be inadequate when a term has more than one 'ordinary' meaning or when reliance on a term's
'ordinary' meaning does not resolve the parties' dispute." 02 Micro, 521 F.3d at 1361. Claim
construction, however, is not an "obligatory exercise in redundancy." U.S. Surgical Corp., 103 F.3d
at 1568. "[M]erely rephrasing or paraphrasing the plain language of a claim by substituting
synonyms does not represent genuine claim construction." C.R. Bard, Inc. v. U.S. Surgical Corp.,
388 F.3d 858, 863 (Fed. Cir. 2004).
IV. LEVEL OF ORDINARY SKILL
In its opening brief, Glycosyn contends, for both asserted patents:
[A] person of ordinary skill in the art for the purposes of this case
would typically have a Ph.D in molecular biology, biochemistry, or
chemical engineering, or an equivalent field, and 1-2 years of
experience working with E. coli bacteria or related systems. Or such
a person could have a lower level degree (e.g., a M.A.) in a slmila.r
field to those listed above, but a greater amount of .relevant working
6experience ( e.g., 5-6 years of experience working with £. Coli bacteria
or related systems).
(CIMB at 17 (citing CIMB, Ex. 4 at ,r 24).)
In its opening brief, Jennewein contends, for both asserted patents:
(RlMB at 14.)
[T]he person of ordinary skill in the field of the Asserted Patents is a
person having a Ph.D. in molecular biology, biochemistry, biological
or chemical engineering, or an equivalent field, and 1-2 years of
experience working with E. coli bacteria or related systems. Or a
person having a lower level degree (e.g., a M.A.) in a similar field to
those listed above, but a greater amount of relevant working
experience ( e.g., 5-6 years of experience working with E. Coli
bacteria or related systems).
These proposed levels of skill are nearly identical, and the Staff indicates agreement with
them. (SIMB at 9.) Accordingly, the undersigned finds that one of ordinary skill in the art would
have (1) a Ph.D in molecular biology, biochemistry, or chemical engineering, or an equivalent field,
and 1-2 years of experience working with E. coli bacteria or related systems, or (2) a lower level
degree (e.g., a M.A.) in a similar field to those listed above, but a greater amount ofrelevant working
experience (e.g., 5-6 years of experience working with E. coli bacteria or related systems).
V. THE ASSERTED PATENTS
A. The '230 Patent
The '230 patent, entitled "Biosynthesis of Human Milk Oligosaccharides in Engineered
Bacteria," issued on September 27, 2016 to Massimo Merighi, John M. McCoy, and Matthew Ian
Heidtman. The '230 patent is assigned on its face to Glycosyn LLC. The '230 patent generally
relates to "compositions and methods for producing purified oligosaccharides, in particular certain
fucosylated and/or sialylated oligosaccharides that are typically found in human milk." ('230 patent
at Abstract.) In particular:
The method for producing a fucosylated oligosaccharide in a
bacterium comprises the following steps: providing a bacterium that
7comprises a functional p-galactosidase gene, an exogenous fucosyltransferase gene, a GDP-fucose synthesis pathway, and a functional lactose permease gene; culturing the bacterium in the presence of lactose; and retrieving a fucosylated oligosaccharide from the bacterium or from a culture supernatant of the bacterium. (Id. at I :48-55.) The '230 patent has 40 claims. As of the date of this order, claims 2 1 , 22, 27, 32, 34-38 are asserted in this Investigation. The asserted claims read as follows (with the first instance of the agreed-upon terms in italics and the first instance of the disputed terms highlighted in bold): 2 1 . A method for producing a fucosylated oligosaccharide in a bacterium, comprising providing an E. coli bacterium, said bacterium comprising a deletion or functional inactivation of the endogenous p-galactosidase gene; a functional exogenous wild type P galactosidase gene inserted into an endogenous gene such that the resultant bacterium comprises a low level of p-galactosidase activity, wherein said p-galactosidase activity comprises between 0.05 and 200 units; an exogenous lactose-accepting fucosyltransferase gene comprising an a.(1,2) fucosyltransferase gene, an a.(1,3) fucosyltransferase gene, or an a.(1 ,4) fucosyltransferase gene; an inactivating mutation in an endogenous colanic acid synthesis gene, wherein said colanic acid synthesis gene comprises an E. coli wcaJ, wzxC, wcaD, wza, wzb, or wzc gene; and a functional lactose permease gene, wherein said lactose permease gene comprises E. coli lacY; culturing said bacterium in the presence of lactose; and retrieving a fucosylated oligosaccharide from said bacterium or from a culture supernatant of said bacterium. 22. The method of claim 21, wherein said P-galactosidase gene inserted into an endogenous gene comprises an E. coli lacZ gene. 8
27. The method of claim 21, wherein said bacterium accumulates an increased intracellular
lactose pool, wherein said increased intracellular lactose pool is at least 10% more than the
levels in a wild type bacterium.
32. The method of claim 21, wherein said lactose permease gene is an exogenous lactose
permease gene.
34. The method of claim 21, wherein said fucosylated oligosaccharide is 2'-fucosyllactose, 3-
fucosyllactose, or lactodifucotetraose.
35. The method of claim 21, wherein said low level of P-galactosidase activity comprises
between 0.05 and 5 units.
36. The method of claim 21, wherein said low level of P-galactosidase activity comprises
between 0.05 and 4 units.
3 7. The method of claim 21, wherein said low level of p-galactosidase activity comprises
between 0.05 and 3 units.
3 8. The method of claim 21, wherein said low level of �-galactosidase activity comprises
between 0.05 and 2 units.
B. The '018 Patent
The '018 patent, entitled "Biosynthesis of Human Mille Oligosaccharides in Engineered
Bacteria," issued on May 15, 2018 to Massimo Merighi, John M. McCoy, and Matthew Ian
Heidtman. The '018 patent is assigned on its face to Glycosyn LLC, and recorded as a continuation
of continuation of a divisional application from the application which became the '230 patent.
The '018 patent generally relates to "compositions and methods for engineering bacteria to produce
fucosylated oligosaccharides, and the use thereof in the prevention or treatment of infection." ('O 18
patent at Abstract.) In particular:
9The method for producing a fucosylated oligosaccharide in a bacterium comprises the following steps: providing a bacterium that comprises a functional p-galactosidase gene, an exogenous fucosyltransferase gene, a GDP-fucose synthesis pathway, and a functional lactose perrnease gene; culturing the bacterium in the presence oflactose; and retrieving a fucosylated oligosaccharide from the bacterium or from a culture supernatant of the bacterium. (Id. at 1:53-60.) The '018 patent has 28 claims. As of the date of this order, claims 1-5, 8, 10, 12, 18, 20, 21, 23-28 are asserted in this Investigation. The asserted claims read as follows (with the first instance of the agreed-upon terms in italics and the first instance of the disputed terms highlighted in bold): 1. A method for producing a fucosylated oligosaccharide in a bacterium, comprising providing an isolated E. coli bacterium comprising, (i) a deletion or functional inactivation of an endogenous p-galactosidase gene; (ii) an exogenous functional P-galactosidase gene comprising a detectable level of p-galactosidase activity that is reduced compared to that of a wild-type E. coli bacterium, wherein the level of (i-galactosidase activity comprises between 0.05 and 200 units; (iii) an inactivating mutation in a colanic acid synthesis gene; and (iv) an exogenous lactose-accepting fucosyltransferase gene; culturing said bacterium in the presence oflactose; and retrieving a fucosylated oligosaccharide from said bacterium or from a culture supernatant of said bacterium. 2. The method of claim 1, wherein said colanic acid synthesis gene comprises an E. coli wcaJ, wzxC, wcaD, wza, wzb, or wzc gene. 3. The method of claim 2, wherein said colanic acid synthesis gene comprises a wcaJ gene. 4. The method of claim 1, wherein the bacterium comprises an increased intracellular guanosine diphosphate (GDP)-fucose level, wherein the increased intracellular GDP-fucose level is at least 10% more than the level of GDP-fucose in a wild-type bacterium. 10
5. The method of claim 1, wherein said exogenous lactose-accepting fucosyltransferase gene encodes a.(1,2) fucosyltransferase and/or a(l ,3) fucosyltransferase. 8. The method of claim 1, wherein said exogenous functional �-galactosidase gene comprises an E. coli lacZ gene. 10. The method of claim 1, wherein said bacterium further comprises a functional lactose permease gene. 12. The method of claim 10, wherein said lactose permease gene comprises an E. coli lacY gene. 18. The method of claim 1, wherein the level of p-galactosidase activity comprises between 0.05 and 5 units. 20. The method of claim 1, wherein said bacterium comprises an increased intracellular lactose level, wherein the increased intracellular lactose level is at least 10% more than the level in a wild-type bacterium. 21. The method of claim 1, wherein said exogenous functional p-galactosidase gene is an E. coli lacZ gene lacking an operably linked promoter, and said colanic acid synthesis gene comprises an E. coli weal, wzxC, wcaD, wza, wzb, or wzc gene. 23. The method of claim 1, wherein said exogenous functional p-galactosidase gene is inserted into an endogenous gene. 24. The method of claim I , wherein said exogenous functional p-galactosidase gene comprises a recombinant �-galactosidase gene engineered to produce a detectable level of � galactosidase activity that is reduced compared to the level of �-galactosidase activity in a wild-type E. coli bacterium. 25. The method of claim 24, wherein the level of p-galactosidase activity comprises between 0.05 and 5 units. 11
26. The method of claim 1, wherein the level of fl-galactosidase activity comprises between 0.05 and 4 units. 27. The method of claim 1, wherein the level of fl-galactosidase activity comprises between 0.05 and 3 units. 28. The method of claim 1, wherein the level of fl-galactosidase activity comprises between 0.05 and 2 units. VI. CLAIM CONSTRUCTION A. Construction of the Agreed-Upon Claim Terms Prior to the Markman hearing, the Parties reached agreement regarding the construction of five terms: Claim Term "providing" "in the presence of lactose" "exogeneous" "colonic acid synthesis gene" Relevant Claims '230 patent claim 2 1 '018 patent claim 1 '230 patent claim 21 '018 patent claim 1 '230 patent claims 21, 32 '018 patent claims 1, 5, 8, 21, 23, 24 '230 patent claim 21 '018 patent claims 1-3, 2 1 12 Agreed Construction A) plain and ordinary meaning: plain and ordinary meaning, i.e., furnishing, supplying, making available, or preparing. A) plain and ordinary meaning: plain and ordinary meaning, i.e., lactose is available to the bacterium A) plain and ordinary meaning: plain and ordinary meaning, i.e., originating outside an organism, tissue, or cell (BJ patentee as lexicographer: By 'colanic acid synthesis gene' is meant a gene involved in a sequence of reactions,
usually controlled and catalyzed by enzymes that result Ill the synthesis of colanic acid. "E. coli lacZ gene" '230 patent claim 22 A) plain and ordinary meaning: '01 8 patent claims 8, 21 plain and ordinary meaning, i.e., a structural gene that encodes the �-galactosidase protein and is part of the lac operon in the DNA of E. coli (JC at 4.) B. Construction of the Disputed Claim Terms 1. "P-galactosidase activity comprises between 0.05 and (200 units / 5 units / 4 units / 3 units / 2 units]" The Parties disagree on the proper claim construction and have proposed the following constructions: Relevant Glycosyn Jennewein Staff Claims '230 patent (B) patentee as INDEFINITE: (B) patentee as claims lexicographer: This term is not lexicographer & 2 1 , 35-38 �-galactosidase activity amenable to (C) disavowal of scope IS defmition with �-galactosidase activity '018 patent measurable at between reasonable is claims 1, exactly 0.05 and exactly certainty to one of measurable at between 18, 25-28 [200/5/4/3/2] Miller ordinary exactly 0.05 and exactly Units, skill in the art, and is [200/5/4/3/2] Miller as defined in Miller, therefore indefinite under Units, J.H., 35 U.S.C. 1 1 2. as defined in Miller, Experiments in In the alternative, to the J.H., Molecular extent that the Experiments in Genetics (Cold Spring Commission Molecular Harbor Lab. 1 972) at finds the term is not Genetics (Cold Spring 352-355 indefinite and requires Harbor Lab. 1 972) at construction, Respondent 352-355 proposes the following construction: (A) plain and ordinary meaning; (B) patentee as lexicoJ!rapher & 1 3
(CJ disavowal ofscope "�-galactosidase activity between exactly 0.05 and exactly [200 units/5 units/ 4 units/3 units/2 units] at substantially all times during culturing of the bacterium and retrieval of the fucosylated oligosaccharide, when measured according to the assay procedures described in J.H. Miller, "Experiment 48," Experiments in Molecular Genetics, Cold Spring Harbor, NY (1972) 352-355." (JC at 2-3.) In its opening brief, Glycosyn argues this term is not indefinite. (CIMB at 1 8.) Glycosyn explains that "P-galactosidase is an enzyme that catalyzes the cleavage of �-galactosidase (i.e., sugars such as lactose) into two parts" and is well-known in the art. (Id. (citing Prather Deel. (CIMB, Ex. 4) at ,r 34).) Glycosyn continues, "[t]he 'activity' of an enzyme is a measure of its ability to convert a certain amount of 'substrate' per unit time" (id. at 19 (citing Prather Deel. at ,r 43)) and "[o]ne of the tests that measures the activity of �-galactosidase, the 'Miller assay,' which reports activity in 'Miller units,' was developed almost 50 years ago (id. (citing CIMB, Ex. 5)). Glycosyn alleges this is "a well-described, uncomplicated procedure." (Id. (citing Prather Deel. at ,r 46).) Glycosyn then goes on to describe the details of the Miller test. (See id. at 20, 21-22.) Thus, reasons Glycosyn, a person of ordinary skill in the art reading the specification and claims of the asserted patents would understand that "units" as used in the claims refers to "Miller 14
units." (Id. at 20-21 (citing, inter alia, '230 patent at 7:26-33; '018 patent at 7:30-37).) Glycosyn
argues that modifications of the Miller test are permitted and do not take away from a person of
ordinary skill's understanding that they have performed the so-named protocol. (Id. at 22 (citing
Prather Deel. at ,r 47).) Glycosyn contends, accordingly, that "[b]oth Complainant and Respondent
have been able to perform the Miller assay on their respective cultures of bacteria that produce P
galactosidase to measure ' measurable' amounts of p-galactosidase activity." (Id. (citing CIMB, Ex.
7 at 12, 33-34, 36-37; CIMB, Ex. 8).)
With this understanding, Glycosyn argues that "P-galactosidase activity comprises between
0.005 and [200 units/5 units/4 units/3 units/2 units]" should be afforded its plain and ordinary
meaning" as defined by the specifications of the '230 and '018 patents. (Id. at 23 (citing '230 patent
at 7:26-33; '018 patent at 7:30-37).) Glycosyn criticizes Jennewein's construction for "insert[ing]
a temporal limitation that is found nowhere in the claim, specification, or prosecution history." (Id.
(citing 3M Innovative Props. Co. v. Tredegar Corp., 725 F.3d 1315, 1333 (Fed. Cir. 2013)).)
Glycosyn argues "[t]he '230 and '018 patents do not specify when the claimed p-galactosidase
activity range must be measured, or for how long the claimed range must be achieved. That is
because these parameters do not matter for purposes of the claimed invention." (Id. at 24-25
(discussing '230 patent at 5:65-6:7, 7:33-41, 9:32-44, 18:23-32; Prather Deel. ,r 50).) Rather,
according to Glycosyn:
[T]he claimed p-galactosidase activity ranges merely need be present
at times useful for the production of 2'-FL. See Prather Deel. at ,r 51.
This could be at the very beginning when the bacterium is being
constructed (for "phenotypic marking of desirable genetic loci during
construction of host cell backgrounds"); it could be later during the
fermentation of the bacteria ("for detection of cell lysis due to
undesired bacteriophage contaminations in fermentation processes");
or it could be even later at the end of the fermentation process ("for
the facile removal of undesired residual lactose at the end of
fermentations"). Id.
15(Id. at 25.) ln its reply brief, Glycosyn argues there is no merit to Jennewein's contention that "comprises," as used in the claim and in connection to the claimed numerical activity range, renders the limitation meaningless under the intrinsic evidence and settled law. (See CRMB at 2 (referring to RIMB at 15).) Glycosyn contends "as noted by Staff, the sue of the term 'comprises' in this context allows for the possibility that ' the action of the P-galactosidase enzyme may also have other, unrecited effects' beyond the claimed p-galactosidase activity between 0.05 and 200 units;" and therefore, the term is sufficiently definite. (Id. at 3 (citing Prather Deel. at ,r 50).) Glycosyn considers Jennewein's claim of indefiniteness (for failure to define when the P-galactosidase activity must be present) as the flip side of Jennewein's use of a temporal requirement in its alternate construction. (Id. (referring to RIMB at 16, 21-22).) Glycosyn argues both sides represent improper interpretations under settled law and the teachings of the specification. (Id. at 3-4 (citing, inter alia, 3M Innovative Props., 725 F.3d at 1 333; Broadcom Corp. v. Emu/ex Corp., 732 F.3d 1325, 1333 (Fed. Cir. 2013); Bell Commc'ns Research v. Vita/ink Commc'ns Corp., 5 5 F.3d 615, 622-23 (Fed. Cir. 1995); '230 patent at 7:33-41; Prather Deel. at ,r 5 1); see generally id. at 6-7.) Further, with respect to any ambiguity in how to implement the Miller test, Glycosyn highlights that principle which states "when a claim does specify a method of measurement, its omission of details about bow to implement the method will not invalidate the claim if a person of ordinary skill in the art could infer the details from industry standards or professional judgment." (Id. at 5 (citing, inter a/ia, Abbot/ GmbH & Co., KG v. Cenocor Ortho Biotech, Inc., 870 F. Supp. 2d 206, 230 (D. Mass. 2012)).) Glycosyn argues, through its expert declaration, that a person of ordinary skill could do exactly that. (Id. (citing Prather Deel. at ,r 46-47).) In its opening brief, Jennewein argues that "[t]his term fails to inform with reasonable certainty to one of ordinary skill in the art the proper scope of the claims, and is therefore indefinite 1 6
under 35 U.S.C.§ 112, if2." (RJMB at 15.) Jennewein reasons that because the range is preceded
by "comprises," an open-ended or unbounded term, "it is hopelessly unclear whether the inventors
intended that P-galactosidase activity would be limited to the claimed range, or not." (Id. at 15; see
RRMB at 2-3 ("The term comprises defines the range of p-galactosidase activity allowed, not the
action of p-galactosidase.").) Jennewein adds "the term 'activity' in the context of the claims is not
amenable to definition with reasonable certainty to one of ordinary skill in the art. Neither the
claims nor the specification define at what point this activity must be present." (R1MB at 16; see
RRMB at 4.) Jennewein explains:
Complainant apparently contends that a process falls within the scope
of the claim if there is activity in the claimed range for any amount of
time, even if only a small percentage, and that the range can be
exceeded during the remaining time. That cannot be correct. Should
activity greatly exceed 200 units during most of fermentation, 2'-FL
may not be produced. High level p-galactosidase activity is contrary
to the purpose of the invention, at least because it could destroy the
intracellular lactose pool and prevent 2'-FL production. Exh. 1, '230
Patent at 7:26-41. Furthermore, low level p-galactosidase activity is a
key distinction between the invention and the Samain patent. Exh. 9,
Confidential Deposition Transcript of John McCoy ("McCoy"), Sept.
10, 2018 at 286:1 1-291: 10. A skilled artisan therefore would not be
able to determine the claim's scope with reasonable certainty.
(RIMB at 16.) Jennewein further argues that different methods for measuring the claimed "Miller
units" "may lead to inconsistent results," causing further indefiniteness. (See id. at 17-18 (citing
Dow Chem. Co. v. Nova Chemicals Corp. (Canada), 803 F.3d 620, 630 (Fed. Cir. 2015)); see RRMB
at 4-5.) Should the undersigned not determine the term is indefinite, Jennewein argues the claimed
range must be strict in light of the prosecution history of the asserted patents (see RIMB at 18-20
(discussing RIMB, Exs. 6, 7)), must be measured using the assay procedures in Miller, and the range
must be satisfied "at substantially all times during culturing of the bacterium and retrieval of the
fucosylated oligosaccharide . . . ." (Id. at 21.) Jennewein argues this is so because:
17Should the P-galactosidase activity fall outside of this low range, one
of two failures could occur. When the activity is too high, the lactose
feedstock will be destroyed before 2'-FL is finished being
constructed. Id. at 7:33-35. But when the activity is too low, the
residual lactose in the fermentation broth will not be destroyed in the
retrieval step, rendering it impractical to retrieve 2'-FL from the
culture, particularly at a commercial scale. See id. at 33-41.
(Id. at 22; see RRMB at 7 ("If Complainant's broad interpretation is adopted, the claims would have
no limit on at what point, or for how long, p-galactosidase activity must be present during production
and purification of 2'-FL"), 8-9 (citing inventor testimony), 10 ("Complainant's construction
therefore allows activity that is contrary to the expressed purposes of the invention explained above
- producing 2'-FL and allowing its facile purification from lactose").)
Further, in its reply brief, Jennewein emphasizes that should the term not be indefinite, "units
must be measured according to the assay procedures in Miller." (RRMB at 5.) Jennewein faults
Glycosyn for "want[ing] to adopt part of the Miller assay - the method for calculating units - but
not the express description of how the assay should be performed." (Id. at 6.) Jennewein argues
"[d]uring the prosecution of the '230 patent, the patentee made clear that units of P-galactosidase
activity must be measured according to the assay procedures in Miller" (id. at 6 (citing RIMB, Ex.
6)) and so Glycosyn is now judicially estopped from arguing otherwise now (id. at 7 (citing Typhoon
Touch Techs. , Inc. v. Dell, Inc., 659 F.3d 1376, 1381 (Fed. Cir. 2011); Omega Eng'g. , Inc. v. Raytek
Corp., 334 F.3d 1314, 1323-24 (Fed. Cir. 2003)).)
In its opening brief, and with respect to indefiniteness, the Staff observes "[t]he term
'comprising' is specifically defined in the patent specification" which "simply provides that the
claimed method may include 'additional, unrecited elements or method steps."' (SIMB at 15-16
(citing '230 patent at 11:43-48); SRMB at 2-3.) The Staff argues one of ordinary skill would
understand the use of "comprises" functions to "not exclude the possibility that the action of the P
galactosidase enzyme may also have other, unrecited effects" and "would easily be able to discern
18the bounds of the invention with reasonable certainty, based on the exact numerical ranges claimed."
(Id. at 16 (citing Nautilus, 134 S. Ct. at 2124).) The Staff further disputes the propriety of imposing
a "at substantially all times . . ." requirement into the construction under the legal principle that an
accused product which sometimes, but not always, practices a claim still practices the claim. (Id. at
16-17 (citing Broadcom Corp. v. Emu/ex Corp., 732 F.3d 1 325, 1333 (Fed. Cir. 2013)).)
In its reply brief, the Staff addresses Jennewein's additional grounds for indefiniteness and
continues to disagree. Regarding the impact of "activity," the Staff faults Jennewein for "not
explain[ing] why one of ordinary skill in the art would be unable to understand what 'P-galactosidase
activity' is without first knowing when that activity occurs" primarily because the definition of
"activity" is agreed (''the process of cleaving the disaccharide lactose into glucose and galactose, as
performed by the intracellular P-galactosidase enzyme") and "does not change depending on when
the activity occurs." (Id. at 3 (citing SIMB, Ex. 7 at 343).) The Staff reasons:
If a p-galactosidase enzyme cleaves lactose at any point during a
process, then there has been "P-galactosidase activity." If that activity
is measurable at between 0.05 and 200 Miller units at any point in the
process, then at that point it is within the scope of the invention
disclosed in claim 1 of the '230 Patent and claim 1 of the '018 Patent.
See SBr. exh. 2 ('230 Patent) at 123:67; SBr. exh. 3 ('018 Patent) at
1 11:49-50. The Staff submits that one of ordinary skill in the art
would be able to discern "with reasonable certainty" whether the level
of p-galactosidase activity at any given point in a process is within the
scope of the invention. See Nautilus, Inc. v. Biosig Instruments, Inc.,
134 S. Ct. 2120, 2124 (2014).
(Id.) Regarding Jennewein's assertion that different Miller tests will produce different results, the
Staff argues "[t]he more reasonable interpretation of the text is that Miller is describing two
interchangeable variations of the Miller assay, either of which would yield the same results.
Respondent has cited no evidence that this is incorrect." (Id. at 4.) For similar reasons to those
discussed above, the Staff does not agree with any of the additional limitations Jennewein places
into its alternative proposed construction. (See id. at 5-6.) The Staff also argues Jennewein's
19construction tries to limit the scope of the invention to the most efficient embodiment of the claim, which is improper. (Id. at 6 (citing Linear Tech. Corp. v. International Trade Comm 'n, 566 F.3d 1049, 1058 (Fed. Cir. 2009); Liebel-Flarsheim Co. v. Medrad, Inc., 358 F.3d 898, 906 (Fed. Cir. 2004); RF Delaware, Inc. v. Pacific Keystone Techs., Inc., 326 F.3d 1255, 1263 (Fed. Cir. 2003)).) Upon review of the evidence, the undersigned finds Jennewein has not shown by clear and convincing evidence that the term is indefinite. In particular, Jennewein's argument that "persons of ordinary skill in the art could not know whether they infringe the claims with reasonable certainty if they had a p-galactosidase activity outside of the recited range" (RJMB at 15-16; see RIMB, Ex. 4 at ,i,r 39-41) is not persuasive. If a person of ordinary skill can know when their P-galactosidase activity falls outside of the recited range, then they can also know if that activity was within the recited range-which would exactly inform them of whether they infringe or not. Moreover, Jennewein's contention that a person of ordinary skill would not understand with reasonable certainty what the range means or how to measure it (see RIMB at 17-18; RRMB at 4-5 (discussing different methodologies of testing and "natural and man-made variations")) is undercut by Jennewein's own expert. For example, while that expert opines "Miller describes two alternative method steps to conduct the assay" and "[o]ne measurement is likely to profuse [sic] higher values on that count and other factors in the assay may act in different directions," that expert also makes predictions on the practical drawbacks of p-galactosidase activity falling above or below the claimed range with9ut reference to which technique is employed and under what conditions: 12. Should P-gaJactosidase activity not fall within the claimed range during the entire process of producing 2' -FL, several problems would anse. 13. Higher levels of P-gaJactosidase activity would destroy lactose faster than a cell could covert lactose to 2'-FL. P-gaJactosidase activity above 200 units dUiing fermentation would likely eliminate or greatly inhibit a cell's ability to produce 2'-FL. Resp. Br., Exh. 6 4/7I16 Declaration of John McCoy. 20
14. On the other hand, p-galactosidase activity below 0.05 units would likely make purification of 2 '-FL impractical, particularly at commercial scale. This is because 2' -FL and lactose are difficult to separate from each other. p-galactosidase destroys lactose that remains after 2'-FL production is complete, allowing for easier purification of2'-FL from the culture medium. Too low of a level P galactosidase activity during [sic] would therefore lose this important benefit of destroying residual lactose in the cell culture after 2'-FL syntheses was complete. (RRMB, Ex. A at ,r,r 12-14.) Further, the undersigned finds Glycosyn's expert more persuasive on this issue. Glycosyn's expert states clearly: Miller assays are conducted in hundreds of labs across the world to this day. Any person of ordinary skill in the art at the time of the invention would not only be familiar with the Miller assay, but also would be able to follow it as its methodology is very clearly described in Miller's 1972 textbook. A person of ordinary skill in the art at the time of the invention would understand that there is flexibility contained within the procedure of the Miller assay, and that scientists routinely modify procedures of assays to better fit within their research needs. (CIMB, Ex. 4 at ,r 46.) Jennewein's expert, on the other hand, paradoxically argues both of "[a] person of ordinary skill in the art understood in 2011 that certain factors can alter the data obtained using the Miller assay, which would result in incorrect readings of P-galactosidase" (RIMB, Ex. 4 at ,r 45) and "[a]n ordinary scientist would not know how the activity would change with alterations in these parameters, and could not predict if his process would infringe the claimed P galactosidase activity based on these variations" (id. at ,r 50). With respect to the timing or duration of the activity within the claimed range, the claims' failure to "specify whether the activity must remain at a low level throughout the claimed process steps of culturing and retrieving or only during part of those steps, and if so, what part of those steps" (RIMB at 16; see RRMB at 4), the undersigned does not find this results in an indefinite claim. Rather, it results in a broad claim which is met when P-galactosidase activity falls within the 2 1
claimed range at some point. This is perfectly compatible with the principle that "[a]n accused product that sometimes, but not always, embodies a claimed method nonetheless infringes." Bell Commc 'ns, 5 5 F.3d at 622-23. Turning to Jennewein's alternate construction, the undersigned declines to include "at substantially all times during culturing of the bacterium and retrieval of the fucosylated oligosaccharide" in the construction. Jennewein argues this added temporal requirement is needed to "resolv[e] the claim's ambiguity" (RRMB at 7), but as discussed above, the claim is not ambiguous as to when the claimed activity range must be met- it need only be met at some point in time. Jennewein also argues the temporal requirement is needed for the invention to have its beneficial effects (see RlMB at 22; RRMB at 8-10) but none of the patent specification excerpts cited by Jennewein for support suggest this dependency (see '230 patent at 5: 13-18, 5:47-6:8, 7:18- 41, 9:28-44, 18:19-31). Further, while Glycosyn and the Staff do not address it, the undersigned finds no reason to read "when measured according to the assay procedures described in [the Miller textbook)" into the claim. To the extent the use of this assay is implied or required when one of ordinary skill is measuring activity in Miller Units (see RRMB at 5), then it is already present through the claim's explicit recitation of Miller Units. Jennewein's argument that "[d]uring the prosecution of the '230 patent, the patentee made clear that units of P-galactosidase activity must be measured according to the assay procedures in Miller" (RRMB at 6 (emphasis added)) is completely unsupported by the prosecution history excerpt cited (RIMB, Ex. 6 at 6/4/14 Reply and Amendment at 11-12) where the patentee simply noted the assay is widely known. This was in no way a clear and unmistakable disclaimer to avoid rejection under Thorner, 669 F.3d at 1366-67. Accordingly, "P-galactosidase activity comprises between 0.05 and [200 units/ 5 units/ 4 units/ 3 units/ 2 units]" is hereby not found to be indeimite and construed as "fl-galactosidase 22
activity is measurable at between exactly 0.05 and exactly [200/5/4/3/2) Miller Units, as defined in Miller, J.H., Experiments in Molecular Genetics (Cold Spring Harbor Lab. 1972) at 352- 355." 2. "functional . . . IJ-galactosidase gene" The Parties disagree on the proper claim construction and have proposed the following constructions: Relevant Claims '230 Patent claim 21 '018 Patent claims 1, 21, 23, 24 (JC at 3.) Glycosyn (A) plain and ordinary meaning: plain and ordinary meaning, i.e., a gene involved in producing a working p-galactosidase e e. Jennewein (A) plain and ordinary meaning: plain and ordinary meaning, i.e., "a gene that encodes a full-length working - alactosidase e e" Staff (A) plain and ordinary meaning: plain and ordinary meaning, i.e., a gene that encodes a working p-galactosidase enzyme For this limitation, the Parties' constructions differ very narrowly. In its opening brief, Glycosyn explains "[i]t appears the parties all agree that a working P-galactosidase enzyme is a P galactosidase enzyme that has the ability to cleave the glycosidic bond between galactose and glucose." (CIMB at 27.) Glycosyn argues, however, that Jennewein's construction involving "full length" is improper on technical grounds because "[w]ith regard to the enzyme produced from tbe lacZ gene, 'a full-length working P-galactosidase enzyme' does not exist."' (Jd. at 28 (citing Prather Deel. at ,r 41).) Glycosyn contends the claim term is deliberately broad as to whether p-galactosidase enzyme needs to be produced by a single full-length gene or multiple genes and "[t]here is nothing in the patents that places any significance on having a single gene produce a 'full-length' P galactosidase enzyme, and nothing in the patent that expressly limits the 'functional . . . P galactosidase gene' to a single 'full-length' gene." (Id. at 28.) Further, Glycosyn contends "[a] person of ordinary skill in the art at the time of the invention would have readily understood that 23
this low-level p-galactosidase activity could have been equally achieved by inserting a full-length
lacZ gene, or by inserting complementary lacZa or lacZQ P-galactosidase genes. (Id. at 28-29
(citing Prather Deel. at 1 38-42).)
Essentially, according to Glycosyn, "[t]he claims are not even limited to lacZ, but instead
include any p-galactosidase gene (of which lacZ is the [sic] only one type)." (Id. at 29.) Glycosyn
argues this is shown through principles of claim differentiation, where lacZ is expressly claimed in
other dependent claims as the recited "P-galactosidase gene." (See id. (citing Phillips, 415 F.3d at
1314-1315); see also CR.MB at 9-10 ("if the dependent claim term 'E. coli lacZ gene' means 'E.
coli lacZ gene that encodes a full-length enzyme,' as Respondent suggests, then the independent
claim would necessarily be broader and would not contain the additional 'full length' limitation."))
With this understanding, Glycosyn adds that there is no meaningful dif ference between its
construction and the Staffs and "the term 'encoding' is just another way of saying 'involved in
producing.'" (CIMB at 30 (citing CIMB, Ex. 4 at 1 33).)
In its reply brief, Glycosyn argues that Jennewein's arguments on whether a fragment of a
P-galactosidase gene can be considered a "functional" gene are belied by Jennewein's technical
documents. (See CR.MB at 8 (citing CR.MB, Ex. 15 at 16967).) Glycosyn argues one such document
is "far better evidence of what a person of ordinary skill in the art would have understood was meant
by a 'functional gene' than any litigation-inspired constructions presented by Jennewein now." (/d. )
Lastly, Glycosyn argues that the specification's identification of only "full-length" p-galactosidase
genes (lacZ and lac4) cannot limit the claims as that would be improper act of limiting the claims
to the specification (see id. at 10 (citing Phillips, 415 F. 3d at 1323)); and, contrary to Staffs
argument, it is not true that the only way to obtain a working enzyme is to encode a "full-length"
enzyme. (See id. at 10-1 1 (discussing SIMB at 18-19).) Glycosyn suggests the Staff confuses the
claim term "functional" as describing the enzyme as opposed to the gene. (Id. at 11.)
24In its opening brief, Jennewein identifies the issue as "whether a proper construction should [] clarify that the p-galactosidase gene must 'encode' a 'full-length' working enzyme." (RIMB at 23.) Jennewein argues the claims themselves and the patents' specifications plainly answer this question in the affirmative. (Id. ; see id. at 24 (discussing '230 patent at els. 2, 22; '018 patent at els. 8, 24).) Jennewein also points to its expert's declaration to support "a P-galactosidase gene would be understood by those of ordinary skill in the art to encode for the full-length P-galactosidase protein from its start codon to the termination codon, and would not encode merely a fragment of it. . . . A skilled artisan intending to cover a gene fragment would not have used use [sic] the word 'gene' alone. Instead the skilled artisan would have used 'fragment' or its equivalent to describe the gene." (Id. at 24 (citing RIMB, Ex. 4 at ,r 26-28).) Jennewein adds that "[t]he specification of the Asserted Patents teaches only two specific P-galactosidase genes, lacZ and lac4, both of which encode a full-length, working p-galactosidase in a different species of bacteria (E. coli and K. lactis, respectively)." (Id. at 25 (citing '230 patent at 2:65-67, 7:34-35).) On technical grounds, Jennewein explains: However, a fragment of the p-galactosidase gene does not encode the p -galactosidase enzyme, but rather only a fragment of the P galactosidase enzyme. Moreover, a "functional p-galactosidase gene" must encode a functional P-galactosidase enzyme, i.e. a "working P galactosidase enzyme," as the parties agree. In contrast, a gene that does not encode a working P-galactosidase enzyme-for example a fragment of a P-galactosidase gene that encodes only a non-working fragment of the enzyme-would not be a "functional P-galactosidase gene." Ex. 4, Stephanopoulos at ,r,r 26-28. (Id. at 23.) Jennewein also explains, with respect to the fragments associated with the technique known as alpha complementation: When expressed separately, each fragment produces a portion of the Lacz protein, but neither portion has p-galactosidase activity alone. Id. When lacZa and lacZw are simultaneously expressed in the san1e cell, their portions of the Lacz protein assemble into one of the four subunits of the Lacz P-galactosidase enzyme. Id. Assembly with the 25
remaining three subunits into a homotetramer results in a functional �-galactosidase enzyme that has �-galactosidase activity. Id (RRMB at 12-13.) Further, in its reply brief, Jennewein argues "[t]here is no support in the intrinsic evidence for Complainant's tortured reading of the claim language" and agrees with the Staff that Glycosyn's construction creates new ambiguities. (RRMB at 10 (citing SIMB at 18).) Jennewein generally disputes that a gene "involved in producing," as in Glycosyn's construction, is interchangeable with a gene that "encodes." (See id at 11-12 (citing, inter alia, RRMB, Ex. [A] at 11 6-7; RRMB, Ex. D at 257-258).) Jennewein also alleges it is improper for Glycosyn to rely on Jennewein's accused process to define the claim term. (See id at 13-14 (citing NeoMagic Corp. v. Trident Microsystems, Inc., 287 F.3d 1062, 1074 (Fed. Cir. 2002)).) With that said, Jennewein finds the Staff's construction amenable in light of the Staff's argument that the term "functional . . . p-galactosidase gene" would not be met by a gene that produces that enzyme only when another undefined gene or gene segment is simultaneously produced. (See id. at 11.) In its opening brief, the Staff understands Glycosyn's construction to cover "any gene that is involved in producing such an enzyme, even if the gene can only do so in conjunction with other genes." (SIMB at 17.) The Staff argues this presents problems for partial genes and whether they are "functional" or not, as "[i]nfringement would depend on the presence or absence of 'other segments' that are not identified anywhere in the claim language, in the specification, or in the prosecution history." (Id. at 18; SRMB at 10.) On the other hand, the Staff finds Jennewein's construction acceptable except for the "full-length" tenn. (See SIMB at 18-19.) The Staff summarizes, "what is important in the context of the asserted patents is whether the gene in question encodes an enzyme that successfully performs its function." (Id. at 19.) 26
In its reply brief, the Staff argues the claim language "a functional promoter-less P
galactosidase gene inserted into an endogenous gene such that the resultant bacterium comprises a
low level of p-galactosidase activity," when read in context, "indicates that the P-galactosidase gene
must be fully 'functional' at the time it is inserted into an endogenous gene." (SRMB at 8.) This,
according to the Staff, contradicts Glycosyn's construction. (Id )
Upon review of the evidence, the undersigned frrst emphasizes that claim terms are not to
be construed in light of the accused device. "[T]his court has repeatedly stated that a court must
construe claims without considering the implications of covering a particular product or process."
SmithKline Beecham Corp. v. Apotex Corp., 703 F.3d 1331, 1339 (Fed. Cir. 2005) (citing
NeoMagic., 287 F.3d at 1074 ("It is well settled that claims may not be construed by reference to
the accused device.")); SRI Int'! v. Matsushita Elec. Corp. ofAm., 775 F.2d l 107, 1118 (Fed. Cir.
1985) ("It is only after the claims have been construed without reference to the accused device that
the claims, as so construed, are applied to the accused device to determine infringement.")
Much of the parties' briefing involves argument over whether a technique known as "u
cornplementation" would fall under the scope of this term. (See CIMB at 26-27, 28-29; CRMB at
7-9, 10 ("There is no dispute that Respondent's E. coli strain produces a working P-galactosidase
enzyme."), 11; RIMB at 24; RRMB at 12-14 (citing NeoMagic, 287 F.3d at 1074); SRMB at 7-1 0.)
This technique is not discussed in the asserted patents. (See generally '230 patent; 'O 18 patent.)
Rather, it became clear at the Markman hearing, on the public record, that a-complementation is
related to Jennewein's accused products in this Investigation. (See, e.g., Hr' g Tr. at 64:5-19, 65: 10-
17, 69:4-10 ("this then means that there is no infringement of any claims of the asserted patents . . .
. ").)
27Thus, the undersigned finds that briefing and argument which concerns whether or not a
complementation falls within the scope of or is covered by "functional . . . P-galactosidase gene" is
not persuasive.
Moving on, the Parties' primary dispute is whether a "functional . . . P-galactosidase gene"
can be any gene that is involved in the production of the p-galactosidase enzyme, as in Glycosyn's
construction, or whether it must be a gene that encodes that enzyme, as in the Jennewein and the
Staff's. Jennewein's construction also uses the term "full-length" to describe a functional enzyme
(see, e.g., RIMB at 25 ("A P-galactosidase enzyme would not be functional unless it is full-length
or substantially full-length, for only those contain enough of the P-galactosidase structure that is
responsible for producing enzymatic activity.")), but the undersigned finds this descriptor is
misplaced given the term to be construed is "functional . . . P-galactosidase gene" and not "functional
P-galactosidase enzyme." Indeed, Jennewein acknowledges that "full-length" is not critical to its
proposed construction. (See RIMB at 27 (noting "full-length" is implicit in the Staff's construction
which omits "full-length.").)
The undersigned finds Jennewein and the Staffs construction more persuasive. The asserted
patents do not specifically explain what is meant when the modifier "P-galactosidase" is placed
before the word "gene," which is what the present dispute turns on. Thus, consideration of extrinsic
evidence is appropriate; and the Parties' experts' explanations of "gene" resolves the issue.
Glycosyn's expert explains "[a] gene is a sequence of DNA that contains the molecular
'code' for producing functional biological molecules, such as proteins." (CIMB, Ex. 4 at ,r 32.)
Jennewein's expert similarly explains, "[w]hen ordinary scientists read the term 'gene,' they think
of the nucleotide (DNA) sequence encoding the amino acid sequence of the an entire protein."
(RIMB, Ex. 4 at ,r 26.) These explanations are consistent and are hereby adopted. Further consistent
are both of Glycoysn's and Jennewein's constructions in their interpretation of "P-galactosidase" in
28"P-galactosidase gene" to mean the creation or production of the enzyme P-galactosidase. Additionally, no party contends that anything other than the plain and ordinary meaning should apply to this term. (See, e.g., CIMB at 25 (table).) Thus, in light of the experts' statements and the parties' constructions, the undersigned finds the plain and ordinary meaning of "functional . . . P-galactosidase gene" is simply "a functional sequence of DNA that encodes p-galactosidase." While Glycosyn's expert also states "to say that a gene 'encodes' a working enzyme is to say that it is 'involved in producing' a working enzyme" (id., Ex. 4 at 1 33), Jennewein's expert squarely takes the opposition position, "[o]rdinary scientists generally do not describe a gene as merely being 'involved' in producing a protein like p-galactosidase. They normally say a gene 'encodes' P-galactosidase" (RIMB, Ex. 4 at 1 25). The undersigned finds Jennewein's expert more persuasive in light of the very particular and detailed nature of this art, and notes that Glycosyn provides no other evidence beyond its expert's opinion to support its "involved in producing" interpretation. Accordingly, "functional . . . p-galactosidase gene" is hereby construed as "a functional sequence of DNA that encodes �-galactosidase." 3. "wild type" The Parties disagree on the proper claim construction and have proposed the following constructions: Relevant Glycosyn Jennewein Staff Claims '230 Patent (A) plain and ordinary (A) plain and ordinary (A) plain and ordinary claims 21, 27 meaning: meaning: meaning: plain and ordinary plain and ordinary plain and ordinary '018 Patent meaning, i.e., the meaning, i.e., "the form meaning, i.e., the claims 1, phenotype most most commonly found in phenotype most 4, 20, 24 commonly found in nature" commonly found in nature nature 29
(JC at 3-4.) For this limitation, the Parties' dispute is also narrow. Glycosyn argues "[t]hroughout the claims and the specification, the term 'wild type' is used to compare observable traits of the E. coli organism as compared to the modified E. coli organism described in the claims." (CIMB at 34-35 (citing '230 patent at els. 2, 8, 21, 27; '0 18 patent at els. 1, 4, 20, 24); see id at 35 (citing '230 patent at 5:6-18, 6:42-46, 16:43-49; '018 patent at 5:6-18, 6:42-46, 16:43-49).) Glycosyn reasons: The picture is clear: every time the term "wild type" is used in the patent claims, it is used in relation to observable traits of the E. coli organism. Such observable traits are referred to by persons of ordinary kill [sic] in the art as "phenotype." They are not a "form," as Respondent contends. (Id. at 35.) Glycosyn argues it and the Staffs proposed construction "comports with how a person of ordinary skill in the art would understand the term 'wild type' at the time of the invention. . . . This also aligns with dictionaries commonly used by people of ordinary skill in the art in question at the time of the invention." (Id. at 35-36 (citing Prather Deel. at � 36; CIMB, Ex. 13 at 68993- 68997).) In its reply brief, Glycosyn contends Jennewein admits "phenotype is defined in term of observable traits or observable characteristics" and "wild-type is used in the patents to describe a phenotype." (CRMB at 14 (citing RIMB at 31).) To the extent Jennewein argues the existence of "wild-type" genotypes, in addition to phenotypes, Glycosyn urges the use of "form" in Jennewein's construction "does not capture this" and "adds complexity and confusion, and leaves the definition of wild-type less apparent and subject to further interpretation." (Id.) In its opening brief, Jennewein highlights that '" [w]ild-type' appears in two contexts in the Asserted Patents: 'wild-type gene' and 'wild-type bacterium"' and argues its own construction "embraces the clear, plain meaning in both contexts: the form most commonly found in nature." (RIMB at 29-30.) Jennewein points out the '230 patent's recitation of both phenotype and genotype (id. at 30 (citing '230 patent at 18: 19-23)) and extrinsic textbook evidence that defines "phenotype" 30
as "distinct from its genotype" (id. (citing RIMB, Ex. 10 at 08, G-13)). Jennewein swnmarizes, "[g]enes have both a phenotype and a genotype, and there is no reason to include one and exclude the other from the plain meaning of 'wild-type"' and a person of ordinary skill would understand "wild-type" is not limited to phenotype of a gene. (Id. (citing RI.MB, Ex. 11 at 977, 1232; RIMB, Ex. I O at 342).) Regarding a phenotype as an "observable" characteristic or trait, Jennewein contends "[a] gene would not have an 'observable' trait or characteristic-that would be the gene's product, not the gene itself." (Id. at 3 1 (citation omitted).) Further, Jennewein reasons "[a]lthough a wild-type bacterium could have the same phenotype as a genetically engineered bacterium, in that case the bacterium would no longer be considered a 'wild type."' (Id. (citing RIMB, Ex. 4 at ,r 56).) Thus, Jennewein explains, "[t]he term 'wild-type' qualifies the thing that appears after it-here, either or a gene or bacteria" and "neither a 'gene' nor a 'bacteria' is a phenotype, and the claim needs no such additional requirement." (Id. at 32.) In its reply brief, Jennewein asserts "[t]he parties agree that a ' wild-type' is the form as it exists in nature. A key aspect of this natural state of 'wild-type' is that it is unchanged by man." (RRMB at 18 (citing RIMB, Ex. 4 at ,r,r 55-56; CIMB, Ex. 13); see id. at 20-21 (citing SIMB, Ex. 10 at 2370).) Jennewein contends the construction from Glycosyn and the Staff "eliminates this 'natural' aspect of 'wild-type' and would include man-made mutants." (Id. at 18-19.) Jennewein continues to add that discussions in the patent specifications of "levels of activity in a wild-type gene or bacterium does not mean that the gene or bacterium is limited to its phenotype" (id. at 19 (citing RRMB, Ex. A at ,r 18)) and "[n]either the claims nor the specification define a wild-type gene as being synonymous with wild-type activity" (id.). In its opening brief, the Staff points to extrinsic dictionary evidence which defines "wild type" as a phenotype, and other extrinsic dictionary evidence which defines the same as a genotype 31
or phenotype. (S1MB at 22 (discussing SIMB, Exs. 10, 11).) The Staff explains it prefers using
"phenotype," as in Glycosyn's construction, over "form/' as in Jennewein's construction, because
"it is a slightly more accurate reflection of the manner in which the term 'wild-type' is used in the
asserted patents." (Id. at 22-23.) The Staff reasons:
Both patents are focused on the behavior of the engineered organisms,
specifically on their ability to produce human milk oligosaccharides
such as 2'-FL, rather than on the specific molecular makeup of the
organisms' genetic structure. In other words, they are focused on the
modified E. coli bacterium's phenotype rather than its genotype. The
Staffs proposed construction reflects this fact.
(Id. at 23 (emphasis in original).) In its reply brief, the Staff repeats "the focus of both asserted
patents is on the behavior of the engineered organism, specifically on its ability to produce human
milk oligosaccharides such as 2'-FL, as well as the effect of the behavior of the specific facZ gene
on the organism's ability to produce 2'-FL." (SRMB at 15 (emphasis in original).) The Staff
continues, "(a)ny genotype of a functional promoter-less p-galactosidase gene will do, so long as it
has the effect of causing a low level of P-galactosidase activity. In other words, it is the effect of
the gene on the bacterium, and not its physical structure, that is important." (Id. ) Thus, the Staff
concludes phenotype is the proper interpretation of "wild-type." (Id. at 16.) The Staff also faults
Jennewein's comparison of phenotypes between man-made and wild organisms as unsupported by
Jennewein's cited expert declaration. (See SRMB at 16-17 (discussing RIMB, Ex. 4 at ,r,r 56, 58).)
Upon review of the evidence, the undersigned finds Jennewein's construction is more
accurate. The claims of a patent are the starting point for claim construction. Interactive Gift
Express, 256 F.3d at 1331. The claims of the asserted patents use "wild type'' or "wild-type" as
descriptors in two distinct contexts-for both a gene (see '230 patent at els. 2, 5, 21, 24) and for a
bacterium as a whole (see '230 patent at els. 8, 27; '018 patent at els. 1, 4, 20, 24). More specifically,
"wild type" is used in the context of a gene which is inserted into another gene ('230 patent at els.
322, 5, 21, 24) and then also in the context of comparing observable traits between two bacteria ('230
patent at els. 8, 27; '018 patent at els. 1 , 4, 20, 24.)
Jennewein's construction is consistent with both of these contexts-the "wild type" gene or
bacterium is the "form" or "type" of the gene or bacterium "most commonly found in nature." It is
this type of the gene which is inserted into another gene (see '230 patent at els. 2, 5, 21, 24) and the
type of bacteria which is compared to the bacterium of the invention (see '230 patent at els. 8,
27; '018 patent at els. 1, 4, 20, 24). Jennewein's construction is further consistent with those portions
of the patent specification which refer to "wild-type" in the contexts of a "coding sequence"
(see '230 patent at 12:64-67 ("DNA fragment carrying . . . a wild-type E. coli lacZ+ coding
sequence")) and "wild-type copy of the lacZ (p-galactosidase) gene" (id at 16:43-47) or "supplying
a wild-type thyA gene" (id at 16:63-65).
Glycosyn and the Staff's construction, interpreting "wild-type" as a "phenotype" is arguably
consistent in the context of comparing organisms with observable traits, but not in the gene context
where there is no observable trait, or "phenotype" under comparison as, for example, in the
following claims:
2. The method of claim 1, wherein the functional promoter-less P
galactosidase gene inserted into an endogenous gene comprises an
exogenous wild type E. coli lacZ gene.
5. The method of claim 1. , wherein said bacterium comprises a
functional promoter-less wild-type E. coli lacz+gene inserted into an
endogenous Ion gene.
24. The method of claim 21, wherein said bacterium comprises a
functional, wild-type, promoter-Jess E. coli lacz+gene inserted into an
endogenous Ion gene.
('230 patent at els. 2, 5, 24.)
Every claim term is presumed to have meaning. Innova/Pure Water, 381 F.3d at 1119
("While not an absolute rule, all claim terms are presumed to have meaning in a claim."). To have
33meaning in these claims, "wild type" must refer to something other than "phenotype." Glycosyn
and the Staff's construction is thus too narrow. Indeed, as demonstrated by these claims, Glycosyn
is incorrect when it argues "[t]he picture is clear: every time the term 'wild type' is used in the patent
claims, it is used in relation to observable traits of the E. coli organism." (CIMB at 35.)
Further, the balance of the extrinsic evidence supports Jennewein's broad construction.
While the dictionary definition cited by Glycosyn does link "wild type" to phenotype, it does so in
the context of a "wild type" as a "member[] of a species." (CIMB, Ex. 13.) Genes are not members
of a species and as noted above, the asserted patents use "wild type" in the contexts of both overall
organisms and genes themselves. Glycosyn's definition, is therefore oflesser probative value. The
Staff's cited dictionary definition linking "wild-type" to phenotype is of similar little value as it too
is in the context of a member of a species-"the phenotype that is characteristic of most of the
members of the species occurring naturally and contrasting with the phenotype of a mutant." (SIME,
Ex. 11.) The Staff's rationale for including "phenotype" in its construction likewise comes from
the viewpoint of the overall organism. (See, e.g., SIMB at 23 ("In other words, [the patents] are
focused on the modified E. coli bacterium's phenotype rather than its genotype. The Staffs
proposed construction reflects this fact."); SRMB at 15 ("the Staff maintains that the focus of both
asserted patents is on the behavior of the engineered organism . . . .")).
On the other band, the Staff's second cited dictionary definition defines "wild type" in the
proper context-that of genetic material-and states "the standard gene, or the standard genotype
or phenotype of an individual, that is found in a wild or natural population [or] a form that is
arbitrarily designated as such." (SIMB, Ex. 10.) Jennewein's cited dictionary definitions also define
"wild type" in the proper context. A fil'st definition defines "wild-type gene" as "the form of a gene
[allele] normally found in nature" (RIMB, Ex. 11 at 977, 1232) and second definition states "the
34' normal, norunutant form of a macromolecule, cell or organism"' (RIMB, Ex. 1 0 at 342 (emphasis added)). Thus, the undersigned finds those dictionary definitions directed to "wild type" genes, or other macromolecules, to be of higher probative value than those directed to "wild type" organisms. As those gene-specific definitions do not link "wild type" to phenotype, a construction not limited to phenotype is warranted. Regarding expert testimony as extrinsic evidence, the undersigned finds Glycosyn's expert to be completely conclusory on this issue, stating only "[a] person of ordinary skill in the art at the time of the invention would understand that 'wild type' as used in the claims and specifications of the Asserted Patents refers to the phenotype most commonly found in nature." (CIMB, Ex. 4 at ,r 36.) Jennewein's expert provides a more persuasive and reasoned justification for his opinion to the contrary. (See RIMB, Ex. 4 at ,r,r 55-66; RRMB, Ex. A at ,r,r 16-19.) The undersigned also finds, however, no particular reason to use the word "form" in place of ''type" as in Jennewein's construction either. Accordingly, "wild-type" or "wild type" is hereby simply construed as "the type most commonly found in nature." SO ORDERED. Chief Administrative Law Judge 35
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND METHODS OF PRODUCING THE SAME INV. NO. 337-TA-1120 PUBLIC CERTIFICATE OF SERVICE I, Lisa R. Barton, hereby certify that the attached Order No. 22 has been served by hand upon the Commission Invest�ative aiti111ley, Lisa Murray, Esq. and the following parties as indicated, on DE1.; 1 8 ZUla FOR COMPLAINANT GLYCOSYN LLC Michael C. Newman, Esq. MINTZ LEVIN COHN FERRIS GLOVSKY AND POPE O PC One Financial Center Boston, MA. 021 1 1 � � � Lisa R. Barton, Secretary U.S. International Trade Commission 500 E Street SW, Room 1 1 2A Washington, D.C. 20436 ( ) Via Hand Delivery ( ) Express Delivery ( V, Via First Class Mail ( ) Other: FOR RESPONDENT JENNEWEIN BIOTECHNOLOGIE GmbH Gary M. Hnath, Esq. ( ) Via Hand Delivery MAYER BROWN, LLP ( ) Express Delivery 1 999 K Street, NW ( v(Via First Class Mail Washington, DC 20006 ( ) Other:
2 printed pages contain little extracted OCR body text; searchable legal-body completeness has not been established for those pages.
OCR transcription for search; preserved printed pages are authoritative
In the Matter of
CERTAIN HUMAN MILK
OLIGOSACCHARIDES AND METHODS OF
PRODUCING THE SAME
337-TA-1120
Publication 5254 February 2022
U.S. International Trade Commission
Washington, DC 20436
U.S. International Trade Commission
COMMISSIONERS
David S. Johanson, Chairman
Rhonda K. Schmidtlein, Commissioner
Jason E. Kearns, Commissioner
Randolph J. Stayin, Commissioner
Amy A. Karpel, Commissioner
Address all communications to
Secretary to the Commission
United States International Trade Commission
Washington, DC 20436
U.S. International Trade Commission
Washington, DC 20436
www.usitc.gov
Publication 5254 February 2022
In the Matter of
337-TA-1120
CERTAIN HUMAN MILK
OLIGOSACCHARIDES AND METHODS OF
PRODUCING THE SAME
1
UNITED STATES INTERNATIONAL TRADE COMMISSION
Washington, D.C.
In the Matter of
CERTAIN HUMAN MILK
OLIGOSACCHARIDES AND METHODS
OF PRODUCING THE SAME
Inv. No. 337-TA-1120
COMMISSION ORDER
On May 19, 2020, the Commission issued a final determination finding a violation of
section 337 of the Tariff Act of 1930, as amended (19 U.S.C. § 1337) (“section 337”), based on
the importation into the United States, the sale for importation, and the sale within the United
States after importation of certain bacterial strains and 2’-fucosyllactose oligosaccharides
produced therefrom that infringe certain claims of U.S. Patent No. 9,970,018 (“the ’018 patent”).
See 85 Fed. Reg. 31549 (May 26, 2020); see also 83 Fed. Reg. 28865 (June 21, 2018) (defining
the scope of the investigation as “2’-fucosyllactose oligosaccharides”). The Commission also
adjudicated infringement with respect to a TTFL12 bacterial strain imported by the named
respondent and determined that it does not infringe the ’018 patent. See id. The Commission
issued a limited exclusion order (“LEO”) barring entry of 2’-fucosyllactose (“2’-FL”)
oligosaccharides that infringe the asserted patent claims but also including an explicit carve-out
for 2’-fucosyllactose oligosaccharides made with the non-infringing TTFL12 bacterial strain.
On June 2, 2020, complainant Glycosyn LLC (“Glycosyn”) filed a petition for
Commission reconsideration of part III(B) of the Commission Opinion (i.e., “Adjudication of
Infringement with Respect to the TTFL12 Strain”). Having considered Glycosyn’s petition, the
responses thereto, and the record in this investigation, the Commission has determined to deny
Glycosyn’s petition for reconsideration.
2
I. BACKGROUND
A. Procedural Background
The Commission instituted this investigation on June 21, 2018, based on a complaint, as
amended and supplemented, filed by Glycosyn of Waltham, Massachusetts. See 83 Fed. Reg.
28865 (June 21, 2018). The complaint alleged violations of section 337 based upon the
importation into the United States, the sale for importation, and the sale within the United States
after importation of certain human milk oligosaccharides, by reason of infringement of certain
claims of U.S. Patent No. 9,453,230 (“the ’230 patent”) and the ’018 patent. See id. The notice
of investigation named Jennewein of Rheinbreitbach, Germany as respondent in this
investigation. See id. The Office of Unfair Import Investigations was also a party to this
investigation. See id.
The Commission partially terminated the investigation as to certain claims of the ’018
patent and all asserted claims of the ’230 patent based on the withdrawal of the allegations
pertaining to those patent claims. See Order No. 5 (Aug. 9, 2018), unreviewed, Comm’n Notice
(Aug. 29, 2018); Order No. 15 (Oct. 30, 2018), unreviewed, Comm’n Notice (Nov. 29, 2018);
Order No. 17 (Nov. 19, 2018), unreviewed, Comm’n Notice (Dec. 12, 2018); Order No. 25 (Feb.
8, 2019), unreviewed, Comm’n Notice (Feb. 28, 2019). Claims 1-3, 5, 8, 10, 12, 18, and 23-28
of the ’018 patent remained pending in this investigation.
On September 9, 2019, the administrative law judge (“ALJ”) issued a final initial
determination (“FID”) finding a violation of section 337 based on the infringement of claims 1-3,
5, 8, 10, 12, 18, and 24-28, but not claim 23 of the ’018 patent based on non-infringement of that
claim. See FID at 35. On May 19, 2020, the Commission affirmed the FID’s finding of
infringement and issued a final determination finding a violation by certain bacterial strains.
3
See 85 Fed. Reg. 31549 (May 26, 2020). In particular, the Commission reversed the FID’s
decision not to adjudicate the TTFL12 bacterial strain and determined that it does not infringe
any of the asserted claims. See id. The Commission issued an LEO barring entry of 2’-FL
oligosaccharides that infringe the Asserted Claims but also including an explicit carve-out for 2’-
FL oligosaccharides made with the non-infringing TTFL12 bacterial strain.1 The Commission
also set a bond in the amount of five (5) percent of the entered value of Jennewein’s 2’-FL
product during the period of Presidential review.
On June 2, 2020, pursuant to Commission Rule 210.47 (19 C.F.R. § 210.47), Glycosyn
petitioned for reconsideration of part III(B) of the Commission Opinion (i.e., “Adjudication of
Infringement with Respect to the TTFL12 Strain”).2 On June 8 and 9, 2020, respectively,
Jennewein and the Commission’s Investigative Attorney opposed Glycosyn’s petition.3
II. STANDARD FOR RECONSIDERATION
Commission Rule 210.47 governs petitions for reconsideration and provides that:
Within 14 days after service of a Commission determination, any
party may file with the Commission a petition for reconsideration of
such determination or any action ordered to be taken thereunder,
setting forth the relief desired and the grounds in support thereof.
Any petition filed under this section must be confined to new
questions raised by the determination or action ordered to be taken
thereunder and upon which the petitioner had no opportunity to
submit arguments. . . .
See 19 C.F.R. § 210.47.
1 Complainant did not request, and the Commission did not issue, a cease and desist order.
2 See Complainant Glycosyn LLC’s Petition for Reconsideration of Part III(B) of the
Commission Opinion (June 2, 2020).
3 See Respondent Jennewein Biotechnologie GmbH’s Opposition to Complainant Glycosyn
LLC’s Petition for Reconsideration of Part III(B) of the Commission Opinion (June 8, 2020);
Response of the Office of Unfair Import Investigations to Complainant’s Petition for
Reconsideration of Part III(B) of the Commission Opinion (June 9, 2020).
4
III. DISCUSSION
Glycosyn’s petition for reconsideration does not identify new questions raised by the ALJ’s FID
or the Commission’s final determination or present arguments that Glycosyn did not have the
opportunity to address in previous filings before either the ALJ or the Commission. As such,
the Commission has determined that Glycosyn’s petition for reconsideration does not satisfy the
requirements of Commission Rule 210.47.4
IV. CONCLUSION
Accordingly, upon consideration of the record and the submissions in this matter, the
Commission hereby ORDERS that:
1. Glycosyn’s petition for reconsideration is DENIED.
2. The Secretary will serve this Order on all parties to the investigation.
By order of the Commission.
Lisa R. Barton
Secretary to the Commission
Issued: October 1, 2020
4 Commissioner Schmidtlein respectfully dissents. In light of the particular facts (including the
new evidence cited by Glycosyn in its petition for reconsideration) and the procedural history of
this investigation, and given the rationale provided in her dissent, in her view, Glycosyn’s
petition should be granted and Part III(B) of the majority’s opinion should be reconsidered.
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND
METHODS OF PRODUCING THE SAME
Inv. No. 337-TA-1120
PUBLIC CERTIFICATE OF SERVICE
I, Lisa R. Barton, hereby certify that the attached COMMISSION ORDER has
been served via EDIS upon the Commission Investigative Attorney, Lisa Murray, Esq., and
the following parties as indicated, on October 1, 2020
Lisa R. Barton, Secretary
U.S. International Trade Commission
500 E Street, SW, Room 112
Washington, DC 20436
On Behalf of Complainant Glycosyn LLC:
Michael C. Newman, Esq.
MINTZ LEVIN COHN FERRIS GLOVSKY AND POPEO, PC
1 Financial Center
Boston, MA 02111
Email: MCNewman@mintz.com
☐ Via Hand Delivery
☐ Via Express Delivery
☐ Via First Class Mail
☒ Other: Email Notification
of Availability to Download
On Behalf of Respondent Jennewein Biotechnologie GmbH:
Gary M. Hnath
MAYER BROWN LLP
1999 K Street, NW
Washington, DC 20006
Email: ghnath@mayerbrown.com
☐ Via Hand Delivery
☐ Via Express Delivery
☐ Via First Class Mail
☒ Other: Email Notification
of Availability to Download
1
UNITED STATES INTERNATIONAL TRADE COMMISSION
Washington, D.C.
In the Matter of
CERTAIN HUMAN MILK
OLIGOSACCHARIDES AND
METHODS OF PRODUCING
THE SAME
Investigation No. 337-TA-1120
NOTICE OF COMMISSION FINAL DETERMINATION FINDING
A VIOLATION OF SECTION 337; ISSUANCE OF A LIMITED EXCLUSION
ORDER; TERMINATION OF THE INVESTIGATION
AGENCY: U.S. International Trade Commission.
ACTION: Notice.
SUMMARY: Notice is hereby given that the U.S. International Trade Commission has found a
violation of section 337 of the Tariff Act of 1930 (“section 337”), as amended, in this
investigation. The Commission has issued a limited exclusion order (“LEO”) prohibiting the
importation by respondent Jennewein Biotechnologie GmbH (“Jennewein”) of Rheinbreitbach,
Germany of certain human milk oligosaccharides that infringe complainant’s asserted claims.
The investigation is terminated.
FOR FURTHER INFORMATION CONTACT: Houda Morad, Office of the General
Counsel, U.S. International Trade Commission, 500 E Street SW., Washington, DC 20436,
telephone (202) 708-4716. Copies of non-confidential documents filed in connection with this
investigation are or will be available for inspection during official business hours (8:45 a.m. to
5:15 p.m.) in the Office of the Secretary, U.S. International Trade Commission, 500 E Street
SW., Washington, D.C. 20436, telephone (202) 205-2000. General information concerning the
Commission may also be obtained by accessing its Internet server at https://www.usitc.gov. The
public record for this investigation may be viewed on the Commission’s electronic docket
(EDIS) at https://edis.usitc.gov. Hearing-impaired persons are advised that information on this
matter can be obtained by contacting the Commission’s TDD terminal on (202) 205-1810.
SUPPLEMENTARY INFORMATION: The Commission instituted this investigation on June
21, 2018, based on a complaint, as amended and supplemented, filed on behalf of Glycosyn LLC
of Waltham, Massachusetts (“Glycosyn”). See 83 Fed. Reg. 28865 (June 21, 2018). The
complaint, as amended and supplemented, alleges violations of section 337 of the Tariff Act of
1930, as amended, 19 U.S.C. 1337 (“section 337”), based upon the importation into the United
States, the sale for importation, and the sale within the United States after importation of certain
human milk oligosaccharides by reason of infringement of claims 1-40 of U.S. Patent No.
9,453,230 (“the ’230 patent”) and claims 1-28 of U.S. Patent No. 9,970,018 (“the ’018 patent”).
2
See id. The notice of investigation named Jennewein as a respondent in this investigation. See
id. The Office of Unfair Import Investigations (“OUII”) is also named as a party to the
investigation. See id.
The ALJ conducted an evidentiary hearing on May 14-17, 2019, and on September 9,
2019, issued the FID finding a violation of section 337 based on the infringement of claims 1-3,
5, 8, 10, 12, 18, and 24-28 of the ’018 patent (hereinafter, the “Asserted Claims”). In addition,
the FID finds that the Asserted Claims are neither invalid under 35 U.S.C. §§ 103 and 112, nor
unenforceable for inequitable conduct. Furthermore, the FID finds that the domestic industry
requirement is satisfied. All asserted claims in the ’230 patent were withdrawn during the
investigation. The FID also contains a recommended determination (“RD”) recommending that
the Commission issue an LEO barring entry of articles that infringe the ’018 patent. The RD
also recommends that the Commission impose a 5 percent bond during the period of Presidential
review. Furthermore, as directed by the Commission, the RD provides findings with respect to
the public interest and recommends that the Commission determine that the public interest
factors do not preclude entry of the proposed LEO. Glycosyn does not seek and the RD does not
recommend issuance of a cease and desist order.
On October 9 and 10, 2019, respectively, Glycosyn and Jennewein filed statements on the
public interest pursuant to Commission Rule 210.50. On October 23, 2019, non-party DuPont
Nutrition & Health filed a public interest submission pursuant to the Commission’s notice
requesting public interest comments. See 84 Fed. Reg. 49335 (Sept. 19, 2019).
On January 30, 2020, the Commission issued a notice determining to review the FID in
part. See 85 Fed. Reg. 6573 (Feb. 5, 2020). The Commission’s notice requested written
submissions in response to certain questions relating to issues under review and on issues of
remedy, the public interest, and bonding. On February 18, 2020, the parties, including OUII,
filed written submissions in response to the notice, and on February 25, 2020, the parties filed
responses to each other’s submissions. On February 18, 2020, non-party Abbott Laboratories
filed a written submission concerning the public interest.
Having examined the record of this investigation, including the FID, the RD, and the
parties’ and non-parties’ submissions, the Commission has determined to affirm with
modification the FID’s determination of a violation of section 337 with respect to claims 1-3, 5,
8, 10, 12, 18, and 24-28 of the ’018 patent. Specifically, as explained in the Commission
Opinion filed concurrently herewith, the Commission has determined to affirm with modification
the FID’s findings with respect to infringement by the accused Jennewein bacterial strains and to
reverse the FID’s decision not to adjudicate infringement with respect to Jennewein’s TTFL12
bacterial strain. As to the TTFL12 strain, the Commission has determined that it does not
infringe the Asserted Claims. All findings in the FID that are not inconsistent with the
Commission’s determination are affirmed.
The Commission has determined that the appropriate remedy is an LEO against
Jennewein’s infringing products. The Commission has also determined that the public interest
factors enumerated in subsection 337(d)(1) (19 U.S.C. 1337(d)(1)) do not preclude the issuance
of the LEO. The Commission has further determined to set a bond during the period of
3
Presidential review at five (5) percent of the entered value of Jennewein’s infringing products
(19 U.S.C. 1337(j)).
The Commission’s order and opinion were delivered to the President and to the United
States Trade Representative on the day of their issuance.
The Commission’s vote for these determinations took place on May 19, 2020.
The authority for the Commission’s determination is contained in section 337 of the
Tariff Act of 1930, as amended (19 U.S.C. 1337), and in part 210 of the Commission’s Rules of
Practice and Procedure (19 CFR part 210).
By order of the Commission.
Lisa R. Barton
Secretary to the Commission
Issued: May 19, 2020
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND
METHODS OF PRODUCING THE SAME
Inv. No. 337-TA-1120
PUBLIC CERTIFICATE OF SERVICE
I, Lisa R. Barton, hereby certify that the attached NOTICE has been served via EDIS
upon the Commission Investigative Attorney, Lisa Murray, Esq., and the following parties
as indicated, on May 19, 2020.
Lisa R. Barton, Secretary
U.S. International Trade Commission
500 E Street, SW, Room 112
Washington, DC 20436
On Behalf of Complainant Glycosyn LLC:
Michael C. Newman, Esq.
MINTZ LEVIN COHN FERRIS GLOVSKY AND POPEO, PC
1 Financial Center
Boston, MA 02111
Email: MCNewman@mintz.com
☐ Via Hand Delivery
☐ Via Express Delivery
☐ Via First Class Mail
☒ Other: Email Notification
of Availability to Download
On Behalf of Respondent Jennewein Biotechnologie GmbH:
Gary M. Hnath
MAYER BROWN LLP
1999 K Street, NW
Washington, DC 20006
Email: ghnath@mayerbrown.com
☐ Via Hand Delivery
☐ Via Express Delivery
☐ Via First Class Mail
☒ Other: Email Notification
of Availability to Download
1
UNITED STATES INTERNATIONAL TRADE COMMISSION
Washington, D.C.
In the Matter of
CERTAIN HUMAN MILK
OLIGOSACCHARIDES AND METHODS
OF PRODUCING THE SAME
Investigation No. 337-TA-1120
LIMITED EXCLUSION ORDER
The United States International Trade Commission (“Commission”) has determined that
there is a violation of Section 337 of the Tariff Act of 1930, as amended (19 U.S.C. § 1337), in
the unlawful importation, sale for importation, or sale within the United States after importation
by Jennewein Biotechnologie GmbH (“Jennewein” or “Respondent”) of certain 2’-fucosyllactose
oligosaccharides that infringe one or more of claims 1-3, 5, 8, 10, 12, 18, and 24-28 (“the
Asserted Claims”) of U.S. Patent No. 9,970,018 (“the ’018 patent”).
Having reviewed the record of this investigation, including the written submissions of the
parties, the Commission has made its determination on the issues of remedy, public interest, and
bonding. The Commission has determined that the appropriate form of relief includes a limited
exclusion order prohibiting the unlicensed entry into the United States of 2’-fucosyllactose
oligosaccharides manufactured abroad by or on behalf of, or imported by or on behalf of, Respondent
or any of its affiliated companies, parents, subsidiaries, or other related business entities, or its
successors or assigns. The exclusion order does not apply to Respondent’s TTFL12 bacterial
strain and 2’-fucosyllactose oligosaccharides produced by that strain, which, as the Commission
determined, do not infringe the Asserted Claims.
The Commission has also determined that the public interest factors enumerated in 19
U.S.C. § 1337(d) do not preclude the issuance of the limited exclusion order, and that the bond
2
during the period of Presidential review shall be in the amount of five (5) percent of the entered
value of the covered articles.
Accordingly, the Commission hereby ORDERS that:
1. 2’-fucosyllactose oligosaccharides that infringe one or more of the Asserted
Claims that are manufactured abroad by or on behalf of, or imported by or on behalf of,
Respondent, or its affiliated companies, parents, subsidiaries, or other related business entities, or
its successors or assigns (“covered articles”), are excluded from entry for consumption into the
United States, entry for consumption from a foreign-trade zone, or withdrawal from a warehouse
for consumption, for the remaining term of the ’018 patent, except under license of the patent
owner or as provided by law.
2. This Order does not apply to Respondent’s TTFL12 bacterial strain and
2’-fucosyllactose oligosaccharides produced by that strain, which, as the Commission
determined, do not infringe the Asserted Claims.
3. Notwithstanding paragraph 1 of this Order, covered articles are entitled to entry
into the United States for consumption, entry for consumption from a foreign trade zone, or
withdrawal from a warehouse for consumption, under bond in the amount of five (5) percent of
the entered value of the infringing products pursuant to subsection (j) of section 337 of the Tariff
Act of 1930, as amended (19 U.S.C. § 1337(j)), and the Presidential Memorandum for the United
States Trade Representative of July 21, 2005, (70 FR 43251), from the day after this Order is
received by the United States Trade Representative, and until such time as the United States
Trade representative notifies the Commission that this Order is approved or disapproved but, in
any event, not later than sixty (60) days after the date of receipt of this Order. All entries of
3
covered articles made pursuant to this paragraph are to be reported to U.S. Customs and Border
Protection (“CBP”), in advance of the date of the entry, pursuant to procedures CBP establishes.
4. At the discretion of CBP and pursuant to the procedures it establishes, persons
seeking to import 2’-fucosyllactose oligosaccharides, that are potentially subject to this Order may
be required to certify that they are familiar with the terms of this Order, that they have made
appropriate inquiry, and thereupon state that, to the best of their knowledge and belief, the
products being imported are not excluded from entry under paragraph 1 of this Order. At its
discretion, CBP may require persons who have provided the certification described in this
paragraph to furnish such records or analyses as are necessary to substantiate this certification.
5. In accordance with 19 U.S.C. § 1337(l), the provisions of this Order shall not
apply to 2’-fucosyllactose oligosaccharides that are imported by or for the use of the United
States, or imported for and to be used for, the United States with the authorization or consent of
the Government.
6. The Commission may modify this Order in accordance with the procedures
described in Rule 210.76 of the Commission’s Rules of Practice and Procedure (19 C.F.R.
§ 210.76).
7. The Secretary shall serve copies of this Order upon each party of record in this
Investigation and upon CBP.
8. Notice of this Order shall be published in the Federal Register.
By order of the Commission.
Lisa R. Barton
Secretary to the Commission
Issued: May 19, 2020
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND
METHODS OF PRODUCING THE SAME
Inv. No. 337-TA-1120
PUBLIC CERTIFICATE OF SERVICE
I, Lisa R. Barton, hereby certify that the attached ORDER, COMMISION has been
served via EDIS upon the Commission Investigative Attorney, Lisa Murray, Esq., and the
following parties as indicated, on May 19, 2020.
Lisa R. Barton, Secretary
U.S. International Trade Commission
500 E Street, SW, Room 112
Washington, DC 20436
On Behalf of Complainant Glycosyn LLC:
Michael C. Newman, Esq.
MINTZ LEVIN COHN FERRIS GLOVSKY AND POPEO, PC
1 Financial Center
Boston, MA 02111
Email: MCNewman@mintz.com
☐ Via Hand Delivery
☐ Via Express Delivery
☐ Via First Class Mail
☒ Other: Email Notification
of Availability to Download
On Behalf of Respondent Jennewein Biotechnologie GmbH:
Gary M. Hnath
MAYER BROWN LLP
1999 K Street, NW
Washington, DC 20006
Email: ghnath@mayerbrown.com
☐ Via Hand Delivery
☐ Via Express Delivery
☐ Via First Class Mail
☒ Other: Email Notification
of Availability to Download
PUBLIC VERSION
1
UNITED STATES INTERNATIONAL TRADE COMMISSION
Washington, D.C.
In the Matter of
CERTAIN HUMAN MILK
OLIGOSACCHARIDES AND METHODS
OF PRODUCING THE SAME
Inv. No. 337-TA-1120
COMMISSION OPINION
The Commission has determined that there has been a violation of section 337 of the
Tariff Act of 1930, as amended, 19 U.S.C. § 1337 (“section 337”), on review of the final initial
determination (“FID”) of the presiding administrative law judge (“ALJ”), based on the
infringement of U.S. Patent No. 9,970,018 by respondent’s accused bacterial strains. The
Commission has also determined to reverse the FID’s decision declining to adjudicate
respondent’s alternative TTFL12 strain and finds no infringement as to that strain. This opinion
sets forth the Commission’s reasoning in support of that determination. In addition, the
Commission adopts the findings in the FID that are not inconsistent with this opinion.
I. BACKGROUND
A. Procedural Background
The Commission instituted this investigation on June 21, 2018, based on a complaint, as
amended and supplemented, filed by Glycosyn LLC (“Glycosyn”) of Waltham, Massachusetts.
See 83 Fed. Reg. 28865-66 (June 21, 2018). The complaint alleged violations of section 337
based upon the importation into the United States, the sale for importation, and the sale within
the United States after importation of certain human milk oligosaccharides, by reason of
infringement of certain claims of U.S. Patent Nos. 9,453,230 (“the ’230 patent”) and 9,970,018
(“the ’018 patent”). See id. The complaint also alleges the existence of a domestic industry.
PUBLIC VERSION
2
The notice of investigation named Jennewein Biotechnologie GmbH of Rheinbreitbach,
Germany (“Jennewein”) as respondent in this investigation. See id. The Office of Unfair
Import Investigations (“OUII”) is also a party to this investigation. See id.
The Commission later terminated the investigation as to all asserted claims of the ’230
patent and certain asserted claims of the ’018 patent based on the withdrawal of the allegations
pertaining to those claims. See Order No. 5 (Aug. 9, 2018), unreviewed, Comm’n Notice (Aug.
29, 2018); Order No. 15 (Oct. 30, 2018), unreviewed, Comm’n Notice (Nov. 29, 2018); Order
No. 17 (Nov. 19, 2018), unreviewed, Comm’n Notice (Dec. 12, 2018); Order No. 25 (Feb. 8,
2019), unreviewed, Comm’n Notice (Feb. 28, 2019). Claims 1-3, 5, 8, 10, 12, 18, and 23-28 of
the ’018 patent remain pending in this investigation.
The ALJ conducted an evidentiary hearing on May 14-17, 2019. On September 9, 2019,
the ALJ issued the FID finding a violation of section 337 based on the infringement of claims 1-
3, 5, 8, 10, 12, 18, and 24-28 (hereinafter, “the Asserted Claims”) but not claim 23 of the ’018
patent, based on non-infringement of that claim.1 See FID at 35. Furthermore, the FID finds
that the domestic industry requirement is satisfied.
The FID also contains a Recommended Determination (“RD”) recommending, should a
violation of section 337 be found, that the Commission issue a limited exclusion order (“LEO”)
barring entry of articles that infringe the Asserted Claims.2 The RD also recommends that the
Commission impose a bond in the amount of five (5) percent of the entered value of the
infringing articles during the period of Presidential review. Furthermore, as directed by the
1 Glycosyn did not petition for review of the FID’s finding that Jennewein does not infringe
claim 23.
2 Glycosyn did not request, and the RD does not recommend, a cease and desist order against
Jennewein.
PUBLIC VERSION
3
Commission (see 83 Fed. Reg. at 28865), the RD provides findings with respect to the public
interest and recommends that the Commission determine that the public interest factors do not
preclude entry of the proposed LEO.
On September 23, 2019, Jennewein and the Commission’s Investigative Attorney (“IA”)
filed petitions for review of the FID.3 Jennewein petitioned for review of the FID’s findings
with respect to claim construction and infringement, and both Jennewein and the IA petitioned
for review of the FID’s decision not to adjudicate infringement with respect to Jennewein’s
TTFL12 bacterial strain, which Glycosyn did not accuse in its complaint. On October 1, 2019,
Glycosyn and the IA filed responses to the various petitions.4
On October 9 and 10, 2019, respectively, Glycosyn and Jennewein filed statements on the
public interest pursuant to Commission Rule 210.50(a)(4), 19 C.F.R. 210.50(a)(4).5 On October
23, 2019, non-party DuPont Nutrition & Health (“DuPont”) filed a public interest submission
pursuant to the Commission’s notice requesting public interest comments, see 84 Fed. Reg.
49335 (Sept. 19, 2019), supporting the ALJ’s recommended LEO and asserting that it has the
capacity to replace the excluded products in a commercially reasonable time.6
3 See Respondent Jennewein Biotechnologie GmbH’s Petition for Commission Review (Sep. 23,
2019) (hereinafter, “Jennewein’s Pet.”); OUII Petition for Review (Sep. 23, 2019) (hereinafter,
“IA’s Pet.”).
4 See Complainant Glycosyn LLC’s Consolidated Response to Respondent Jennewein
Biotechnologie GmbH’s and Office of Unfair Import Investigations’ Petitions for Commission
Review (Oct. 1, 2019) (hereinafter, “Glycosyn’s Pet. Resp.”); Office of Unfair Import
Investigations’ Response to Respondent’s Petition for Review (Oct. 1, 2019) (hereinafter, “IA’s
Pet. Resp.”).
5 See Complainant Glycosyn LLC’s Statement of Information Relating to the Public Interest
(Oct. 9, 2019) (hereinafter, “Glycosyn’s PI Br.”); Public Interest Statement of Respondent
Jennewein Biotechnologie GmbH (Oct. 10, 2019) (hereinafter, “Jennewein’s PI Br.”).
6 See Public Interest Submission of DuPont Nutrition & Health (hereinafter, “DuPont PI Br.”).
PUBLIC VERSION
4
On January 30, 2020, the Commission issued a notice determining to review the FID in
part. See 85 Fed. Reg. 6573-75 (Feb. 5, 2020) (“the WTR/Remedy Notice”). Specifically, the
Commission determined to review: (1) the FID’s infringement findings with respect to
Jennewein’s bacterial strains adjudicated in this investigation; and (2) the FID’s decision not to
adjudicate infringement as to Jennewein’s alternative bacterial strain, i.e., the TTFL12 strain.
See id. The Commission determined not to review the remainder of the FID. See id. The
notice invited written submissions from the parties on issues under review, and from the parties,
interested government agencies, and any other interested parties on issues of remedy, the public
interest, and bonding. See id.
On February 18, 2020, the parties, including OUII, filed written submissions in response
to the WTR/Remedy Notice,7 and on February 25, 2020, the parties filed responses to each
other’s submissions.8 Also on February 18, 2020, non-party Abbott Laboratories (“Abbott”)
filed a written submission concerning the public interest in response to the WTR/Remedy Notice,
7 See Complainant Glycosyn LLC’s Response to Questions in the Commission’s Notice of
Commission Decision to Review in Part a Final Initial Determination Finding a Violation of
Section 337 (Feb. 18, 2020) (hereinafter, “Glycosyn’s Resp.”); Complainant Glycosyn LLC’s
Initial Submission on the Form of Remedy, the Public Interest, and Bonding Pursuant to the
Commission’s Notice of Commission Decision to Review in Part a Final Initial Determination
Finding a Violation of Section 337 (Feb. 18, 2020) (hereinafter, “Glycosyn’s Remedy Br.”);
Respondent Jennewein Biotechnologie GmbH’s Responses to Questions Raised by the
Commission (Feb. 18, 2020) (hereinafter, “Jennewein’s Resp.”); Brief of the Office of Unfair
Import Investigations on Issues under Review and on Remedy, the Public Interest, and Bonding
(Feb. 18, 2020) (hereinafter, “IA’s Resp.”).
8 See Complainant Glycosyn LLC’s Reply to Respondent’s and OUII’s Responses to the
Commission’s Questions regarding Final Initial Determination Finding a Violation of Section
337 (Feb. 25, 2020) (hereinafter, “Glycosyn’s Reply”); Respondent Jennewein Biotechnologie
GmbH’s Reply to Responses by Glycosyn LLC and the Office of Unfair Import Investigations to
Questions Raised by the Commission and Responses to Glycosyn’s and OUII’s Submissions on
Remedy, the Public Interest, and Bonding (Feb. 25, 2020) (hereinafter, “Respondents’ Reply”);
Reply Brief of the Office of Unfair Import Investigations on Issues under Review and on
Remedy, the Public Interest, and Bonding (Feb. 25, 2020) (hereinafter, “IA’s Reply”).
PUBLIC VERSION
5
and alleged that “Jennewein is the only supplier whose product has been fully qualified through
Abbott’s quality and regulatory processes, raising public interest concerns from remedial
relief.”9
B. The Asserted Patent
The ’018 patent issued on May 15, 2018. See JX-3, ’018 Patent. The ’018 patent, titled
“Biosynthesis of Human Milk Oligosaccharides in Engineered Bacteria,” relates to
“compositions and methods for producing fucosylated oligosaccharides” which are “typically
found in human milk” and which “serve critical roles in the establishment of a healthy gut
microbiome, in the prevention of disease and in immune function.” See id. at 1:27-39. The
specification of the ’018 patent states that “the invention . . . makes use of an engineered
bacterium E. coli or other bacteria engineered to produce” fucosylated oligosaccharides. See id.
at 15:66-16:4.
The ’018 patent specification explains that “[b]iosynthesis of fucosylated HMOS10
requires the generation of an enhanced cellular pool of both lactose and GDP11-fucose.” See id.
at 16:27-29; see also id. at Figure 3 (requiring both lactose and GDP-fucose for the synthesis of
2’-fucosyllactose). For example, the specification discloses that “[t]he ability of the E. coli host
strain to accumulate lactose was . . . engineered by simultaneous deletion of the endogenous
β-galactosidase gene (lacZ) and the lactose operon repressor gene (lacI)” while “the lacIq
promoter was placed immediately upstream of the lactose permease gene, lacY.” See id. at
16:37-43 (Example 1). The specification states that “[t]he modified strain thus maintains its
9 See Public Interest Submission of Abbott Laboratories (Feb. 18, 2020) (hereinafter “Abbott’s
PI Br.”).
10 “HMOS” refers to Human Milk Oligosaccharides.
11 “GDP” refers to guanosine diphosphate. See JX-3, ’018 Patent at 1:61-63.
PUBLIC VERSION
6
ability to transport lactose from the culture medium via LacY” but the lacZ (β-galactosidase)
gene responsible for lactose catabolism (i.e., breakdown) is deleted. See id. at 16:43-47
(Example 1). Therefore, the specification continues, “[a]n intracellular lactose pool is . . .
created when the modified strain is cultured in the presence of exogenous lactose.” See id. at
16:47-49 (Example 1).
The specification also describes “bacterial host cells with the ability to accumulate a[n]
intracellular lactose pool while simultaneously possessing low, functional levels of cytoplasmic
β-galactosidase activity for example as provided by the introduction of a functional recombinant
E. coli lacZ gene or by a β-galactosidase gene from any of a number of other organisms.” See
id. at 7:22-28. The specification explains that “low level of cytoplasmic β-galactosidase activity
while not high enough to significantly diminish the intracellular lactose pool is nevertheless very
useful for tasks such as phenotypic marking of desirable genetic loci during construction of host
cell backgrounds, for detection of cell lysis due to undesired bacteriophage contaminations in
fermentation processes, or for the facile removal of undesired residual lactose at the end of
fermentations.” See id. at 7:37-45.
With regard to GDP-fucose production, the specification of the ’018 patent further states
that “[o]ne strategy for GDP-fucose production is to enhance the bacterial cell’s natural synthesis
capacity,” e.g., “by inactivating enzymes involved in GDP-fucose consumption, and/or by
overexpressing a positive regulator protein, RcsA, in the colanic acid (a fucose containing
exopolysaccharide) synthesis pathway.” See id. at 17:4-10. The specification explains that
“this metabolic engineering strategy redirects the flux of GDP-fucose destined for colanic acid
synthesis to oligosaccharide synthesis.” See id. at 17:10-12.
PUBLIC VERSION
7
Still further, the specification of the ’018 patent describes a “bacterium [that] possesses
fucosyl transferase activity,” e.g., “an exogenous fucosyltransferase gene.” See id. at 5:28-32.
The specification explains that “[a]n exemplary . . . fucosyltransferase gene is the wcfW gene”
and that “[p]rior to the present invention, this wcfW gene . . . was not suspected to possess the
ability to utilize lactose as an acceptor sugar,” i.e., as a substrate for HMOS synthesis. See id. at
5:28-38; see also id. at Figure 3 (involving α(1,2)FT, i.e., fucosyltransferase, in the synthesis of
2’-fucosyllactose).
Claim 1 of the ’018, from which the remaining asserted claims depend, patent recites the
following invention (with the disputed claim limitations in bold):
A method for producing a fucosylated oligosaccharide in a
bacterium, comprising
providing an isolated E. coli bacterium comprising,
(i) a deletion or functional inactivation of an endogenous
β-galactosidase gene;
(ii) an exogenous functional β-galactosidase gene
comprising a detectable level of β-galactosidase activity that
is reduced compared to that of a wild-type E. coli bacterium,
wherein the level of β-galactosidase activity comprises
between 0.05 and 200 units;
(iii) an inactivating mutation in a colanic acid synthesis
gene; and
(iv) an exogenous lactose-accepting fucosyltransferase gene;
culturing said bacterium in the presence of lactose; and
retrieving a fucosylated oligosaccharide from said bacterium or
from a culture supernatant of said bacterium.
See id. at 111:41-57 (claim 1).
C. Domestic Industry Product
The FID identifies Glycosyn’s E997 bacterial strain and its production of
2’-fucosyllactose (2’-FL) as practicing at least one claim of the ’018 patent. See FID at 7. The
FID also determines that Glycosyn satisfies the domestic industry requirement. See id. at 61-67,
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96-113. No party petitioned for review of these findings, and the Commission determined not to
review these findings.
D. Accused and Redesigned or Alternative Products
The accused product in this investigation is Jennewein’s 2’-FL product which was
produced using E. coli bacterial strains #1540 and a derivative thereof, known as “the #1540
derivative” or “the #2410 strain” (collectively, “Accused Strains”). See FID at 7. The FID
finds that the Accused Strains infringe the Asserted Claims of the ’018 patent.
Jennewein also requested adjudication as to its redesigned or alternative TTFL12
bacterial strain in this investigation. Glycosyn did not accuse that strain in this investigation and
the FID declined to adjudicate infringement with respect to that strain. See id. at 28-35. The
Commission determined to review the FID’s decision not to adjudicate infringement with respect
to the TTFL12 strain. See 85 Fed. Reg. at 6574.
II. LEGAL STANDARDS
A. Standard on Review
Commission Rule 210.45(c) provides that “[o]n review, the Commission may affirm,
reverse, modify, set aside or remand for further proceedings, in whole or in part, the initial
determination of the administrative law judge” and that “[t]he Commission also may make any
findings or conclusions that in its judgment are proper based on the record in the proceeding.”
See 19 C.F.R. § 210.45(c). In addition, as explained in Certain Polyethylene Terephthalate
Yarn and Products Containing Same, “[o]nce the Commission determines to review an initial
determination, the Commission reviews the determination under a de novo standard.” Inv. No.
337-TA-457, Comm’n Op., 2002 WL 1349938, *5 (June 18, 2002) (citations omitted). This is
“consistent with the Administrative Procedure Act which provides that once an initial agency
PUBLIC VERSION
9
decision is taken up for review, ‘the agency has all the powers which it would have in making
the initial decision except as it may limit the issues on notice or by rule.’” Id. (citing 5 U.S.C.
§ 557(b)).
B. Infringement
“An infringement analysis entails two steps. The first step is determining the meaning
and scope of the patent claims asserted to be infringed. The second step is comparing the
properly construed claims to the device accused of infringing.” Markman v. Westview
Instruments, Inc., 52 F.3d 967, 976 (Fed. Cir. 1995) (en banc), aff’d, 517 U.S. 370 (1996)
(citations omitted). Infringement must be proven by a preponderance of the evidence. See
SmithKline Diagnostics, Inc. v. Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988). The
preponderance of the evidence standard “requires proving that infringement was more likely than
not to have occurred.” Warner-Lambert Co. v. Teva Pharm. USA, Inc., 418 F.3d 1326, 1341
n.15 (Fed. Cir. 2005).
Literal infringement requires the patentee to prove that the accused device contains each
and every limitation of the asserted claim(s). See Frank’s Casing Crew & Rental Tools, Inc. v.
Weatherford Int’l, Inc., 389 F.3d 1370, 1378 (Fed. Cir. 2004). Where literal infringement is not
found, infringement can still be found under the doctrine of equivalents. See TIP Sys., LLC v.
Phillips & Brooks/Gladwin, Inc., 529 F.3d 1364, 1376 (Fed. Cir. 2008) (“Infringement under the
doctrine of equivalents may be found when the accused device contains an ‘insubstantial’ change
from the claimed invention.”) (citations omitted).
III. DISCUSSION
The Commission determined to review: (1) the FID’s infringement findings with respect
to Jennewein’s bacterial strains adjudicated in this investigation; and (2) the FID’s decision not
PUBLIC VERSION
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to adjudicate infringement as to Jennewein’s alternative or redesigned bacterial strain, i.e., the
TTFL12 strain. See 85 Fed. Reg. at 6574.
A. Infringement as to the Term Exogenous Functional β-Galactosidase Gene
The previously presiding ALJ12 construed “functional β-galactosidase gene” to mean
“functional sequence of DNA that encodes β-galactosidase.” See Order No. 22 at 29 (Dec. 18,
2018). No party petitioned for review of that construction. The parties also agreed that
“exogenous” is properly construed as “originating outside an organism, tissue, or cell.” See id.
at 12.
The FID finds that the Accused Strains do not literally satisfy the claim term “an
exogenous functional β-galactosidase gene,” but that the term is satisfied under the doctrine of
equivalents. See FID at 38-45. The FID reasons that Jennewein’s Accused Strains include two
distinct DNA sequences, namely, lacZα and lacZΩ, which, together, encode for the
β-galactosidase enzyme. See id. at 38-39. The FID concludes that “Jennewein’s Accused
Strains do not literally infringe ‘an exogenous functional β-galactosidase gene’ because they lack
a single sequence of DNA which functions to create a β-galactosidase gene.” See id. at 39.
Nevertheless, the FID finds “no difference between the combination of lacZα and lacZΩ genes
on the one hand, and any particular individual ‘functional β-galactosidase gene’ on the other.”
See id. at 40.
In addition, the FID recognizes that “lacZα in the Accused Strains was not added by
Jennewein, but was present in the original BL21 (DE3) strain which Jennewein engineered to
achieve the Accused Strains.” See id. at 44-45. The FID finds, however, that “the exogenous
12 At the time of Order No. 22, the investigation was assigned to the Chief ALJ. On April 2,
2019, the investigation was transferred to Judge Elliot.
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nature of lacZΩ is enough to meet the limitation” at issue. Id. The FID explains that “[i]t is the
combination of lacZα and lacZΩ which is equivalent to the claimed ‘β-galactosidase gene,’ and
this combination does not exist until lacZΩ is inserted into the bacterium’s genome from outside
the organism.” See id. at 45. Thus, the FID concludes, “the combination is ‘exogenous’ and
satisfies the claim limitation at least under the doctrine of equivalents.” See id.
Jennewein petitioned for review of the FID’s infringement findings with respect to the
claim term “an exogenous functional β-galactosidase gene.” Jennewein’s Pet. at 30-35.
Jennewein did not dispute the FID’s findings that the combination of the lacZα and lacZΩ genes
is equivalent to a functional β-galactosidase gene, but Jennewein argued that the combination is
not exogenous because only lacZΩ is exogenous while lacZα is endogenous.13 See id. at 31.
Jennewein reasoned that the FID “departs from the parties’ agreed-upon construction for
‘exogenous’” and “incorrectly concludes that ‘[i]t is the combination of lacZα and lacZΩ which
is equivalent to the claimed ‘β-galactosidase gene,’ and this combination does not exist until
lacZΩ is inserted into the bacterium’s genome from outside the organism.’” See id. (citation
omitted) (emphasis in original). Jennewein explained that “[t]he claim language does not
encompass a combination of gene fragments that did not ‘exist’ until one fragment is inserted
into the genome” but “[r]ather, it requires that the combination itself originated outside of
Jennewein’s strain.” See id. (citation omitted).
The Commission finds that the FID correctly determined that Jennewein’s Accused
Strains include a combination that is equivalent to the claimed “exogenous functional
β-galactosidase gene.” See FID at 38-45. Jennewein argued that the ID’s finding that the
13 Jennewein explains that “‘endogenous’ genes are those present in the host strain prior to any
genetic engineering.” Jennewein’s Pet. at 34 (citing Hr’g Tr. (Prather) at 441:25-442:4).
PUBLIC VERSION
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combination “does not exist” in the host strain until lacZΩ is inserted into the bacterium’s
genome, is incorrect because, in Jennewein’s view, the construction of “exogenous” (i.e.,
“originating outside an organism, tissue, or cell”) requires that “the combination itself
originate[s] outside of Jennewein’s strain.” See Jennewein Pet. at 31. This alleged distinction,
however, is unpersuasive. Indeed, as the FID finds, the combination does not exist in the
original strain, and therefore the combination itself does not originate from within the organism.
See FID at 44-45 (citing CX-213 at Figure 2, 5158). Thus, the Commission agrees with the FID
that “the exogenous nature of lacZΩ is enough” to make the combination exogenous and any
difference between the claim term “an exogenous functional β-galactosidase gene” and the
accused products is insubstantial. See id. at 45; accord Glycosyn’s Pet. Resp. at 28; IA’s Pet.
Resp. at 10.
In addition, the Commission finds that lacZα, which is present in the genetically-
engineered strain, i.e., BL21[DE3], is also exogenous as compared to the wild-type E. coli
bacterium. See Glycosyn’s Pet. Resp. at 30-31. As Glycosyn explains, “[i]t is . . . undisputed
that the lacZα gene exists in the BL21(DE3) genome only by way of human intervention.” See
id. at 30 (citing CX-213 (Jennewein’s GRAS Notice) at CX-213.297 (“Since its isolation in
1818, the E. coli B strain has also undergone multiple rounds of genetic manipulation resulting in
the strain BL21 (DE3).”); RX-386C (Parschat14) at Q/As 68-69). In addition, “it is undisputed
that the DE3 is derived from a prophage, or in other words, a virus, that infects E. coli. to insert
foreign DNA into the E. coli.” See id. at 31 (citing RX-386C (Parschat) at Q/As 133-134 (“We
discovered there was actually a lacZ[α] like fragment already present in the DE3 prophage in the
14 Katja Parschat is Jennewein’s Deputy Head of Research and Development.
PUBLIC VERSION
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genome of strain #1540. . . . A prophage is the genome [of] an E. coli virus or phage or part of
that genome that is integrated into the bacterial chromosome replicate.”)).
The language of the Asserted Claims and the specification of the ’018 patent make clear
that the claimed genetically-engineered bacterium and its “exogenous functional β-galactosidase
gene” are to be compared to the native or wild-type E. coli bacterium rather than to a genetically-
engineered strain, i.e., BL21[DE3]. See JX-3, ’018 patent at 111:45-49 (claim 1) (“A method
for producing a fucosylated oligosaccharide in a bacterium comprising[:] providing an isolated
E. coli bacterium comprising . . . an exogenous functional β-galactosidase gene comprising a
detectable level of β-galactosidase activity that is reduced compared to that of a wild-type E. coli
bacterium.”) (emphasis added); id. at 5:1-5 (“The bacteria used herein to produce HMOS are
genetically engineered to comprise an increased intracellular guanosine diphosphate (GDP)-
fucose pool, an increased intracellular lactose pool (as compared to wild type) and to comprise
fucosyl transferase activity.”) (emphasis added); id. at 6:45-53 (“In the case of lactose and GDP-
fucose, endogenous E. coli metabolic pathways and genes are manipulated in ways that result in
the generation of increased cytoplasmic concentrations of lactose and/or GDP-fucose, as
compared to levels found in wild type E. coli. For example the bacteria contain at least 10%,
20%, 50%, 2x, 5x, 10x or more of the levels in a corresponding wild type bacteria that lacks the
genetic modifications described above.”) (emphasis added).
There is no dispute that, as compared to the wild-type E. coli bacterium, both lacZα and
lacZΩ are exogenous, i.e., they “originat[e] outside an organism, tissue, or cell.” See CX-213 at
CX-213.297; RX-386C (Parschat) at Q/As 68-69, 133-34. Thus, the Commission has
determined to affirm with modification the FID’s finding that the Accused Strains infringe the
PUBLIC VERSION
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Asserted Claims under the doctrine of equivalents, and supplements the FID’s analysis as
discussed above.
B. Adjudication of Infringement with Respect to the TTFL12 Strain
During the investigation, Jennewein sought adjudication of infringement with respect to its
TTFL12 bacterial strain, which Glycosyn did not accuse in its complaint. Jennewein identified
the TTFL12 strain on September 14, 2018, in its Ground Rule 7.2 disclosure15 (CX-226C) and in
its interrogatory responses served on November 5, 2018 (CX-237C). Jennewein further
provided two documents, RX-320C (a draft article) and RX-382 (European Patent Application
No. 14 162 869.3) (both produced on August 21, 2018), to establish the relevant features of the
TTFL12 strain.
The FID declines Jennewein’s request for adjudication, reasoning that “there can be no
dispute that Glycosyn has not accused [the TTFL12 strain] of infringement.” See FID at 28.
The FID states that Commission precedent follows “a four-factor test as to whether a respondent
has met its burden to show that infringement of a redesigned product should be adjudicated,”
namely, whether “[t]he product [is]: (1) within the scope of the investigation, (2) imported,
(3) sufficiently fixed in design, and (4) subject to extensive discovery.” See id. at 29 (citing
Certain Two-Way Radio Equipment and Systems, Related Software, & Components Thereof, Inv.
No. 337-TA-1053, Comm’n Op. at 8, 2018 WL 8648379 (Dec. 18, 2018) (“Two-Way Radio”)).
“Of these factors, [the FID] finds Respondents have not met their burden as to the fourth
factor, subject to extensive discovery.” See id. Specifically, the FID determines that
Jennewein failed to “provide[] ‘extensive’ or ‘sufficient’ discovery on the TTFL12 strain.” See
15 Ground Rule 7.2 relates to the “Disclosure of Products Within the Scope of the [Notice of
Investigation].” See Order No. 2 (June 21, 2018).
PUBLIC VERSION
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id. at 32. The FID reasons that “while Jennewein identified TTFL12 as falling under the scope
of the investigation in its Ground Rule 7.2 disclosure [(CX-226C)], and identified the ‘draft’
article, RX-0320C, as evidence of TTFL12’s relevant features, it did not identify the patent
application [(RX-382)] such that Glycosyn would have been on notice of it,” because the patent
application “does not refer to TTFL12 by name.” See id. at 32-33. The FID further finds that
“RX-0320C may provide information on the conception of TTFL12, but it does not sufficiently
identify and describe a product that could serve as an accused product.” See id. at 34.
The FID also rejects Jennewein’s discovery responses as insufficient because they were
served on the last day of discovery, which ended on November 5, 2018. See id. The FID
determines that Jennewein’s failure to identify TTFL12 in response to Glycosyn’s request for
admission on importation “was more than enough to dissuade Glycosyn from investigating
anything other than the #1540 strain during discovery.” See id. at 34-35. The FID further finds
that “Glycosyn [was] on notice of just three things: a strain referred to as TTFL12 exists and
was described in an unpublished, undated article as lacking a lacZ gene (CX-0226; CX-0320C);
at some point the strain was used to create an unspecified amount of 2’-FL (CX-2037C at 1-2);
but that 2’-FL had not been imported into the United States (CX-0216C at 5).” See id. at 34.
The FID recognizes that “Glycosyn failed to take discovery of its own on [the TTFL12]
issue . . . and to respond to Jennewein’s own requests for admission on TTFL12,” but the FID
finds that “it is Jennewein’s burden to introduce TTFL12-based 2’-FL into the case.” See id. at
35 (citing Two-Way Radio). Thus, the FID concludes that “adjudication of whether the TTFL12
strain infringes [is not] appropriate at this time because the discovery on TTFL12 was not
adequate.” See id.
PUBLIC VERSION
16
Jennewein and the IA petitioned for review of the FID’s alleged failure to adjudicate
infringement with respect to Jennewein’s TTFL12 bacterial strain. Jennewein’s Pet. at 35-41;
IA’s Pet. at 5-22. Jennewein argued that the FID errs in requiring a heightened burden of
“extensive discovery” where Commission precedent requires only that the respondent “provid[e]
sufficient information to put the complainant on notice that [the TTFL12 strain] may be at issue.”
See Jennewein’s Pet. at 37-38 (citing Certain Television Sets, Television Receivers, Television
Tuners, & Components Thereof, Inv. No. 337-TA-910, Order No. 46 at 23 (Nov. 28, 2014),
unreviewed, Comm’n Notice (Dec. 3, 2014)); accord IA’s Pet. at 22 (“[T]he [FID’s] conclusion
that the disclosure was somehow not ‘sufficient’ was a clearly erroneous finding of material fact
that merits review by the Commission.”).
Jennewein also argued that the FID should have adjudicated non-infringement because
the “TTFL12 strain lacks a functional β-galactosidase gene, and therefore it is incapable of
having any β-galactosidase activity as the claim clearly requires.” See Jennewein’s Pet. at 39.
Jennewein asserted that “[its] witnesses explained the structure and capabilities of the TTFL12
strain such that a noninfringement opinion would be straightforward.” See id. at 39-40 (citing
RX-320C (Jennewein draft manuscript produced August 2018) (“[g]enes encoding proteins
involved in pathways that compete with 2’-FL biosynthesis were inactivated or deleted”); RX-
409C (Stephanopoulos16 RWS17) at Q/A 278 (testifying that the lacZ gene has been deleted or
inactivated and that TTFL12 was not further engineered to insert a functional exogenous
β-galactosidase gene); Hr’g Tr. (Parschat) at 384:10-17 (“The complete lacZ gene as occurs in
16 Gregory Stephanopoulos was Jennewein’s technical expert in this investigation.
17 “RWS” refers to Rebuttal Witness Statement.
PUBLIC VERSION
17
the operon is not present in the TTFL-12 strain.”); RX-387C (Parkot18 Witness Statement
(“WS”)) at Q/A 85 (“The TTFL12 strain is a 2’-FL production strain that has no β-galactosidase
(lacZ) gene and does not use lactose to synthesize 2’-FL.”); see also IA’s Pet. at 16-17 (“Unlike
in the bacterial strain discussed in the ’018 Patent, in the TTFL12 strain the inactivated lacZ gene
was not replaced with an exogenous functional β-galactosidase gene.”) (citing RX-320C).
Accord IA’s Resp. at 3-7; Jennewein’s Resp. at 2-11.
Jennewein further argued that the FID “improperly rewards Glycosyn for its refusal to
take discovery on the TTFL12 strain.” See Jennewein’s Pet. at 40. Jennewein reasons that
“Glycosyn never tested the TTFL12 strain during its inspection of Jennewein’s facilities in
Germany, even though it had every chance to do so” and “never asked its expert, Dr. Prather, to
opine on TTFL12.” See id. (citing Hr’g Tr. (Prather19) at 558:11-14 (“Q. . . . So you at least
never asked, through Dr. Wheeler or otherwise, to test the TTFL-12 strain; correct? A. That’s
correct. We never asked for it.”), 509:17-25); see also id. at 530:17-19 (“Q. So you did not
analyze the TTFL-12 strain for the purpose of this investigation? A. I did not.”); accord IA’s
Pet. at 14-15 (“A complainant cannot willfully ignore evidence of noninfringement presented in
discovery and then expect that any remedy imposed will apply to the products that the
complainant declined to investigate.”) (citing Certain Electronic Digital Media Devices &
Components Thereof, Inv. No. 337-TA-796, Comm’n Op., 2013 WL 10734395, *71 (Sept. 6,
2013) (“Electronic Digital Media Devices”) (“When confronted with Samsung’s evidence of
noninfringement, Apple had an obligation to either present evidence of infringement or withdraw
its allegations concerning these products, but it did neither.”)).
18 Julia Parkot is Jennewein’s Head of Quality Management.
19 Kristala L. Jones Prather was Glycosyn’s technical expert in this investigation.
PUBLIC VERSION
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Glycosyn argued that Jennewein failed to satisfy its burden under Two-Way Radio to
establish that the TTFL12 product is fixed in design and that it was imported, and that Jennewein
did not provide sufficient discovery on TTFL12. See Glycosyn’s Pet. Resp. at 33-34.
Glycosyn reasoned that “Jennewein failed to produce even the most basic common laboratory
documents for any of its strains, including its #1540 production strain.” See id. at 34.
Glycosyn further argued that “Jennewein and Staff are . . . wrong to suggest that Glycosyn
should have done more to obtain discovery regarding Jennewein’s TTFL12 strain” and that
“Glycosyn sought, and Jennewein failed to produce, documents sufficient to describe the nature
or use of TTFL12.” See id. at 41.
The Commission has determined to reverse the FID’s decision not to adjudicate the
TTFL12 bacterial strain.20 The Commission previously stated that the test for determining
whether a respondent has met its burden for adjudication of a redesigned or alternative product
includes four factors: (1) whether the product is within the scope of the investigation;
(2) whether it has been imported21; (3) whether it is sufficiently fixed in design; and (4) whether
it has been sufficiently disclosed by respondent during discovery. See Two-Way Radio, 2018
WL 8648379 at *13-14. The Commission also reiterates its policy in favor of adjudicating
redesigns to prevent subsequent and potentially burdensome proceedings that could have been
resolved in the first instance in the original Commission investigation. See, e.g., Certain
20 Commissioner Schmidtlein dissents from Part III(B) of the Commission’s decision and has
filed a separate opinion concurring in part and dissenting in part.
21 The Commission notes that while importation may be relevant to the inquiry, actual
importation of the redesign is not a mandatory requirement. See, e.g., Certain Multiple Mode
Outdoor Grills and Parts Thereof, Inv. No. 337-TA-895, Comm’n Op. at 20 (July 23, 2014);
Certain Television Sets, Certain Television Receivers, Television Tuners, and Components
Thereof, Inv. No. 337-TA-910, Order No. 46 (Initial Determination) at 29 (Nov. 28, 2014) (Lord,
J.) (not reviewed).
PUBLIC VERSION
19
Television Sets, Television Receivers, Television Tuners, & Components Thereof, Inv. No. 337-
TA-910, Order No. 46 at 23-24 (Nov. 3, 2014), unreviewed, Comm’n Notice (Dec. 3, 2014) (“As
a policy matter, ‘consideration of design around products during the course of the proceedings
before the ALJ provides predictability in enforcement of the order by U.S. Customs and Border
Protection.”) (quoting Certain Multiple Mode Outdoor Grills & Parts Thereof, Inv. No. 337-TA-
895, Comm’n Op., 2014 WL 12890485, *10 (July 23, 2014)). However, redesigned products
are still within the scope of remedial orders that are issued upon the termination of the
investigation even if such products were not adjudicated for infringement in the original
investigation. See Certain Optical Disk Controller Chips & Chipsets & Prods. Containing
Same, Including DVD Players & PC Optical Storage Devices, Inv. No. 337-TA-506, Comm’n
Op., 2007 WL 4713920, *64 (Sept. 28, 2005) (“[W]hile individual models may be evaluated to
determine importation and infringement, the Commission’s jurisdiction extends to all models of
infringing products that are imported at the time of the Commission’s determination and to all
such products that will be imported during the life of the remedial orders.”) (internal quotation
omitted); cf. IA’s Pet. at 8 (“[A]lthough it refused to identify TTFL12-based 2’-FL as an accused
product, Complainant argued that the product should nevertheless be covered by any exclusion
order that issues in this investigation.”). To the contrary, once a respondent has been
determined to be in violation of the Commission’s remedial orders, such orders extend to all
infringing products (e.g., respondent’s redesigned products), whether or not they were
adjudicated in the original investigation.
The Commission agrees with the FID that the record evidence establishes that the first
three factors specified above are satisfied. See FID at 29. With respect to factor (1) (scope of
the investigation), there is no dispute that the 2’-FL produced with the TTFL12 strain is within
PUBLIC VERSION
20
the scope of the investigation, which is defined in the notice of investigation as
“2’-fucosyllactose oligosaccharides.” See 83 Fed. Reg. at 28865. As to factor (2)
(importation), although Jennewein did not identify TTFL12 in its September 20, 2018 response
to Glycosyn’s request for admission as to importation (because it had not been imported at the
time), see CX-216C at 5, there is ample evidence that the 2’-FL product from that strain was
subsequently imported on October 11, 2018, prior to the close of fact discovery. See IA’s Pet. at
10-12 (citing FID at 34; RX-278C (Jennewein shipping invoice); RX-279C (Jennewein 2’-FL
material safety data sheet); RX-280C (summary of Jennewein 2’-FL importation); RX-385C
(Jennewein WS) at Q/As 135 (“180 g of 2’-FL produced by using the TTFL12 strain were
imported into the U.S.”), 171-72; RX-387C (Parkot WS) Q/As 101-110); Hr’g Tr. at 347:6-22,
348:7-25 (Parkot); id. at 215:24-216:7 (Jennewein)).
The record evidence also demonstrates that the TTFL12 strain satisfies factor (3)
(sufficiently fixed in design). As Jennewein’s witnesses testified, see Hr’g Tr. at 197:12-21
(Jennewein), “[t]he strain has been in development since 2012” and “[a] lot of different
fermentation runs have been done since then.” See also id. at 347:6-22 (Parkot) (discussing
certain records showing that Jennewein has actually produced 2’-FL using the TTFL12 strain).
Lastly, as to factor (4) (sufficient disclosure in discovery), the Commission disagrees
with the FID’s conclusion that Jennewein has not met its burden to establish that this factor is
satisfied. See FID at 29. Jennewein was required to provide sufficient (not extensive)22 fact
and expert discovery to put Glycosyn on notice of that strain and its relevant features. Cf. Two-
22 The FID recites both “sufficient” and “extensive” evidence (see, e.g., FID at 29, 32), but as
explained herein, the test for adjudicating redesigns does not require extensive discovery.
Rather, the test requires discovery that is sufficient for the complainant to assess the features
relevant to the asserted patent claims.
PUBLIC VERSION
21
Way Radio, 2018 WL 8648379 at *14 (“[T]he principal issues on review are (1) whether
[respondent] produced discovery that is sufficient to inform [complainant] with respect to the
redesigned product features relevant to the asserted . . . patents . . . ; and (2) whether
[complainant’s] decision not to assert infringement by the redesigned products with respect to
these [asserted] patents constitutes a failure to satisfy its burden to prove infringement.”).
The Commission finds that Jennewein presented sufficient documentary evidence as well
as fact and expert testimony to put Glycosyn on notice of the relevant features of the TTFL12
strain.23 Specifically, Jennewein identified the TTFL12 strain on September 14, 2018, in its
Ground Rule 7.2 disclosure (CX-226C) and in its interrogatory responses served on November 5,
2018 (CX-237C). Jennewein also produced two key documents, RX-320C and RX-382 (both
produced on August 21, 2018, well before November 5, 2018, the close of fact discovery),
supported by expert and witness testimony, showing the relevant features of the TTFL12 strain
and establishing that the strain does not infringe the asserted patent because it lacks an
exogenous functional β-galactosidase gene (lacZ). See Jennewein’s Resp. (citing RX-382 at 24
(Eur. App. No. 14 162 869.3) (showing that the TTFL12 strain was engineered to make lactose
inside the cell and to lack or inactivate the β-galactosidase gene because the gene otherwise
destroys the lactose feedstock needed to make 2’-FL)); see also RX-409C (Stephanopoulos
RWS) at Q/As 279-280 (“[RX-382] describes a preferred bacterial host cell lacking expression
of lacZ in one embodiment.”); RX-386C (Parschat WS) at Q/As 161 (“The lacZ gene . . . is
23 The Dissent dismisses witness testimony provided after the close of discovery and/or at the
hearing but such testimony is based on expert reports or deposition testimony which must be
produced during discovery (generally, such reports are not included in the record evidence). See
Order No. 24, Ground Rule 11.5.5 (“An expert’s testimony at the trial shall be limited in
accordance with the scope of his or her expert report(s), deposition testimony, or within the
discretion of the Chief Administrative Law Judge. Direct testimony from an expert that is
outside this scope will be excluded.”).
PUBLIC VERSION
22
actually detrimental since it degrades the lactose substrate needed to make 2’-FL. . . . Since no
addition of lactose is needed for 2’-FL production using the TTFL12 strain there is no lactose to
remove and the lacZ gene is unnecessary.”); Hr’g Tr. (Jennewein) at 226:25-227:7 (testifying
that TTFL12 strain lacked a lacZ gene because there is no surplus of lactose which would have
required β-galactosidase to eliminate the surplus); RX-385C (Jennewein24) at Q/As 166-174.
The FID finds that exhibits RX-320C and RX-382 have low probative value or provide
unreliable evidence of an accused product’s features. See FID at 33-34. However, the
testimonial (fact and expert) evidence establishes the relevance of the documents to Jennewein’s
non-infringement claims. See, e.g., RX-409C (Stephanopoulos RWS) at Q/As 272-86
(discussing RX-320C and Jennewein’s non-infringement theory, i.e., that the lacZ gene has been
deleted or inactivated and that TTFL12 was not further engineered to insert a functional
exogenous β-galactosidase gene); Hr’g Tr. (Parschat) at 384:10-17 (testifying that “[t]he
complete lacZ gene as occurs in the operon is not present in the TTFL-12 strain”); RX-387C
(Parkot WS) at Q/A 85 (“The TTFL12 strain is a 2’-FL production strain that has no β-
galactosidase (lacZ) gene and does not use lactose to synthesize 2’-FL.”); accord IA’s Pet. at 13-
14, 16-17, 19-22, 19-20 (“[T]he ALJ appears to have overlooked the hearing testimony of . . .
Ms. Parkot . . . [which] is sufficient to supply the missing link between the 2’-FL that was
‘actually produced’ and the TTFL12 strain described in the draft Jennewein article, RX-320C.”),
20 (“RX-382 demonstrates that Respondent had developed a ‘total fermentation’ strain by no
later than early 2014, when the European patent application was filed.”).
With regard to the FID’s comment that “[a]n earnest effort to force TTFL12 into the
investigation would have seen Jennewein prove to Glycosyn the nature of TTFL12, and how it
24 Stefan Jennewein is the Managing Director of Jennewein.
PUBLIC VERSION
23
had been used to produce imported 2’-FL, before the very last day of fact discovery,” FID at 35,
the Commission notes that the parties do not dispute that Jennewein produced relevant discovery
as to TTFL12 within the fact discovery period established by the procedural schedule. If
Glycosyn and its expert deemed such evidence to be insufficient, Glycosyn could and should
have taken available procedural steps, such as a motion to reopen discovery or to compel further
discovery, because the burden of establishing infringement remains with Glycosyn.25
The Commission also finds that Glycosyn failed to satisfy its burden of establishing
infringement with respect to Jennewein’s TTFL12 strain. See Medtronic, Inc. v. Mirowski
Family Ventures, LLC, 571 U.S. 191, 194 (2014) (holding that the burden of proving
infringement remains with the patentee even in a declaratory judgment action to establish non-
infringement); Electronic Digital Media Devices, 2013 WL 10734395, *71 (“When confronted
with Samsung’s evidence of noninfringement, Apple had an obligation to either present evidence
of infringement or withdraw its allegations concerning these products, but it did neither.”).
Unlike the accused #1540 strain and its derivative, there is no evidence that a lacZΩ
fragment was inserted into the TTFL12 strain or any of its precursors. See RX-320C at 17-18
25 In Glycosyn’s submissions to the Commission in response to the notice of review, Glycosyn
does not contend that the testimony of fact witnesses or the opinions of Jennewein’s expert
witness provided in discovery were insufficient to apprise it of information relating to the
TTFL12 strain or Jennewein’s non-infringement theory. Glycosyn’s Resp. at 35-39, Glycosyn’s
Reply at 13-16. Indeed, the IA points out that “Glycosyn failed to question any witnesses about
the product during fact discovery, or to test a sample of the TTFL12 strain or 2’-FL made using
the TTFL12 strain during its onsite testing at Jennewein’s facility.” IA’s Resp. at 34; see also
Jennewein Resp. at 32-33 (“Glycosyn never questioned any of Jennewein’s fact witnesses at
their depositions about the properties of the TTFL12 strain. SIB at 71. And when it traveled to
Jennewein’s German facility to conduct testing of Jennewein’s other production strains – six
weeks after Jennewein had disclosed TTFL12 and its genetic composition – Glycosyn never
asked to test it.”). Glycosyn does not deny the IA and Jennewein’s assertions that it chose not to
question witnesses or to test the TTFL12 strain or 2’-FL made using the TTFL12 strain during its
on-site testing in Germany. Glycosyn’s Reply at 15.
PUBLIC VERSION
24
(Table 1); RX-409C (Stephanopoulos RWS) at Q/As 277-278 (testifying that “the lacZ gene has
been deleted or inactivated” and that “TTFL12 was not further engineered to insert a functional
exogenous β-galactosidase gene”); see also Hr’g Tr. (Parschat) at 384:10-17 (“The complete
lacZ gene as occurs in the operon is not present in the TTFL-12 strain.”); RX-386C (Parschat
WS) at Q/As 159-160 (“[T]here is no β-galactosidase gene so the strain cannot produce
β-galactosidase.”); RX-387C (Parkot WS) at Q/A 85 (“The TTFL12 strain is a 2’-FL production
strain that has no β-galactosidase (lacZ) gene and does not use lactose to synthesize 2’-FL.”);
RX-385C (Jennewein) at Q/As 160-62, 176-177 (testifying that “[Jennewein] deleted the lacZ
gene and also did not insert any β-galactosidase gene or complementary β-galactosidase gene
fragments so there can be no β-galactosidase activity”); Hr’g Tr. (Jennewein) at 227:8-13
(testifying that he wrote the RX-320 article). Thus, based on the record evidence, the
Commission finds that the TTFL12 strain does not contain an “exogenous functional β-
galactosidase gene comprising a detectable level of β-galactosidase activity” as required by the
Asserted Claims. Accord IA’s Resp. at 3-7; Jennewein’s Resp. at 2-11.
Unlike Jennewein, Glycosyn presented no expert evidence to establish the presence of a
lacZ gene or lacZΩ fragment in the TTFL12 strain, and thereby infringement by that strain,
arguing instead that Jennewein presented insufficient discovery. See Glycosyn’s Resp. at 11;
see also Centricut, LLC v. Esab Group, Inc., 390 F.3d 1361, 1370 (Fed. Cir. 2004) (finding no
infringement where “a patent law plaintiff who presents complex subject matter without inputs
from experts qualified on the relevant points in issue when the accused infringer has negated
PUBLIC VERSION
25
infringement with its own expert.”).26 Glycosyn asserts that “TTFL12[] contain[s] a functional
lacZα β-galactosidase gene,” but Glycosyn says nothing about lacZΩ. See Glycosyn’s Resp. at
11-14. As the FID finds, “[i]t is the combination of lacZα and lacZΩ which is equivalent to the
claimed ‘β-galactosidase gene,’ and this combination does not exist until lacZΩ is inserted into
the bacterium’s genome from outside the organism.” See FID at 45; see also Hr’g Tr. (Prather)
at 436:1-6 (agreeing that “the alpha fragment[] . . . cannot make beta-galactosidase on its own”).
Nor is there any evidence that the lacZΩ was inserted in the TTFL12 strain. Thus, the
Commission finds that Glycosyn failed to establish that the TTFL12 strain contains an
“exogenous functional β-galactosidase gene comprising a detectable level of β-galactosidase
activity” as required by the Asserted Claims. Accordingly, Glycosyn failed to satisfy its burden
to establish infringement by the TTFL12 strain.27
Thus, the Commission has determined to reverse the FID’s decision not to adjudicate
infringement with respect to the TTFL12 strain and provides its reasoning above as to why such
adjudication is warranted. The Commission further finds that the TTFL12 strain does not
infringe the Asserted Claims as discussed above.
26 The ALJ determined that “one of ordinary skill in the art would have (1) a Ph.D in molecular
biology, biochemistry, or chemical engineering, or an equivalent field, and 1-2 years of
experience working with E. coli bacteria or related systems, or (2) a lower level degree (e.g., a
M.A.) in a similar field to those listed above, but a greater amount of relevant working
experience (e.g., 5-6 years of experience working with E. coli bacteria or related systems).” See
Order No. 22 at 7.
27 Glycosyn also argues that 35 U.S.C. § 295 creates a presumption that Jennewein’s product
was made by the patented process, and that Jennewein has the burden to establish that the
product was not made by the patented process. See Glycosyn’s Resp. at 14-18. Glycosyn
waived this argument both before the ALJ and the Commission. See Order No. 38 at 2-3 (June
14, 2019); 19 C.F.R. § 210.43(b)-(c); see Finnigan Corp. v. ITC, 180 F.3d 1354, 1362-63 (Fed.
Cir. 1999) (“A party seeking review . . . of a determination by the Commission must specifically
assert the error made by the ALJ in its petition for review to the Commission.”). In any event,
the record in this investigation shows that any presumption under 35 U.S.C. § 295 is overcome
by Jennewein as to the TTFL12 strain.
PUBLIC VERSION
26
IV. REMEDY, PUBLIC INTEREST, AND BONDING
The RD recommends that the Commission issue an LEO barring entry of Jennewein’s
articles that infringe the asserted patent claims. See RD at 116-18. The RD does not
recommend that the Commission issue a CDO against Jennewein.28 The RD further
recommends that the Commission impose a five (5) percent bond during the period of
Presidential review. See id. at 118-19. Still further, as directed by the Commission, the RD
provides findings with respect to the public interest and recommends that the Commission
determine that the public interest factors do not preclude entry of the proposed LEO. See id. at
119-20.
A. Limited Exclusion Order
The Commission has “broad discretion in selecting the form, scope, and extent of the
remedy.” Viscofan, S.A. v. US. Int’1 Trade Comm’n, 787 F.2d 544, 548 (Fed. Cir. 1986).
Section 337(d)(1) provides that “[i]f the Commission determines, as a result of an
investigation under this section, that there is a violation of this section, it shall direct that the
articles concerned, imported by any person violating the provision of this section, be excluded
from entry into the United States, unless, after considering the [public interest], it finds that such
articles should not be excluded from entry.” 19 U.S.C. § 1337(d)(1). See also Spansion, Inc. v.
Int’l Trade Comm’n, 629 F.3d 1331, 1358 (Fed. Cir. 2010) (“[T]he Commission is required to
issue an exclusion order upon the finding of a Section 337 violation absent a finding that the
effects of one of the statutorily-enumerated public interest factors counsel otherwise.”).
The RD recommends that the Commission issue an LEO excluding Jennewein’s
infringing 2’-FL product. See RD at 117. Consistent with its decision not to adjudicate the
28 Glycosyn does not request a CDO against Jennewein.
PUBLIC VERSION
27
TTFL12 strain, the RD recommends against a carve-out for 2’-FL product made with the
TTFL12 strains. See id. The RD, however, recommends “a certification provision, wherein
said certification is required to state with particularity the grounds of non-infringement of the
imported oligosaccharide and be accompanied by sufficient corroborating evidence of the type
provided in discovery in this investigation.” See id. at 118.
The Commission has determined to issue an LEO barring importation of
2’-fucosyllactose oligosaccharides that infringe the Asserted Claims. Consistent with its finding
that the TTFL12 strain does not infringe the Asserted Claims, the Commission has determined to
include an explicit carve-out for 2’-FL product made with the TTFL12 strain. In addition, the
Commission has determined that the LEO should include the standard certification provision.
The Commission finds that the certification provision is justified because it may not be readily
apparent by inspection whether the imported article is covered or exempted by the LEO, i.e.,
whether the imported 2’-FL product is made by an infringing strain (e.g., bacterial strains #1540
and its derivative) or by a non-infringing strain (i.e., the TTFL12 strain). See Certain Graphics
Sys., Components Thereof, & Consumer Prods. Containing the Same, Inv. No. 337-TA-1044,
Comm’n Op. at 65-66 (Sept. 18, 2018). To be clear, as the Commission has previously held,
“[t]he standard certification ‘does not apply to redesigns that have not been adjudicated as non-
infringing.’” See Automated Teller Machines, ATM Modules, Components Thereof, & Prods.
Containing the Same, Inv. No. 337-TA-972, Comm’n Op., 2017 WL 11198798, *16-17 (June
12, 2017) (quoting Certain Marine Sonar Imaging Devices, Including Downscan & Sidescan
Devices, Prods. Containing the Same, & Components Thereof, Inv. No. 337-TA-921, Commn
Op., 2016 WL 10987364, *53 (Jan. 6, 2016)).
PUBLIC VERSION
28
Thus, the Commission has determined to issue an LEO: (1) covering “2’-fucosyllactose
oligosaccharides that infringe the Asserted Claims”; (2) including the standard certification
provision in the LEO; and (3) including an explicit carve-out for 2’-FL product made with the
TTFL12 strain.
B. The Public Interest
Section 337 requires the Commission, upon finding a violation of section 337, to issue an
LEO “unless, after considering the effect of such exclusion upon the public health and welfare,
competitive conditions in the United States economy, the production of like or directly
competitive articles in the United States, and United States consumers, it finds that such articles
should not be excluded from entry.” 19 U.S.C. § 1337(d)(l).
The RD “do[es] not find the requested [LEO] would meaningfully impact public health
and welfare, competitive conditions, domestic production of articles, or U.S. consumers.” See
RD at 120. The RD finds that “the purpose of providing 2’-FL in infant formula is to improve
public health, [but] the evidence shows that the otherwise well-established market has only
recently begun including 2’-FL into its products, and with amounts that have unclear efficacy
levels.” See id. The RD concludes that “[t]he U.S. public is therefore not dependent on such
products, as of yet.” See id.
1. Public Health and Welfare
Jennewein argues that “2’-FL has important health benefits, including its use in infant
formula,” and “at this time, Jennewein is the only company that can supply 2’-FL to the U.S.
market in commercial quantities.” See Jennewein’s PI Br. at 1. Jennewein further argues that
its product is incorporated as an ingredient in Abbott’s Similac® product which is “the number
one selling infant formula” in the U.S. See id. (citing RX-385C (Jennewein WS) at Q/A 187).
PUBLIC VERSION
29
Jennewein faults the RD for stating that the “market has only recently begun including”
its 2’-FL product. See id. at 2. To the contrary, Jennewein continues, “Abbott has been adding
2’-FL in its infant formula since 2016” and “there is no reason to doubt that Abbott chooses to
include 2’-FL in its Similac® because of the health benefits of 2’-FL.” See id. (citing CX-205);
accord Abbott’s PI Br. at 1-3.
Glycosyn does not dispute that “HMOs provide health benefits.” See Glycosyn’s
Remedy Br. at 2. Glycosyn, however, argues that the proposed LEO will not adversely impact
the public health or welfare. See id. at 2-4. Glycosyn reasons that “only a subsection of infant
formulas in the United States contain 2’-FL, and that even in those that do, the amounts ‘have
unclear efficacy levels.’” See id. at 3 (citing RD at 120); accord IA’s Resp. at 39-40.
Glycosyn also explains that there are “many entities that can meet the demand for 2’-FL in the
United States.” See Glycosyn’s Remedy Br. at 4; IA’s Resp. at 40-42; DuPont PI Br. at 1-2.
The Commission finds no evidence that the LEO would adversely affect the public health
and welfare, particularly in view of the Commission’s determination that using the TTFL12
strain does not infringe the Asserted Claims. For example, Jennewein can import its 2’-FL
product if it certifies that such product was produced using the TFL12 strain.
Thus, the Commission finds that the LEO discussed supra section IV(A) would not have
an adverse effect on the public health and welfare.
2. Competitive Conditions in the United States Economy
Jennewein argues that “[it] is the only company currently producing 2’-FL for infants in
the U.S. market on a commercial scale.” See Jennewein’s PI Br. at 4 (citing Hr’g Tr.
(Newburg29) at 57:3-4; RX-385C (Jennewein WS) at Q/A 188). According to Jennewein, “there
29 Howard Newburg is Co-Chief Executive Officer and Chief Financial Officer of Glycosyn.
PUBLIC VERSION
30
is no showing that Glycosyn can offer any product at this time or in the near future, let alone
produce quantities sufficient to replace Jennewein’s production.” See id. at 4.
Glycosyn disagrees and argues that “[its] licensee, Friesland, and other third-party
industry leaders can replace the subject articles in the U.S. in a commercially reasonable time.”
See Glycosyn’s Remedy Br. at 4-5; accord IA’s Resp. at 44; DuPont PI Br. at 1-2.
The Commission finds no evidence that the LEO would adversely affect the competitive
conditions in the United States economy, particularly in view of the Commission’s determination
that using the TTFL12 strain does not infringe the Asserted Claims. For example, Jennewein
can import its 2’-FL product if it certifies that such product was produced using the TTFL12
strain. Moreover, the evidence indicates alternative suppliers (including Glycosyn,
FrieslandCampina, Glycom, and DuPont) can also replace the excluded products within a
commercially reasonable time. See IA’s Resp. at 41-42 (citing, inter alia, RX-385C (Jennewein
WS) at Q/A 135; CX-3C (Newburg WS) Q/As 76, 79-80).
Thus, the Commission finds that the LEO discussed supra section IV(A) would not have
an adverse effect on the competitive conditions in the United States economy.
3. The Production of Like or Directly Competitive Articles
Jennewein does not address this factor specifically, but its arguments as to this factor
appear to be the same as discussed above in connection with competitive conditions in the
United States economy. See Jennewein’s PI Br. at 3-4. Both Glycosyn and the IA argue that
the proposed LEO will have no effect on this factor because there is no evidence that the 2’-FL
product is produced domestically in the United States. See Glycosyn’s Remedy Br. at 7; accord
IA’s Resp. at 45.
The Commission finds that the presence of alternative suppliers capable of providing
alternative non-infringing 2’-FL product (including Glycosyn, DuPont, and Jennewein itself)
PUBLIC VERSION
31
negates any evidence that the LEO would adversely affect the production of like or directly
competitive articles, particularly in view of the Commission’s determination that using the
TTFL12 strain does not infringe the Asserted Claims. For example, Jennewein can import its
2’-FL product if it certifies that such product was produced using the TTFL12 strain.
Thus, the Commission finds that the LEO discussed supra section IV(A) would not have
an adverse effect on the production of like or directly competitive articles.
4. United States Consumers
Jennewein argues that the requested LEO would have a severely negative impact on U.S.
consumers. See Jennewein’s PI Br. at 4-5. Jennewein explains that it is “the only company
making GRAS-approved 2’-FL on a commercial scale for the U.S. market.” See id. Glycosyn
asserts that “alternative suppliers of biosynthesized 2’-FL by Glycosyn’s licensee Friesland,
Glycom, and DuPont can provide ample replacement articles of like or directly competitive
products.” See Glycosyn’s Remedy Br. at 8; accord IA’s Resp. at 46. Glycosyn also notes that
“Friesland received GRAS approval from the FDA on April 6, 2018, to manufacture 2’-FL.”
See Glycosyn’s Remedy Br. at 4.
The Commission finds that the presence of alternative suppliers capable of providing
non-infringing 2’-FL product (including DuPont and Jennewein itself) negates any evidence that
the LEO would adversely affect U.S. consumers, particularly in view of the Commission’s
determination that using the TTFL12 strain does not infringe the Asserted Claims. For example,
Jennewein can import its 2’-FL product if it certifies that such product was produced using the
TTFL12 strain.
Thus, the Commission finds that the LEO discussed supra section IV(A) would not have
an adverse effect on U.S. consumers.
PUBLIC VERSION
32
5. Conclusion
Based on the record evidence, the Commission finds that an LEO directed against
Jennewein’s infringing articles, and including a standard certification provision and an explicit
carve-out for articles produced using Jennewein’s non-infringing TTFL12 strain, would cause
little to no harm to the public health and welfare, the competitive conditions in the United States
economy, the production of like or directly competitive products in the United States, and United
States consumers. Thus, after considering the parties’ submissions and the effect that remedial
orders would have on the public interest, the Commission has determined to issue a limited
exclusion order.
C. Bonding
If the Commission enters an exclusion order or a cease and desist order, a respondent
may continue to import and sell its products during the 60-day period of Presidential review
under a bond in an amount determined by the Commission to be “sufficient to protect the
complainant from any injury.” 19 U.S.C. § 1337(j)(3); see also 19 C.F.R. § 210.50(a)(3).
When reliable price information is available in the record, the Commission has often set
the bond in an amount that would eliminate the price differential between the domestic product
and the imported, infringing product. See Certain Microsphere Adhesives, Processes for
Making Same, & Prods. Containing Same, Including Self-stick Repositionable Notes, Inv. No.
337-TA-366, USITC Pub. No. 2949, Comm’n Op. at 24 (Jan. 16, 1996). The Commission also
has used a reasonable royalty rate to set the bond amount where a reasonable royalty rate could
be ascertained from the evidence in the record. See, e.g., Certain Audio Digital-to-Analog
Converters & Prods. Containing Same, Inv. No. 337-TA-499, Comm’n Op. at 25 (Mar. 3, 2005).
Where the record establishes that the calculation of a price differential is impractical or there is
insufficient evidence in the record to determine a reasonable royalty, the Commission has
PUBLIC VERSION
33
imposed a 100 percent bond. See, e.g., Certain Liquid Crystal Display Modules, Prods.
Containing Same, & Methods Using the Same, Inv. No. 337-TA-634, Comm’n Op. at 6-7 (Nov.
24, 2009). The complainant, however, bears the burden of establishing the need for a bond.
Certain Rubber Antidegradants, Components Thereof & Prods. Containing Same, Inv. No. 337-
TA-533, USITC Pub. No. 3975, Comm’n Op. at 40 (July 21, 2006).
As stipulated by the parties, the RD recommends a bond of five (5) percent of the entered
value of Jennewein’s 2’-FL product during the period of Presidential review. See RD at 114-
115 (citing JX-7 (stipulation regarding bond)). Consistent with the parties’ agreement and the
RD’s recommendation, the Commission has determined that a bond in the amount of five (5)
percent of the entered value of the imported products is appropriate for subject imports entered
during the period of Presidential review.
V. CONCLUSION
For the reasons set forth herein, the Commission determines that complainant Glycosyn
has established a violation of section 337 by respondent Jennewein based on the infringement of
the Asserted Claims of the ՚018 patent. Accordingly, the investigation is terminated with a
finding of a violation of section 337. The Commission determines that the appropriate remedy
is an LEO directed against Jennewein’s infringing human milk oligosaccharides, that the public
interest factors do not weigh against issuing that remedy, and that the bond during the
Presidential review period is set in the amount of five (5) percent of the entered value of the
infringing articles.
By order of the Commission.
Lisa R. Barton
PUBLIC VERSION
Secretary to the Commission
Issued: June 8, 2020
34
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND
METHODS OF PRODUCING THE SAME
Inv. No. 337-TA-1120
PUBLIC CERTIFICATE OF SERVICE
I, Lisa R. Barton, hereby certify that the attached COMMISSION OPINION has
been served via EDIS upon the Commission Investigative Attorney, Lisa Murray, Esq., and
the following parties as indicated, on June 8, 2020.
Lisa R. Barton, Secretary
U.S. International Trade Commission
500 E Street, SW, Room 112
Washington, DC 20436
On Behalf of Complainant Glycosyn LLC:
Michael C. Newman, Esq.
MINTZ LEVIN COHN FERRIS GLOVSKY AND POPEO, PC
1 Financial Center
Boston, MA 02111
Email: MCNewman@mintz.com
☐ Via Hand Delivery
☐ Via Express Delivery
☐ Via First Class Mail
☒ Other: Email Notification
of Availability to Download
On Behalf of Respondent Jennewein Biotechnologie GmbH:
Gary M. Hnath
MAYER BROWN LLP
1999 K Street, NW
Washington, DC 20006
Email: ghnath@mayerbrown.com
☐ Via Hand Delivery
☐ Via Express Delivery
☐ Via First Class Mail
☒ Other: Email Notification
of Availability to Download
PUBLIC VERSION
1
UNITED STATES INTERNATIONAL TRADE COMMISSION
Washington, D.C.
In the Matter of
CERTAIN HUMAN MILK
OLIGOSACCHARIDES AND
METHODS OF PRODUCING
THE SAME
Inv. No. 337-TA-1120
SEPARATE VIEWS OF COMMISSIONER SCHMIDTLEIN
CONCURRING IN PART AND DISSENTING IN PART
I concur with and join Part III(A) of the majority opinion, which affirms the ID’s finding
that the Accused Strains include an exogenous functional β-galactosidase gene. I respectfully
dissent from Part III(B) of the majority opinion, which concludes that the administrative law
judge (“ALJ”) should have adjudicated whether the TTFL12 strain infringes the asserted method
claims. Given the parties’ briefing and the evidence and exhibits cited therein, I would affirm
the ID’s conclusion that the TTFL12 strain was not subject to sufficient discovery and not reach
the question of whether using the TTFL12 strain infringes the asserted claims.
In determining whether an alternative or redesigned product identified by a respondent
should be adjudicated, the Commission has considered whether there has been sufficient
discovery on the product. See, e.g., Certain Electronic Digital Media Devices and Components
Thereof, Inv. No. 337-TA-796, Comm’n Op. at 103–05 (Sept. 6, 2013) (“Electronic Digital
Media Devices”) (finding that the complainant took substantial discovery on the design-around
products, which included product inspections by complainant’s expert, source code production,
and depositions of respondent’s witnesses); Certain Multiple Mode Outdoor Grills and Parts
Thereof, Inv. No. 337-TA-895, Comm’n Op. at 15–20 (July 23, 2014) (“Outdoor Grills”)
PUBLIC VERSION
2
(finding that the respondent produced photographs and product manuals that were sufficient to
show that certain redesigned products did not infringe the asserted claims); Certain Television
Sets, Certain Television Receivers, Television Tuners, and Components Thereof, Inv. No. 337-
TA-910, Order No. 46 (Initial Determination) at 23–29 (Nov. 28, 2014) (Lord, J.) (“Television
Sets”) (not reviewed) (listing 22 facts establishing that respondents had provided sufficient
discovery on an alternative product; notably, the respondents identified the alternative product
before the investigation was instituted, produced 9,000 pages of technical documents, and
submitted an expert report opining on non-infringement). Further, as these decisions show, the
Commission’s analysis of the “sufficient discovery” question focuses on the documents and
contentions produced before the close of fact and expert discovery.
In the present investigation, the majority opinion finds that Jennewein provided sufficient
discovery on the TTFL12 strain by combining the limited disclosures and documents produced
during discovery with hearing testimony and witness statements provided after the close of
discovery. With regard to the information produced during the discovery period, the majority
opinion points to (1) the mandatory Ground Rule 7.2 disclosure and interrogatory responses
served on the last day of fact discovery that identified the TTFL12 stain and (2) a draft article
and patent application that purportedly disclose the TTFL12 strain.1 Maj. Op. at 21–22. Like
1 The majority opinion states that a respondent must present “sufficient documentary evidence as
well as fact and expert testimony to put [the complainant] on notice of the relevant features of
the [alternative or redesigned product].” Maj. Op. at 21 (emphasis added, footnote omitted).
But, as the decisions cited above show, the threshold for demonstrating that the respondent has
provided sufficient discovery on a redesigned or alternative product is higher than simply putting
the complainant “on notice” of a product or its relevant features. For example, the Commission
has considered whether the discovery proffered on the redesigned products was analogous to the
information and materials the parties cited in their infringement arguments. See Outdoor Grills,
Comm’n Op. at 18 (“the parties premised their infringement positions based on photographs or
diagrams, thereby demonstrating that this particular limitation was readily ascertainable from the
PUBLIC VERSION
3
the ALJ, I find this discovery insufficient.
A review of Jennewein’s discovery responses show that Jennewein overwhelmingly
focused on the #1540 strain and, importantly, repeatedly disavowed importation of 2’-FL product
made by any other strain besides the #1540 strain. For instance, during discovery, Jennewein
identified the #1540 strain as its only production strain for the U.S. market2 and admitted in
response to requests for admissions that the “#1540 is the only strain Jennewein uses to produce
the 2’-FL that is imported into the United States.”3 In the mandatory ground rule disclosure
cited by the majority opinion, Jennewein identified the TTFL12 strain by referencing just one
document, the undated, unpublished draft article (RX-320C).4 Subsequent to this disclosure, on
October 20, Jennewein’s founder testified in a deposition that the #1540 strain was “the only
strain that Jennewein was using to create” the product that was being imported.5 Four days later,
Jennewein provided interrogatory responses stating that Jennewein had imported 2’-FL made
with the TTFL12 strain.6 On the last day of discovery, Jennewein provided supplemental
responses stating that Jennewein had imported 2’-FL made with the TTFL12 strain on October
discovery provided by Respondents at the time the motion was filed.”); Television Sets, Order
No. 46 at 21, 27–28; see also Certain Coaxial Cable Connectors, 337-TA-938, Order No. 9
(Initial Determination) at 4 (Aug. 21, 2015) (Lord, J.) (“Cable Connectors”) (not reviewed) (in
finding that respondent’s new designs did not infringe, the ALJ noted that the same type of
evidence used to show infringement of the legacy designs “applies to all of the new C3 designs,
for which [respondent] produced technical drawings and expert [deposition] testimony”).
2 See CX-228C (Interrogatory Responses) at 5.
3 See CX-215C (Responses to Requests for Admission) at 4–5.
4 Because the draft article is undated, it does not show when Jennewein produced 2’-FL with the
TTFL12 strain. Thus, the article does not show that the 2’-FL sample Jennewein imported was
made with the TTFL12 strain.
5 See Tr. (Jennewein) at 189 (affirming Oct. 20, 2018 deposition testimony).
6 See CX-236C (Interrogatory Responses) at 4–6.
PUBLIC VERSION
4
12.7 In the supplemental responses, Jennewein provided, for the first time, its contentions that
using the TTFL12 strain does not infringe the asserted claims.8
Given that Jennewein repeatedly disavowed during discovery that it was producing and
importing product made with an alternative strain, I do not consider that the initial ground rule
disclosure of an undated, unpublished article, along with Jennewein’s crafty approach to
responding to written discovery, to provide a basis for finding that Jennewein provided
“sufficient” discovery.
Moreover, the absence of the type of discovery that typically informs the “sufficient
discovery” inquiry also shows that Jennewein did not provide sufficient discovery on the
TTFL12 strain. For example, Jennewein points to no expert report in relation to the TTFL12
strain.9 Indeed, the statement of undisputed material facts from Jennewein’s motion for
summary determination lacks an allegation that its expert opined on TTFL12. 10 While the
majority opinion relies on witness statements provided after the close of discovery and hearing
testimony to buttress the documents produced during discovery, this evidence simply is not
discovery.11 As such, that evidence is not germane to the question before the Commission,
7 See CX-236C (Interrogatory Responses) at 4–6; CX-237C (First Amended Interrogatory
Responses) at 2, 9, 18–20; RX-278C (delivery slip dated Oct. 12, 2018, indicating 180g of 2’-FL
was imported); RX-280C (production summary indicating 180g of 2’-FL made using the
TTFL12 strain had been imported).
8 See CX-237C (First Amended Interrogatory Responses) at 2, 9, 18–20.
9 See, e.g., Electronic Digital Media Devices, Television Sets, Cable Connectors, supra. In these
investigations, respondents’ experts’ opinions were relied on to conclude the alternative products
had been subject to sufficient discovery and that they did not infringe.
10 See Jennewein Mem. in Supp. of Mot. for Summary Det. at 8–10 (EDIS Doc. ID No. 663068,
filed Nov. 30, 2018).
11 The majority opinion observes that this opinion “dismisses” witness testimony provided after
the close of discovery and finds that the “testimony is based on expert reports or deposition
PUBLIC VERSION
5
which concerns what was provided during the discovery period.
Likewise, the total absence of materials similar to what the parties used in their
infringement and domestic industry technical prong contentions further shows that the discovery
Jennewein provided is insufficient. For instance, Glycosyn’s expert relied on lab notebooks,
weekly lab meeting presentations, internal databases and bioreactor run spreadsheets, Glycosyn’s
GRAS notice, and analytical testing in formulating her opinion that Glycosyn practices claim 1
of the asserted patent.12 In opining on infringement, Glycosyn’s expert relied on many sources
of evidence, including Jennewein’s responses to Glycosyn’s requests for admission, Jennewein’s
interrogatory responses, Jennewein’s GRAS notice, photographs of Jennewein’s production
equipment, and Jennewein’s in-house analytical testing.13 Jennewein’s expert, in opining on
non-infringement, relied on Jennewein’s GRAS notice and analytical testing of the #1540 and
#1540 derivative strains.14 In my view, the absence of any of these types of documents further
indicates that Jennewein failed to provide sufficient discovery. Accordingly, Glycosyn was not
testimony which must be produced during discovery (generally, such reports are not included in
the record evidence).” Maj. Op. at 21 n.23. The majority opinion, however, points to no portion
of an expert report or deposition transcript addressing the TTFL12 strain, but rather just assumes
that Jennewein’s expert’s report and its employees’ deposition testimony pertain to the relevant
hearing testimony. Further, this aspect of the majority opinion stands apart from Commission
precedent that has explicitly credited expert reports and deposition testimony in concluding that
the respondent provided sufficient discovery. See Two-Way Radio, Comm’n Op. at 26 (noting
the respondent “produced discovery (including source code, corporate witness depositions, and
expert reports), as well as testimonial evidence at the hearing, regarding its non-infringement
contentions”); Television Sets, ID at 30 (noting that respondents submitted “an extensive expert
report . . . on non-infringement”); Cable Connectors, ID at 2 (noting that respondents “submitted
a noninfringement expert report”). Ultimately, the sufficient-discovery factor hinges on what the
respondent provided in discovery, not on what evidence may have been introduced at a hearing.
12 See CX-4C (Prather WS) at Q/A 107, 112, 124, 125, and 149.
13 Id. at Q/A 434, 435, 437, 440, 486.
14 See RX-409C (Stephanopoulos RWS) at Q/A 13, 43–46.
PUBLIC VERSION
6
provided sufficient information regarding the TTFL12 strain prior to the close of discovery to
allow it to decide whether to assert infringement.15
In sum, while I do not mean to suggest that all or even a substantial number of the types
of discovery discussed above must be provided in order to put a redesigned or alternative product
at issue, it is my view that the total absence of these types of documents in this case along with
Jennewein’s repeated assertions that it was not producing and importing 2’-FL made with the
TTFL12 strain demonstrates that Jennewein did not provide sufficient discovery on the TTFL12
strain.16 Consequently, I find no error in the ALJ’s decision and therefore respectfully dissent
from Part III(B) of the majority opinion.
15 The majority opinion finds that Glycosyn “does not contend that” the discovery Jennewein did
provide was “insufficient to apprise it of information relating to the TTFL12 strain or
Jennewein’s non-infringement theory.” Maj. Op. at 23 n.25. This approach, however, obligates
a complainant to investigate alternative or redesigned products of dubious viability, including
products that a respondent has repeatedly represented were not made altogether, intended for, or
imported into the U.S. market.
16 As I find that Jennewein failed to provide sufficient discovery on the TTFL12 strain, I also
find that Jennewein failed to show that its process of making 2’-FL with the TTFL12 strain is
sufficiently fixed in design. Compare Maj. Op. at 20 (finding the TTFL12 strain fixed in
design). For this factor, the majority relies on two citations to the hearing transcript. See id. In
the testimony, Dr. Jennewein averred that Jennewein has been developing the strain since 2012
and that it has conducted “[a] lot of different fermentation runs” since 2012. See Tr. (Jennewein)
at 197. Dr. Parkot averred that she prepared the TTFL12 sample for importation and that the
company could provide “manufacturing documentation” on request. See Tr. (Parkot) at 347.
During discovery, however, Jennewein repeatedly disavowed that it was producing and
importing product made with the TTFL12 strain. Similarly, although Jennewein apparently can
provide manufacturing documents that might substantiate its argument, it did not produce them
during discovery. Taken together, this testimony does not establish that the TTFL12 strain and
its attendant production process is sufficiently fixed in design. See Certain GPS Chips,
Associated Software and Systems, and Prods. Containing Same, Inv. No. 337-TA-596, USITC
Pub. No. 4133, Initial Determination at 51–55 (June 13, 2008) (Luckern, J.) (unreviewed)
(declining to adjudicate a new product, where, amongst other things, the product was subject to
modification in light of subsequent testing); see also Tr. (Jennewein) at 205–206 (describing a
lengthy document-finalization process and the need for additional analysis of the TTFL12
strain).
UNITED STATES INTERNATIONAL TRADE COMMISSION
Washington, D.C.
In the Matter of
CERTAIN HUMAN MILK _ _
InVۤtlgatl0Il N0.
METHODS OF PRODUCING
THE SAME
NOTICE OF COMMISSION DECISION TO REVIEW IN PART A FINAL
INITIAL DETERMINATION FINDING A VIOLATION OF SECTION 337;
SCHEDULE FOR FILING WRITTEN SUBMISSIONS ON THE ISSUES UNDER
REVIEW AND ON REMEDY, THE PUBLIC INTEREST, AND BONDING
AGENCY: U.S. Intemational Trade Commission.
ACTION: Notice.
SUMMARY: Notice is hereby given that the U.S. International Trade Commission has
determined to review in part a final initial determination (“FID”) of the presiding administrative
law judge (“ALI”) finding a violation of section 337 of the Tariff Act of 1930, as amended.
The Commission requests briefing from the parties on certain issues under review, as set forth in
this notice. The Commission also requests briefing from the parties, interested persons, and
government agencies on the issues of remedy, the public interest, and bonding.
FOR FURTHER INFORMATION CONTACT: Houda Morad, Office of the General
Counsel, U.S. International Trade Commission, 500 E Street SW., Washington, DC 20436,
telephone (202) 708-4716. Copies of non-confidential documents filed in connection with this
investigation are or will be available for inspection during official business hours (8:45 a.m. to
5:15 pm.) in the Office of the Secretary, U.S. International Trade Commission, 500 E Street
SW., Washington, D.C. 20436, telephone (202) 205-2000. General information concerning the
Commission may also be obtained by accessing its Internet sewer at httgs://www.usitc.gov. The
public record for this investigation may be viewed on the Commission’s electronic docket
(EDIS) at httgs://edis. usitc.gov. Hearing-impaired persons are advised that information on this
matter can be obtained by contacting the Commission’s TDD terminal on (202) 205-1810.
SUPPLEMENTARY INFORMATION: The Cormnissioninstituted this investigationon Jtme
21, 2018, based on a complaint, as amended and supplemented, filed on behalf of Glycosyn LLC
of Waltham, Massachusetts (“Glycosyn”). See 83 Fed. Reg. 28865 (June 21, 2018). The
complaint, as amended and supplemented, alleges violations of section 337 of the Tariff Act of
1930, as amended, 19 U.S.C. 1337 (“section 337”), based upon the importation into the United
States, the sale for importation, and the sale within the United States after importation of certain
human milk oligosaccharides by reason of infringement of claims l-40 of U.S. Patent No.
9,453,230 (“the ’230 patent”) and claims 1-28 of U.S. Patent No. 9,970,018 (“the ’0l8 patent”).
1
See id. The notice of investigation named Jennewein Biotechnologie GmbH (“Jennewein”) of
Rheinbreitbach, Germany as a respondent in this investigation. See id. The Office of Unfair
Import Investigations (“OUII”) is also named as a party to the investigation. See id.
On August 9, 2018, the ALJ partially terminated the investigation as to claims 4-7, 9-12,
14, 23-26, 28-31, 33, and 39-40 of the ’230 patent and claims 6, 7, 9, ll, 13-17, 19, and 22 of
the ’018 patent based on the withdrawal of the allegations pertaining to those claims. See Order
No. 5 (Aug. 9, 2018), unreviewed, Comm’n Notice (Aug. 29, 2018). On October 30, 2018, the
ALJ partially terminated the investigation as to claims 1-3, 8, 13, and 15-20 of the ’230 patent
based on the withdrawal of the allegations pertaining to those claims. See Order No. 15 (Oct. 30,
2018), unreviewed, C0mm’n Notice (Nov. 29, 2018). On November 19, 2018, the ALJ partially
terminated the investigation as to claim 27 of the ’230 patent and claims 4, 20, and 21 of the ’018
patent based on the withdrawal of the allegations pertaining to those claims. See Order No. 17
(Nov. 19, 2018), unreviewed, Comm’n Notice (Dec. 12, 2018). On February 8, 2018, the ALJ
partially terminated the investigation as to claims 21, 22, 32, and 34-38 of the ’230 patent based
on the withdrawal of the allegations pertaining to those claims. See Order No. 25 (Feb. 8, 2019),
unreviewed, Comm’n Notice (Feb. 28, 2019). Claims 1-3, 5, 8, 10, 12, 18, and 23-28 ofthe ’018
patent remain pending in this investigation.
The ALJ conducted an evidentiary hearing on May 14-17, 2019, and on September 9,
2019, issued the FID finding a violation of section 337 based on the infringement of claims 1-3,
5, 8, 10, 12, 18, and 24-28 of the ’018 patent. In addition, the FID finds that the asserted claims
are neither invalid under 35 U.S.C. §§ 103 and 112, nor unenforceable for inequitable conduct.
Furthermore, the FID finds that the domestic industry requirement is satisfied. The FID also
contains a recommended detennination (“RD”) recommending that the Commission issue a
limited exclusion order (“LEO”) barring entry of articles that infringe the ’018 patent. The RD
also recommends that the Commission impose a 5% bond during the period of Presidential
review. Furthermore, as directed by the Commission, the RD provides findings with respect to
the public interest and recommends that the Commission determine that the public interest
factors do not preclude entry of the LEO.
On September 23, 2019, Jennewein and OUII filed petitions for review of the FID. On
October 1, 2019, Glycosyn and OUII filed responses to Jennewein’s and the IA’s petitions.
Having examined the record of this investigation, including the FID, the RD, and the
parties’ submissions, the Commission has determined to review the FID in part. Specifically, the
Commission has determined to review the FID’s infringement findings with respect to
Jennewein’s bacterial strains adjudicated in this investigation. In addition, the Commission has
determined to review the FID’s decision not to adjudicate infringement as to Jennewein’s
alternative bacterial strain, the TTFL12 strain. The Commission has determined not to review
the remainder of the FID.
In connection with its review, the Commission requests written responses regarding the
following inquiries:
2
Assuming that the Commission determines to adjudicate
infringement with respect to JenneWein’s TTFL12 bacterial
strain, please provide your position, with support from the
evidentiary record, as to whether the TTFL12 strain
infringes or does not infringe the asserted patent claims.
Should the Commission adjudicate infringement with
respect to Jennwein’s alternative strain? Is the
Commissi0n’s determination of whether to adjudicate an
alternative or redesigned product a legal question, a factual
question, a mixed question of law or fact, an exercise of
discretion, or something else?
Is the TTFL12 strain within the scope of the investigation?
What criteria and evidence normally informs this analysis?
Does a respondent need to import an alternative or
redesigned product for the product to be adjudicated?
What evidence corroborates Jennewein’s assertion that the
products listed in the shipping documents (RX-278C and
RX-280C) were produced with the TTFL12 strain? Please
provide your answers in a table with citations in one column
and a brief explanation in a second column.
What is the effect of Jennewein’s responses to Glycosyn’s
request for admission? Why has Jennewein failed to amend
its responses if they are incorrect or misleading?
Is the TTFL12 strain sufficiently fixed in design? What
criteria and evidence normally informs this analysis? Is
there any declaratory judgment precedent that is relevant?
Which party bears the burden of showing that an alternative
or redesigned product is fixed in design?
Has the TTFL12 strain been subject to sufficient discovery?
What criteria and evidence normally informs the “sufficient
discovery” analysis?
Should the Cormnission issue remedial orders that are
directed to the adjudicated strains (the #1540 and #1540
derivative) at this juncture?
Responses to the above questions should not exceed 40 pages, and replies
should not exceed 20 pages.
In addition, in connection with the final disposition of this investigation, the statute
authorizes issuance of (1) an order that could result in the exclusion of flie subject articles from
3
entry into the United States, and/or (2) a cease and desist order that could result in the respondent
being required to cease and desist from engaging in unfair acts in the importation and sale of
such articles. Accordingly, the Commission is interested in receiving written submissions that
address the form of remedy, if any, that should be ordered. If a party seeks exclusion of an
article from entry into the United States for purposes other than entry for consumption, the party
should so indicate and provide information establishing that activities involving other types of
entry either are adversely affecting it or likely to do so. For background, see Certain Devicesfor
Connecting Computers via Telephone Lines, Inv. No. 337-TA-360, USITC Pub. No. 2843,
Comm’n Op. at 7-10 (Dec. 1994).
The statute requires the Commission to consider the effects of any remedy upon the
public interest. The public interest factors the Commission will consider include the effect that
an exclusion order and/or cease and desist orders would have on (l) the public health and
welfare, (2) competitive conditions in the U.S. economy, (3) U.S. production of articles that are
like or directly competitive with those that are subject to investigation, and (4) U.S. consumers.
The Commission is therefore interested in receiving written submissions that address the
aforementioned public interest factors in the context of this investigation.
If the Commission orders some form of remedy, the U.S. Trade Representative, as
delegated by the President, has 60 days to approve, disapprove, or take no action on the
Cornmission’s determination. See Presidential Memorandum of July 21, 2005, 70 FR 43251
(July 26, 2005). During this period, the subject articles would be entitled to enter the United
States under bond, in an amount determined by the Commission and prescribed by the Secretary
ofthe Treasury. The Commission is therefore interested in receiving submissions conceming the
amount of the bond that should be imposed if a remedy is ordered.
WRITTEN SUBMISSIONS: The parties to the investigation are requested to file written
submissions limited to the briefing questions above. Parties to the investigation, interested
government agencies, and any other interested parties are encouraged to file written submissions
on the issues of remedy, the public interest, and bonding. Such initial written submissions
should include views on the recommended determination by the ALJ on remedy, the public
interest, and bonding. Complainant and the Commission Investigative Attorney are also
requested to identify the form of remedy sought and to submit proposed remedial orders for the
Commission’s consideration in their initial written submissions. Complainant is further
requested to state the date that the asserted patent expires and the HTSUS numbers under which
the accused products are imported, a.ndto supply the names of known importers of the products
at issue in this investigation.
Initial written submissions and proposed remedial orders must be filed no later than close
of business on February 18, 2020. Reply submissions must be filed no later than the close of
business on February 25, 2020 and must be limited to issues raised in the initial written
submissions. No further submissions on any of these issues will be permitted unless otherwise
ordered by the Commission.
Persons filing written submissions must file the original document electronically on or
before the deadlines stated above and submit eight (8) true paper copies to the Office of the
4
Secretary by noon the next day pursuant to section 21O.4(t) of the C0mmission’s Rules of
Practice and Procedure (19 CFR 210.4(t)). Submissions should refer to the investigation number
(“Inv. No. 337-TA-1120”) in a prominent place on the cover page and/or the first page. (See
Handbook for Electronic Filing Procedures, https://Www.usitc.gov/documents/
handbook_on_filingJ:>rocedures._pdt). Persons with questions regarding filing should contact the
Secretary (202-205-2000).
Any person desiring to submit a document to the Commission in confidence must request
confidential treatment. All such requests should be directed to the Secretary to the Commission
and must include a full statement of the reasons why the Commission should grant such
treatment. See 19 CFR 201.6. Documents for which confidential treatment by the Commission
is properly sought will be treated accordingly. All information, including confidential business
information and documents for which confidential treatment is properly sought, submitted to the
Commission for purposes of this Investigation may be disclosed to and used: (i) by the
Commission, its employees and Offices, and contract personnel (a) for developing or
maintaining the records of this or a related proceeding, or (b) in internal investigations, audits,
reviews, and evaluations relating to the programs, personnel, and operations of the Commission
including under 5 U.S.C. Appendix 3; or (ii) by U.S. govemrnent employees and contract
personnelm, solely for cybersecurity purposes. All non-confidential written submissions will be
available for public inspection at the Office of the Secretary and on EDIS.
The authority for the Commission’s determination is contained in section 337 of the
Tariff Act of 1930, as amended (19 U.S.C. 1337), and in part 210 of the Commission’s Rules of
Practice and Procedure (19 CFR part 210).
By order of the Commission.
/ C i\\
/‘t I V‘ Lisa.R. Barton
ti V Secretary to the Commission
Issued: Januaiy 30, 2020
[1]All contract personnel will sign appropriate nondisclosure agreements.
5
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND Inv. N0. 337-TA-1120
METHODS OF PRODUCING THE SAME
PUBLIC CERTIFICATE OF SERVICE
I, Lisa R. Barton, hereby certify that the attached NOTICE has been sewed by hand
upon the Commission Investigative Attorney, Lisa Murray, Esq., and the following parties as
indicated, on January 30, 2020. I
W%@Lisa R. Barton, Secretary
U.S. International Trade Commission
500 E Street, SW, Room 112
Washington, DC 20436
On Behalf of Complainants Glvcosvn LLC:
Michael C. Newman, Esq. El Via Hand Delivery
MINTZ LEVIN COHN FERRIS GLOVSKY ANDPOPEO, PC |:| Via Express Delivery
1 Financial Center , 1 V‘ ~ - 1 -1
Boston, MA 021 I 1 Via First C ass Mai
U Other:
On Behalf of Respondent Jennewein Biotechnologie GmbH:
Gary M. I-Inath II] Via Hand Delivery
MAYER BROWN LLP El Via Express Delivery
1999 K Sire“, NW Via First Class Mail
Washington, DC 20006 U other
UNITED STATES INTERNATIONAL TRADE COMMISSION
Washington, D.C.
In the Matter of
CERTAIN HUMAN MILK Inv. No. 337-TA-1129
OLIGOSACCHARJDES AND METHODS
OF PRODUCING THE SAME
INITIAL DETERMINATION ON VIOLATION OF SECTION 337 AND
RECOMMENDED DETERMINATION ON REMEDY AND BOND
Administrative Law Judge Cameron Elliot
(September 9, 2019)
Pursuant to the Notice of Investigation and Rule 2i0.42(a) of the Rules of Practice and
Procedure of the United States International Trade Commission. this is my Initial Determination
in the matter of Certain Human Milk Oligosaccharides and Methods 0_fPr0dt.-cing the Same,
Investigation N0. 337-TA-1120.
TABLE OF CONTENTS Page
l. INTRODUCTION ............................................................................................................. I
A. Procedural Background .......................................................................................... ..l
B. The Parties ............................................................................................................. ..3
C. The Asserted Patent and Claims ............................................................................ ..4
D. Products at Issue .................................................................................................... ..6
l. Domestic Industry Products........
2. Accused Product ........................................................................................ ..7
II. STANDARDS OF LAW ................................................................................................... 7
A. Claim Construction ................................................................................................ ..7
B. Infringement ......................................................................................................... ..l 1
C. Domestic Industry ................................................................................................ ..I2
1. Technical Prong ....................................................................................... .. l2
2. Economic Prong ....................................................................................... ..l3
D. Invalidity.......................................................................................................... ..l5
1. 35 U.S.C. § l02......... ........l5
2. 35 U.S.C. I03 ........................................................................................ ..l6
3. 35 U.S.C. § 112........................................................................................ ..1S
E. Unenforceability .................................................................................................. ..20
III. JURISDICTION AND IMPORTATION ..................................................................... 22
IV. U.S. PATENT NO. 9,970,018 ................................................................... ................... 24
A. Level of Ordinary Skill in the Art ........................................................................ .24
B. Claims-at-Issue ........24
C. Claim Construction .............................................................................................. ..26
D. Infringement ......................................................................................................... ..27
l. Regarding the Jenncwein TTFLIZ Strain .................................................28
2. Direct Infringement bytheJcnncwein #1540—
_ ...................................................................................................... ..35
a. Undisputed Claim Limitations ..................................................... ..36
b. Disputed Claim I Limitation “an exogenous functional [3
galactosidase gene comprising a detectable level of B~
galactosidase activity that is reduced compared to that of a
wild-type E. colt bacterium" .........................................................38
i
c. Disputed Claim I Limitation “wherein the level of [3
galactosidase activity comprises between 0.05 and 200 units”
d. Disputed Claim S “the method of claim 1, wherein Said
exogenous functional |3-galactosidase gene comprises an E.
coir lacZ.gene" ....................................................................... ..
e. Disputed Claim 23 “the method ofclaim l, wherein said
exogenous functional |3-galaetosidase gene is inserted into an
endogenous gene” .................................................................. ..
E. Domestic Industry —Technical Prong............................................................ ..
1.
2.
3.
4.
Undisputed Claim Limitations ........................................................... ..
Disputed Claim I Limitation “wherein the level of [3-galactosidase
activity comprises between 0.05 and 200 units" ................................ ..
Disputed Claim 9 “the method of claim 8, wherein the lacZ gene is
inserted into an endogenous Ion gene” .............................................. ..
Disputed Claim 23 “the method of claim I, wherein said exogenous
functional Ii-galactosidase gene is inserted into an endogenous gene"
......68 F. Validity and Enforceability ............................................................................ ..
I.
2.
3.
4.
5.
Asserted Prior Art .............................................................................. ..
35 U.S.C. § I03 (Obviousness) .......................................................... ..
35 U.S.C. § ll2,1l I (Enablement) .................................................... ..
35 U.S.C. § 112,1] I (Written Description) ....................................... ..
.....45
......57
......60
......6l
......62
.... ..65
......67
67
......68
......69
...."82
......89
Inequitable Conduct ................................................................................. ..9U
V. DOMESTIC INDUSTRY - ECONOMIC PRONG .................................................. 96
A. Qualifying Investments ........................................................................................ ..97
B. "Significant" or “Substantial” ......................................................................... ..l l l
VI. CONCLUSIONS OF LAW ......................... ............................................................ 114
VII. RECOMMENDED DETERMINATION ON REMEDY AND BOND ................... 114
A. LIMITED EXCLUSION ORDER ..................................................................... ..l I6
................................................................................................................ ..l I8
C. PUBLIC INTEREST ......................................................................................... ,,l I9
VII]. INITIAL DETERMINATION AND ORDER ........................................................... 121
B. BOND
ii
CDX
TABLE OF ABBREVIATIONS
Complainant’s Demonstrative Exhibit
CIB Cornplainanfs Revised Initial Post-Hearing Brief
CPB Cornplainant’s Prc-Hearing Brief
CPX C-ornplainant‘s Physical Exhibit
CRB Comp1ainant’s Reply Post-Hearing Brief
CX Cornplainant’s Exhibit
Dep. Tr. Deposition Transcript
i Hr’g Tr. Hearing Transcript
i]X Joint Exhibit
RDX Respondents’ Demonstrative Exhibit
RIB Respondents’ Initial Post-Hearing Brief
RPB Respondents’ Pre-Hearing Brief
RPX Respondents’ Physical Exhibit
RRB Respondents’ Reply Post-Hearing Brief
RX Respondents‘ Exhibit
SDX Staffs Demonstrative Exhibit
SIB Staff’s Initial Post-Hearing Brief
SPB Staff s Pre-Hearing Brief
SPX Staffs Physical Exhibit
SRB Staffs Reply Post-Hearing Brief
SX Staffs Exhibit
iii
I. INTRODUCTION
A. Procedural Background
Complainant Glycosyn LLC (“Glycosyn” or “Comp1ainant") filed the complaint
underlying this Investigation on April 2, 2018, and then filed an amended complaint on May 16,
2018. 'I'he complaint alleged respondent Jennewein Biotechnologie GrnbH (“Jennewein” or
“Respondent”) imports certain products that infringe one or more claims of U.S. Patent Nos,
9,453,230 (the ‘"230 patent”) and 9,970,018 {_the ‘"018 patent” also referred to as JX-0003).
By publication of a notice in the Federal Register on June 21, 2018. the U.S. International
Trade Commission ordered that:
Pursuant to subsection (b) of section 337 of the Tariff Act of 1930, as
amended, an investigation be instituted to determine whether there is a
violation of subsection (a)(l)(B) of section 337 in the importation into the
United States, the sale for importation, or the sale within the United States
after importation of products identified in paragraph (2) by reason of
infringement of one or more of claims 1-40 of the ’230 patent; and claims
1-28 of the ‘O18patent; and whether an industry in the United States exists
as required by subsection (a)(2) of section 337[.]
83 Fed. Reg. 23,865 (June 21, 2018). On July 16, 2018, the presiding administrative law judge set
a target date of October 21, 2019 for completion of this investigation and set the evidentiary
hearing for February 22, 2019. (Order No. 4.) On August 20, 2018, the administrative lawjudge
issued the procedural schedule. (Order N0. 6.) On September 4, 2018, and due to the retirement
of the presiding administrative law judge, the investigation was reassigned to the Chief
Administrative Law Judge. (EDIS Doc. ID 654642.)
In accordance with the issued procedural schedule, on October I6, 2018, the Chief
Administrative Law Judge held a technology tutorial and Markman hearing, and on December 18,
2018, issued Order No. 22, construing certain terms of the asserted patents.
At times throughout the investigation, Glycosyn moved for the termination of certain
asserted claims from those identified in the complaint. Specifically, on July 27, 2018, Glycosyn
moved to terminate claims 4-7, 9-12, 14, 23-26, 28-31, 33, and 30-40 ofthe ’230 patent and claims
6, 7, 9, 11, 13-17, 19, and 22 of the ’018 patent. The presiding administrative law judge at the
time granted Glycosyn’s motion on August 9, 2018 with Order No. 5. The Commission
determined not to review Order No. 5 on August 29. 2018. (EDIS Doc. l.D654274.) On October
18, 2018, Glycosyn moved to terminate claims 1-3, 8, 13, and 15-20 ofthe ’230 patent. The Chief
Administrative Law Judge granted G1ycosyn‘s motion on October 30, 2018 with Order No. 15.
The Commission determined not to review Order No. 15 on November 29, 2018. (_EDISDoc. ID
662881.) On November 9, 2018, Glycosyn moved to terminate claim 27 of the ’230 patent and
claims 4, 20, and 21 ofthe ’0l8 patent. The Chief Administrative Law Judge granted G1ycosyn‘s
motion on November 19, 2018 vfitb Order No. 17. The Commission determined not to review
Order No. 17 on December 12, 2018. (EDIS Doc. 1D 663942.) Lastly, on January 30, 2019,
Glycosyn moved to terminate claims 21, 22, 32, and 34-38 of the ’230 patent. The Chief
Administrative Law Judge granted G1ycosyn‘s motion on February 8, 2019 with Order No. 25.
The Commission determined not to review Order No. 25 on February 28, 2019. (EDIS Doc. ID
668665.) lmportantly, Order No. 25 terminated the last remaining asserted claims of the ’230
patent, thereby tenninating that patent in its entirety fi'on1 the investigation. Thus, the sole
remaining patent in this investigation is the T113patent.
Also during the investigation, Jennewein filed two summary determination motions of non
infringement with respect to certain of their processes for the manufacture of its accused product.
The Chief Administrative Law Judge denied both motions on March 8, 2019 with Order Nos. 27
and 28.
2
With respect to the procedural schedule, the govemment shutdown occurring between
December of 2018 and January 0f2019 necessitated an extension of all deadlines and the target
date in this investigation. At the completion of the shutdown, on January, 29, 2019, the Chief
Administrative Law Judge issued Order No. 23 which moved the start of the evidentiary hearing
to May l3, 2019. Accordingly, the Chief Administrative Law Judge set a new procedural schedule
for all remaining deadlines on February 7, 2019 with Order No. 24 and also extended the target
date of the investigation approximately eleven weeks to January 9, 2020 with Order No. 26, issuing
on February 21, 2019. The Commission determined not to review Order No. 26 on March 14,
2019. (EDIS D00. ID 670060.)
Finally, on April 2, 2019 the investigation was reassigned a second time from the Chief
Administrative Law Judge to me. (EDIS Doc. ID 671950.) I then conducted an evidentiary
hearing between May I4, 2019 and May 17, 2019.
Following the evidcntiary hearing, and pursuant to the procedural schedule, the parties
submitted initial and reply post-hearing briefs on June 3, 2019 and June 17, 2019 respectively,
Further, on June 10, 2019, Jertnewein moved to strike certain portions of Glycosyn’s initial post
hearing brief-—-amotion which I granted-in-part on June I4, 2019 with Order No. 38. On June l7.
2019, Glycosyn submitted a revised initial post-hearing brief in accordance with that order.
As of the date of this initial determination. no motions remain pending.
B. The Parties
Complainant Glycosyn LLC is organized and exists under the laws of Massachusetts. (SIB
at .2.) ll was founded in 2002 to pursue research and development “of commercially-viable
methods for synthesizing and producing human milk oligosaccharides, commonly known as
HMOs. (CIB at 7.) While Glycosyn conducts its research and development in the United States,
3
it is currently linked with a Dutch production partner, Royal FrieslandCampina N.V., to
manufacture and distribute the 2‘-FL HMO for the infant formula market. (Id. at T-3; see RlB at
3 (citing RX-0056).}
Respondent Jennewein Biotechnologie GmbH is based in Germany, and founded in 2005
for the similar purpose of researching means of manufacture for HMOs. (CIB at 8.) Jennewein
claims it “is the true innovator and market leader for 2‘-FL in the United States" as “[n]o other
company, including Glycosyn or its partner, is supplying Z‘-FL to American consumers.” (RIB at
4 (citing Hr’g Tr. at 57:3-4; RX-0385C at Q1813);see SIB at 3.) in this investigation, and as
described further below, Glycosyn has alleged Jenncwein‘s methods of producing 2‘-FL imported
into the United States infringe the ’018 patent. Ud.)
C. The Asserted Patent and Claims
The asserted patent relates to compositions and methods for providing engineered bacteria
to produce certain HMOs. The following claims remain at issue in this investigation:
Patent Number Infringement Claims DomesticIndustry Claims
"U18 patent l~3, 5, S, l0, 12, 18, 23—2S l-3, 5, 8-I4, l8, 22~28
(See CIB at l5-16.)
The ’O]8 patent is entitled, “Biosynthesis of Human Milk Oligosaccharides in Engineered
Bacteria." (JX-0003.) It was tiled on September 2], 2017, and claims priority as a continuation
application of an application filed on February 24, 2017, itself a continuation of an application
filed on September 23, 2013, which was a division of an application filed on February I6. 2012.
4
(10/.) Through these applications, the ‘U18 patent also claims liirther priority to a provisional
application filed on February 16, 2011. (1d.) ' The ‘O18patent issued on May 15, 2018.
The ‘O18 patent generally describes “compositions and methods for engineering bacteria
to produce fueosylated oligosaeeharides, and the use thereof‘ in the prevention or treatment of
infection." (See id. at Abstract.) The patent explains:
Human milk contains a diverse and abundant set of neutral and acidic
oligosaceharides (human milk oligosaceharides, HMOS). Many of these
molecules are not utilized directly by infants for nutrition, but they
nevertheless serve critical roles in the establishment of a healthy gut
microbiome, in the prevention of disease, and in immune function. Prior to
the invention described herein, the ability to produce HMOS inexpensively
at large scale was problematic. For example, HMOS production through
chemical synthesis was limited by stereo-specificity issues, precursor
availability, product impurities, and high overall cost. As such, there is a
pressing need for new strategies to inexpensively manufacture large
quantities of HMOS for a variety ofeommercial applications.
(Id. at 1:34-47.) In some methods disclosed in the patent, an E. colt‘ bacterium is used. The
bacterium is engineered in several ways that assist the production and collection of the desired
oligosaceharide. For example, the bacterium may be engineered by the addition, deletion, or
inactivation of genes to: create the desired oligosaceharide from first and second basic sugar
building blocks (ve.g.,fueosyltranslerase gene, GDP-fucose synthesis pathway); improve the ability
to intake the sugar building b1ock(s) from an outside medium (e.g., lactose pcrmease gene);
inactivate certain pathways that compete with oligosaeeharide production (e.g., colonic acid
synthesis gene); and produce certain enzymes which compete with oligosaccharide production but
otherwise assist later steps of purification and retrieval of the oligosaccharide (e.g., functional 13
galaetosidase gene). (See id. at 1:51-60, 3:44-50.)
' The effective date of the asserted patents pre-dates the America lnvents Act (“ALA”)
enacted by Congress on September 16, 2011.
5
This last purpose, involving [3-galaetosidase activity, is pointedly in dispute in this
investigation. The ’0l 8 patent describes one particularly relevant example of E. coli engineering
and culturing:
Also described herein are bacterial host cells with tl1eability to accumulate
a[n] intracellular lactose pool while simultaneously possessing low,
functional levels of cytoplasmic B-galactosidase activity, for example as
provided by the introduction of a functional rccombinantE. coli laeZ gene,
or by a B-galactosidase gene from any of a number of other organisms . . ..
Low, functional levels of cytoplasmic B-galactosidase include [3
galactosidase activity levels, of between 0.05 and 200 units, e.g., between
0.05 and 5 units. between 0.05 and 4 units, between 0.05 and 3 units, or
between 0.05 and 2 units (for unit definition see: Miller J H, Laboratory
CSH. Experiments in molecular genetics. Cold Spring Harbor Laboratory
Cold Spring Harbor, N.Y.; I972; incorporated herein by reference). This
low level of cytoplasmic B-galactosidase activity, while not high enough to
significantly diminish the intracellular lactose pool. is nevertheless very
useful for tasks such as . . . the facile removal ofundesired residual lactose
at the end of fennentations.
(‘O18 patent at 7:22-45.) In this art, and as used throughout this initial determination, genes are
normally identified with a starting lower-ease letter and in italics (e._g.,lm;'Z), and the peptide
created from that gene starts in upper case with no italics (e.g., LaCZ). (RX-0384C at Q1511;(IX
0004C at Q6l.)2
Glycosyn contends it owns the ‘O18patent, which is reflected in the assignment filed with
its prosecution history (CIB at 31 (citing JX-0006 at -4790; ’0l 8 patent)) and neither Jennewein
nor the Staffdisputes ownership (see SIB at 3; see generalfiz RIB; RRB).
D. Products at Issue
I. Domestic Industry Products
The domestic industry products in this investigation consist of certain non comn1ercial~
level amounts of 2’-FL produced by Glycosyn within the United States as part of its research and
2 The ‘O18 patent does not itself necessarily follow the italics scheme for genes. (See,
e.g., ’0l8 patent at T126.)
6
development efforts. (CIB at 92 (citing CX-0059C; CX-0131C; CX-0064C); CX-0004C at Q124
l25.) Glycosyn identifies its E997 bacterial strain as practicing at least one claim of the ‘O18
patent. and contends many other strains are fairly represented by E997 with respect to this issue.
(CIB at 15-16 (citing CX-0004 at Q99, 123), 126 n.8, 9.) Glycosyn claims the following strains,
developed since 2015, are represented by its E997 strain as patent practicing:
Products at Issue | Representative Product
E997
(C-[B at 126 n.9 (citing CXJJOUZC at Q10"/A108; CX~l)06UC; CX~OO5SC;CX~OO59C; CX-0130(1).)
2. Accused Product
The accused product in this case is 2‘-FL which Jennewein has imported or sold for
importation into the United States (“Accused Product”) using methods claimed in the ‘O18 patent.
In this investigation, Glycosyn has accused Jennewein’s 2’-FL production methods based on an E.
mam-1
Th==#154@Jenneweinseeksadjudicationof- knownas TTFL]2. For reasonsdiscussedbelow, I do not
find adjudication ofTTFL12 is warranted at this time.
ll. STANDARDS OF LAW
A. Claim Construction
“The construction of claims is simply a way of elaborating the normally terse claim
language in order to understand and explain, but not to change, the scope of the claims.” Emlirex,
Inc. v. Serv. Engjg Corp, 216 F.3d 1343, 1347 (Fed. Cir. 2000). Although most of the disputed
7
claim terms were construed in an earlier order, some of the issues presented below are only
resolvable with additional claim construction. (See Order No. 22.)
Claim construction focuses on the intrinsic evidence, which consists of the claims
themselves, the specification, and the prosecution history. See Pfiillips v. AWH Corp., 415 F.3d
I303, I314 (Fed. Cir. 2005) (en bane); see also Marlcrnan v. Westview Instri, Inca, 52 F.3d 967,
979 (Fed. Cir. 1995) (en bane). As the Federal Circuit in Phillips explained, courts must analyze
each of these components to determine the “ordinary and customary meaning of a claim term” as
understood by a person of ordinary skill in art at the time of the invention. 415 F.3d at 1313.
“Such intrinsic evidence is the most significant source of the legally operative meaning of disputed
claim language.” Bel! Ail. Network Servs., Inc. v. Comd Coimrtdns Grp., IPILZ,262 F.3d 1253,
1267 (Fed. Cir. 2001).
"lt is a ‘bedrock principle’ of patent law that ‘the claims of a patent define the invention to
which the patentee is entitled the right to exclude?” Phillips, 41.5 F.3d at 1312 (quoting
lrmova/Pure Water. Inc". v. Sajiari Water Filtration S_}’S.,Ina, 38] F.3d llll, lll5 (Fed. Cit‘.
20l)4')). “Quite apart from the written description and the prosecution history, the claims
themselves provide substantial guidance as to the meaning ofpaiticular claims terms.” Id. at 1314;
see Interactive Gift Fbrpress, Inc. v. Conrpuserve Ina, "256F.3d l323, I331 (Fed. Cir. 2001) (“In
construing claims, the analytical focus must begin and remain centered on the language of the
claims themselves, for it is that language that the patentee chose to use to ‘particularly point [ ] out
and distinctly claim [ ] the subject matter which the patentee regards as his invention.”). The
context i.nwhich a term is used in an asserted claim can be “highly instructive.” Phillips, 415 F.3d
at l3|4. Additionally, other claims in the same patent, asserted or unasserted, may also provide
guidance as to the meaning of a claim term. hi “Courts do not rewrite claims; instead, we give
8
effect to the terms chosen by the patentcc.” K-2 Corp. v. Salomon S.A., 191 F.3d 1356, 1364 (Fed.
Cir. 1999).
“[T]he specification ‘is always highly relevant to the claim construction analysis. Usually
it is dispositive; it is the single best guide to the meaning ofa disputed term.’” Phillips, 415 F.3d
at I315 (quoting V.r'rrom'csCorp. 11.Conceptromic, Inc, 90 F.3d 1576, ISSZ (Fed. Cir. 1996)).
“[T]he specification may reveal a special definition given to a claim term by the patentee that
differs from the meaning it would otherwise possess. In such cases, the inventor‘s lexicography
governs.” Id. at I316. “ln other cases, the specification may reveal an intentional disclaimer, or
disavowal, of claim scope by the inventor.” Id. As a general rule, however, the particular examples
or embodiments discussed in the specification are not to be read into the claims as limitations. Id.
at I323. In the end, “[t]he construction that stays true to the claim language and most naturally
aligns with the patent’s description ofthe invention will be the correct construction." Id. at 1316
(quoting Renishaw PLC v. Morposs S0ciela'per Azioni, 158 F.3d I243, l25D (Fed. Cir. 1998)).
lu addition to the claims and the specification, the prosecution history should be examined,
iI'in evidence. Id. at 1317; see Liebe!~FIai'she1‘mC0. 1/.Medrad, Inc, 358 F.3d 893, 913 (Fed. Cir.
2004). The prosecution history can “often inform the meaning of the claim language by
demonstrating how the inventor understood the invention and whether the inventor limited the
invention in the course of prosecution. making the claim scope narrower than it would otherwise
be.” Piwillips,415 F.3d at 1317; see Chimie v. PPG Indus. Int-., 402 F.3d I371, I384 (Fed. Cir.
2005) (“The ptupose of consulting the prosecution history in construing a claim is to exclude any
interpretation that was disclaimed during prosecution”).
When the intrinsic evidence does not establish the meaning of a claim, then extrinsic
evidence (i‘.e., all evidence external to the patent and the prosecution history, including
9
dictionaries, inventor testimony, expert testimony, and learned treatises) may be considered.
Phillips, 4l5 F.3d at I317. Extrinsic evidence is generally viewed as less reliable than the patent
itself and its prosecution history in determining how to define claim tem-ts. Id. “The court may
receive extrinsic evidence to educate itself about the invention and the relevant technology, but the
court may not use extrinsic evidence to arrive at a claim constmction that is clearly at odds with
the construction mandated by the intrinsic evidence.” Elkay Mfg. C0. v. Ebco Mfg. Co., I92 F.3d
973, 977 (Fed. Cir. 1999).
The construction of a claim term is generally guided by its ordinary meaning. However,
courts may deviate from the ordinary meaning when: (1) “the intrinsic evidence shows that the
patentee distinguished that term from prior an on the basis of a particular embodiment, expressly
disclaimed subjeet matter, or described a particular embodiment as important to the invention;” or
(2) “the patentee acted as his own lexieographer and clearly set forth a definition of the disputed
claim term in either the specification or prosecution history.” Edwards LzfesciencesLLC v. Cook
inch, 582 F.3d 1322, i329 (Fed. Cir. 2009); see GE Lighting Sols., LLC v. Agilight, 11:13.,750 F.3d
I304, 1309 (Fed. Cir. 2014) (“the specification and prosecution history only compel departure
from the plain meaning in two instances: lexicography and disavowal”); Omega Eng ‘g, Inc, it
Raytek Corp, 334 F.3d l3l4, 1324 (Fed. Cir. 2003) ("[W]here the patentee has unequivocally
disavowed a certain meaning to obtain his patent, the doctrine ofprosecution disclaimer attaches
and narrows the ordinary meaning of the claim congruent with the scope of the surrenden”); Rheox.
Inc. v. Entact, Inc, 276 F.3d 1319, 1325 (Fed. Cir. 2002) (“The prosecution history limits the
interpretation of claim terms so as to exclude any interpretation that was diselaimed during
prosccution.”). Nevertheless, there is a “heavy presumption that a claim term carries its ordinary
and customary meaning." CCS F itness, Inc. v. Br:-mswickCorp, 288 F.3d 1359, 1366 (Fed. Cir.
I0
2002) (citations omitted). The standard for deviating from the plain and ordinary meaning is
“exacting” and requires “a clear and unmistakable disclaimer.“ Thor-tierv. Sony Computer Emm ‘t
Am. LLC, 669 F.3d 1362, 1366-67 (Fed. Cir. 2012); see Epistar Corp. v. In! '1Trade Comm '12,566
F.3d 1321, 1334 (Fed. Cir. 2009) (requiring “expressions of manifest exclusion or restriction,
representing a clear disavowal of claim scope” to deviate from the ordinary meaning) (citation
omitted).
B. Infringement
"An infringement analysis entails two steps. The first step is detemiining the meaning and
scope of the patent claims asserted to be infringed. The second step is comparing the properly
construed claims to the device accused of infringing." Markmari, 52 F.3d at 976.
A patentee may prove infiingement either literally or under the doctrine of equivalents.
Infringement of either Sort must be proven by a preponderance of the evidence. Smi'thK1ine
Diagnostics, Inc. v. Helena Labs. Corp, 859 F.2d S78, 889 (Fed. Cir. 1988). A preponderance of
the evidence standard “requires proving 1.l1atinfringement was more likely than not to have
occurred.” Warner-Lambert Co. v. Teva Pharm. USA, Inc-.,418 F.3d 1326, 1341 n.l5 (Fed. Cir.
2005)
Literal infringement, a form of direct infringement, is a question of fact. Fittisar Corp. 1*.
DirecTV Group, [rtc., 523 F.3d 1323, 1332 (Fed. Cir. 2008). “To establish literal infringement,
every limitation set forth in a claim must be found in an accused product. exactly." Microsqfi
Corp. V. GeoTag, Ina, S17 F.3d I305, 1313 (Fed. Cir. 2016) (quoting Scmtltwal! Techs., Inc. v.
Cardina!1G Ct;-.,54 F.3d I570, I575 (Fed. Cir. 1995). If any claim limitation is absent, there is
no literal infringement of that claim as a matter of law. Bayer AG v. Elan Piiarm. Research C0rp.,
2.12 F.3d 1241, 1247 (Fed. Cir. 2000).
ll
Doctrine of equivalents is also a form of direct infringement. One rubric Forevaluating if
a claimed feature is not literally, but nonetheless equivalent to, a claimed feature is known as the
fimction-way-result test. Under this test, the accused feature is equivalent to the claim limitation
when “it performs substantially the same fimction in substantially the same way to Obtain the same
result.” Duncan Parking Techs, Inc. v. IPS Grp.. Ina, 914 F.3d 1347, I362 (Fed. Cir. 2019)
(quoting Graver Tank & Mfg. Co. v. Linda Afr Prods. Ca, 339 U.S. 605, 608 (1950)). Another
test is known as in the insubstantial differences test, where “[a]n element in the accused device is
equivalent to a claim limitation if the only differences between the two are insubstantial." Veda
v. Gordie Corp, 536 F.3d 131l, l 139 (Fed. Cir. 2003). The Supreme Court has further instructed,
"the proper time for evaluating equivalency . . . is at the time of infringement, not at the time the
patent was issued." Warner‘-Jenkinson Ca, inc. v. Hilton Davis Chem. C0., 520 U.S. I7, 37
( I997).
C. Domestic Industry
ln an investigation based on a claim of patent infringement, Section 337 requires that an
industry in the United States, relating to the articles protected by the patent, exist or be in the
process of being established. I9 U.S.C. § l337(a)(2). Under Commission precedent, the domestic
industry requirement has been divided into (i) a “technical prong” ” (which requires articles
covered by the asserted patent) and (ii) an “economic prong” (which requires certain levels of
activity with respect to the protected articles or patent itself). See Certain Video Game i511/stems
and C0m'r0Ner'.s',lnv. No. 337-TA-743, Co'mm’n Op. at 6-7 (April 14, 2011) (“Video Game
Systems“).
l. Technical Prong
The technical prong of the domestic industry requirement is satisfied when the complainant
in a patent-based section 337 investigation establishes that it is practicing or exploiting the patents
I2
at issue. See 19 U.S.C. §§ 1337 (a)(2), (3); Certain Mir-rospiiere Adhesives, Pracessjbr Making
Same and Prods. Containing Same, Incliiding Sei;'¥.S‘iick Repositionable Notes, lnv. No. 337-TA
366, C0mm’n Op. at 8 (U.S.l.T.C. Jan. 16, 1996). “In order to satisfy the technical prong of the
domestic industry requirement, it is sufficient to show that the domestic industry practices any
claim of that patent, not necessarily an asserted claim of that patent.” Certain Ammonium
Ocfarnuivbdaie isomers, lnv. No. 337-TA-477, Comofn Op. at S5 (U.S.l.T.C. Aug. 28, 2003).
The test for claim coverage for the purposes of the technical prong of the domestic industry
requirement is the same as that for infiingement. See Certain Doxoriibicin and Preparations
Containing Same, Inv. No. 337-TA-300, initial Determination at 109 (U.S.l.T.C. May 21, 1990),
affd, Views of the Commission at 22 (U.S.l.T.C. Oct. 31, 1990); Aiioc, Inc. v. Int’! Trade
Comm ‘ii, 342 F.3d 1361. 1375 (Fed. Cir. 2003). “First. the claims of the patent are construed.
Second, the complainant‘s article or process is examined to determine whether it falls within the
scope of the claims.” Certain Doxorabicin and Preparations Containing Same, Inv. N0. 337'-TA
300, Initial Detennination at 109. As with infringement, the technical prong of the domestic
industry can be satisfied either literally or under the doctrine of equivalents. Certain Dynamic‘
Sequential Gradient Devices and Component Parts Thereof] Inv. No. 337-TA-335, ID at 44, Pub.
No. 2575 (U.S.l.T.C. May 15, 1992). ln short, the patentee must establish by a preponderance of
the evidence that the domestic product practices one or more claims of the patent.
Z. Economic Prong
The “economic prong” of the domestic industry requirement is satisfied when there exists
in the United States, in connection with products practicing at least one claim of the patent at issue:
(A) significant investment in plant and equipment; (B) significant employment of labor or capital;
or (C) substantial investment in its exploitation, including engineering, research and development,
and licensing. 19 U.S.C. § l337(a')(3). Establishment of the “economic prong" is not dependent
I3
on any “minimum monetary expenditure" and there is no need for complainant “to define the
industry itself in absolute mathematical terms.“ Certain Stringed Musical’ Instruments and
Components Thereof, lnv. No. 337-TA-586, Comm‘n Op. at 25-26 (May 16. 2008) (“Stringed
instrttmems”). However. a complainant must substantiate the significance of its activities with
respect to the articles protected by the patent. Certain Printing and imaging Devices and
Components Thereof, Inv. No. 337-TA-690, Comnfn Op. at 30 (Feb. 17, 20] I) (“Imaging
Devices”). Further, a complainant can show that its activities are significant by showing how those
activities are important to the articles protected by the patent in the context of the company’s
operations, the marketplace, or the industry in question. Id. at 27-28. That significance, however.
must be shown in a quantitative context. Lela inc. v. Int’! Trade Comm 'n, 786 F.3d 879, 886 (Fed.
Cir. 20 l5). The Federal Circuit noted that when the ITC first addressed this requirement, it found
the word “‘significant‘ denoted ‘an assessment of the relative importance of the domestic
activities.” Id. at 883-4 (internal citation omitted) (emphasis added). In general, “[t]he purpose
of the domestic industry requirement is to prevent the ITC from becoming a forum for resolving
disputes brought by foreign complainants whose only connection with the United States is
ownership of a U.S. patent." Certain Battery-Powered Ride-On Toy Vehicles, Inv. No. 337-TA
314, USITC Pub. No. 2420, Initial Determination at 2t (Aug. 1991).
The Commission “has long recognized that the ‘its’ in the phrase ‘investment in its
exploitation’ in subparagraph (C) refers to the asserted patent or other intellectual-property right
being asserted. That conclusion is supported by the clear text of the statute.” Certain Integrated
Circuit Chips and Products Containing the Same, lnv. No. 337-TA-S59, Comm’n Op. at 36 (Aug.
l l, 2014) (“[m'eg1'a.redCircuit Chips”). This connection between the investment and the patent is
known as the “nexus” requirement. Id. at 38. “To the extent that the patented technology arises
I4
from endeavors in the United States, such a nexus would ordinarily exist.” Id. at 39.
“'Exploitation’ is a generally broad term that encompasses activities such as efforts to improve,
develop, or otherwise take advantage of the asserted patent." Id. Similarly, investments in plant
and equipment, labor, and capital that may fairly be considered investments in research and
development are eligible for consideration under subsections (A) and (B), in addition to subsection
(C). See Certain Solid Store Storage Drives, Stocked Electronics Components, and Products
Con-raimngSome, lnv. No. 337-TA-1097, Comm’n Op. at l4 (June 29, 2018) (“Solidiitore Storage
Drives”).
D. Invalidity
1. 35 U.S.C. § 102
Pursuant to 35 U.S.C. § 102, a patent claim is invalid as anticipated if:
ta) the invention was known or used by others in this country, or patented
or described in a printed publication in this or a foreign country, before the
invention thereof by the applicant;
(b) the invention was patented or described in a printed publication in this
or a foreign country or in public use or on sale in this country, more than
one year prior to the date ofthe application for patent in the United States;
(e) the invention was described in (1) an application for patent, published
under section l22(b), by another filed in the United States before the
invention by the applicant for patent or (2) a patent granted on an application
for patent by another filed in the United States before the invention by the
applicant for patent;"
(g)(2) before such person’s invention thereof, the invention was made in
this country by another inventor who had not abandoned. suppressed, or
concealed it.
35 U.S.C. § 102 (pre—AlA). “A patent is invalid for anticipation if a single prior art reference
discloses each and every limitation of the claimed invention. Moreover, a prior art reference may
anticipate without disclosing a feature of the claimed invention if that missing characteristic is
15
necessarily present, or inherent, in the single anticipating reference." Schering Corp. i.-.Geneva
Pharm.. 1210.,339 F.3d 1373, 1377 (Fed. Cir. 2003) (citations omitted).
2. 35 u.s.c.§ 103
Section I03 of the Patent Act states:
A patent may not be obtained though the invention is not identically
disclosed or described as set forth in section 102 of this title, if the
differences between the subject matter sought to be patented and the prior
an are such that the subject matter as a whole would have been obvious at
the time the invention was made to a person having ordinary skill in the art
to which said subject matter pertains. Patentability shall not be negated by
the manner in which the invention was made.
35 U.S.C. § 103(a) (pre-AIA). “Obviousness is a question of law based on underlying questions
of fact.” Scar-met‘ Techs. Corp. v. [COS Vision .S:ys.Corp. N.V., 528 F.3d 1365, 1379 (Fed. Cir.
2008). The underlying factual determinations include: “(l) the scope and content of the prior art,
(2) the level of ordinary skill in the art, (3) the differences between the claimed invention and the
prior art, and (4) Objective indicia of non-obviousness." Id. (citing Graham v. John Deere C0. of
Kansas C.iljP,383 U.S. I, I7-I S (l966)). These factual determinations are oflen referred to as the
"Graham factors.”
The critical inquiry in determining the differences between the claimed invention and the
prior art is whether there is a reason to combine the prior art references. KSR In: '1Co. v. Teleflex
Iricz,550 U.S. 398, 418-2] (2007). IIJKSR, the Supreme Court rejected the Federal Circuit’s rigid
application of the teaching-suggestion-motivation test. While the Court stated that “it cmt be
important to identify a reason that would have prompted a person of ordinary skill in the relevant
field to combine the elements in the way the claimed new invention does,” it described a more
flexible analysis:
Ofien, it will be necessary for a court to look to interrelated teachings of
multiple patents; the effects of demands known to the design community or
present in the marketplace; and the background knowledge possessed by a
l6
person having ordinary skill in the art, all in order to determine whether
there was an apparent reason to combine the known elements in the fashion
claimed by the patent at issue . . . . As our precedents make clear, however,
the analysis need not seek out precise teachings directed to the specific
subject matter of the challenged claim, for a court can take account of the
inferences and creative steps that a person of ordinary skill in the art would
employ.
Id. at 413. Since KSR, the Federal Circuit has announced that, where a patent challenger contends
that a patent is invalid for obviousness based on a combination of prior art references, “the burden
falls on the patent challenger to show by clear and convincing evidence that a person of ordinary
Skill in the art would have had reason to attempt to make the composition or device . . _and would
have had a reasonable expectation of success in doing so.” Pr'mrrnaSIem Therapeutics, Inc. v.
ViaC'e!t',[nc.. 491 F.3d l342, I360 (Fed. Cir. 2007); see KSR, 550 U.S. at 399 (“The proper
question was whether a pedal designer of ordinary skill in the art, facing the wide range of needs
created by developments in the field, would have seen an obvious benefit to upgrading Asano with
a senson”).
In addition to demonstrating that a reason exists to combine prior art references, the
challenger must demonstrate that the combination of prior art references discloses all of the
limitations Of the claims. Hearing Camp0nem‘s, Inc‘. v. Share I;m:'.,600 F.3d 1357, l3’/'3-4 (Fed.
Cir. 2010) (abrogated on other grounds by Nautilus, Inc. v. Biosig Instruments, Ina, I34 S.Ct.
2120 (2014)) (upholding finding of non-obviousness based on the fact that there was substantial
evidence that the asserted combination of references failed to disclose a claim limitation); Velander
v. Gamer, 348 F.3d l359, i363 (Fed. C‘-ir.2003') (explaining that a requirement for a finding of
obviousness is that “all the elements of an invention are found in a combination of prior art
references").
“A reference qualifies as prior art for a deter-mirialion under § 103 when it is analogous to
the claimed invention.” fmiavenrion Toys, LLC v. MG/1 Erirm‘t_1:16.,637 F.3d l3l4, 132i (Fed.
17
Cir. 201 I) (citing In re Clay, 966 F.2d 656, 658 (Fed. Cir. 1992)). “Two separate tests define the
scope of analogous prior art: ( I) whether the art is from the same field of endeavor, regardless of
the problem addressed and, (2) if the reference is not within the field of the inventors endeavor,
whether the reference still is reasonably pertinent to the particular problem with which the inventor
is involved.“ In re Bigio, 33! F.3d 1320, 1325 (Fed. Cir. 2004) (citing In re Deminslci, 796 F.2d
436, 442 (Fed. Cir. 1986]). One way of evaluating whether a reference is reasonably pertinent is
to consider if, “logically [it] would have commended itself to an inventor's attention in considering
his prolnlern.” K-TEC. Inc. v. Vita-Mix Corp, 696 F.3d 1364, 1375 (Fed. Cir. 2012) (citing
hmovenrion, 637 F.3d at 13211). The requirement for prior art to be analogous is “meant to defend
against hindsight." In re Khan, 441 F.3d 977, 986-937 (Fed. Cir. 2006).
An obviousness determination should also include a consideration of “secondary
considerations” such as “commercial success, long felt but unsolved needs, failure of others, etc.,
might be utilized to give light to the circumstances surrounding the origin of the subject matter
sought to be patented.” Graham, 338 U.S. at l7-IS. “For [such] objective evidence to be accorded
substantial weight, its proponent must establish a nexus between the evidence and the merits of
the claimed invention." In re GPAC Inn, 57 F.3d 1573, 1580 (Fed. Cir. 1995); see Merry’:& Cie
v. Gnosis S.P.A., 808 F.3d 829, 837 (Fed. Cir. 2015). “Where the offered secondary consideration
actually results from something other than what is both claimed and novel in the claim. there is no
nexus to the merits of the claimed invention.” In re Hnaf-Hung Koo, 639 F.3d 1057, I068 (Fed.
Cir. 201i).
3. 35 U.S.C. § 112
Pursuant to 35 U.S.C. § 112, a patent claim is invalid for lack of written description ifthe
patent’s specification fails to “reasonably c0nvey[] to those skilled in the art that the inventor had
possession of the claimed subject matter as of the filing date." Ariad Pharm., Inc. v. Eli Lilly &
18
Co., 598 F.3d 1336, I351 (Fed. Cir. 2010) (en bane). “[T]hc test requires an objective inquiry into
the four corners of the specification fiom the perspective of a person of ordinary skilled in the art,“
fol, and “the level ofdetail required to Satisfy the written description requirement varies depending
on the nature and scope of the claims and on the complexity and predictability of the relevant
technology," id. (citing Capon v. Eshnr, 418 F.3d 1349, 1357-58 (Fed. Cir. 2005)).
Additionally, under 35 U.S.C. § H2, a patent claim is invalid for indefiniteness if “its
claims, read in light of the specification delineating the patent, and the prosecution history, fail to
inform, with reasonable certainty, those skilled in the art about the scope of the invention."
Nautilus, Inc. v. Biosig Instruments, Ina, 134 S. Ct. 2120, 2124 (2014), lndefiniteness can result
from a single claim covering both an apparatus and a method of use of that apparatus, as “a
manufacturer or seller of the claimed apparatus would not know from the claim whether it might
also be liable for contributory infringement because a buyer or user of the apparatus later performs
the claimed method using the apparatus." [PXL Holdings v. Amozoncom, 430 F.3d I377, 1334
(Fed. Cir. 2005); see UIfimorePot'm‘er_L.L.C. v. Nintendo Co., S16 F.3d 816, 326 (Fed. Cir. 2016)
(holding these types of claims may make it “unclear whether infringement . . . occurs when one
creates an infringing system, or whether infringement occurs when the user actually uses the
system in an infringing manner") (citation omitted). “[A]pparatus claims are not necessarily
indefinite for using functional language," however, as in, for example, means-plus-function
formatted claims. MasterMi'rie Software, Inc. v. Microsoft Corp, 874 F.3d 1307, 1313 (Fed. Cir.
2017) (citing Microprocessor Enhcmcernen! Corp. v. Tex. Instruments Ina, 520 F.3d I367, 1375
(Fed. Cir. 2003)). Another example may be when the claim merely recites “that the system
‘possesses the recited structure which is capable of performing the recited functions.” Id. at 13l 5~
I6 (quoting Microprocessor Enhancemem‘, 520 F.3d at 1375).
I9
Further. under 35 U.S.C_.§ 112, a patent specification must contain a description “of the
manner and process of making and using” the invention. 35 U.S.C. § ll2. This is referred to as
the enabiement requirement, and a patent claim is sufficiently enabled only when the specification
teaches “those skilled in the art how to make and use the full scope of the claimed invention without
undue experimentation. " Genentech, Inc. v. Nova Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir.
1997). To determine whether the specification leaves a person of ordinary skill to perform undue
experimentation, the Federal Circuit has identified the following factors to consider: (1) the
quantity of experimentation necessary; (2) the amount of direction or guidance presented; (3) the
presence or absence of working examples; (4) the nature of the invention; (5) the state of the prior
art; (6) the relative skill of those in the art; (7) the predictability or unpredictability of the art; and
(8) the breadth of the claims. In re Wands, 585 F.2d 731, 737 (Fed. Cir. 1988). “[1]t is not
necessary that a court review all the Wands factors to find a disclosure enabling. They are
illustrative, not mandatory.“ Amgen, Inc. v. Chugai Pharm. C0., Ltd, 927 F.2d 1200, 1213 (Fed.
cit. 1991).
E. Unenforeeahility
“Each individual associated with the filing and prosecution of a patent application has a
duty of candor and good faith in dealing with the Office, which includes a duty to disclose to the
Office all information known to that individual to be material to patcntability as defined in this
section.“ 37 C.F,R. § l.56(a). Thus, a patent may become unenforceable if “the applicant
misrepresented or omitted material information with the specific intent to deceive the PTO.“
Theraserio'e, Inc. v. Bec!o.=i.Dickinson and CCL,649 F.3d 1276, 1287 (Fed. Cir. 2011) (en bane).
“Unlike validity defenses, which are claim specific, see 35 U.S.C. § 288, inequitable conduct
Ztl
regarding any single claim renders the entire patent unenforceable.“ Id. at 1288 (citing Kingsdown
Med. Consultants, Ltd. v. Hollister Inc, S63 F.2d S67, 877 (Fed. Cir. 1988)).
“Intent and materiality are separate requirements.” Id. at 1290 (citing Hofinrorr-Lo Roche,
Inc. v. Promego Corp., 323 F.3d 1354, 1359 (Fed. Cir. 2003)). With respect to materiality:
[T]he materiality required to establish inequitable conduct is but-for
materiality. When an applicant fails to disclose prior art to the PTO, that
prior art is but-for material if the PTO would not have allowed a claim had
it been aware of the undisclosed prior art. Hence, in assessing the materiality
of a withheld reference, the court must determine whether the PTO would
have allowed the claim if it had been aware of the undisclosed reference.
Id. at 1291. With respect to intent:
A finding that the misrepresentation or omission amounts to gross
negligence or negligence under a "should have known" standard does not
satisfir this intent requirement. Kingsdown, 363 F.2d at 876, "In a case
involving nondisclosure of information, clear and convincing evidence
must show that the applicant mode o deliberate decision to withhold
a known material reference." Molina, 48 F.3d at 1181 (emphases added). In
other words, the accused infringer must prove by clear and convincing
evidence that the applicant knew of the reference, knew that it was material,
and made a deliberate decision to withhold it.
Id. at 1290. Further, the evidence of specific intent must “require a finding of deceitful intent in
the light of all the circumstances“ such that “when there are multiple reasonable inferences that
may be drawn, intent to deceive cannot be found.” Id. at 1290-91 (citations omitted). In the
context of withheld prior art, “[p]artia1disclosure of material information about the prior art to the
PTO cannot absolve a patentee of intent if the disclosure is intentionally selective." Am. Caleor,
Inc. v. Am. Honda Motor’ C'o., 768 F.3d 1185, l 190 (Fed. Cir. 2014) (citing Aventis Phorma S./-1.
v. Hospiro, Ina, 675 F.3d 1324, 1335-36 (Fed. Cir. 2012)); Semiconolnctorjy Energy Lab. Co. v.
Samszmg Elecs. C0,. 204 F.3d 1368, 1376 (Fed. Cir. 2000)). lt is also true that “[a]n inference of
intent to deceive is appropriate where the applicant engages in ‘a pattern of lack of candor,’
including where the applicant repeatedly makes factual representations ‘contrary to the true
2|
inforrnation he had in his possession?” Regeneron Pharm, Inc. v. M€t‘llS'N. V., 364 F.3d i343,
I351 (Fed. Cir. 2017) (citing Aporex Inc. v. UCB, Inc, 763 F.3d 1354, 1362 (Fed. Cir. 2014)).
Nevertheless, “the specific intent to deceive must be ‘the single most reasonable inference able to
be drawn fi"omthe evidence.” Theraseivse, 649 F.3d at 1290 (citation omitted).
Ill. JURISDICTION AND IMPORTATION
Jcnnewein has stipulated to importation, as noted in its own briefing. (See RIB at 10(citing
IX-0003C; JX-0D09C').) l therefore find the importation requirement under 19 U.S.C. §
l337(a)( 1)(B) satisfied. and find the Commission has in rem jurisdiction over the Accused Product.
See S'ea1edAir Corp. v. Int ‘ITrade Comm ‘:1,645 F.2d 976. 935 (C.C.P.A. 198]),
One of Jennewein’s fact witnesses, Dr. Stefan
Jennewein, testified that an exhibit, RX-0280C, “is a summary of the 2‘-FL we produced and
imported into the U.S. according to strain." (RX-0385C at Q132-133.) He explained the
information came from Jennewein’s CFO, who “prepared it from our accounting system in
response to one ofGlycosyn‘s discovery requests.” (Id. at QI34.) Based on this document, he
mludsd tha1— TTFLI-'1— 11¢ at
Q135.)
The importation record, RX-0280C, is briefand shows the following:
21
(RX-028°C at -284583->
D1 Jelmewees testimony
confinns it (RX-0385C at Q135) as docs Jcnncwcin’s final response to Glycosyrfs request for
admission on this issue:
REQUEST FOR ADMISSION 7:
Admit that .Iennewein‘s strain #1540 is the only strain Jennewein
uses to produce the 2’-FL that is imported into the United States.
AMENDED RESPONSE TO REQUEST NO. 7
Jennewein objects to this Request as vague and ambiguous with
respect to the terms “uses” and “produce.” Subject to its objections,
Jennewein responds as follows:
tcx-0216c at 5).
23
IV. ll.S. PATENT NO. 9,970,018
A. Level of Ordinary Skill in the Art
In Order No. 22, the Chief Administrative Law Judge found a person of ordinary skill in
the art for the asserted patent at the time of the invention would have (1) a Ph.D in molecular
biology, biochemistry, or chemical engineering, or an equivalent field, and 1-2 years of experience
working with E. coli bacteria or related systerns, or (2) a lower level degree (tag, a MA.) in a
similar field to those listed above, but a greater amount of relevant working experience (e.g., 5-6
years ofexperienee working with E. colt bacteria or related systems). (Order No. 22 at 7.) I find
no reason to diverge from this definition and apply it throughout this initial determination.
B. Claims-at-Issue
Claims l-3, 5, 8-I4. 18, and 22-28 ofthe ’0l 8 patent are at issue in this investigation, either
through allegations of infringement or of the domestic industry technical prong:
1. A method for producing a fiicosylated oligosaccharide in a bacterium,
comprising
providing an isolated E. coir‘bacterium comprising,
(i) a deletion or functional inactivation of an endogenous [3
galaetosidase gene;
(ii) an exogenous functional B-galactosidase gene comprising a
detectable level of B-galaetosidase activity that is reduced compared
to that of a wild-type E. coir‘ bacterium, wherein the level of B
galactosidase activity comprises between 0.05 and 200 units;
(iii) an inactivating mutation in a colanic acid synthesis gene; and
(iv) an exogenous lactose-accepting fucosyltransferase gene;
culturing said bacterium in the presence of lactose; and
retrieving a fucosylated oligosaecharide from said bacterium or
from a culture supernatant of said bacterium.
2. The method of claim 1, wherein said colanic acid synthesis gene
comprises an E. calf weal, wzxC, weal), wza, wzb, or wzc gene.
24
3. The method of claim 2, wherein said colanic acid synthesis gene
comprises a weal gene.
5. The method of claim 1, wherein said exogenous lactose-accepting
fiscosyltrarisferase gene encodes 041,2) fucosyltransferase and/or oi.(1,3)
fucosyltransferase.
8, The method of claim I. wherein said exogenous functional [3
galactosidase gene comprises an E. cofi 1:102gene.
9. The method of claim 8. wherein the IacZ gene is inserted into an
endogenous Ion gene.
10. The method of claim l, wherein said bacterium further comprises a
functional lactose permease gene.
ll. The method of claim l0, wherein said lactose permease gene is an
endogenous lactose permease gene.
12. The method ofelaim 10, wherein said lactose permease gene comprises
an E. colt lacY gene.
13. The method of claim I, wherein said bacterium further comprises an
exogenous E. coir‘rcsA or E colt resB gene.
14. The method of claim 1, wherein said bacterium funher comprises an
inactivating mutation in a lacA gene.
18. The method of claim l. wherein the level of [3-galactosidase activity
comprises between 0.05 and 5 units.
22. The method ofclaim l, wherein said bacterium comprises the genotype
of
(a) ampC::(PtrpB?tcl+), Placl q {Alacl-lacZ)lacY+. Aweal,
1hyA::Tn10, Alon::(kan, lacZ+); or
(b) ampC'::(PtrpB?tcl+), Placl q (Alacl-lacZ)1acY+, Awca.L
thyA::Tnl0, Alon::(kan, lacZ+), AlacA.
25
23. The method of claim l, wherein said exogenous flinctional B
galactosidase gene is inserted into an endogenous gene.
24. The method of claim l, wherein said exogenous filnctional B
galactosidase gene comprises a recombinant B-galactosidase gene
engineered to produce a detectable level of B-galaetosidase activity that is
reduced compared to the level of [3-galactosidase activity in a wild-type E.
colt bacterium.
25. The method of claim 24. wherein the level of [5-galactosidase activity
comprises between 0.05 and 5 units.
26. The method of claim 1, wherein the level of ll-galactosidase activity
comprises between 0.05 and 4 units.
27. The method of claim 1, wherein the level of B-galactosidase activity
comprises between 0.05 and 3 units.
28. The method of claim 1, wherein the level of [3-galactosidase activity
comprises between 0.05 and 2 units.
(CIB at I5-16.)
C. Claim Construction
As pan of the Mar'k)ira:iprocess, the following terms of the ’0l8 patent were construed,
either as-agreed between the parties or detennined by Order No. 22:
Claim Term CtJ_l18_tllI_Qljlllj______ __ _ 0
“providing” plain and ordinary meaning. i.e., furnishing,
supplying, making available, or preparing.
“in the presence oflactose” plain and ordinary meaning, i'.e., lactose is
available to the bacterium
“exogenous” plain and ordinary meaning, 1'.e., originating
outside an organism, tissue, or cell
“colonic acid synthesis gene” “By ‘colanic acid synthesis gene’ is rneant a gene
involved in a sequence of reactions, usually
controlled and catalyzed by enzymes that result in
the synthesis ofeolanic acid.“
ooh"lacZ gene” plain and ordinary meaning, 1'.e., a structural gene
that encodes the [5-galactosidase protein and is
part of the lac operon in the DNA of E. colt
26
“[3-galactosidase activity comprises Not indefinite; “fl-galactosidase activity is
between 0.05 and [200 units / 5 units / 4 measurable at between exactly 0.05 and exactly
units I 3 units / 2 unitsj" [200/5/4/3/2] Miller Units, as defined in Miller,
J.l-l., Experiments in Molecular Genetics (Cold
Spring Harbor Lab. I972) at 352-355“
“functional . . . [5-galactosidase gene” “a Functional sequence of DNA that encodes EI
galactosidase”
“wild type“ “the type most commonly found in nature”
(See Order No. 22 at I2-I3, 22-35.) None of Glycosyn, Jennewein, or the Staff specifically
identify any remaining claim construction issues for this initial determination. (See CIB at 32-33;
RIB at 16-17; SIB at 29-30.)
D. Infringement
According to Glycosyn‘s post-hearing briefing, and not contested by Jennewein or the
Staff, the following products are within the scope of the Investigation and accused ofinfringing
the following claims ofthe ‘U18patent:
Product Claims
Jennewein #1540 and I-3, 5, 8, 10, 12, 18, 23-28
[CIB at 15.) As referred to above, Jennewein and the Staff each argue that another of Jennewcin’s
E. calf strains is properly within the scope of the investigation and subject to a determination of
infi-ingcrncntea strain designated TTFLI 2. Glycosyn disputes that an infiingement determination
on TTFLl2 is appropriate given the circumstances.
27
l. Regarding the Jennewein TTFLIZ Strain
With respect to Jcnnewein’s 2 ’-FL produced by the TTFLI 2 Strain. there can be no dispute
that Glycosyn has not accused it of infringement such that it is an “accused product.” (CPB at 27
(“E. The Accused Process. At the hearing, Glycosyn will demonstrate that [] Jennewein’s method
ofmaking 2’-FL using Jennewein’s #1540 z
K) infringes the asserted claims of the ’0lS Patent”); SIB at 61 (‘Glycosyn has not alleged
that 2'—FLmade using Jennewein’s TTFLIZ strain infringes any claim of the asserted patents,
either literally or under the doctrine ofequivalents.").) Nevertheless, Jennewein contends itplaced
this strain into the scope ofthe investigation such that an infringement determination is warranted.
(RIB at 66 (“Despite being aware of Jennewein‘s TTFLI2 strain since August 21, 2018, Glycosyn
failed to accuse 2’-F L made using this strain of infringing any claim of the ‘O18patent.").) The
Staff concurs. (SIB at 63.) As noted, Glycosyn disputes that such a determination should he made.
tens at 67.)
The Commission has recently addressed the circtunstances under which non-accused
products nonetheless fall within the scope of an investigation. tn Certain Two-Way Radio
Equipment and Syslerm‘, Related Software, and Compotrerifs Thereof (“Two—Way Radio”), the
Commission had determined to review “(5) the [final] lD’s finding that insufficient record
evidence exists to make a conclusive detennination as to whether any redesigned products infringe
the "701 patent and the 1D‘s lack ofan express finding on this issue with respect to the ‘S69 or '99l
patenI[s]." lnv. No. 337-TA-1053, Comm’n Op. at S (Dec. 18, 2018) (public version). Contraljl
to that [D‘s finding, the Commission held “[respondent] has met its burden to show that the
redesigned products are fixed in design, have been imported, and have been sufficiently disclosed
by respondents during discovery.” Id. at 23 (citations omitted). The Commission also noted that
in a prior opinion, it had affirrned an ID which found that “redesigned products should be
28
adjudicated where ‘the design around products are within the scope of the investigation, have been
imported into the United States or sold in the United States, [and] were the subject of extensive
discovery as well as testimony during the cvidentiary hearing in this investigation.'” Id. at 24
(citation Omitted);see id. at 27 (“sufficiently fixed, have been subject to extensive discovery, and
have been imported“).
From these discussions in Twu~Way Radio, I divine a four—factortest as to whether a
respondent has rnet its burden to show the infringement of a redesigned product should be
adjudicated. The product must be: (I) within the scope of the investigation, (2) imported, (3)
sufficiently fixed in design, and (4) subject to extensive discovery. Of these factors, I find
Respondents have not met their burden as to the fourth factor, subject to extensive discovery.
Technically, the issue of whether TTFLIZ was subject to extensive discovery is not
actually disputed, given that when Glycosyn first attempted to argue this in their initial post
hearing brief, it was struck upon motion by Order No. 38. (See Order No. 38 at 3-4.) I understand
from the parties’ reply briefing that Glycosyn has resurrected this line of argument in its reply brief
(CRB at 35-37 (Section II.B.2)), but I disregard this content and do not depend on it in reaching
the present finding.
Both Jennewein and the Staff contend that Glycosyn either was aware or should have been
aware of the TTFLIZ strain on August 21, 2018. (RIB at 66; SIB at 6|.) Jennewein cites no
evidence to explain why this is (see RIB at 66), but the Staff states this date is “when Jennewein
produced documents describing that product, including the TTFI_.l2 strain‘s genotype and
construction.” (SIB at 6|.) To support its assertion, the Staff cites two documents, RX-0320C
and RX-0332, which I infer to mean these documents were produced on or before that day. (See
SIB at 61.)
29
The first, RX-0320C, is an article authored by certain Jennewein personnel, characterized
by Jcnnewein as a “draft article” (RIB at 67), and which Dr. Jcnnewein tcstified was submitted for
publication but then withdrawn to protect the information disclosed in it (_R){—O385C at Q160-1 65).
The article bears Bates numbers of JENNITCI l20_OO2Ol76-210. The document discusses
Jennewein’s strain engineering activities which resulted in
(RX
oazoc at -20177.)
(id. at -20192, -20207).
The second document, RX-03 82, is described as a European patent application (FLLBat 9
n.2), although it is unclear ifthe particular copy is the EPO publication of that application or a
copy ofa Jennewein submission as part of that application process; Dr. Jennewein offered a third
explanation, that RX-0382 is the issued patent itse|f(RX—0385C at Ql66-167). hi any event, the
document bears Bates numbers of JENN ITC1 l2UA00006729-S5 and discloses a “present invention
re]at[ing] to a method for producing oligosaccharides comprising a terrninal galaetose-91->4}
glucose disaccharide.“ (RX-U382 at -6729.) Importantly, it discloses bacterial strains that
intentionally lack B-galactosidase activity as we-llas bacteria including that activity. (Id. at [0084]~
[[)USS]). The document does not appear to refer to any of its embodiments or strains as TTFLIZ.
In any event, on September 14. ZOIB, Jennewein complied with its Ground Rule 7.2
obligation to identify those of its products it understood to be within the scope of the Investigation.
(See RIB at 9 n.2; SIB at 70.) In this mandatory disclosure. CX-0226C. Jennewein provided, in
relevant pan:
Pursuant to Ground Rule 7.2.I(2), Jennewein identifies the following
processes that are within the scope of the investigation:
30
TTFLl2. See, e.g., JENNEITCI lZU_UU2Ul76-JENNITCI l2O_UUZO2lU.
(CX-0226C at 2.) Notably! the production numbers listed here correspond only to the draft article.
which is RX-0320C, and not RX-0382.
Six days later, on September 20, ZOIS, Jerutewein amended a response to one ofGlycosyn’s
requests for admission regarding importation (SIB at 3384). On that day. Jennewein provided the
following:
REQUEST FOR ADMISSION 7:
Admit that Jennewein°s strain #1540 is the only strain Jennewein
uses to produce the 2’-FL that is imported into the United States.
AMENDED RESPONSE TO REQUEST NO. 7
Jennewein objects to this Request as vague and ambiguous with
respect to the terms “uses” and “produce.” Subject to its objections,
Jennewein responds as follows:
(CX-0216C at 5.) Notably, this response does not mention TTFLIZ at all.
The last important discovery date is November 5, 2018, the close offact discovery, which
saw Jennewein provide a final round of discovery responses, CX-0237C. (RRB at 7; SIB at 70.)
According to Jennewein, it “plainly disclosed the TTFLIZ strain to Glycosyn during discovery,
first in its [Ground Rule 7.2 disclosure] and again in its discovery responses on November 5,
ZOIS." (RRB at 7.) The Staff also characterizes that day as when “Jennewein amended its
31
interrogatory responses to clearly identify the TTFLIZ strain.” (SIB at 70.) In both of their
descriptions, Jennewein and the Staff reference page 2 of CX-0237C, where Jennewein provided
the following:
INTERROGATORY NO. 21
For each version, commercial name, and internal code name or other
unique identifier of Jennewein 2’-FL identified in response to [nterrogatory
No. l, identify all corresponding bacterial strains used to produce
Jennewein 2’-FL.
RESPONSE TO INTERROGATORY NO. 2
Jennewein objects to this interrogatory as Dverbroad, unduly
burdensome and seeking information not reasonably calculated to lead to
the discovery of admissible evidence or not proportional to the needs of this
case to the extent that it encompasses products Jennewein does not import
commercially into the U.S. or are not the subject of this investigation, or
strains used to produce such products.
Subject to and without waiving general and specific objections, and
subject to Jennewein’s objections to lnterrogatory No. l, Jennewein
responds to this interrogatory as follows: Jennewein identifies the
production strain it uses to produce Jennewein 2"-FL for commercial
importation into the United States as E. colt strain BL2l (DB3) #1540.
FIRST SUPPLEMENTAL RESPONSE TO INTERROGATORY NO. 2
[ll/‘S/18!:
Subject to Jennewein’s prior objections to Interrogatoiy No. 22
Jennewein incorporates by reference its
1 ' 1 nd hi
- TTFLI
(CK-0237C at 1-2.) Again, November 5, 20lS was the day fact discovery closed.
Thus, on the question of whether Jenncwein provided “extensive” or “sufficient” discovery
on the TTFLl2 strain, I find it did not. Only two documents provide any specific information on
TTFLI 2; the undated “draft” article which describes the development strain and identifies it by
name (see, e.g., RX-0320C at -20191, Fig. 1); and the ZOI4 patent application specification, which
32
does not refer to TTFLIZ by name and simultaneously discusses strains that could be TTFL12 (see
SIB at 74 n.23 (discussing RX-0382 at 111][D084], [l]085])) as well as strains that are definitely not
rrruz (see rd. (discussingax-03s2 at'll1|
[U087], [0OS3])). An accused infringer's own patents (RX-0382 in the case of Jcnnewein) are
generally not Considered reliable evidence of an accused product's features in the first place. Sea
Forest Labs, Inc. v. Abbot Labs, 239 F.3d 1305, 1313 (Fed. Cir. 2001). Further, while Jennewein
identified TTFLIE as falling under the scope of the investigation in its Ground Rule 7.2 disclosure,
and identified the “draft” article, RX-0320C, as evidence ofTTFLl2’s relevant features, it did not
identify the patent application such that Glycosyn would have been on notice of it. Thus, in an
effort to meet its burden on sufficient discovery, Jennewcin has effectively pointed to just one
document that Glyeosyn could have used—-theundated article (RX-0320C).
Moreover, the probative value of that article is low. While Jennewcin argues it “includes
a complete description of the genetic makeup of the TTFL12 strain; no more is required to
conclude that the use of this strain cannot infringe the Asserted Claims” [RIB at l4 n.3), it does
not show that any 2’-FL which Glycosyn might accuse of infringement was actually produced in
this way, l find it perplexing why there were no other documents produced (or at least identified
in .lennewein‘s briefing as having been produced) and/or identified to Glycosyn during discovery
to confirm this basic fact, especially given: (I) the prevalence of batch or fermentation run records
in this industry (see RIB at 145 (“Jennewein can readily determine the strain used to make any
particular lot of 2‘~FL. As Dr. Parkot testified, Jermewein can identify the strain used to produce
each lot number of2’-FL within Fourhours of a request”) (citing Hr’g Tr. at 34810-21)); (2) the
fact that Jennewein seems to have produced its first and only TTPL l2 2’-FL during the discovery
period of this investigation (RX-0385C at Q170 (“Qt When did Jermewein start producing 2’-FL
33
using the TTFL12 strain?" Dr. Jennewein himself testified, "[w]e performed a fermentation run in
the summer M2018.” (emphasis added))); and (3) .lennewein’s claim that TFFLIZ is so fixed in deem t1(RRB at 4 (citing Hr’g Tr. at 204:] 5720516)). RX»O32OCmay provide information on the
conception ofTTFLl2. but it does not sufficiently identify and describe a product that could serve
as an accused product.
The discovery responses which Jenneweirt and the Staff point to add little. Again, while
TTFLIZ was identified on September 14, 2018 as a product alleged to he within the scope ofthc
investigation (CX-0226). the earliest interrogatory responses identified as mentioning TTFL l2 are
those Jennewein provided on the last day of discovety (CX-0237C at I-2). Perhaps more
important are Jenneweirfs responses to Glycosyn’s request for admission on importation. Here.
the request asked Jetmewein to admit that #1540 was the only strain they use to produce 2’-FL
imported into the U.S. (CX-0216C at 5.) Jermewein had initially answered with reference to just
the #1540 strain, but updated that answer toinclude t
andthe neverupdatedit ism This
was done despite Jennewein‘sfirst ever importation of TTFLI2-based 2’-FL on October 1l, 2018.
(PUBat I l (citing, inter alia, RX-0278C; RX-280C; Hr’g Tr. at 347:6-22).) Then, on the very last
day of fact discovery, Jennewein added TTFLIZ to its response to an interrogatory asking for
simply “all corresponding bacterial strains used to produce Jenneweio 2’-FL.” (CX-0237C at I
2.) In total, these responses put Glycosyn on notice of just three things: a strain referred to as
TTFL12existsandwasdescribed inanunpublished, undated article— (CK
0226; CX-0320C); at some point the strain was used to create an unspecified amount of 2‘-FL
(CX-2037C at I-2); but that 2’-FL had not been imported into the United States (CX-0216C at 5).
34
It is the burden of the respondent to provide the “extensive” or “sufficient” discovery on
the redesigned product, Tw0—WayRadio, Con'im’n Op. at 23, and Jennewein has not met this
burden, from either a document production or discovery response perspective. An eamest effort
to force TTFL12 into the investigation would have seen Jettnewein prove to Glycosyn the nature
of TTFLIZ, and how it had been used to produce imported 2’-FL, before the very last day of fact
discovery. This was not done, however.
Admittedly, Glycosyn failed to take discovery ofits own on this issue (see Rll-3at 9-1(J. 14.
66; RRB at 2-4) and to respond to Jc11newein's own requests for admission on TTFL12 (see RIB
at 68-69 (citing RX-03 17C)). As Jennewein summarizes, “Glycosyn has been hard at work trying
to keep this product out of‘this investigation on procedural grounds." (Id. at 9.) Nevertheless, it
is Jennewein’s burden to introduce TTFL I2-based 2’»FL into the case, Two-WayRadio, Cornm’n
Op. at 23, and Jenneweir1’sinaccurate response to Glycosyn‘s request for admission on importation
was more than enough to dissuade Glycosyn from investigating anything other than the #1540
strain during discovery.
Accordingly, I do not find adjudication of whether the TTFLl2 strain infringes to be
appropriate at this time because the discovery on TTFL 12 was not adequate.
2. DirectInfringement bythe Jennewein #1540and—
Strains
Glycosyn has shown by a preponderance of the evidence that the Accused Strains (#1540
a meet thelimitations ofasserted claims l-3,5,S,10,I2,18,
and 24-23 either literally or under the doctrine of equivalents, and thus, Jennewein directly
infringes those claims. Jennewein has not been shown to infringe dependent claim 23.
35
a. Undisputed Claim Limitations
The parties do not dispute most of the asserted claim limitations of the ‘O18 patent as
compared to Jennewcin‘s Accused Strains. (See, e.g., CIB at 33-34; RIB at 18; SIB at 33-36; RRB
at B-41.) Commission Rule 2l0.3l(d) states in relevant part, “[a]ny matter admitted under this
section may be conclusively established unless the administrative law judge on motion permits
withdrawal or amendment ofthe admission.” I9 C.F.R. § 2l0.3l(d). l agree with Glycosyn that
this rule allows me to conclusively find for the purposes of this investigation that the Accused
Strains meet each of the claim limitations admitted to in Jenneweirfs responses to requests for
admission (CX-0215C; CX-0216C; CX-0217C), and I do so find. (CIB at 34 (citing CX-02l5C
at l-2, 4-7, 8, .39-40; CX-0216C at l-2, 4-7, 8, 39-40, 25-33, 63, 69; CX-02l 7C at 72-74).) As to
independent claim 1, these limitations include:
I. A method for producing a fueosylatcd oligosacchariclc in a bacterium,
comprising
providing an isolated E. calf bacterium comprising,
(_i) a deletion or Functional inactivation of an endogenous B
galactosidase gene;
(iii) an inactivating mutation in a colanie acid synthesis gene; and
(iv) an exogenous lactose-accepting fucosyltransferasc gene;
culturing said bacterium in the presence of lactose; and
retrieving a fueosylated oligosaccharide Erom said bacterium or
from a culture supernatant of said bacterium.
PO18 patent at cl. 1.)
With respect to the asserted dependent claims, .leru1ewein’smethod of producing 2‘-FL
practices the additional elements recited in dependent claims 2, 3, 5, 10, l2, I8, and 24-28. (See
CIB at 63-64 (citations omitt-ed').) The Staff agrees these claim elements are met. (See SIB at S7
36
60.) Jennewein does not dispute the claims are practiced either, apart from their dependence on
independent claim I. (See RIB at 66; RRB at 8-4| .)
a dispute over these claims, I find they are met by Jennewein’s Accused Strains. These claims
include
In light of the evidence identified by Glycc-synand discussed by the Staff, and the lack of
2. The methed of claim 1, wherein said colanic acid synthesis gene
comprises an E. colt weal, wzxC, wcaD, wza, wzb, or wze gene.
3. The method of claim 2, wherein said colanic acid synthesis gene
comprises a wcaJ gene.
5. The method of claim 1, wherein said exogenous lactose-accepting
fucosyltransferase gene encodes n.(_l,2) fueesyltransferase andfor rx(1,3)
fucosyltransferase.
10. The rnethed of claim 1, wherein said bacterium further comprises a
Functional lactose permease gene.
12. The method efclaim IO, wherein said lactose permease gene comprises
an E. coir‘ lacY gene.
18. The method of claim l, wherein the level of B-galaetosidase activity
comprises between 0.05 and 5 units.
24. The method of claim l, wherein said exogenous functional _B
galactosidase gene comprises a recombinant B-galactosidase gene
engineered to produce a detectable level cf [3-galactosidase activity that is
reduced compared to the level of |3-galactosidase activity in a wild-type E.
0011'bacterium.
25. The method of claim 24. wherein the level of B-galaetesidase activity
comprises between 0.05 and 5 units.
37
26. The method of claim l. wherein the level of [3-galactosidase activity
comprises between 0.05 and 4 units.
27. The method of claim I, wherein the level of B-galactosidase activity
comprises between 0.05 and 3 units.
28. The method of claim l,, wherein the level of B-galactosidase activity
comprises between 0.05 and 2 units.
(’()l8 patent at cls. 2, 3, 5. It], 12, l8, 24-28.)
b. Disputed Claim 1 Limitation “an exogenous functional B
galactosidase gene comprising a detectable level of [£
galaetosidase activity that is reduced compared to that of
a wild-type E. coli bacterium”
Lnaddition to those undisputed limitations listed above. claim 1ofthe ’0lS patent requires:
(ii) an exogenousfiincrionai B-gaiaciosidase gene comprising a detectable
level’0f,B-gaiactosidase activity that is reduced compared to that of a wild
iype E. coii bacterium, wherein the level of [3-galactosidase activity
comprises between 0.05 and 200 units;
(‘0l8 patent at cl. l (emphasis added).)
For the emphasized portion of this limitation, Glyeosyn alleges it is met in the Accused
Strains both literally and under the doctrine of equivalents through the strains‘ use of lacZa and
lricZ.Qgenes. (CIB at 35, 42.) More specifically, Glycosyn contends that lacZ0t encodes the
“LacZo. portion" and lat-ZQ encodes the “LacZQ portion” “of the full LacZ B-galactosidase
enzyme“ and thus, together, they “literally comprise a sequence of DNA that encodes |3
galactosidase“ under the claim construction ordered by Order No. 22. (See id. at 35-36.)
l disagree it is literally met. To repeat, the claim recites “a[] . . . fiinctional [3-galactosidase
gene," which Order 22 construed as “a functional sequence of DNA that encodes 0-galactosidase."
(Order No. 22 at 29.) This limitation requires “a sequence” of DNA that encodes for the enzyme
known as [3-galactosidase. Jcnnewein has put forward persuasive evidence that 11202::and lacZQ
arc, in fact, distinct sequences of DNA in which neither by itself comprises the full collection of
38
nucleotides needed for a B-galactosidase enzyme. (See. e.g., RIB at 26-27 (citing l-Ir‘g Tr. at
435:l8-436:6; RX-0386C at Q56, 64-66; RX-0409C at Q329-330; RX-0408C at Q63-64).)
The Staff agrees with Jennewein (see SIB at 39) and Glycosyn acknowledges that IacZa
and IQCZQare distinct: "[i]n other words, 13-galactosidase can be encoded by either two sequences
OTDNA, i.e., IacZa and IacZ.Qgenes together, or by a single sequence ofDNA, 1'.e.,the laeZ gene.”
(C-IBat 37.) Nonetheless, Glycosyn disputes that “a sequence,” as used in the ordered construction
of “gene,” means “that the ‘functional sequence of DNA’ be a single contiguous sequence within
the bacterial genome." (CIB at 38.) Glycosyn offers no evidence in support, however, and I find
a plain and ordinary meaning of “sequence” does imply contiguity. Indeed, if “sequence” did not
mean a contiguous string of nucleotides (i.e., a contiguous string of DNA), then Glycosyn and its
expert would not bother to refer to [acZa and lacZQ as separate genes, as they do in the excerpt
above and throughout the record. (See, e.g., CIB at 3, ll, 35, 36, 36 n.3, 38, 39, 43, 44, 64, 117;
CX-0004C at Q62, 458, 462, 468, 477. 48!. 578. S95, 596.)
Accordingly, .len.newein’s Accused Strains do not literally infringe “an exogenous
fimctional B-galactosidase gene” because they lack a single sequence of DNA which fimctions to
create a [3-galactosidase gene. As G]ycosyn’s own expert states, Jennewein “uses two shorter,
functional sequences of DNA (lac'Z'a and 1'acZ.Q)which, together, encode B-galactosidase.” (CK
t)OO4Cat Q475.) The use of such shorter fimctional sequences, which encode for enzyme
fragments, is called o.-complemcntation. (RX-0011 at -14798 (“[t]his cornplcmentation involves
noncovalent reassociation ofcomplementary fragments of the [1-galactosidasesubunit polypeptide
chain, which then reassemble into an enzymatically active tetrameric structurc.”).)
Glyeosyn also argues, however, that Jennewein’s IacZa and IHCZQmeet “an exogenous
Functional [3-galactosidasegene" under the doctrine of equivalents filnction-way-result test. (CIB
39
.. -‘
at 42.) Its expert testitied that Jennewein's use or ‘ two shorter. functional sequences" as compared
to “one long, functional sequence” “is a quintessential example of ‘equivalence,’ because in both
cases a functional B-galaetosidase enzyme, with a low level of activity, is obtained.“ (CX-0004C
at Q475.) To understand why Ci]ycosyn’s expert is correct, it is llfllpflll to break the analysis into
two parts; (1) “a[] . . t functional [3-galactosidase gene”; and (2) “exogenous.”
Regarding “a[] . . . fimctional B-galactosidase gene,” the term was construed in Order 22
as “a fiinctional sequence of DNA that encodes [5-galactosidase.” (Order 22 at 29.) As for function
and result, there is no difference between the combination of lacZtt and lacZS2 genes on the one
hand, and any particular individual “fitnctional ii-galactosidase gene” on the other. The function
and result of the “fimctional B-galactosidase gene” are baked right into its name--to provide
expressible DNA which, when expressed through understood pathways, results in the creation of
a [3-galactosidase enzyme:
Also described herein are bacterial host cells with the ability to accumulate
a intracellular lactose pool while simultaneously possessing low, ftmetional
levels of cytoplasmic B-galactosidase activity, Forexample as provided by
the introduction ofa functional recombinant E. coii lacZ gene, or by a B~
galactosidasc gene from any of a number of other organisms (e.g., the lac4
gene of Kluyveromyces lactis (e.g., GenBank Accession Number M84410
(GI: 173304), incorporated herein by reference).
(See. é'.g., ’0 18 patent at 7:22-30.) Nowhere in this claim element is there any limit on: the amount
or type of DNA; the location of the DNA in the genome; the amount or type of peptides expressed
from that DNA; or the nature or way those peptides assemble into [3-galactosidase.
Similarly, the function and result of the lncZa and i'acZ.Qgenes is also the provision of
DNA which, when expressed, results in the creation of a B-galactosidase enzyme. This function
and result are communicated clearly in Jcn11cwein’s submission to the U.S. Food and Drug
Administration (the “GRAS notice”) for the #1540 strain. (See CX-0240C at -6804 (describing
inseflion of lacZa and iacZ.Q“for the degradation ofexcess lactose”), -6805 (“Verification oflacZ
40
integrations and 13-galactosidaseactivity"), -6806 (“The clones having the !aeZ omega fragment
integrated were analyzed for 2‘-FL productivity and LacZ activity"), -6807 (“Clones showing B
galactosidase activity at 42°C but not at 30°C were selected for further modifications.”); see also
RX-0387C at Q77-78.)
And the way the result is achieved is substantially the same as claimed. Inasmuch as the
"way" analysis focuses on gene expression, that is, the role of the “functional 13-galactosidase
gene," the claim term imposes no limits on the way the result is achieved apart from the basic
process applicable to all DNA*the gene is transcribed and translated, resulting in peptides which.
through folding and/or combination with one another, become the |3-galactosidase enzyme. (See
C-X-0004C at Q53-54, 60 (discussing gene expression basics); RX-0384C at Q 103-1 14 (discussing
same); RX-0386C at Q93-97.) The evidence shows that this universal process also applies to
lacZ-1;:and !acZQ in the Accused Strains such that when these genes are expressed (i.e., transcribed
and translated), the peptides necessary to eventually become the B-galactosidase enzyme are
created. (See, e.g., CX-0004C at Q62, 468, 475-481; CDX-0032; RX-0384C at QI49-151; RDX
0005; RX-0386C‘ at Q90, 94, 98, 102; RX-0387C at Q77-78; RX-0409C at Q21-24. 252; l{r’g Tr.
at 435:5-14, 523:lS-524:l4_, 6l5:l6-25.) Inasmuch as the “way” analysis focuses on genome
structure, because the first step in the method of claim 1 is “providing an isolated E. calf bacterium"
possessing “a . . . functional [3-galactosidasc gene,“ the evidence shows that t1-Complementation
was well-known in the afl. (I-lr’gTr. at 265:5-I6, 664:6-7.) Persons ofordinary skill would have
known that using !acZ'a and MCZQas the relevant structure, instead of a single gene, would have
been effective, albeit “overco1nplicatcd.“ (I-Ir‘gTr. at 265:1"!-266: l, 664:6-7.)
I am not persuaded by Dr. Stephanopoulos‘ (.lenncwcin's expert) testimony on this point.
His witness statement cites three basic differences between the claimed invention and the use of
4l
lacZ0: and lacZQ: (1) the two gene fragments were inserted at different times and in different
genome locations; (2') assembling a B-galactosidase enzyme using lacZa and Im:ZQ involves a
process with more steps than assembling it after a single gene is expressed; and (3) the two gene
fragments are temperature dependent, that is, there is no expression unless temperature conditions
are satisfied. (RX-0409C at Q332-335.) The first two differences are seemingly foreseeable
aspects of employing t1—COmp lementation, so these differences are not substantial. (See CX-0004C
at Q4’/7.) As for the third difference, Dr. Stephanopoulos points out that “.lermewein’s [lacZ.Q] is
under temperature-sensitive repression C1357,” which allows for temperature control of
expression of the lrrcZ$'2fragment. (See RX~O4U9Cat Q335.) But as Dr. Prather (Glyeosyn’s
expert) explains, C1857 is a protein added to the Accused Strains, and one which is not always
effective. {l-Ir’gTr. at 540:3-18, 543121-23.) That is, when the C1857 is not present, or when it
“leaks,” expression of the lacZa and 1'acZQwill not be temperature-dependent. (Id. at 540115-18.)
And because Cl857 is apparently not a part of either the lacZrx or !acZ.Q gene fragments
themselves, temperature-dependence has nothing to do with “providing . . Aa . . . functional B
galactosidase gene,” and it is therefore not a substantial difference between the way claim l of the
‘U18 patent achieves its result and the way the Accused Strains do. (RX-0407C at Q26-28 (“A
temperature-sensitive repressor is another genetic regulatory element that represses expression of
a gene.").)
Jennewein makes two further arguments against equivalence. First, Jennewein argues its
vrfldustisn Paws is ash 1hfl1
time at 19.)
Jennewein reasons that “[s]ince all parties admit !acZQ is required to produce B~galactosidase,
Jennewein’s process cannot be equivalent to the claims.” Ud.) [do not agree. Claim l covers a
42
method Forproducing a fucosylated oligosaccharide in a bacterium, comprising three overall steps:
( I) providing a bacterium having certain characteristics; (2) culturing the bacterium in the presence
of lactose; and (3) retrieving, in this case, 2’-FL. (‘O18 patent at cl. 1.) The claim limitation at
issue here falls under the first step, requiring that the bacterium have a particular characteristic,
namely, a functional [3-galactosidase gene. (ldf) .le11newein’sargument is about how the bacterium
is cultured to produce ZKFL, which falls under the second step. (MI) How Jennewein cultures a
bacterium has no bearing on whether the bacterium possesses a functional [3-galactosidase gene.
The combination of lacZa or1ru."Z.Qis unquestionably functional—thc fragments sewe no other
purpose except to produce B-galactosidase. (CX-0004C at Q48l (“That is their only funetion.").)
That they can be repressed under certain conditions does not affect whether they are fimctional,
and, similarly, does not affect whether an
equivalent to the claimed gene is present within the Accused Strains. (Hr'g Tr. at 631:3-6 (“Q ls
it Fairto say that in your view, the [!acZ0:and lacZ'.Q]fragments are functional genes, they’re just
not beta-galactosidase genes? A. Correct.”).) .Iermewein‘s temperature-induced trigger is
lherefore irrelevant
Second, Jennewein argues against equivalence because lacZa and !ncZ.Qwere known to
the ‘Ol 8 patent inventors, but they "chose not to disclose it in their patent or claim this foreseeable
mmmatomww-ga1mdas=
_ (RRBat 19(citingH1"g Tr.94:12-l5, 265:1?-266:1, JX-0022C at
l22:l l-l-4).] Jennewein reasons “[t]hus, 0.-complementation cannot be equivalent to a normal [5
galactosidase gene." (Id. (citing Forest Labs. , 239 F.3d at 1313).) Again, 1do not agree, primmily
because I do not see a connection between this supposed choice of the inventors and the function
way-result test. Moreover. to the extent inventor Dr. Massimo Merighi testifiecl U.
43
cornplementation “seems like an overcomplication.” he also testified moments later that “[b]ut
alpha complementation [gives you] a iilnctional beta-galactosidase polypeptide. So under that
interpretation, yeah, we talk about it because the whole engineering we did was try to make a
functional beta-galactosidasc polypeptide inside a strain.” (Hr’g Tr. at 266:5-l 1.)
Accordingly, the i'acZn and lacZQ genes in Jcnnewein‘s Accused Strains are equivalent to
“a[] . . . functional B-galactosidase gene.” See Ajinomoto C0., Inc. v. 1211'!Trade Comm '11,Nos.
2018-I590. 4629, -- F.3d --, 2019 WL 3558560 at *9-l0 (Fed. Cir. Aug. 6, 2019) (holding
substantial evidence supported finding equivalence between two proteins exporting same aromatic
compounds, consisting of 85-95% identical structure, and resulting in increased production ot
same L-tryptophan).
I also find the lncZa and facZ.Q genes are equivalent to “an exogenous fitnctional B
galactosidase gene.” Jennewein advances two arguments on this issue, First, it argues that
“[n]either lacZ0cnor !acZQ encodes for or can produce a fiinetional 13-galactosidaseenzyme or B
galactosidase activity when exogenous, or outside of, the production strain." (RIB at 32 (citing
RX-0409C at Q25S).) But in the Markmcm process, the parties agreed to a construction oi
“exogenous” as “originating outside an organism, tissue, or cell." (Order 22 at I2.) Whether or
not a gene, like [acZa and 1acZ.Qindividually, can produce B-galactosidasc activity outside of the
production strain is irrelevant to where a gene “originated.”
Jennewein secondly argues that because the lacZa in the Accused Strains was not added
by Jennewein, but was present in the original BL2l (DE3) strain which Jennewein engineered to
achieve the Accused Strains. the “exogenous” limitation is not literally present in those strains.
(RJB at 32-33.) However, lcrcZ.Qwas not originally in strain l54O, but was added during the
sti-ain's development, and it is therefore exogenous. (CX-02 l3 at Fig. 2, -5158 (“Strain 1540 was
44
~
derived from its parental strain I242 by integrating a heat inducible lacZ§l gene fragment . . . .").)
Because !cicZa and lat-Z52together are equivalent to “a[] . . . functional |3-galactosidase gene," the
exogenous nature of laeZQ is enough to meet the limitation. It is the combination of !acZa and
1acZQ which is equivalent to the claimed “|3-galactosidasc gene," and this combination does not
exist until 1aeZ£2is inserted into the bacteriunfs genome from outside the organism. Therefore,
the combination is “exogenous” and satisfies the claim limitation at least under the doctrine of
equivalents, whether or not the IacZa alone is literally endogenous or exogenous.
Accordingly, I find the IacZ0t and IoeZ.Q genes in Jcnnewein’s Accused Strains are
equivalent to “an exogenous functional ‘B-galactosidasegene."
e. Disputed Claim l Limitation “wherein the level of B
galaetosidase activity comprises between 0.05 and 200
units”
In addition to those undisputed limitations listed above, claim l of the ‘O18 patent requires;
(ii) an exogenous functional B-galactosidase gene comprising a detectable
level of B-galactosidase activity that is reduced compared to that of a wild
type E. coli bacterium, wherein the level of fl’-galactosfdase acfiviifv
comprises between 0.05 and 200 uiiits;
(‘0l8 patent at cl. l (emphasis added).)
For this limitation, “wherein the level of B—galactosidaseactivity comprises between 0.05
and 200 units,” Order 22 clarified that the term is not indefinite and means “I3-galactosidase
activity is measurable at between exactly 0.05 and exactly [200/5/4/3/2] Miller Units, as defined
in Miller, _l.H.,Experiments in Molecular Genetics (Cold Spring Harbor Lab. 1972) at 352-355.”
(Order 22 at 22-23.) Thus, regardless of whether the Miller protocol is scientifically sound or
reliable (see RIB at 41 (citing RX-0003)), it is the test to be used to determine it'a bacterium falls
within the scope of the claims. Glycosyn provides a rough surnmary of the Miller protocol as
follows:
45
(1) taking a sample from a culture of growing cells, (2) “permeabilizing"
the cells, (3) incubating the penneablizecl cells with a chemical compound
l-cnownas ONPG (a colorless compound which is specifically recognized
and cleaved by [3-galactosidase to yield a yellow product), and (4)
measuring with a spectrophotometer the amount of yellow color that
develops over a known period of time.
The values recorded by the spectrophotometer are then entered into a
mathematical equation to yield the level of B-galactosidase activity in
“Miller units.“
(CIB at 48-49 (citing CX-0251; Hr’g Tr. at 3:15:19-318:12).)
Upon a review of the parties’ testing methods, it is clear .lennewein‘s (both that which it
conducted itself and hired third-party Battelle to perform) diverges further from the Miller protocol
than Glycosyn‘s. Jennewein‘s methods are therefore less reliable evidence on whether Jennewein
“provides” an colt‘ bacterium" which “comprises” Miller Unit activity within the claimed
range. (’0l3 patent at cl. 1.)
Considering Glycosyn bears the burden on this issue, I begin with its testing and
Jennewein’s criticisms thereof. Many of these criticisms are not rooted in a failure to follow the
Miller protocol, however, but rather a failure to: (1) perform additional steps Jenncweill deems
necessary or appropriate to properly identify exactly that amount of Miller Unit activity is
attributable to what would be the “functional B-galaetosidase gene” (z'.e.,the combination of1acZ0i
and .l'acZQ) in the strain (see RIB at 38-39; R_R_Bat 20-21, 24-27, 29); or (2) perform testing that
reflects .lennewein‘s actual manufacturing process (see RJB at 38, 50, 54-55; RRB at 21-23. 28).
Starting with the issue of Jennewein’s manufacturing process, Jennewein alleges Glycosyn
improperly:testedwithshakerflasks;didnot culturethe strainsinthe presenceoflactosc;
(RIB B15455 (stations
omitted); see RRB at 28.) These criticisms are misplaced. The test is not whether Jennewein’s
46
accused strains exhibit the Miller Unit activity level during Jennewein’s production process, but
whether Jennewein “provides” an “E. coir‘bacterium" which “comprises” Miller Unit activity
within the claimed range when put through the procedures outlined in Miller. (’0l 8 patent at cl.
1; Order 22 at 22-23.) In other words, .lennewein’s manufacturing process could involve chilling
the E. coli to 10°C or boiling to 100°C. for 10 minutes or 10 hours, and any other number of
variations, but that would not bear on whether the E. calf which Jennewein "provides" to its process
exhibits Miller Unit activity within the claimed range when put through Miller's protocol.
Jennewein also complains that the Miller protocol is simply unreliable on its face and
“insufficient to prove infringement." (See RIB at 4| (“A paper by Giacomini shows that. even
following Miller's methods. Miller Units varied wildly. . . . This variability means that the Miller
assay is not reliable proof of infringement, particularly at very low levels near the limit of the
assay’s detection"), 53-54 (citing, inter alia, RX-0409C at Ql96; RX-0008; RX-0037); see also
RIB at 19 {citing Aporex. Inc. v. Cephalon, Inc._ No. 2:06-cv-2768, 20l2 WL 1080148 at *1l-12
(ED. Pa. Mar. 28, 20121).) This complaint is beside the point. The U.S. Patent and Trademark
Office issued claims to Glycosyn which expressly define the invention’s scope in terms of Miller
Units customized by the Miller protocol. Thus, reliable or not, it is the test to he used—a point
Jennewein concedes in other portions of its brief. (See RIB at 49 (“Third, Glycosyn failed to
follow Miller in performing its testing, and its test results are thus unreliablc.“).) l also agree with
the Staff that any complaint over unreliability in defining an invention by reference to Miller Units
is effectively an indeflniteness argument that was not included in Jennewein‘s pre-hearing brief
and is therefore waived. (SRB at 3-9 11.3.)
Jennewein makes two other unpersuasive arguments regarding the Millet‘protocol. First,
Jcnnewein argues Glycosyn’s results vary “significantly” (RIB at 53) or “much more . . . than other
47
testing” (id. at 55-56) such that they have a lack of reproducibility leading to unreliability. The
argument is largely conclusory, however, offering no discussion of Glycosyn’s results or why their
variance is “significant[].” (R_lBat 53 (citing Hr’g Tr. at 505: I -I5 (discussing general importance
of reproducibility)).) Based on my own review of the data, I do not [ind Glycosyn‘s results vary
meaningfully more than Jennewein‘s. (Compare CX-0258C with CX-0292C with CX-0294C.)
Second, Jcnnewein argues Glycosyn failed to subtract Miller Unit levels associated with Aim-Zor
lacZ“ control strains. (See, e.g., RIB at 50-S2.) This step is indisputably not found in Miller (see
gerieraliy CX-0251), and, for reasons discussed further below, I do not find it has been shown to
be necessary or even appropriate.
Finally, of all the criticisms Jennewein lodges against Glycosyn‘s testing, only two are
based in a deviation from the Miller protocol: (I) Glycosyn failed to test with toluene in addition
to SDS/chloroform (RIB at 56 (citing RX-0409C at Q2l4-216: RX-0408C at Ql25; RX-0008;
Hr’g Tr. at 509:4-16); and (2) Glycosyn failed to test at longer incubation times than 60 and 120
minutes (id. at 56-57 (citing RX-0409C at Q2lS; RX-0408C at Q1 13, 1I4, l39; I-lr‘gTr. at 307:3
308:25, 309;7- 16).) On the first, Miller teaches use oftoluene and SDS/chloroform as alternative
techniques. (CX-0251 at -1810, -I B12.) Therefore, using one technique but not the other does not
render testing unreliable. On the second, it was not wrong for Glycosyn to fail to test at “extended
incubation times,” because Miller does not specify a reaction time. Miller instead states “[s]top
the reaction by adding 0.5 ml of a [stop solution] afier sufficient yellow color has developed."
(CX-D251 at —l8lt).) Glycosyn's expert persuasively testified that sampling should occur while
the reactions are linear (a point reinforced by Miller (CX-0251 at -1809)) and she confirmed that.
for her experimental assays, 60-minute incubations gave a sufficient amount of visible yellow
color, and times after that no longer represented linear reactions. (CX-0004C at Q502.)
48
Taming now to Glycosyn‘s criticisms of Jennewein’s testing, I find these have more merit,
but to varied effect. For example, a primary dispute in this investigation is whether Jem1ewein’s
additional step of subtracting a AlacZ or lacZ’ control strain’s Miller Units from each accused
sample’s measured Miller Units is necessary—-—a step perfonned in Jenneweitfs own testing and
that of third-party Battelle. Jennewein argues this step “is not only appropriate, but necessary”
(RIB at 39) to correct for any agent within the strain that causes “enzymatic cleavage of ONPG by
other enzymes besides [J-galactosidase" (RX-0409C at Q99)?
Jen.newein'S point is seemingly scientifically valid, but the fact of the matter is that the
Miller pt‘0tOCOldoes not include this step. (See generally CX-0251.) Further, the record does not
identify any such “other enzyme[] besides |3-galactosidase,” let alone one present in Jenncwcin’s
2 and #1540 strains. (See RIB at 41, 43, 45, 52-.54,60, 104; RRB at 21-23, Z3, 30.) Given the
supposed importance of this control step, Jennewein‘s expert's immense metabolic engineering
experience (RX-0384C at Q9-40), and the well-studied properties of E. colt, I do not understand
how this agent was not identified. Indeed, when pressed, both parties’ experts testified they were
unaware of such substances. (Hr‘g Tr. at 454:9-23, 680:3-10.)
And in many cases, Jennewein‘s subtraction resulted in negative Miller Unit levels for an
accused sample. The Staff presents one such instance taken from .lenneweiI1’Sin—housetesting:
3 Other sources of “background noise” .lennewein’s expert identifies (RX-0409C at Q96-99;
RDX-0013) are Lutderstood to be controlled for by techniques already disclosed in Miller itself
(see CX-0251 at -1810-l l (describing 550 nm optical reading or centrifugation to correct for cell
debris affecting 420 nm light reading); -1811 (describing Z buffer with no cells to correct for
spontaneous splitting of ONPG)) or otherwise implemented in Jennewt-:in’stesting (RIB at 43
(describing washing for fermentation media), 52 (describing time:O reading for spontaneous
ONPG hydrolysis)).
49
(SIB at 51 (showing excerpt of RX-0029C); see RX~OD29C(columns “O” and “P” at various
w0rksheets).) There are negative results in Battelle’s data as well:
(CX-0294C; see generally CX-0294C (columns “P” and “R"); CX-0292C (columns “P” and ”R”).)
These negative values in particular should have put Jennewein on notice that its negative
control technique was unreliable on its face, or implemented unreliably, or some other assumption
was(MB M5-56— The
50
Staff notes that the Battelle Scientist involved in the testing testified that such negative values
“would correspond, correlate to a zero value,“ but, in the Staffs view, it is really “an impossible
result." (SIB at Sl n.l6 (citing Hr’g Tr. at 32'/‘:4-19).) [agree with the Staff.
I also find the scientist’s explanation unacceptable given other evidence in the record that
Jennewein may have chosen its‘ control strain over alternatives because of the effect it would
have on infringement testing. The following email was produced during discovery (see Order No.
30) in which testing protocols were discussed between Jemtcwein personnel and a third party in
the context ofwhether a “0.05" valuc would be met:
It-o_.ztt1'dt11gthe Mullet assm
(CX—04'.?.2Cat -0306730-l; see CXYDllO4Cat Q534-538; SIB at 53.) It is likely that the “U115”
value is the bottom of the claimed range “0.05 to ZOOunits," that is, Jertrtewein sought a control
strain that would minimize the measured Miller Units. (‘DIBpatent at cl. I.)
Moreover, of the two testifying experts who offered contrasting opinions on whether
negative control strain subtraction is necessary (see, e.g., CX-0004C at Q534, 539; RX-0409C at
92-I0], 196-20]), .lennewein’s expert was shown to have a significant lack of experience and
familiarity with Miller testing prior to this litigation (see CIB at 57-59 (citing, inter alia. Hr’g Tr.
51
at 582:8-604:l8)), while G|ycosyn's expert has “performed the Miller assay many times [as] a
graduate student [and] was able to reference my notes on those assays, which assisted me in my
review of the documents in this investigation“ (CX-0004C at Q86). l therefore assign Jennewein’s
expel-t’s testimony less weight on this issue.
For at lcast these reasons, subtraction ofa negative control strain was inappropriate for the
purposes of determining infringement of “wherein the level of B-galactosidase activity comprises
between 0.05 and 200 units.“ Nevertheless, .lennewein‘s data clearly shows the Miller Unit levels
prior to the subtraction, so the reliability ofJennewein’s testing can be assessed without reference
to the negative control strain.
Two of Glycosyrfs other critiques call that reliability into question. The first involves
Jennewein’s exclusive reliance on Miller Unit sampling at no less than 120 minute reaction times.
(See RX-0333C at Q99 (Battelle testing); RX-0386 at Q22O (Jennewein in-house testing); RX
O4-OSCat Q1 13 (Jennewein in-house testing); see, e.g., RX-0292C (Battelle testing): CX-D29-4C
(Battelle testing); RX-0029C (Jennewein in-house testing); CX-0275C; see also CIB at 56-57.)
Jennewein justifies its choice “because it was authorized by Miller and Jennewein believed it
needed to incubate its strains for a minimum of 120 minutes to obtain interpretable results in the
Miller assay.” (RRB at 3| (citing RX-0408C at Q1 13).) More specifically, Jennewein states
“incubation time should be extended if the yellow color develops slowly, which would be expected
for low-level [5-galactosiclase activity, such as near 0.05 Miller Units." (RIB at 56 (citing RX
O409C at QZIS; Ht"g Tr. at 307:8-308325, 30917-16).) Yet, testimony from the Battelle scientist
who performed the experiments indicates Jennewein instructed her to measure at 120 min without
regard to how color was developing in the samples. (Hr‘g Tr. at 318:1"/-320:6 (“Jennewein
52
provided a protocol to me that l followed, and it was consistent with the Miller assay. So yes, that
is what I did.").)
This is problematic because in Order 22, the presiding ALJ determined that “wherein the
level of [3-galactosidase activity comprises between 0.05 and 200 units" was not shown to be
indefinite because the patent failed to identify for how long the activity level must be maintained
or when it must be measured. (Order 22 at 21-22.) Order 22 concluded, "the claim is not
ambiguous as to when the claimed activity range must be met—it need only be met at some point
in time." (Id. at 22 (citation omittcd).) Given this flexibility in the temporal scope of the claim,
and Millcr’s instruction that the reaction should be stopped “alter sufficient yellow color has
developed" (CX~025l at A1810),Jennewein’s justification for its minimum I20 minute sample
rings hollow.
Moreover, the evidence shows it likely would have made a difference to take a sample at
an earlier time. In a chart Jennewein prominently presents as summarizing the highest Miller unit
values third-party Baltelle recorded (CX-0291C), a trend of decreasing Miller unit activity levels
with respect to time is visible:
53
(CX-0291C at -308410; see RIB at 44.) Given this trend, Miller's instruction to stop the reaction
when sufficient color is present, and the breadth of the claim term, it would seem readings at less
than I20 minutes are required in order to ascertain ifthe activity falls within the range. (See. e.g.,
CX-0004C at Q502, 513.) Indeed, the same Battelle scientist acknowledged a time less than I20
minutes would have been advisable:
Q. And at your deposition, you testified that you probably should have done
an OD420 nanometer reading for a time period less than I20 minutes;
correct‘?
A. I did, but due to time constraints while I was at their Facility, I did not
perform those —those steps, But what I did perform was consistent with
what's described in the Miller assay, along with what’s in the Jennewein
protocol.
Q. But you did testify that you probably should have measured attime point
ofless than I20 minutes; correct?
A. Yes, I did.
54
(Hr‘g Tr. at 320117-321:3.) Glycosyn’s test results support this conclusion. When it sampled at
both 60 and I20 minutes, Miller Unit levels decreased over time. (See CX-0004C at Q5013-S04;
CX-0258C; CX-0203C at CX-0203C.0004.) Glycosyn has also shown that in an earlier testing
session, when Jennewein did sample at limes less than 120 minutes, Miller Units Within the
claimed range were found. (CIB at S7 (citing CX~024lC; CX-0271C); see RX-0408C at Q10]
IU6.) Unlike the negative control strain subtraction discussed above, the effect on Miller Unit
activity resulting from measuring only at times after I20 minutes cannot be undone. The reliability
of this testing is therefore diminished.
Glycosyn’s second critique of Jerincwein’s testing is that Jennewein improperly took an
initial OD420 inn (yellow light) reading before the ONPG reaction begun, and subtracted that
reading from the OD-420 nm reading taken at the 120 minute or greater sampling time. This is
described in the briefs as the “time=0" or “t=0“ reading. This step is clearly not found in Miller
(seegenera/{)1 CX—025l). yet Jermewein describes its use as “to correct[] for the absorbance before
[3-galactosiclaseactivity could start, which was at the t=0 time point." (RIB at 43 (citing CX-0338C
at Q1 15, 120), 52, 52 n.ll (citing Hr’g Tr. at 592:l8-22, 593:6-1 l; RX-0386C at (1202)). More
specifically, Jeimewein contends it is necessary to account for non-enzymatic hydrolysis of ONPG
(i.e., spontaneous ONPG hydrolysis). (RIB at 52~53 (citing I-lr’g Tr. at 557:3-7), 45 (citing RX
0409C at Q98-99; I-1r’gTr. at 455;?-16, 559:9-13); RRB at 23 (citing, im‘era1i'a, RX-0385C at
Ql8l-l 84).)
Setting aside whether this technique accurately controls for non—enzymatic (i.e.,
spontaneous) hydrolysis ofONPG, it introduced significant effects into the results. Namely, this
subtraction caused negative values of Miller Units in some circumstances even before the negative
control strain values were considered (see CX~U292Cat Column “O”; CX-0294C at Column "O";
55
RX-029C at Column “O”), and in other circumstances, greatly diminished the OD420 I1I1'lvalue
that serves in the numerator position of the Miller equation:
. . _ (.)i.)4*>,) " 71 01);“;
.' ‘. 1-‘= l i l C -“ ,_- i i
[I11 :> OJJ ‘» I K F R Uijmm
[1l)+3,. and UlI)==Uare read from the reaction snireturc.
£)I),,,,.-. lellects the cell den.~1il_v_iu.~n before zissav.
.1 L lime’ tit‘ the l'¢.‘;!i.lt|L'tI'llfl minutes.
1: —' \’Oll.i1‘tl<3 ofculturc tised to the ussat\, lfl ml.
(CX~O25l at —lS1 1; See CX-0292C at Columns “H” and “J”; CX—(l294Cat Columns “H” and “J”;
RX-0029C at Columns “I” and "J”.) The effect of this “control” is clear—Miller Unit values will
decreaseiancl while .lennewein‘s records make it possible to undo this subtraction, l decline to
wade through the dozens of samples to do so. The fact remains this step is not in Miller and greatly
affected the results.
To the extent Jcnnewein argues its IiI'l'1t.F0subtraction is effectively the same as Miller’s
ONPG hydrolysis control (CX-D251 at -I81 l), I find it is not. Miller teaches that correction for
ONPG hydrolysis is only needed if the reaction runs for extended periods, like overnight, and
should be measured via a blank with no cells. (See CRB at l7-18; CX-O25] at -l8l 1.) Clearly,
Jennewein‘s 120 minute Samples and time=O readings on samples with cells do not meet tbcsc
criteria.
Taken altogether, there is insufficienl reason to discount or view as wholly unreliable
G1ycosyn’s testing of the Accused Strains, but there is such reason to discount Jennewein’s. Apart
from reliability concerns, Glycosyqfs testing simply hewecl more closely to the Miller protocol,
i.e., the terms in which the invention is defined. The Staff takes the position that Glycosyn’s
testing is therefore more relevant for infringement analysis purposes (SIB at 56), and I agree. That
56
testing showed a large majority of samples exhibiting Miller Unit activities within the claimed
range. (See CX-0004C at Q504-505; CX-0258C; see afsu CX-0004C at QSI6, 527; CX-0241C.)
It is therefore more likely than not that .lem1cwein‘sAccused Strains meet the limitation “wherein
the level of B-galactosidase activity comprises between 0.05 and 200 units."as in claim 1. It is also
more likely than not that Jertneweit-i’s Accused Strains infringe claim 1 of the ‘O18 patent.
d. Disputed Claim 8 “the method of claim 1, wherein said
exogenous functional B-galactosidase gene comprises an
E. coli lacZ gene”
Dependent claim 8 of the ’0l 8 patent requires;
The method ofclaim l, wherein said exogenous functional B—galactosidase
gene comprises an E. coir‘iar:Z gene.
("O18 patent at cl. 3.)
For this claim, Whichdepends from independent claim l and adds fitrther narrowing detail
to the “exogenous fiinctional B-galactosidase gene“ recited therein, Glycosyn alleges it is met by
Jcnnewein’s Accused Strains both literal1_yand through the doctrine of equivalents. (CIB at 64
65.) Jermewein’s IacZr;tand lacZ!J genes are neither individually nor collectively a “filnctional I3
galactosidase gene” in the literal sense, so they are also not literally “an E. calf lac-Zgene,” despite
.Iennewein’s GRAS notice describing lacZ0t and lacZ.Q as “originating from E. coll [(12 DH5o.“
(CIB at 64 (citing CX-0213) (emphasis removed).) Therefore, claim S is not literally infringed.
Regarding doctrine of equivalents, the function and result of the ‘O18patcnfs “E. colt lacZ
gene" is no different than the fiinction and result of the “firnctional B-galactosidase gene" of claim
l—namcly, to provide expressible DNA which, when expressed through understood pathways.
results in the creation of a B-galactosidase enzyme. (See, e.g.. ’0l8 patent at 7:22-30.) To be sure,
the “way” the shared result is achieved is more specific in the “E. calf t'acZ gene" than the more
generic “filnctional B-galactosidase gene“ of claim l. The parties are in agreement as to the
57
technical details of this process, however; and those details are best explained with the following
joint demonstrative:
. __-V _ 7
t____ _ _ __/
Four larl Monomers Enwme ‘“l""e
l.ai:/IQ l\-'lonumi:rs (1 "'39 '9' 7
l - I ~ 8 I V
. ‘I X‘
,
___..
t ,2
I
_ G‘ .‘ i '
3 1" “. '§*"—' T' s “T
Fnwrnre inm".1iu= Fnryrne ar:lr.Io
(CDX-0032; RDX-0005 (excerpted); see CX-0004C at Q62; RX-0384C at Ql49-151; see also
SIB at 7-8.) In this figure, and as explained by both experts, the upper box is a depiction of how
four LacZ peptides (i.e., monomers), produced from the naturally occurring “E. coll lacZ gene"
spontaneously fold and combine into the tetramer (r'.e., four monomers) or homeotetramer (i.e.,
four identical monomers) which is the [3-galaetosidase enzyme. (CX-0004C at Q54, 62; RX
0384C at Q98, 109, 150.) Similarly agreed to, the lower box is a depiction of how four LacZQ
peptides, produced from the [acZ.Q gene, and four LaeZo. peptides, produced from the lacZ0cgene,
spontaneously combine into the [3-galactosidasehomeotetratner. (CX-0004C at Q62; RX-0384C
at QISO-151.) As shown, the LacZQ and LaeZntpeptides complement each other so as to result
in a structure similar to a LacZ peptide, with spontaneous assembly into [3-galaetosidase.
Jer1newein’s expert nonetheless asserts that due to nucleotide differences between the
combination of ¢'acZaand lacZQ and !acZ, “combining LacZ0tand LaeZQ leads to a heterodimerie
enzyme that differs from wild-type LaeZ.” (RX-0384C at QI57; see Hr‘g Tr. at 565:1-3.) In fact,
58
however, four of those heterodimers spontaneously combine to form the complete LacZ. Indeed,
an article cited by Jennewein‘s expert (albeit on the written description issue) describes the
structure produced by er.-complementation as “tetrameric,” rather than dimeric. (RX~00ll at v
14798 (“[t]his complementation involves noncovalent reassociation of complementary fragments
of the [3-galactosidasc subunit polypeptide chain, which then reassemble into an enzytnatically
active tetrarneric structure.").) That is, with !acZ the [3-galactosidase result starts with four
subunits, and with IacZa and lacZQ the B-galactosidase result starts with eight subunits; this is not
a substantial difference. And the various peptides are otherwise created in substantially the same
wayeamino acids produced by the two step process of DNA transcription and translation.
Jennewein additionally emphasizes how laeZ0.and lac-Z.Qare not simply chopped portions
of !acZ, and include their own start codons, stop codons, promoters, and other regulatory elements
(RIB at 33-37; RRB at 18, 38-39), as well as how the LacZ.ctand L~acZQpeptide combination are
not “contiguous” or bonded in the same way as LacZ monomers are (RRB at 17-I8). These
structural differences are undisputed, but all they show is that the limitation is not literally met, as
opposed to a substantial difference in function (supply necessary DNA). way (create spontaneously
folding and combining proteins), or result ta B-galactosidase enzyme). (See Hr’g Tr. at 221 :20
222:7 (“Q. . . . Why do you use two fragments? A. . . . the fact is that the lacZ gene cannot be
completely regulated by itselfin the E. coli —in E. coli, unfortunately. That is [why] we’re talking
about the fi.|lllength gene here. And if you cut the gene into several fragments, then this improves
its ability to be regulated. . . . that also enhances e lowers the stability of the protein, which is also
advantagcous.”).)
59
Accordingly, I find the lacZa and lacZQ genes in .lennewein's Accused Strains are
equivalent to the “E. coir‘!acZ gene“ of claim 8. Thus, the Accused Strains infringe claim S of the
‘O18 patent.
e. Disputed Claim 23 “the method of claim 1, wherein said
exogenous functional B-galactosidase gene is inserted
into an endogenous gene”
Dependent claim 23 of the ’0l8 patent requires:
The method of claim l, wherein said exogenous functional |3-galactosidase
gene is inserted into an endogenous gene.
(‘O18 patent at cl. 23.)
For this claim, Glycosyn alleges it is met in the Accused Strains under the doctrine of
equivalents. (CIB at 65.) Specifically. Glycosyn argues that the development of the strains saw
Jennewein intentionally insert the Iacza gene into an endogenous gene known as yihQ. (Id. at 66
(citing CX-0240C; CX-U29'7C)._)Glycosyn acknowledges, however, Jcnnewein’s claim that this
version of !acZa “simply felt out” and ceased to exist in the strain. (Id. (citing CX-0237C at 7~9;
JX-0012C at 29-30, 79:23-806).) Glycosyn argues this makes no difference because it was
subsequently discovered that t'acZa nevertheless continued to exist in the strain from a much earlier
insertion “into the int gene of the DE3 prophage” by other groups of scientists. (Id. (describing a
BL2l host strain convened to BL?.l (DE3).) Glycosyn concludes, “[w}hat is clear, is that the
difference between Dr. Parschat inserting the facZo gene into the endogenous gene yihQ gene, and
someone else inserting the [acZo: into the DE3 prophage’s inf gene are so insubstantial that
Jennewein never even noticed it for years, and only after this investigation began." (Id. at 66-67
(citing Tom C0. v. White Consul. Indus, 266 F.3d 1367, 1370 (Fed. Cir. 200l)).) Glycosyn does
not address [£262-Q.
60
The Staffs argument on this point is persuasive: “both the IacZ.Q fragment and the DE3
prophage itself,” into which the la.-:Z'Qfragment was inserted, “were introduced into the original
host strain.” (SIB at 60 (citing CX-0004C at Q598 (Prather).) That is, "either both are exogenous
to Jennewein’s production strains or both are endogenous.” Ud.) But because claim 23 requires
an exogenous gene inserted into an endogenous gene, the Accused Strains cannot literally infringe
it. And because this claim limitation cannot be met through the doctrine of equivalents without
viliating it entirely, Warner-Jerikinsoii, 520 U.S. at 39 n.8, dependent claim 23 is not infringed.
E. Domestic Industry - Technical Prong
According to Glycosyifs post-hearing briefing, and not contested by Jennewein or the
Staff, the following domestic industry products are alleged to practice the following claims of
the ‘O18 patent:
Product Claims
Glycosyn's E. coir’production strains ofwhich l-3, 5, 8-14, 18, 22-28
E. calf strain E997 is representative
(CIB at 15-I6.) With respect to those strains allegedly represented by E997, Glycosyn argues:
Glycosyn has developed strain E997 as well as several other E. cnli
bacterium strains that practice claims l-3, 5, 8-14, 18, and 22-28 ofthe ’0l8
Patent, and thus are domestic industry strains. See CX-0059C (curated 258
strainsxlsx). Since Fall of 2015, Glycosyn has documented the amounts of
2'-FLproduced bythesedomesticindus strainstobe—
2, with ab being produced by E997.
See C-X-0131C (!All Runs Sunimaiyxlsx); CX-0064C (!All Runs
Summaiyxlsx).
(Id. at 92; see id. at l5 (citing CX-0004C at Q99, I23); see also CX-0004C at QI64.) l do not
observe any dispute from Jennewein or the Staff over Glycosyrfs contention of representativeness
6]
of E997. I therefore accept Glyeosyn’s claim of representation for the ptuposes of evaluating
domestic industry.
Further, for the reasons explained below, I find Glycosyn has shown by a preponderance
of the evidence that its production of 2’-FL using its E997 strain practices claims l-3, 5, 8, IO-I4,
18, 22, and 24-28 ofthe “O18patent. Glyeosyn has not shown it practices claims 9 or 23.
I. Undisputed Claim Limitations
As with infringement by the Accused Strains, discussed above, and as reflected in the
parties’ posbhearing briefing, the practice of a large majority of the ’Ol8 patent claim limitations
by Gly-::esyn‘s E997 strain is not in dispute. (See, e.g., CIB at 92; RIB at 69-72; SIB at 76-86;
RRB at 41-43; SRB at 20-22.) With respect to independent claim I, and in reference to claim
limitation identifiers used within the witness statement of Glyeosyn‘s expert (CX-1004(1),
Glycosyii asserts “that [it] literally produces 2’-FL, a fucosylated oligosaccharide, in a bacterium
using a method that practices claim elements l(pre), 1(a), l(e), l(d), I(e), and I(f)," an assertion
supported by its expert's witness statement. (CIB at 92 (citing CX-0004C at Q! IU-126, I27-I34,
I69-I 75, I76-I87, 188-192, I93-209).) Glycosyn also demonstrates that, for the remaining
limitation, E997 includes “an exogenous fiinctional I5-galactosidase gene comprising a detectable
level ofB-galaetosidase activity that is reduced compared to that of a wild-type E. colt bacterium.“
(Id. (citing RPB at 76; CX—O0O4Cat QI27-134).) The Staff agrees these limitations are met. (See
SIB at 77-79.) Jennewein does not dispute the limitations are met, either. (See RIB at 69~72; RRB
at 4] -43.)
In light of the evidence identified by Glycosyn and discussed by the Staff, and the lack of
dispute. l find they are practiced by Glycosyrfs E997 strain. These limitations include:
1. A method for producing a fucosylated oligosaccharide in a bacterium,
comprising
62
providing an isolated E. calf bacterium comprising,
(i) a deletion or Functional inactivation of an endogenous 13
galactosidase gene;
(ii) an exogenous functional I3-galactosidase gene comprising a
detectable level of I3-galaetosidaseactivity that is reduced compared
to that of a wild-type E. coir‘bacterium,
(iii) an inactivating mutation in a colanic acid synthesis gene; and
(iv) an exogenous laetose~accepting fueosyltransferase gene;
culturing Said bacterium in the presence of lactose; and
retrieving a fucosylated oligosaccharide from said bacterium or
from a culture supernatant of said bacterium.
(‘O18 patent at cl. 1.)
With respect to the asserted dependent claims, Glycosyn argues it “practices the additional
claim elements present in dependent claims 2, 3, 5, 8, 9, ll], l 1, 12, 13, 14, 18, 22, 23, 24, 25, 26,
27, and 23 ofthe ’0l 8 Patent.” (CLBat 96 (citing CX-0004C at Q21!)-294; CX-0065).) Jennewein
indeed does not dispute this. (See RIB at 69-72; RRB at 41-43.) The Staffi however, does
challenge Glyc0syn’s practice of claims 9 and 23, and I address these below. (SIB at S2-86.)
l also address the B-galactosidase activity level of claim 1 below. Otherwise, in light of
Glyeosytfs expert evidence, and the lack of a dispute from Jennewein or the Staff, I find the
following claims are practiced by Glycosyn’s E997 strain:
2. The method of claim l, wherein said colanic acid synthesis gene
comprises an E. cnii weal, wzxC_,wcaD, wza_ wzb, or wzc gene.
3. The method of claim 2, wherein said colanic acid synthesis gene
comprises a weal gene.
63
5. The method of claim l, wherein said exogenous lactose-accepting
fucosyltransferase gene encodes o(l,2} fucosyltransferase and/or a(_l_.3)
fucosyltrarlsferase.
8. The method of claim l, wherein said exogenous functional [5
galactosidase gene comprises an E. calf lacZ gene.
IO. The method of claim l, wherein said bacterium fiirther comprises a
functional lactose permease gene.
ll. The method of claim 10, wherein said lactose pennease gene is an
endogenous lactose permease gene.
I2. The method of claim 10, wherein said lactose permease gene comprises
an E. coli lac‘? gene.
13. The method of claim l, wherein said bacterium further comprises an
exogenous E. coli rcsA or E. calf rcsB gene.
14. The method of claim l, wherein said bacterium Further comprises an
inactivating mutation in a lacA gene.
I8. The method of claim l, wherein the level of [5-galactosidase activity
comprises between 0.05 and 5 units.
22. The method of claim 1, wherein said bacterium comprises the genotype
of
(a) ampC::(PtrpB?tcl+), Placl q (Alacl-lacZ)laeY+. Awcal,
thyA::Tn10, A|on::(kan, 1aeZ+);or
(b) ampC::(PtrpB7l.cl+), Placl q (Alacl-lacZ)lacY+, Awcal,
thyA::Tnl0, Al0n::(kan, lacZ+), AlacA.
24. The method of claim 1, wherein said exogenous filnctional [3
galactosidase gene comprises a recombinant B-galaotosidase gene
engineered to produce a detectable level of [3-galactosidase activity that is
reduced compared to the level of I3-galactosidase activity in a wild-type E.
coli bacterium.
64
25. The method of claim 24, wherein the level of B-galactosidase activity
comprises between 0.05 and 5 units.
26. The method of claim l, wherein the level of B-galactosidase activity
comprises between 0.05 and 4 units.
27. The method of claim 1. wherein the level of B-galactosidasc activity
comprises between 0.05 and 3 units.
28. The method of claim l. wherein the level of B-galactosidase activity
comprises between 0.05 and 2 units.
(‘O18 patent at cls. 2, 3, 5, 8, l0-14, 18, 22, 24-28.)
2. Disputed Claim 1 Limitation “wherein the level of B
galactosidase activity comprises between 0.05 and 200 units”
The only claims and limitations in dispute for the domestic industry technical prong are the
B-galactosidasc activity level of claim 1, which Jennewein contests, and dependent claims 9 and
23, which the Staffcontests. Claim l of the “O18patent requires:
(ii) an exogenous functional B-galactosidase gene comprising a detectable
level of [l-galactosidase activity that is reduced compared to that of a wild
type E. coli bacterium, wherein the level of fignlactosidase activitfv
comprises between 0.05 and 200 units;
(’0l8 patent at cl. 1 (emphasis added).)
For this limitation, Glycosyn’s evidence shows that “E997. and other Glycosyn strains that
contain a re-introduced lacZ gene at the same location and direction. reproducibly exhibit [3
galactosidasc activity between l and 3 Miller units." which is well below the approximately 1000
Miller units exhibited by wild-type E. coir’bacteria. (CIB at 94 (citing CX-0024C; CDX-0070C:
CX-0021C; CX-0049C; CX-0050C; CX-0251.) Jennewein, however, complains that “Glycosyn
relics solely on its own in-house testing to support the technical prong of the domestic industry
requirement“ as specified by an intemal index card of instructions. (RIB at 70 (citing Hr‘g Tr. at
76:5-12, 2'71:19-272:8, 514118-22; RX-0409C at Q349).) Jenncwein repeats its non~infi'ingemeI1t
position (discussed and rejected above) that the testing method suffers from no negative controls
65
(id. at 70-7!) and adds, as Glycosyn anticipated, criticisms ofGlycosyn‘s incubation temperature
-we-= as1h@ we
id. at 7!-72.)‘
As noted above, failure to subtract negative control strain Miller Units does not constitute
deficient testing. Jennewein’s remaining criticisms regarding temperature and redundant sample
preparation steps also lack merit. On temperature, Glyco-syn’sresults show that testing was done
— butalsoat 28"Cand30°C-—the tormerofwhichJcnnewcinclaimsisthecorrect
temperature. (RIB at 71; RRB at 4|-42; CX-0004C at Ql65-167; CX-0048C.) As shown below,
Miller Unit levels within the claimed range were met at all temperatures:
0 I
(ox-0043c at -122123.) Regarding Glycosyifs
— whichJcnneweincorrectlyobservedis redundantaccordingto Miller('CX
025l at-I81 I), I am persuaded that use ofj ust one of these preparation steps would have increased
Miller Unit values but not so much as to travel outside of the claimed 0.05 to 200 range. (CK
0251C at-1810-I811 (describing formulae in which 550 nm readings are used to lower Miller Unit
4 While Jennewein and Glycosyn refer to the 28°C as an incubation temperature, it is likely
more accurately described as a reaction temperature. {CX-0251 at -I310 (cells are grown at 37°C
but driven to 23°C right before ONPG is added).)
66
calculated amounts); Hr’g Tr. at 536: l-9.) Lndced,Jem1ewein’s argument is limited to an assertion
that the Miller Units would simply be “altered”~—apremise that it otherwise provides little support
for. (RIB at 72 (citing RX-0409C at Q350 (withdrawn testimony)); RRB at 42 (citing Hr’g Tr. at
305:7-l5; R.X—0409Cat Q2l2 (discussing Jennewein strains and inapplicable)).)
Accordingly, I find Glycosytfs E997 strain practices this limitation of independent claim
1, and in light of the other limitations not in dispute, all of independent claim l.
3. Disputed Claim 9 “the method of claim 8, wherein the lacZ
gene is inserted into an endogenous lon gene”
Dependent claim 9 of the ‘O18patent requires:
The method of claim 8, wherein the lacZ gene is inserted into an
endogenous Ion gene
(‘O18 patent at cl. 9.)
Glycosyn‘s own expert interpreted Glycosyn’s GRAS Notice No. 735 as evidence that the
‘loo’ gene was modified with a ‘complete deletion and replacement with a gene cassette . . . .‘
(CX-0004C at Q229; see CX-0065 at Table l.) Clearly, “complete deletion” of a gene precludes
insertion into that gene, so claim 9 is not practiced. Glycosyn does not dispute this in their reply
brief. (See CRB at 47.)
4. Disputed Claim 23 “the method of claim l, wherein said
exogenous functional B-galactosidase gene is inserted into an
endogenous gene”
Dependent claim 23 of the ‘O18patent requires:
The method of claim l, wherein said exogenous functional B-galactosidase
gene is inserted into an endogenous gene.
(‘O18 patent at cl. 23.)
For the same reasons outlined above with respect to claim 9, l agree that claim 23 is not
practiced. Glycosyn does not dispute this in their reply brief. (See CRB at 47.)
67
F‘. Validity and Enforceability
Jennewein‘s initial post-hearing brief identifies the following invalidity and
unenforceability theories against the asserted claims of the ‘O18 patent;
Claims Theory
l-3, 5, 8, IO, 12, IS, and 23-28 Rendered obvious under 35 U.S.C. § 103 by Samain
(RX-0002) in view of Kawano (RX-0014) and the
knowledge of one of skill in the art as shown by
Drouillard (RX-0015), Geisser (RX-0016), and Dekany
{RX-0017).
l-3, 5, 8, I0, I2, l8, and 23-28 Indefinite under 35 U.S.C.§ 112, 1]2
(included solely for right ofappeal in light of Order 22)
1-3, 5, s, 10, 12, 1s, 23, and 24 Lack of enablement under 35 U[s.eT§ *1512,-111
1-3, 5,3, 10, 12, 18, 23, and 24 2Lack ofwritten description 35 u.s.c. § 112,11 1
1-3, 5, 3, 10, 12, 13, and 23-28 Unenforceable due to inequitable conduct K
I. Asserted Prior Art
Jennewein alleges the “Samain” reference, U.S. Patent No. 7,521,212 (RX-0002) is prior
art to the ’OlS patent because it issued from an application filed on May Z4, 2002 and further
claims priority from international applications to July 7, L999. (RIB at 75.) Glycosyn does not
contest the prior art status of Samain (see CIB at 96-109; CRB at 47-54), and l find it qualifies as
prior art under pre-AIA 35 U.S.C. § 102(a), (b), and (e).
Jenneweiri alleges the “l(awano" reference, a publication Foundin “Volume 33 ofNucleic
Acids Research“ (RX-0014) is prior art to the ’0I 8 patent because it was published in 2005. (RIB
at 75.) Glycosyn does not contest the prior art status OfKBWfll'lO(see CIB at 96-109; CRB at 47
54), and I find it qualifies as prior art under pre--AIA 35 U.S.C. § lU2(a) and (b). 35 U.S.C. §
68
ltl2(e) only applies to patent applications and issued patents, which Kawano is not; Jcn11ewein"s
contention to the contrary is not well-taken. (See RIB at 75.)
Jennewein alleges the “Drouillard” reference, a publication found in “Volume ll8 of the
Angewandte C-hemie(German for ‘Applied Chemistry’) journal" (RX-0015) is prior art to the ’DI8
patent because it was published in 2006. (RIB at 77.) Glycosyn does not contest the prior art
status of Drouillard (see CIB at 96-109; CRB at 4'/~54), and l find it qualifies as prior art under
pre-ALA 35 U.S.C. § ]O2(a) and (bl.
Jennewein alleges the “Geisser“ reference, a publication found in “the Journal of
Chromatography A" (RX-D016) is prior art to the ‘O18patent because it was published in 2005.
(RIB at 77.) Glycosyn does not contest the prior art status of Geisser (see CIB at 96-109; CRB at
47-54), and I find it qualifies as prior art under pre-ALA 35 U.S.C. § l02(a) and (b).
Jennewein alleges the “Dekany” reference, published application number W0
ZOIO/l 15935 (RX-DOl7) is prior 311to the ’0l S patent because it “was filed on April 7, 2010, and
claims priority to a Danish application filed on April 7, 2009.” (RIB at 78.) Glycosyn does not
contest the prior art status of Dekany (see CIB at 96-109; CRB at 47-54), and l find it qualifies as
prior art under pre-AIA 35 U.S.C. § lO2(a).
2. 35 U.S.C. § 103 (Obviousness)
Jennewein contends that “claims l-3, S, S, 10, 12, 18, and 23-28 ofthe ’Ol8 patent are each
obvious, and thus are invalid, based on Samain [RX-0002] in combination with Kawano [RX
OOI4] and optionally one of Drouillard [RX-0015], Geisser [RX-0016], or Dckany [RX-0017]."
(lei) More specifically, and with respect to claim l from which all other asserted claims depend,
Jennewein°s theory is that Samain teaches all elements of this claim except for “(ii) an exogenous
functional 13-galactosidase gene comprising a detectable level of [3-galactosidase activity that is
reduced compared to that of a wild-type E. coir"bacterium. wherein the level of [3-galactosidase
69
activity comprises between 0.05 and 200 units.” (See RIB at 7'9(citing RX-0384C at Q20], 202;
Hr‘g Tr. at 707:2-7l2:l9).) For this missing element, Jennewein claims it is taught by Kawano,
and that a person of ordinary skill in the art would have been motivated to incorporate this teaching
ofKawai1o into Samain‘s fiicosylated oligosaccharide-producing strains. (See id. at 79-80 (citing
RX-0384C at Q206-209; RX-ODI4 at -2244-45).)
.lennewein’s expert testified in support of that motivation in several places, as part of
his ‘230 and ’0l8 patent discussions:
Ln my opinion, it would have been obvious to use a low lcvcl of $3
galactosidase activity in Samairfs E. cuff strain, less than wild-type activity,
to solve the known problem of purifying oligosaccharides from lactose, as
taught by Druillard, Geisscr or Dekany, but keeping the level low enough
to avoid preventing 2‘-FL production as taught by Sarnain.
(RX-0384C at QZO3(citing RX-0015 at *l8lO; RX-0016 at *lS; RX-0017 at *1-5));
Lactose as a feedstock would necessarily be present in Significant amounts
in the fermentation medium as l explained above. and would be difficult
and impractical to separate from 2’-FL, particularly at large scale, due to
these known difficulties in separating 2’-FL from lactose. Keeping the level
of lactose inside the cell low also would have been desired to avoid lactose
toxicity and degrading the substrate for 2‘-FL production, for which some
level of [Lgalactosidase activity would have been an obvious solution.
(id. at QZO4);
To avoid impacting 2‘-FL production, but still allow excess lactose to be
eliminated, a low level of B-galactosidase activity would have been desired,
including as low as 0.05 to ZOOunits.
(id. at (2206);
A POSA would have been motivated to combine Kawano’s low level offi
galactosidase activity with Samain to address the known problem of
purification of Fucosylalecloligosaccharides like 2“-FL from lactose, while
not destroying too much lactose substrate to prevent production of any 21
FL. B-galactosidase was known to destroy lactose.
(id. at Q2091;
70
One of ordinary skill would have been motivated to modity Samain with a
reasonable expectation of success by introducing a low-level of B
galactosidase activity according to Kawano to aid in the purification of the
fucosylated oligosaccharidcs produced by eliminating other
oligosaccharides present, like lactose.
(id. at Q2l9 (citing RX-0015 at *18l0; RXAOUI6at *18; RX-0017 at *1-5); see also id. at Q259,
262 (citing RX-0015 at *lSlO; RX-U016 at *lS; RX-D017 at l-5)). The expert further testified
that a person of ordinary skill would have known how to accomplish this given “the teachings of
Kawano, which teaches a POSA how to engineer E. cofi to have a low level of B-galactosidase
activity, including activity of l30-200 Miller units.” (Id. at Q206 (citing RX-U014at Table 2, Fig.
1); see id. at QZI6, 258.)
I find that a person of ordinary skill in the art would not have been motivated to combine
the teachings of Sarnain and Kawano, without the benefit of hindsight fiom the ‘O18patent, for
two primary reasons.
First, a fair reading of Samain shows that it teaches away from the proposed combination.
Samain not only fails to teach “(ii) an exogenous functional [3-galactosidase gene comprising a
detectable level of [5-galactosidase activity that is reduced compared to that of a wild-type E.
cnii bacterium, wherein the level of B-galactosidase activity comprises between 0.05 and 200
units,” but it repeatedly insists that no [3-galactosidaseactivity be present to avoid consuming the
lactose “precursor” outside the production pathway of 2’-FL:
[S]aid method comprising the steps (i) of obtaining a cell that comprises at
least one recombinant gene encoding an enzyme capable of modifying said
exogenous precursor or one of the intermediates in the biosynthetic pathway
of said oligosaccharide from said exogenous precursor necessary for the
synthesis of said oligosacchariden from said precursor, and also the
components for expressing said gene in said cell, said cell‘ locking any
enzymatic activity Ifabfe to degrade said 0lig0.rac'charfde,said precursor
and said intermediares[.]
(RX-0002 at 2:38-4'7 (emphasis added));
7!
According to one preferred embodiment of the invention, the bacterium
is Escherichia coli. According to another embodiment of the invention, the
cell is a yeast that is preferably Sacclraromyces cerevsae, Saccharomyces
pombe or Candida albicaas. The cell according to the irivetitiorzlacks any
enzymaticactivity liable to degrade said oligosaccltaride, said precursor or
said metabolic intermediates.
(Id at 3:35-41 (emphasis added));
The B-galactosides are normally hydrolyzed in the cytoplasm of the
bacterium by the B-galactosidase encoded by the LacZ gene. ht order to
overcome this problem, a lacZ* bacterial mutant lacking [3-galactosidase
activity is used when the precursor used is lactose andlor a B-galactoside.
One of the objects of the invention is tlms also to provide the method
according to the lnverition that is characterized in that said cell lacks
enzymatic activity liable to degrade said precursor or said metabolic
intermediates.
(id at 7:6-14 (emphasis added));
in the method according to the invention, said cell may be lacking in
enzymatic activity liable to degrade said precursor(s). According to one
preferred embodiment, the method is characterized in that said cell has 21
genotype chosen from LacZ‘ andtor NanA‘.
at 7:25-30 (emphasis added));
FIG. lt . . . Lactose (,5-D—Gal-[1-4]-/3‘-D-Glc)is transported into the cell by
lactose permease (Lac permease). The lactose cannot be hydrolyzed in the
cell since the strain is a LacZ' mutant.
(id at 10:66-1 I :9 (emphasis added); see also id. at l 1:40-51 (emphasis added));
FIG. 9: . . . Lactose and sialic acid (Nemic) are internalized in the cell by
lactose permease (lacy) and sialic acid permease (nanT). These two
cornpottnds are not degraded in the cell since the strain is a lac? and
nan/I‘ mtitant. The expression ofCMP-l\leuA synthase and ofo-2,3-sialyh
transferase allows the activation of the sialic acid internalized into CMP~
NeuAc and its transfer onto the intracellular lactose.
(id at I l:63-12:3 (emphasis adcled)).
Sarnain achieves this lack of B-galactosidase activity by maintaining a LacZ‘ status in
multiple disclosed embodiments (through deletion or inactivation):
72
Thus, according to one preferred embodiment . . . it is characterized in that
said cell is a bacterium of LacZ‘, LacY* genotype, said enzyme is [3-1,3-N
acetyl-glucosaminy]»transi'erase, said substrate is glycerol, said inducer is
isopropyl B-D-thiogalactoside (IPTG) and said precursor is lactose.
According to a second preferred embodiment, the method according to the
invention is used for the production of lacto-N-neo-tetraose and
polylactosamine; it is characterized in that said cell is a bacterium of LacZ‘,
LacY* genotype[.]
According to a third preferred embodiment, the method according to the
invention is used for the production of allyl 3-O-(2-acetamido-2-deoxy-{L
D-glucopyranosyl)-|3-D-galactopyranoside, ([3-D-GleNac-[1—>3]-[i-D-Gal
IHO-allyl); it is characterized in that said cell is a bacterium of LacZ',
LacY* genotype[.]
According to a fourth preferred embodiment. the method according to the
invention is used for the production of analogs of lacto-N-nee-tetraose and
of polylactosarnines in which the glucose residue is replaced with an allyl
group; it is characterized in that said cell is a bacterium of LacZ’,
LacY‘ genotype[.]
According to a fifth preferred embodiment, the method according to the
invention is used for the production of allyl-B-D-laetosamine (I3-D-Gab
[l—>4]f:-D-GlcNac-l—>Orallyl); it is characterized in that said cell is a
bacterium of LacZ‘, LacY"genotype[.]
(rd at 7:43-8:19);
Another subject of the invention relates to a method described above for the
production of 3’-sialyllactose (ct-NeuAc-[2—r3]-—>-D-Gal-[ l —>~4]-B-D-Gle)
or 6'-sialyllactose (0.-NeuAc-[2—+6]-fa-D-Gal-[l —+4]'fi»D~Glc),
characterized in that:
said cell is a bacterium of LacZ', LacY*, l‘-lanA_or NanT"genotype[.]
at9:1-12);
According to a seventh preferred embodiment, the method according to the
invention is used for the production of 3'-fucosyllactose (B-D-Gal-[l—>4]
73
(tit-L-Fuc-[l—>3]-D-Glc) or 2'-fucosyllactose ([3-D-Gal-[I—>2]-(a-L-Fuo
[l—>3]-D-Glc), characterized . . . in that the cell has a wcaj_ Iacfffgenotype
and overexpresses the rcsA gene and in that said precursor is lactose.
(id. at 9:39-46; see also id. at 16:1-I 5 (“The strain JM I09 is lacZ‘, that is to say that it is incapable
of hydrolyzing lactose.”)).
Notably, Jennewein’s expert does not squarely address this important aspect of Samain’s
disclosure in his direct witness testimony. He responds in conclusory fashion, “Q. What about
Glycosyn‘s argument that the prior art teaches away from their invention? A. I do not find that
Jenn-=:wein’spatent or Samain ‘teach away’ from the claimed inventions or evidence skepticism
relating to the alleged inventions." (RX-0384C at Q31 5; see RIB at 96-97 (citing sarne).) Based
on the above excerpts, Sarnain clearly expresses skepticism as to the value of re-introducing LacZ
activity into its strains. Similarly, Jennewein is wrong in asserting that the above excerpts amount
only to “lacking a limitation” and not “teaching away." (See RRB at 45.) Samain"s consistent
emphasis on a LacZ‘ status for its strains is too great to be written off in this way.
Jcnnewein cites Sanlorus, Inc. v. PaI'Pharm., Inca, 694 F.3d 1344, l355 (Fed. Cir. Z012)
and Galderma Labs., LP. v. Tolmar, Ina, 737 F.3d 731, 739 (Fed. Cir. 2013) to show otherwise
(RIB at 45), but I am not persuaded. For one, Samarus actually Supportsteaching away by Samain.
In that case, the court held that a reference did not teach away from a drug formulation claim
limitation because it advocated for a first version of that fonnulation while also advocating for a
second. 694 F.3d at I355 (“Although Pitbrant ‘ruled out’ conventional dosage forms such as
tablets, capsules, or granules with non-enteric coated PPIs, it states that a ‘rapidly dissolving
suspension of micronized omeprazole is the second best choice as the reference fonnulation.‘“).
But it held the reference did teach away from the first version, specifically through a discussion of
stomach degradation problems it would encounter. Id. In this case, there is no instance of Samain
74
advocating for LacZ activity, and, like the first version of the formulation in Snnrams, Sarnain
discourages LacZ use because of precursor consumption problems.
In Gafderma Labs, the court held that the prior art articles only taught an optimal
ingredient percentage For a phan-naceutical (0.1%), as opposed to discouraging the patent‘s
claimed percentage (0.3%), before disagreeing with the lower court over whether the references
taught away. 737 F.3d at 738-9 (“Mort-:over, there is nothing in either of these references to
indicate that increasing the concentration to 0.3% would be unproductive . . . ."). In this case,
Sarriain actively discourages LacZ activity in its strains, setting it apart from Galderma Labs.
And Jetmeweirfs expert agreed under cross-examination that “the teachings of Samain are
so compelling that you can’t fathom a reason that someone would use an E. colt strain with a low
level of beta-galactosidase activity to produce 2‘-FL, as opposed to using a strain with zero beta
galactosidase activity”:
Q. And the reason Samain doesn't teach this element is because Samain
teaches no beta-galactosidase activity. not a low level of beta-galactosidase
activity; correct?
A. Yes.
Q. And you think that zero beta-galactosidase activity is the ideal situation;
correct‘?
A. Yes.
Q. And, in fact, the teachings of Sarnairi are so compelling that you can‘t
fathom a reason that someone would use an E. eoli strain with a low level
of betavgalactosidasc activity to produce 2‘-FL, as opposed to using a strain
with zero beta-galactosidase activity; correct?
A. Correct.
Q. Okay. And you can't fathom that they would do that with any low level
oi'beta~galactosiclase activity, whether it's .04, .05, .06, or .07 units; correct?
A. Correct.
75
(I-lr’g Tr. at 625:1"/—626:2O.)
Jennewein also seeks to bolster its motivation to combine theory based on the disclosed
use of a certain “JM 109" or “JM 109” bacterial strain. (See RIB at 73-74, 83, 85, 90.) Jennewein
argues:
But, as Dr. Stephanopoulos explains and Dr. Prather acknowledges, Samain
discloses a IMIO9 strain of E. coll, which already possesses a low level of
[3-galactosidase activity. RX-0384-C (Stephanopoulos WS) at QIA 218; Tr.
(Prather) at 7 12: l 7-7 13:19; see RX-U002 (Samain) at l2:5-22 (Example 1).
Dr. Stephanopoulos also testifies that this would not change were the strain
to be used for 2’-FL production. RX-0384C (Stephanopoulos WS) at Q/A
218. Indeed, the ordinarily skilled artisan would have been motivated to
have used a strain with a low level of |3- galactosidase activity (such as the
IM 109 strain described in Example I of Sarnain) in order to avoid
destroying the lactose feedstock necessary to produce lactose-containing
oligosaccharides like 2'-FL. 1d.; see RX-0002 (Samain) at 7:6-15.
(Id. at 73-74 (wherein cited expert testimony further cites RX-0008 (Giacomini) at *88).) In Fact,
the JM I09 strain disclosed in Samain has zero [5-galactosidase activity (see RX-0002C at 16:]
15), although the seemingly identical strain disclosed in Giacomini has substantial [3-galactosidase
activity (see RX-0008C at -H693). Dr. Prather testified that it was “impossible to believe that
those were actually the same strains,” and in any event Giacomini merely malyzes the effects of
various parameters on measuring I3-galactosidaseactivity using the Miller assay, and says nothing
about 2’-FL production. (Hr’g Tr. at 748114-I5; RX-OUOSC.)So the disclosure of.lM 109 in both
Samain and Giacomini would not motivate a skilled artisan to combine their teachings.
Nor does Kawano provide a motivation to combine. Although Kawano “teaches inserting
a 13-galactosidase gene into a gene construct in E. 0011',producing a low-level [3-galactosidase
activity, including 130-220 Miller Units“ (RIB at 76 (citing RX-0014 at -22445, Table 2; Hr‘g Tr.
at 462125-4632)), Kawano also teaches insertion ofthe same gene so as to produce much higher
levels of B-galactosidase activityfialong the lines of 5.000-12,000 Miller Units (RX-0014 at
76
22443, Table I). In fact, Kawano discloses an extremely wide range of Miller Unit activities
resulting from the insertion of a B-galactosidase gene into E. coir‘:
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(RX-OOI4 at -22443, Table l, Q2445, Table 2 (aI1notated).) As shown in the above combined
table, the lowest Miller Unit level reported is 130. While Kawano makes reference to additional
strains with promoters causing Miller Unit activities below l30, it does not disclose the details of
those strains (see id. at -22444, Figure l) nor does it disclose why any particular activity level
would be preferable over any other (see generally id.HKawano is solely directed to “a direct
experimental approach for identifying chromosomal sequences with promoter activity” (id. at
22441) and not any particular use for resultant B-galactosidase.
77
This 130 Miller Unit level is important to a motivation to combine because it is the
testimony of Jennewein‘s expert, given in the context of enablemcnt, that “beta-galactosidase
activity well above 5.8 would be expected to destroy lactose too quickly for the cell to use it to
produce 2’-FL”:
Q. So you agree that those claims are enabled?
A. Up to about 5 Miller units, l think so, yes.
Q. It’s your opinion that beta-galactosidase activity well above 5.8 units
ivoufd be expected to destroy lactose too quickly for the cell to use it to
produce 2’-FL; is that right?
A. Correct.
(I-Ir’g Tr. at 644:l l~l7 (emphasis added); RX-03 84C at Q1236(stating same); see RX-0384C at
QI77-178 (“One better fit would be linear, for example one which shows about zero 2’-FL
production at approximately 40 [Miller units]. This would be realistic as it reflects that higher B
galactosidase activity would essentially prevent a cell from making a decent amount of 2’-FL.”).)
l emphasize “would be” in the above excerpt because enablemcnt, like obviousness, is evaluated
from the perspective of one having ordinary skill in the art:
The specification shall contain a written description of the invention, and of
the manner and process of making and using it, in such full, clear, concise,
and exact terms as to enable any person skilled in the art to which it pertains,
or with which it is most nearly connected, to make and use the same, and
Shall Set forth the best mode contemplated by the inventor of carrying out
his invention.
35 U.S.C. § l 12 (pre-AIA); .S':'rri'ckv. Dreamworks, LLC, 5 l6 F.3d 993, 999 (Fed. Cir. 2003) (“The
‘enablcrncnt requirement is satisfied when one skilled in the art, afier reading the specification,
could practice the claimed invention without undue experirnentation.’”) (citation omitted).
Thus, Jermewein‘s expert pleads both sides of the same coin: a person of ordinary skill in
the art would be motivated to incorporate ](awano’s l30 Miller Unit plasmids into Samairfs
78
processes to help purify the oligosaccharides (RX-0384C at Q25?-258). but would also expect that
any Miller Unit activity above 5.8 would degrade lactose faster than it could be used for
oligosaecharide production (id at Ql86). This contradictory picture significantly diminishes the
persuasiveness of the purported motivation to combine.
Nor do the other references cited by Jcnnewein support a motivation to combine. Geisser
(RX-0016), for example, is not directed to enzymatic production through modified organisms at
all, but instead to “[t]he SLICCE-5Sfi.ll separation of the disaccharide lactose from a complex mixture
of human milk oligosaccharides (HMOS) with the continuous chromatography of simulated
moving bed (SMB) technique." (RX-0016 at Abstract.) Glycosyn's expett persuasively testified
that “to the extent a person of skill in the art could learn anything from Geisser about B»
galactosidase activity, they would understand that a high level, not a low level. of B-galactosidase
activity would he preferred” to enhance the separation of lactose from other oligosaccharides in
the milk. (CX-0487C at Ql57.) Drouillard (RX-0015) discloses synthesis of 2’-FL through
metabolically engineered E. colt, but it claims in both of its setups that no leftover lactose
remained, that is, it does not address 2‘-FL purification at all, nor does it even reference 13
galactosidase. (RX-0015 at -15184 (“Alter 22 h of incubation, the lactose was completely
consumed" and “To produce [2’-FL] without [LNnF-1] . . . . After 25 h incubation, lactose was
completely consumed and converted into [2’FL].”).) Lastly. Dekany discloses enzymatic methods
for creating oligosaccharides. but only in background and with general discouragement:
Either genetically engineered microorganisms or mammals are used in
biotechnological methodologies for the synthesis of 2’-O-fucosyllactose.
Such technologies use complex enzymatic systems facilitating both the
biosynthesis of precursors and the required glycosylations. To date, such
approaches face severe regulatory approval hu.rdles due to the use of
genetically engineered organisms and potential contaminations of non
natural oligosaccharides.
(RX-O01’? at -22356-7);
79
Enzymatic methodologies suffer from the low availability of enzymes,
extremely high sugar nucleotide donor prices and regulatory difficulties clue
to the use of enzymes produced in genetically modified organisms.
(id. at -22359). I therefore do not see this reference as useful or related to a motivation to combine
I3-galactosidase activity into the enzymatic techniques disclosed in Samain.
Apart from the lack of motivation to combine, some secondary considerations of non
obviousness further undermine Jennewein‘s case, Jennewein does not dispute the existence of a
long felt, but unresolved need. (RRB at 50.) As for teaching away, Samain and three Jennewein
patents all disclose the importance of inactivating the facZ gene to preserve lactose for 2’-FL
production. (CIB at 107 (citing CX-0487C at Ql9l-198).) The Iennewein patents demonstrate
the existence of the conventional outlook: any other lactose-consuming processes should be
deleted or inactivated during 2‘-FL production. (See CX-0504 at 6:4-20; CX-0506 at [O0l4].) As
the rc-introduction of a filnctional |3-galactosidase enzyme into E. colt during 2'—FLproduction is
a central inventive aspect of the ’0l 8 patent, I find the requisite nexus is met here. Merck & Cie,
SOS F.3d at 837; In re Hm2i—HzmgKoo, 639 F.3d at H168. And as for unexpected results,
Jcnnewein‘s own expert was surprised that using a low level of [3-galactosidaseactivity to produce
oligosaccharidcs works, since it is contrary to what he believes even today is the preferable method
for producing oligosaccharicles, namely, use of an E. coll strain with no B-galactosidase activity.
(Hr‘g Tr. at 625:l2-626:2O.) Moreover, a non-testifying experfs issued patent states that the use
of a low level of [3-galactosidase activity had unexpected and surprising results in the production
ofoligosaccharides. (CX-0507 at 7:1 l-l5.) For clarity, that reference, filed after the ‘OI8 patent,
teaches:
Surprisingly, it was determined that microorganisms that produce less B
galactosidase activity than a microorganism with a non-defective lacZ gene
are the best producers of 2-FL (as compared to microorganisms that express
normal levels of [5-galactosidase or express no [3-galactosidase).
80
(Id. at 7:] l-I 5.) So non-obviousness is supported by a long felt, but unresolved need, teaching
away, and unexpected results.
However, I arn not persuaded that the failure of others supports a finding of non
obviousness. To be sure, Glycosyn‘s evidence shows it is not only hard to make 2‘-FL in
bioengineered organisms, but also hard to make it in sufficient quantifies for commercial purposes,
such as an ingredient in baby formula, so much so that “many have tried and failed.“ (RRB at 50:
CIB at 105 (citing CX-0004C at Q52; Hr’g Tr. at 18:3-12; C-X-0001C at Q34-35; RX-0320C at
20] 87).) ln particular, the evidence shows that “there was no prior art solution for manufacturing
liueosylated oligosaccharides that did not suffer from either low yields or purification difficulty“
even though others, such as Jennewein, Abbott, and Nestle’, tried. (CIB at 106-107 (citing CX
048'/‘Cat Ql9l-198).) Nonetheless, Jennewein is the only current commercial provider of 2‘-Fl.
in the United States. (See id. at 93; RX-0384C at Q3l4.) And the failure of others is readily
attributable to the inability to make 2‘-FL in sufficient quantities and with necessary purity
required for use in baby formula, while also making it cost-efficient. (See CIB at 105-106; CX
0487C at Ql72, l78~l8l .) None of these goals are recited or necessarily accomplished through
the simple practice of the ‘U13 patent claims. (See, e.g., ’Ul8 patent at cls. 1-28 (not reciting
amount of fueosylated oligosaccharide produced, cost, or purity leve1).) Based on the stage of
Glycosyn’s collaboration with production partner FrieslandCampina, it seems too early to tell if
the '01 S patent answers the identified comiirercfal needs. It was confirmed at the hearing that such
production has not even begun. (Hr’g Tr. at 45:3-2|, 48:1-17.)
l therefore do not find that the failure of others supports a finding of non-obviousness. The
other three secondary considerations asserted by Glycosyn do support such a finding, however,
and Jennewein has additionally failed to demonstrate a motivation to combine references. On
8]
balance, therefore, neither claim 1 of the ‘O18 patent, nor any of the dependent claims, are invalid
for obviousness.
3. 35 U.S.C. § I12, 1l 1 (Enahlement)
In its opening brief, Jennewein contends “[c]laims l-3. 5, 8, 10, 12, 18, 23, and 24 are
invalid for failing to satisfy the enablement requirement of 35 U.S.C. § 112, 1] l." (RIB at 99.)
Jennewein presents two specific arguments that “[t]he '01 8 patent‘s specification does not enable
the full range of 15-galactosidase activity" because it only shows fitcosylated oligosaccharide
production at an activity level of 1-2 Miller Units, while claim 1 recites a much broader range of
0.05 to 200 Units. (See id. at l00 (citing ’0l 8 patent at 18:23-32).)
First, Jennewein contends that “it would require undue experimentation to make a
fucosylated oligosaceharide at such higher levels of [3-galactosidase activity.” (RIB at 109; see,
e.g., RIB at 101-102 (“[A] person of ordinary skill in the art would need undue experimentation to
produce 2’-FL at these high leve|[s] of [3-galactosidaseactivity"), 102 (“A person of ordinary skill
in the art would need to conduct periodic experiments over the entire range of 0.05 to 200 . . , to
ensure that the B-galaetosidase level at each measurement would both (a) not be so high as to halt
production of the fucosylated oligosaccharides and (la) eliminate residual lactose after 2‘-FL
production to allow isolation of the 2’-FL product, as claimed by Glyeosyn during prosecution of
the '0l8 parent's parent"), I02 (“significant experimentation would be necessary to ensure that
the fi.1llscope of values within the claimed range of 0.05 to 200 units would ‘strike a balance
between production of desired fucosylatecl oligosaceharides and the level of 13-galactosidase
produced“), 106 (“Three data points over a relatively narrow range would be deemed as
insufficient to show that strains having activity up to 200 units could in fact make 2‘-FL.").) This
position is tied to the claim limitation "retrieving a fucosylated oligosaccharide from said
bacterium or from a culture supernatant of said bacterium.” (‘DIS patent at cl. 1.) It revolves
S2
around the argument that at higher [3-galactosidase activity levels, the [3-galactosidase "would
destroy intracellular lactose "Fasterthan it could be processed into significant amounts of 2‘-FL”
such that “it would require undue experimentation to make a fucosylated oligosaccharide at such
higher levels of 13-galactosidaseactivity.” (RIB at I09.)
To the extent this argument avers lack of enablement for producing “significant,” useful,
or “commercial levels“ of a fucosylated oligosaccharide (RIB at 100 (citing RX-038-4Cat Ql86)),
it is entirely misplaced. No asserted claim requires any particular amount of fucosylated
oligosaccharide to be produced or “retriev[ed].” (See, e.g., ‘U18patent at cl. 1.)
To the extent this argument avers lack of enablement for producing any fitcvosylated
oligosaccharide whatsoever at high I3-galactosidase activity levels, there is a lack of clear and
convincing evidence on this point. Jennewein relies on the testimony of its expert to make the
claim (see RIB at 108-109 {citing RX-0384C at Ql86))5, but this testimony is contradicted by
.lennewein‘s own obviousness arguments:
Fttrthermore, shottlalthe claims encompass producing any amozmtaf2 '-FL,
2 '-FL would be produced even in the presence offl-galactosidase activity
within the claimed range. This occurs because the [3-galactosidaseenzyme
and the 2‘-FL-producing fucosyltransfcrase enzyme are competing
simultaneously for lactose. See Tr. (Prather) 730:l5-73l:l4, RX-0384
(Stcphanopoulos WS) at Q/A 195. . . . As shown in RDX-0012, should
fttcosyltransferase [be] present, some 2‘-FL will be produced, even though
less 2’-FL would be produced if |3-galactosidase is also present. See id. It
is also worth noting that Jennewein’s fucosyltransferase attaches fucose to
the galactose moiety of lactose.
(RIB at 83-84 (emphasis added).) That is, Jennewein concedes in its discussion of obvtousness
that simultaneous competition between B-galactosidase and fucosyltransferase will still result in
5 Jennewein also cites hearing testimony from Glycosyn‘s expert here, but that testimony
does not support the concept that competition will prevent any 2‘-FL production. (RIB at 108-109
(citing Hr‘g Tr. at 73016-21. 131 ;1-14).)
S3
some 2’-FL production, even when that competition is stiff. A person of ordinary skill would
know this. (Hr’g Tr. at 730115-731:l4, 743:5-18. 737114-73820.)
Even setting aside this concession, I agree with Glycosyn (CIB at I 12) and the Staff (SIB
at 98) that Jennewein’s expert testimony on the destruction of 2’-FL at higher [5-galactosidase
activity levels is largely conclusoty and thus entitled to little weight. Cephalon, Inc. v. Watson
Pharm.v.. Ina, 707 F.3d 1330, 1338 (Fed. Cir. 2013). For example, the expert claims that the data
points contained in Dr. McCoy’s declaration submitted during prosecution are better Iit by a linear
line than the exponential fit Dr. McCoy employed, but he provides no explanation for why it would
be bcttcr—cspecia1ly with regard to the science ofsimultaneous competing enzymatic pathways
he acknowledges elsewhere. (Compare RX-0384C at Q178, 195 (discussing RDX-0012) with
I-Ir‘gTr. at 743:5-18.) The expert's claim that “[3-galactosidaseactivity well above 5.8 units would
be expected to destroy lactose too quickly for the cell to use it to produce 2’-FL” is similarly
conclusory. (See RX-0384C at Ql86.) Dr. Stephanopoulos did not perform any experiments or
cite any disclosures in connection with his contention that high B-galactosidase activity will
prevent any 2’-FL production. (I—lr’gTr. at 644: 13-646:4.)
Thus, I find it far from clear and convincing that higher 13-galactosidaseactivity levels (i.e..
higher than ~6 Miller Units) would result in no 2‘-FL production whatsoever. Jennewein does not
explicitly address the Wands factors on this point, and, therefore, neither do I. (See RJB at I06
llflj
.lennewein’s second enablement contention is that “undue experimentation would be
required to modify microorganisms having |3-galactosidase activity for the entire range.” (RIB at
102; see RIB at 100 (“The specification fails to enable the full scope of the claim limitation ‘the
level of [5-galactosidase activity comprises between 0.05 and 200 units" of claim 1 of the ‘O18
84
patent“), IO] (“[T]he evidence showed that undue experimentation is required to produce strains
with any specific activity in the claimed range“), I03 (“The specification . . . leav[es] a person of
ordinary skill completely in the dark about how to create modified bacteria that could, taken
together, cover the entire claimed range”), 105 (“The highly complex nature of this invention in
this unpredictable field also contributes to a high level of experimentation necessary to achieve the
claimed range of [5-galactosidase activity/.”).) This position is tied to the claim limitation "(ii) an
exogenous Functional [5-galactosidase gene comprising a detectable level of B-galactosidase
activity that is reduced compared to that of a wild-type E. colt’bacterium, wherein the level oft?
galactosidase acrwity comprt'.re.rbetween (1.05 cmd 200 tmits.” {"018 patent at cl. l (emphasis
added).)
This contention is a closer call. The ‘O18 patent specification only discloses a single
species of‘bacteria which produces between l and 2 Miller units of [5-galactosidase activity:
The lon mutation in E390 increases intracellular levels of RcsA, and
enhances the intracellular GDP-fucose pool. The inserted lacZ+ cassette not
only knocks out lon, but also converts the lacZ—host back to both a lacZ+
genotype and phenotype. The modified strain produces a minimal (albeit
still readily detectable) level of B-galactosidase activity (1-2 units), which
has very little impact on lactose consumption during production runs, but
which is useful in removing residual lactose at the end of runs, is an easily
scorable phenotypic marker for moving the lon mutation into other lacZ—
E. coir‘strains by P1 transduction, and can be used as a convenient test for
cell lysis (e.g. caused by unwanted bacteriophage contamination) during
production runs in the bioreactor.
(‘O18 patent at 18:19-32; see RIB at I03; SIB at 94 (not disputing Examiner’s observation); see
generm"iy CIB at 109-116.) Thus, the issue is whether this limited species disclosure sutficiently
enables a person having ordinary Skill in the art to practice the limitation “(ii) an exogenous
functional [3-galactosidase gene comprising a detectable level of [3-galactosidase activity that is
reduced compared to that of a wild-type E. colt bacterium, wherein the level offl-galactosidase
activity comprises between 0.05 and 200 units," over the full range without undue experimentation.
S5
Resolving this issue requires consideration _of the Wands factors: (1) the quantity of
experimentation necessary; (2) the amount of direction or guidance presented; (3) the presence or
absence of working examples; (4) the nature of the invention; (5) the state of the prior art; (6) the
relative skill of those in the art; (7) the predictability or unpredictability of the art; and (8) the
breadth of the claims. Wands, 585 F.2d at 737.
In reviewing fllese factors, I have avoided relying on the evidence cited in Dr. McCoy’s
declarations during prosecution. Declarations submitted during prosecution, while nndisputedly
part of the intrinsic record, are not part of the specification, but it is the specification that is the
focus of the enablement inquiry. And as for the Wands factors themselves, factor one. “the
quantity of experimentation necessary,” outweighs all others in significance, and I consider it last.
The second and third Wands factors, “the amount of direction or guidance presented” and
“the presence or absence of working examples.” favor Jennewein. The ’0l8 patent specification
provides just one example of an engineered bacterium with Miller Units of any amount (l-2 units).
(‘O18 patent at 18:9-32.) And although Glycosyn’s expert testified that “[t]he ’0l8 specification
and the documents cited therein provide significant guidance on how to modify a bacterium to
express different levels offi-galactosidase activity and/or produce different amounts of 2‘-FL," her
testimony is conclusory. (CIB at 115 (citing CX-0487C at Q59-64).) She merely cites passages
in the ‘O18 patent (CX-0487C at Q61 (citing ’OlS patent at l6:31-35, 18:12-l3)) which mention
that an increased cellular pool of lactose and the lon replacement mentioned above were achieved
using “Jr Red combineering” or "X Red recombineering.” The expert does not explain what this
technique is or how it can be used to achieve varied |3-galactosidase activity levels.
The fourth and eighth factors, “the nature ofthe invention" and “the breadth of the claims,”
do not favor either side. While the obviousness discussion above identifies “wherein the level of
86
[3-galactosidase activity comprises between 0.05 and 200 tmits” as a key distinguishing feature
over the prior art, engineering a bacterium with this level of activity is not by itself an aspect of
the invention. (See, e.g., RX-0014 at -22443-S, Table l, Fig. 1, Table 2.) Rather, the benefit of
the invention comes from the combined use of a bacteria producing the claimed activity range,
alongside those other techniques implemented for increased oligosaccharide production within the
bacteria. And the recited 0.05 to 200 Miller unit range is not particularly broad. Prior art references
such as Kawano (RX-0014) show that, depending on the promoter used, B-galactosidase activity
within an E. colt‘bacterium can run anywhere between 0 and 12,200 Miller units. (See RX-0014
at -22443, Table l. -22445, Table 2.)
The filth, sixth, and seventh factors. “the state of the prior art," “the relative skill of those
in the art," and “the predictability or unpredictability of the art,” also do not favor either side.
There is persuasive evidence in the record that this art is generally unpredictable, in that those
skilled in the art understand and expect experimentation to he performed before conclusions on
genetic or enzymatic activity can be reached. (See Hr’g Tr. at 676:1?-678:4 (“You would not
know the results. You expect results, but you do not know the results until you do the
experiment. . . . You have to do the experiment"); CX-0002C at Q36 (“This is how genetic
engineering works, you try several different modifications unit you get the result you want”); see‘
generally JX-0002 at -296] -2963 (rejecting claims due to unpredictability in the field); RX-0384C
at Q1815, 190; Hr’g Tr. at 296:l3-23, 640:l6-641:5, 505:1-15, 1-47:18-149:t8; CX-0053C at
H7388; CX-0483C at QZOQ3, 39.) Yet, there is also evidence showing the person of ordinary
skill in the art at the time of invention would have known how to conduct this experimentation and
would be aware of various E. cob‘lacZ promoters to try. (See, e.g., JX-0002 at -2934 (citing prior
87
art investigation of promoters); RX-0014; I-lr’g Tr. at 619:4-624:l2; CX-0468; CX-0469; CK
0487C at Q64.)
Turning finally to the first Wands factor, “the quantity of experimentation necessary,” I
find this favors Giycosyn. Again, Kawano is instructive. While Jennewein is correct that Kawano
explicitly teaches bacteria strains for only a portion of the claimed 0.05-200 Miller Unit range
(RIB at 105), it is also true that o:°Kawano‘s 105 randomly selected strains for potential promoter
activity, a vast majority exhibited Miller Unit activity levels within the 0.5-200 range. This is
explained alongside Kawano’s Figure l:
53 § '
aw
wt
an
20*;
my
D ‘ . .
{3-galactosidasa activity {MU}
88
|l-'i;,;urc l. The tllhl.E‘li‘*L1lllI€t ol' [?Z‘l3i'l‘iC!ll-Ii’{'15-gaiae:<isidz=..s-.>i :1-.’ti\‘iti==::~;of ID5
l't1fli.l\'I|i'l i‘:‘ag|1ii':1is<it !;'.= ->2’!as n.'i55E\:iL.l_iin tin: |"'l'i1I‘I‘t~"lll;'i'li.‘\.‘i itir'?Tii?stc:' plesiiiitl,
].Il{\'.’i.‘5 . We tit-‘t'i|::':l zi ~.='i}\e\¢'t|t'eus hilt-ing giiileiiiitzl ;I1‘s'u|i-.ilcr iiL"ll\*ll}*\.\-‘lien the
B-g.1l.'a-msitinsc .1‘.-ri'~.'itfv' or the srrai n was i:1crnnst*i1 l‘»_\_= F-told or niorc ovcrrism
of the snniii '~\'ll.l.1the paizental pizlstuid pRS:'i3l l1.c‘.to 1-1!)ML? L We found that
fit: l5.'i".*i-'|of the. ilti-L'l‘l:~.(it-stctl lil only one nrlcelntéolij eiihibaled prnn‘.oicr
.t\.'il‘~'ll_\ by this \_‘l‘llL‘l'laHl.l'lU‘.\'i_'-\'i,'T.sonii: ii: th: il1HL'll.~imay t'na:t;n1i rnore than
one pit‘-motor. Ap|il)-ing the Poisson zlisiiliuiion. Pill: _ c ' i‘_wlierc PID: is -lie
pi'\>i\z1hilil}-iiféisiding no kl-.'t1\ity tic. ilic null tflizibsiil'pl;isn:iés |_‘.\pl".‘55il'l§{E ii}
lvill -_ -1’I”'i=t, 2Ii'l\.l-.|1!~.'i|1;_gIn: 3..liliv ave;a_::,a' {'Ellll‘li‘\‘_‘l':'ii‘pulcr|li;il [=i'n|:1ul:;'r»~ pa:
lnwrl J. we a..":ili;'tsl:1te1l1t':ie ant:on:m::.:ig:'£3.7611J'o:|ai'iics‘s perl'|':tgnu:nLl‘i|'1oo|.it'>t'
the mo pt.-ssibl-_' 0li|_‘;ll.1tli\.!l‘1:.'J.We |11cret‘o1'::coiiclmle that tiien: are \ 1.51
"1'.-\'ic;r£1.76} ;\1't':n".->tL‘i'~. pt‘! lhi lip or HEN‘full promoter in citlicr dirt-riiuii
]h'l' -- It.-'.-' li|'=.
(RX-0014 at -22444.) This data strongly suggests that when a person of ordinary skill in the art,
and familiar with E. calf gene manipulation techniques, searches for promoters to use with a
functional B-galactosidase gene to accomplish “wherein the level of B-galactosidase activity
comprises between 0.05 and 200 units," they will find one with little trouble, possibly just through
a review of the literature. Kawano shows that the process is not like searching for a needle in a
haystack. “The test is not merely quantitative, since a considerable amount of experimentation is
permissible, if it is merely routine, or if the specification in question provides a reasonable amount
of guidance with respect to the direction in which the experimentation should proceed[.]” Wands,
858 F.2d at 737.
On balance, although several factors are neutral and two factors favor Jennewein, the
weightiest factor, the quantity of experiment necessary, favors Glycosyn, so much so that it
outweighs the factors that favor Jennewein. Therefore, Jennewein has not shown by clear and
convincing evidence that the asserted claims of the ’Ol8 patent are not enabled.
4. 35 U.S.C. § 112, {I1 (Written Description)
l.naddition to lack of enablement, Jennewein argues “[c]laims 1-3, 5, S, 10, 12, 18, 23, and
24 are also invalid for failing to satisfy the written description requirement of 35 U.S.C, § l 12, 1l
89
1.” (RIB at l I0.) Specifically, Jermewein refers to the tr-eomplementation technique used in its
Accused Strains and argues “[i]f interpreted broadly enough (as Glycosyn does) to encompass o.
complementation, the patent fails to show possession of the full scope of the term ‘functional . t .
13-galactosidasegene.” (Id. at ll l.) This argument is clearly conditioned on interpretation of the
claims as covering Lt-complementation. (See RIB at l l3 (“Glycosyn‘s argument that Jennewein
literally infringes the ‘O18 Patent requires the claims to literally encompass not just o.
complementation, but also the unique form of at-complementation employed by .lennewein.”);
RRB at 58 (“As the written description requirement cannot be applied to equivalents, Jennewein
is not conflating the written description requirement with the doctrine of equivalents“); id. (“If
interpreted broadly enough . . . to include uacomplernentation, the specification fails to Show
possession of the full scope of the term ‘functional . . . B-galactosidase gene . . . .“); SRB at 28-29
l“The Staffagrees with Jennewein that [ct-eomplernentation]does not literally infringe the asserted
claims. . . . If the Administrative Law Judge adopts this interpretation of the claim language, then
Jenneweirfs written description argument is moot.").) As explained above, Jennewein‘s o
cornplementation technique does not fall within the literal scope of “functional . . . B-galactosidase
gene." Therefore, Jennewein has failed to prove that the claims in suit fail the written description
requirement.
S. lnequitable Conduct
A patent may become unenforceable it'“the applicant misrepresented or omitted material
information with the specific intent to deceive the PTO.” Therasense, 649 F.3d at 1287.
According to Jennewein:
Glyoosyn intentionally withheld information that was plainly material to
patentability and was known to it during prosecution of the ’0] 8 Patent and
its parent (the ’23l) Patent). Co-inventor Dr. John McCoy intentionally
withheld information that contradicted his affirrnative representations to
Examiner Rebecca Prouty, which she relied upon to grant the ‘O18 patent
90
Accordingly, inequitable conduct renders the Asserted Claims
unenforceable.
(RIB at I 18.) More specifically, Jennewein contends that Dr. McCoy knew of certain Glycosyn
testing data that, as characterized by Jennewein, “reveals that bacterial strains having B
galactosidase activity within the claimed range of 0.05 to 200 Miller units actually failed to
produce 2’-FL. . . . but chose not to disclose any of it to the Examiner." (RIB at 123.) Jennewein
has not shown inequitable conduct by clear and convincing evidence, with respect to both
materiality and intent.
Understanding why requires consideration of the prosecution history. On August 8, 2014,
the Examiner rejected the claims of the application that would become the ’23Dpatent “under 35
U.S.C. l l2(a) or 35 U.S.C. I12 [pre-AIA), first paragraph, as failing to comply with the written
description requirement.” (JX-0002 at Y2728.) The Examiner explained the rejection as follows:
The specification includes no evidence that the presence of any modified
lacZ gene wherein the bacterium has between 0.5 and 200 units of [3
galactosidase activity when grown under inducing conditions is not
detrimental to producing a fucosylated oligosaccharide as would be
expected since [3-galactosidase will degrade the lactose acceptor necessary
for the fi.tCOSylEl[i0l1,yet the claims clearly encompass any functional |3
galactosidase gene having up to I00 fold more B-galactosidase activity than
the single disclosed species.
(Id. at -2730-l.) The Examiner issued a parallel rejection based on the same facts under
enablement. (See id. at -2732-34.)
On February 9, 2015. Glycosyn amended the claims (IX-0002 at -2916-22) and provided
a first declaration from Dr. John McCoy to overcome the written description and enablement
rejections (id. at -2924-7). On May 8, 20l5, the Examiner issued the same rejections. (JX-0002
at -2953-68.) With respect to the declaration, the Examiner stated:
Applicants argue that the declaration of John McCoy shows that even
relatively high levels of 13-galactosidaseproduced by the Lac? bacteria of
FIG. 2 did not deplete the lactose pool such that the desired titcosylated
91
(JX-0002 at -2964-5.) The Examiner provided similar commentary in the context of the renewed
oligosaccliaride end product was not made by the engineered bacteria.
However, this is not persuasive as the declaration does not show that the
range of activity of the bacteria of Figure 2 of the declaration encompasses
the claimed range of 0.05-200 units claimed. Without any indication of the
level of B-gal activity present in the bacteria of Fig. 2 of the declaration, the
declaration does not provide evidence that the claimed range of B-gal
activities will not deplete the lactose pool such that the desired fiicosylatcd
oligosaccharide end product will not be made.
enablemcnt rejection. (See id. at -2966-8.)
3|.) With respect to the § 112 rejections, and the previous declaration in particular, Glycosyn
On November 9, 2015, Glycosyn responded and amended the claims. (JX-0002 at -3025
argued;
Fig. 2 of the Declaration is a photograph of the art-recognized X-GAL
colorimetric assay for [5-galactosidase in which low levels of the enzyme
appear as light blue colonies/streaks and high levels appear dark blue [,]
thus providing an art-recognized and standard indication of B-galactosidase
enzyme activity. Applicant's statement (copied above) also addresses the
Exarniner‘s concern that the claims may encompass bacteria that do not
make the fucosylated oligosaccharide, stating that even relatively high
levels of I3-galactosiclase produced by the LacZ+ bacteria (dark blue
streaked colonies in Fig. 2) did not deplete the lactose pool such that the
desired fiicosylated oligosaccharide end product was not made by the
engineered bacteria. In view of the foregoing clarifications and arguments,
Applicant respectfully requests withdrawal of this rejection.
(JX-OOO2at -3038-9.)
Following this, on January 22, 2016, the claims were again rejected on the same written
description and enablement grounds. (See JX-0002 at -3044-53.) In the context of the alleged
written description problem and the X-GAL assay image above, the Examiner stated
However, this is not persuasive as it is not clear how much B-galactosidase
activity is necessary to obtain a light blue or dark blue color and a quick
intemet search by the examiner did not provide this infonnation such that
there is still no indication whether the colonies of Fig. 2 of the declaration
span the claimed range or not.
92
(JX-0002 at -305 1.) However, the Examiner invited Glycosyn to submit a declaration stating “that
the bacteria of Figure 2 of [a] previous declaration all successfully produced fucosylated
oligosaccharides and include strains with B galactosidase activities of about 20 units (or more),"
and, if so submitted, “the examiner will withdraw the instant rejection." (JX-D002 at -3051.)
LnApril 2016, Dr. McCoy submitted the suggested declaration, containing data for three
exemplary 2’-FL producing strains, E997, E890x4l6/pG2l7, and E890x422fpG2l7, and
affii-matively stated that “good levels of 2’-FL are produced in all 3 strains.“ (RX-0396 at 3.)
These strains had B-galactosidase activities of 1.5, 2.5, and 5.8 Miller Units, respectively. (hi)
The declaration also contained an extrapolation of the measured data to 200 Miller Units in graph
form, accompanied by a statement that “even strains producing 200 Miller Units of galactosidase
would be capable of producing significant levels of 2’-FL in the femienter (>2g/L).” (RX-0396 at
4.) After tiling the declaration, first in the prosecution of the ‘Z30 patent, and then in the
prosecution of the ’0l 8 patent, all claims were allowed. (JX-0002 at -1750; JX-0004 at -304-310.)
Jemiewein contends, in summary, that:
Dr. McCoy withheld material information not once, but at least three times.
First, he withheld the fact that the only strain with beta-galactosidase
activity of about ZOOMiller Units that Glycosyn had actually tested prior to
McCoy’s declaration in fact failed to make 2’-FL. CX-0053C at 7. Second,
he withheld the fact that two strains that Dr. McCoy represented as
producing 2’-FL actually failed to produce it reliably. Id. at 6. Third,
demonstrating a pattem of lack of candor, he also withheld material
information from the European Patent Offiee.
(RIB at l34-l35.) I consider these points individually.
First, Jennewein argues that CX-0053C, a slide deck summarizing certain research and
development activities and dated almost a year before Dr. McCoy’s second declaration, shows no
2’-PLby a we — with
approximately 200 Miller Units of |3-galactosidase activity. (RIB at 125 (citing CX-0053C).) But
93
these test results were not germaneto the invention,becausethe - strain was not
comparable to the strains Dr. McCoy identified in this second declaration, for two reasons. First,
t made itapoor candidate For creating 2’-FL, regardless ofits
[3—galactosidase activity. As Dr.Merighi,the creatorof the slidedeck,testified,- wasa
- so it was not fullyexpressingthe pathwayfor making2’-FL. So it didn’tsurpriseme
too much that we were not making it. I was hoping that we would make some.” (_Hr’gTr. at
281:3-25;see CX-0053C at -I 17382 (“Next Make a lon- version"}.) In contrast, each ofthe E997,
E390x4]6/pG2l7, and E890x422/pG217 strains used as the basis for Dr. McCoy‘s declaration
(andshownin ex-0053c) were- (Id.at 227124-238:5.)Indeed,Dr.Merighi,=1non
party,testifiedthatcomparing- and_ isnotmeaningful. (Id.(“Youshowed
me the slide, it was the. units. That was not ready for apple to apple comparison, because it
was- correct.Sothesestrainsareall- soyoucancomparethern.”).)Second,it
is not a mere “technicality” (RRB at 62) that the 2’-FL production rate in a large scale ferrnentor
does not match smaller tube-scale runs. (See. e.g., CX-0053C at ~l 17379, -117381, -117388;CX*
0488C at Q9, Q20-22, 39; Hr’g Tr. at 1-47:18-l50:25, 295:20-296:2}, 63920-641:19, ‘[25:14
727:9; RX-0409C at Ql67.) Dr. McCoy, in particular, testified at length about the differences
between the two test methods. (Hr‘g Tr. at 147118-l50:25.) The fact that Dr, McCoy’s declaration
was in the context ofthc former (JX-0002 at -321 l (“significant levels of2’FL in the fermc11tor")).
whereas Dr. Men'ghi’s experiment was the latter (CX-0053C at -1 1'73S2 (“(tube scale)"))__
diminishes therelevance ofthe_ result.
Second, Jennewein argues that of the three strains discussed in Dr. McCoy's declaration as
producing “good levels of2‘-FL,” CX-0053C shows two, E890x416/pg217 and E890x422/pG2l7,
'-)4
actually failed to make Z’FL. [RIB at l32.) Jennewein bases this claim on the following line from
CX-0053C:
i
(RIB at 132 (citing CX-0053C at -117381).) As Dr. McCoy testified, however, this comment
could not have referred to testing of ES9(]x4l6/pg2l7 and E89Ox422/pG2l7, because those tests
(which are documented a few pages earlier in CX-0053C) did show 21FL production. (Hr‘g Tr.
at l 15:1-2 (bullet point 5 is “clearly not referring to the ones that we werejust looking at, because
they produced 2’-FL”).) And Dr. Merighi, the bullet p0int‘s author, testified that he was unsure
whatit referenced,but thathe thoughtatwastrdistinctstrain,- (Id.at 2s1;19-23.)
Third, Jennewein points to other B-galactosidase experimental data that Dr. McCoy did not
submit to the USPTO, including one set that was submitted to the European Patent Office for
similar prosecution purposes. (See RIB at 131-132 (citing RX-0067C; JX-0019C at 35O:l9-21
(non-designated») Jennewein asserts that Dr. McCoy “demonstrate[ed] a pattern of lack of
candor” by withholding information from the European Patent Office. (RIB at 135.) But
Jcnnewein makes no effort to demonstrate that he had a duty to disclose such allegedly withheld
information to the EPO. (See id. at I34-135.) Moreover, the information pertains to a strain,
EH77, that produced 2’-FL with B-galactosidase activity far outside the claimed range, and
therefore of little relevance. (RIB at l3l.) And Jcr1newein‘s discussion of the evidence cites
principally to a 246-page laboratory notebook of Dr. McCoy, which appears to be admitted as CK
0025C. but without citing to page numbers. (Id. at I3 l-I32.) Nor does it appear that Jermewcin
questioned Dr. McCoy about this exhibit during the hearing. On balance, Jertnewein has failed to
prove that Dr. McCoy withheld anything from the PTO regarding E1277, and I do not address this
argument further.
95
Overall,Dr.McCoy‘sfailuretodisclosethe— tube-runexperiment and
WhatDr. Merighibelievedwas the— tube run, as recordedin CX-0053C,was not material
to the patentability of the claims. The Federal Circuit has explained, “the materiality required to
establish inequitable conduct is but-for materiality. . . . in assessing the materiality of[witl1he1d
information], the court must determine whether the PTO would have allowed the claim if it had
been aware of the undisclosed [inforrnalion].“ The-rasense,649 F.3d at 1291-92. Admittedly, it
was material to patentability whether the claims were enabled at 200 Miller units. But if Dr.
McCoy’s second declaration had included the challenged tube runs, and also explained why he
subjectively did not consider them relevant, there is every reason to believe the Examiner would
have allowed the claims.
And because of his subjective views of the two challenged tube runs, the requisite deceptive
intent is also lacking. As acknowledged by both parties, a specific intent to deceive must be “the
single most reasonable inference able to be drawn from the evidence.“ Tlrerasense, 649 F.3d at
1290 (citation omitted). Dr. McCoy, who testified at the hearing with a confident but otherwise
unremarkable demeanor, doesnotviewthe— testresultandthe] tuberuns
_ bulletpointin CX-0053Cas contradictingthe statementsmadein his second
declaration; Jcnnewein. by contrast, offers only innuendo and case citations in support ofdcceptivc
intent. (See generally CX-0488C at Q19-39; RIB at 134-36.) The most reasonable inference to
be drawn from the evidence is that Dr. McCoy sincerely believed that the challenged evidence was
immaterial. and there is therefore no inequitable conduct.
V. DOMESTIC INDUSTRY - ECONOMIC PRONG
In a patent-based complaint, a violation of Section 337 can be found “only if an industry
in the United States, rclating to the articles protected by the patent concerned, exists or is in the
process of being established.” 19 U.S.C. § l337(a)(2). Under Commission precedent, this
96
“domestic industry requirement” of Section 337 consists of an economic prong and a technical
prong. StringedInstruments, lnv. No. 337-TA-586, Comm’n Op. at 12-14. The complainant bears
the burden of establishing that the domestic industry requirement is satisfied. See Certain Set-Top
Boxes and Components Thereofl lnv. No. 337-TA-454, TDat 294 (June 21, 2002) (not reviewed
by Commission in relevant part).
The economic prong of the domestic industry requirement is defined in subsection (a)(3)
of Section 337 as follows:
(3) For purposes of paragraph (2), an industry in the United States shall be
considered to exist if there is in the United States, with respect to the articles
protected by the patent, copyright, trademark or mask work concerned -
(A) Significant investment in plant and equipment;
(B) Significant employment of labor or capital; or
(C) Substantial investment in its exploitation, including engineering,
research and development, or licensing.
19 U.S.C. § l337(a)(3). The economic prong of the domestic industry requirement is satisfied by
meeting the criteria of any one of the three factors listed above. Importantly, the Commission has
clarified that investments in plant and equipment, labor, and capital that may fairly be considered
investments in research and development are eligible for consideration lmder Subsections (A) and
(B), in addition to subsection (C). See Solid State Storage Drives, Comm’n Op. at I4.
Here, Glycosyn alleges a domestic industry exists under all three factors. I agree.
A. Qualifying Investments
For subsection (A). and investments in plants specifically, the evidence shows Glycosyn
conducted engineering, research and development activities related to the production of 2‘-FL by
E. coir‘bacteria at two domestic locations in Medford, Massachusetts and Wobum, Massachusetts
between 2015 and the filing of the amended complaint in May 2018. (CX-0003C at Q1 I-14, Z3,
97
39-41.) The evidencealso showsGlycosynspent approximately- per month in rent on
caeh location,suchthatbetweenJanuaryl, 20!5 and May l6, 2018,Giycosyninvested
in these facilities. (Id. at Q44-52; CX-0087C.) Glycosyn acknowledges that, between 2015 and
May 2018, however, these locations were used for the development of 2‘-FL as well as other
compounds which do not fall under the scope of the asserted claims. (CIB at 128, I30-132; see
CX-0003C at Q7, 23, 31-33; EX-0002C at Q93, I I i.) In order to accommodate expenditures
unrelated to the ’()l8 patent, Glyeosyn applies an allocation percentage to its facility investments.
wherein said percentage is based on the amount of time its scientists at these locations spent on
developing 2‘-FL production per the ’Ol8 patent. (See CIB at 129-13] (citing, inter alto, CX—
Ot]D3C at Q26, 27, 30-32, 44-53; CX-OOOZC at Q33, 93, 94; CX-0089C; CX-OUS7C].} The
resulting claimed investment in facilities directed to the development of 2'-FL produced under the
claims ofthe ’0l8 patent is summarized in the below table;
The Staff agreeswith this-r figureas the amountin facilitiesexpensesattributableto the
‘DIS patent for purposes ofdomestic industry under subsection (A). (SIB at I I7; SRB at 34.)
.!ennewein’s dispute with respect to this investment in facility is that “Glyeosyn attributes
all of that rent to its domestic industry expenditures, even though it conducts R&D related to other
acti'vities— at thisfacility."(RIBat I39;RRBat 67.) Thispointis notwelltaken;
Glycosyn has reasonably apportioned its Facilities expenses based on its labor expenses. In any
event, Glycosyn’s witness testimony on this issue (CX-0003C at Q30-53; CX-UOUZCat Q33, 92
98
94) is credible and its documentary records (CX-0089C; CX-0037C) are reliable. Thus, I find the
record supportsa facility investmentamountof - for purposesof domesticindustry,
subsection (A).
With respect to equipment under subsection (A), Glycosyn has presented evidence
showing its various investments in equipment used at the Medford and Wobum locations discussed
above. (See CIB at I32.) Glycosyn’s witness testified that equipment purchases include
“ferrnenter machines, a recirculate chiller/pressure reducer, Visiferm DO optical oxygen sensor,
steam generator, sterilizers, a Biosat B plus Fermentation Control System, and a Touch Panel and
Conversion Kit for the Biosat B equipment“ as well as other equipment and tools attributable to
the development ot‘2’-FL. (CX-ODOBCat Q55 (citing CX~OUS5C).)That witness also categorized
each purchase in the year it was incurred (id. at Q56 (citing CX-0085(3)), identified the costs
expended with the maintenance of this and previously purchased equipment (id. at Q57 (citing
CX-0085(1)), and described depreciation costs incurred in 2017 for that equipment purchased prior
to 2015 (id. at Q58 (citing CX-00S6C)). Further, Glycosyn witnesses identified an additional
equipment purchase for the two locations made on behalf of Glycosyn in 2016 by an organization
called Glycosyn Health lnitiatives, Inc, “an organization that provides funding, donations, and
research sponsorship to various institutions in support of 2‘-FL research experiments,” which
included “a Synergy H4 M‘Pate Reader. an anaerobic chamber, camera, and freezer.” (Id. at Q56.)
Additional testimony elicited at the cvidcntiary hearirigexplained that Glycosyn Health Initiatives,
Inc., a non-party, and Glycosyn, the complainant, have “interlocking leadership and board
members." (Hr’g Tr. at 28:22-29:23.) In sum, the claimed investments in equipment at Glycosyifs
research and development facilities are summarized in the below table:
99
TheStaffessentiallyagreeswithtl1ts_ figureas the amountin equipmentinvestment
attributable to the ’Ol S patent tor purposes ofdomestic industry under subsection (A). (SIB at l 18
(calculating_); SRB at34(calculating -)
Jemieweiifs dispute with respect to this investment in equipment is that it includes amounts
“wholly unrelated to Glycosyrfs 2’-FL R&D efforts” because there is no apportionment between
“activities related to 2’-FL and activities related to other molecules unrelated to the claims of the
’O18patent." (RIB at I39; see RRB at 68.) Jennewein provides examples of a security alarm
system, certain sterilizers, and a fermentation control system as equipment which a Glyeosyn
witness admitted at the hearing may not be solely related to 2’-FL development. (See RIB at I39
(citing Hr’g Tr. at 52: 14421,52:22-27, 53:S—l7).) Jenncwein fitrther argues, inter aim, the timing
of Glycosyrfs switch to developmentof the - in mid-2017,£15comparedto Several
equipment purchases after this time, shows “Glyeosyn’s equipment expenses are therefore suspect
and should be disregarded as unreliable.” (See id. at I39-140.)
“ Both Glycosynand the Staff incorrectlyre ort this amountas‘ (CIB at 132 SIB
at ll8.i It is understood that this 1s a typo; H would be the correct rounding-Lipof
l (ill
Here. l find .lennewein’s criticisms have merit. Of primary importance, Glycosyn directly
acknowledges. and the evidence shows. that its concentration on 2‘-FL greatly diminished
following July 20l7. (See CX-0089C at -74622 (showing scientist time changing from lO0% to
25%);CX-OOUZC at Q93(“Aroundthe end of 20]’/,ourprojectwith—
— started ofGlycosyifs resources
went there starting around mid-20177).) It is natural to assume, therefore. that the use of its
equipment for 2‘-FL development similarly diminished; yet Glycosyn has not applied any
allocation percentage in the way it had done for facility and labor.
The Staff agrees that Glycosyn has not done this but contends applying the 2’-FL allocation
percentage derived front labor records makes little difference. (SRB at 35.) In its reply brief,
Glyeosyn similarly does not dispute that no allocation was applied or that one should have been.
(See CRB at 66.)
Given the record. and Glycosyrfs application of an allocation to both of its facility and
labor expenses, l find the same allocation should be applied to equipment. Glycosyn’s witness
does not sufficiently make clear that every item listed in the equipment record, C-X-0085C, has
been used solely for 2’-FL development work (see CX-0093C at Q54-59). which is important
giventhe clearrecognitionthat only. ofscientists’timein 2017and] in 2018was related
to 2’~FL (see CIB at 130-13 I). I do not agree. however, that this failure to allocate means all of
the equipment investments are unreliable and should be disregarded. as Jennewein urges. When
applied, GlycoSyn’s domestic investment in equipment, for purposes of subsection (A), becomes:
lUl
With respect to labor under subsection (B)s, the evidence shows Glycosyn employed
several scientists and corporate officers between 2015 and May 2018 to develop and improve
manufacturing methods of2‘-F L under the ‘O18 patent. with respect to both bacterium engineering
and fermentation procedures. (See CIB at 125-133; CXYODOZCat Q92»l22; CX-0089C.) A
Glycosyn witness identified, for each of these employees, “allocated amounts of salaries and
benefits per year [] based on the percentage of time each individual employee spent dedicated to
2’-FL“ in each ofthe years 2015 through May 2018. (CX-0003C at Q31-37 (citing CX-0089(1).)
That witness, Howard Newburg, explained that the allocation of time for the scientists, as reflected
in CX-0089C, was created by one of the scientists, Dr. John McCoy, whereas he generated the
allocation for corporate officers. (CX-0003C at Q32; see CIB at 130 (citing, inter cilia, CX-0002C
at Q93-94).) The document, CX-0089C. reflecting the allocations of time spent towards 2’-FL
showspercentagesof either- dependingon theemployee,priorto July2Ol7;and
percentagesof_ oi‘ dependingontheemployee,forJuly2017throughMay2018.
(CX-0089C at -74621-2.) The resulting claimed investment in labor directed to the development
oF2’~FL produced under the claims ofthe ’Ol8 patent is summarized in the below table:
i See FN 6.
H As described below, Glycosyn names a fourth category of expenses as “Research and
Development” and considers them as subsection (C) expenditures, rather than capital expenditures
under subsection (B). (See CIB at 132-133, 138-140.)
I02
The Staffagreeswiththis— figureas the amountin laborinvestmentattributableto
the ‘O18patent for purposes ofdomestic industry under subsection (B). {SIB at I20; SRB at 34.)
Jertrtewein’s dispute with respect to this investment in labor is three fold. First, Jenneweirt
criticizesGlycosynForfailingto breakoutlaborassociatedwith— to foreign
corporation FrieslandCampina. (See RIB at 140443.) Jcnncwein claims this assistance cannot be
counted for multiple, disparate, reasons: (l ) because it “rctlect[s] work done outside ofthe U.S..
(2) “because it has not established that FrieslandCarnpi1ta
is practicing any claims ofthe *018 patent”; and (3) because FrieslandCampina did not sufficiently
participate in discovery such that Glycosyn “[did not] request assistance from Fries1andCampina,
Glyeosyn carutot now rely on any activities related to FricslandCampina in support ofits domestic
industry.” {See id.) These arguments lack merit. That Glycosytfs research and development of
2'—FLproduction has some relation. or value, to FrieslandCarnpina does not take away from the
Factthat the investments occurred in the United States and have a connection to the ‘O18 patent.
Similarly, Jennewein cites no authority for discounting the labor costs of a domestic employee
when that employee temporarily travels overseas and does work in a foreign location. Such hyper
particularity is not consistent with Commission precedent. Stringed Insrruntenrs, lnv. No. 337
I03
TA-586, Comm’n Op. at 26 (“[a] precise accounting is not necessary; as most people do not
document their daily affairs in contemplation of possible litigation"). Even then, the record only
supportsfindingthatsuchphysically-overseas— wouldhavebeena fewdays
of labor. (See generefiy Hr’g Tr. at 60:18-61:1, 43:1-23, 50:7-5| :23; CX-0003C at Q13-21; CK
OUUZCat Q92-94, I20, 122.) Nonetheless, the Staffs “u.nderstand[ing oi] Mr. Ncwburg's
testimony to mean that hours worked outside the United States were not included in Glycosyn’s
economic prong calculations" (SRB at 36 (citing I-lr‘gTr. at 60: l l—6l:l)) is likely incorrect. CX
(JU39Cis a record of gross wages and benefits paid to Glycosyn employees. not hours worked.
(See CX-0089C at -74621-2.) Thus. unless employees who traveled and worked overseas were
compensated apart from these gross wages, that expense is included in Glycosyn’s economic prong
calculations. And the fact that Frieslandtlampina did not participate in discovery and may or may
not be practicing the ‘O18patent outside the United States is irrelevant.
Jenneweirfs second criticism of the claimed labor investment is that it improperly includes
general and administrative expenses. (RIB at 142 (citing Certain Clidfnittnr Bromide & Prods‘.
Containing Same, Inv. No. 337-TA-l I09, Order No. l I at 5-6 (July 25, 2018) (public version)
(“Clidirzitrm Bromide"); Certain Kinesiorherapy Devices & Components T!rere0j,' Inv. No. 337
TA-823, Comrn’n Op. at 29 n.S (June I7, 2013) (“Kinesior/rerapy Devices"), rev 'd on other
gr'0tmds,Le10, 736 F.3d 879).) To make the argument, however, Jennewein eonflates general and
administrative expenses in support of domestic engineering with the more commonly prohibited
sales and marketing expenses of an importer—and it is the latter which .Iennewein's cited caselaw
is concerned with. See, e.g., Ciidiniztm Bromide, lnv. No. 337-TA-llO9, Order No. ll at 5-6
(“Paying wholesalers to distribute pharmaceutical products is a cost oi‘ sale borne by
pharmaceutical manufacturers selling to those entities, regardless of whether or not the
l (J4
pharmaceutical is imported or rnade domestically. . . . [The] fees are nothing more than standard
U.S. expenses of a mere importer, which should not be considered in a domestic industry
analysis"). Even then, the Commission has shown latitude in including sales, marketing, or
general administrative investments when they are provided in support of other qualifying
activities:
ln the case at hand, P0pSockets is not relying solely on marketing and sales
expenditures to satisfy the economic prong. While PopSockcts has included
sales and marketing expenditures. it has also provided evidence of
significant expenditures in its employment of labor in other qualifying
activities, such as engineering, product development, product assembly,
supply chain and operation management, and customer service, as well as
capital expenditures for fixtures, furniture, software, and equipment used
for design. engineering, and operation management, which are sufficient to
establish the existence of a domestic industry under subsection (B).
Certmn Collapsible Sockets for Mobile Electronic Devices and Components Thereof; Inv. No.
337-TA-I056, Comm’n Op. at I9-20 (July 9, 2018) (public version).
Jennewein’s third criticism of the claimed labor investment is that Glycosyn’s allocation
percentage of time spend on 2’-FL is flawed and unreliable, pointing to testimony from Dr.
Merighi. an ex-employee of Glycosyn, where he explained that “he did not devote all of his time
to 2*-rr:* (RIB at 141 (citing I-lr’g Tr.
at 292:1-14).) Jennewein contrasts this with the record of CX-0089C, where 2 of Dr.
Merighi"s time is listed as spent on 2‘-FL. (CX-0089C at -74621.) Neither the Staffnor Glycosyn
addresses this discrepancy in their post-hearing briefs. (See CIB at 124-140; CRB at 64-68; S[B
at I I4-125; SRB at 33-39.) An expanded view ofthe testimony shows there many not necessarily
be a conflict. DrrMerighi states that at times he wouldhave been- focusedon 2’-FL or.
Q. Just a couple more questions. At Glycosyn you worked on projects other
than 2‘-FL, correct‘?
I05
A. Yes.
Q. So you didn’t spend 100 percent of your time working on 2‘~FL at
Glycosyn. correct‘?
A. If you did —ifthe time is —what is —the five, six years‘? No. But l had
like this big s rin sometime where it would be - percent of my week
was on2’-FL“
Q. And then other times you would he devoted to other projects‘?
A. Yes, yes. l think at this time if you look at my notebook, it would be
like a mix of —because we had to —we were supposed to keep the book in
a chronological order, so you will see how much time I was doing one thing
or the other. Just count the pages, because it’s pretty much in chronological
order.
(Hr’g Tr. at 292:]-19.) I therefore do not find this to be a reason to consider Glycosyrfs records
tlawedor unreliable,andI detemiinethat_ of laborinvestmentis attributableto the
’UI8 patent for purposes of domestic industry under subsection (B).
With respect to research and development under subsection (C), Glycosyn’s claimed
investment includes the aforementioned plant, equipment, and labor expenses“ in addition to a
fourth category of miscellaneous research and development expenses allegedly attributable to 23
FL development in the relevant time period of 2015 through May 2018. (CIB at 132-133, l3S~
I40.) A Glycosyn witness identified these expenses as: ( l ) “costs for the FDA’s GRAS assessment
ol'Glycosyn’s purified 2‘-FL for the U.S. market"; (2) “manufacturing run of a test batch of 2’-FL
(3) “lab supplies purchased for use
in Glycosyn’s R&D of 2’-FL”; (4) “software subscriptions For its laboratory facilities, for
Glycosytt scientists’ use in their research and development efforts”; and (5) domestic travel
Q For subsection (C) only, Glycosyn excludes its general and administrative labor costs.
I06
=XP¢nS~=S in “mhaical marketing *=t1°°fl$
— (cx-0003catQ61-65(citingcx-0091c;CX-0092C; cx-0093c;cx~0094c;ex
0O95C).) Of these, Glyeosyn’s witness applied the time allocation percentages derived from the
labor to only the software subscriptions, to accommodate any usage not attributable to 2‘-FL
development. (Id. at Q63.) The resulting amounts of these miscellaneous investments are
summarized in the below table:
Further, in light of subsection (_C)’srequirement that a complainant must show a nexus
between the research and development investment and the invention of the asserted patent. see,
e.g., Solid .S't‘a!eStorage Drives, lnv. No. 337-TA-1097, Comm’n Op. at I4, Glycosyn applied a
second allocation percentage “according to the proportion ofGlyoosyn‘s 2’-FL fermentation runs
of using 2’-FL strains that practice the patented technology, as opposed to other 2“-FL strains."
(CIB at 138.) A second Glyeosyn witness testilied that, based on a record of all fermentation runs
since August 2015: - ot“2‘-FL runs in 2015 were done with ‘O18 patent practicing bacteria
strains;— ot'2‘-FLrunsin2Ol6;- of2'-FLrunsin2017;and- of2’-FLrunsin
‘D The documents reflecting purchases of lab supplies, CX-0093-C through CXAOOQSC,are
limited to the years 2015, 2016, and 2017.
I O7
2018. (CX-0002C at Ql ll (citing CX-0131C‘); see CX-OOOZCat Q] 13.) Glycosyn further
removed the labor costs associated with its general and administrative officers. (CIB at I38.) The
resulting table of investments, for all categories Glycosyn alleges qualify Forsubsection (C), is as
lbllows:
The Stafffinds a — figureas the amountin researchand developmentinvestment
attributable to the ‘O18 patent for purposes of domestic industry under subsection (C). (SIB at
I22; see SRB at 34, 38.) ln reaching this amount, which is higher than Glyeosyn’s, I understand
the Staff either takes the position that general and administrative labor can be included or did not
observe that Glycosyn removed this item.
Here, .Iennewein’s dispute is a general assertion that “Glycosyn has failed to provide
Sufficient evidence on the extent ofany nexus between its investments and the ‘Ul S patent." (RIB
at 142 (citing 1m‘t=.gra.tea'Cr'rcz4irChips, Inv. No. 337-TA-S59, Comm’n Op. at 38 (Aug. 22, 2014)
(public version)).) Jennewein does not, however, acknowledge Glycosyn’s two-tier application of
a 2“~FL»rclatedallocation percentage (based on labor) and then a ‘O18patent-practicing allocation
“ See FN 6,
:03
percentage (based on termenter runs) to its investments. I find this two-step allocation is probative
of the value of investment related to the invention of the ‘O18patent; i.e., the required “nexus.”
Integrated Circuit Chips, Con-tm‘nOp. at 42 (holding domestic industry under subsection (c) can
ordinarily be infened from investment in a practicing [method] and “[r]equiring an extensive
inquiry as to the adequacy of nexus when it is not challenged on the merits by respondents would
unduly consume [1 time and resources . . . ."). Again, Jcnnewein does not appear to dispute
Glycosyn‘s claim of which strains. and thus which of its fermentation runs, practice the claims of
the ‘O18 patent.
I also find nexus based on the nature ofGlycosyn’s activities at its Massachusetts locations
as compared to the subject matter of the asserted claim limitations. Glycosyn‘s activities, such as
“all aspects of continued genetic engineering on our E. colt strains" and “improving the
fennentation process for our production strains” (CX-0002C at Q92) relate directly to claim
limitations, such as “providing an isolated E. coli bacterium comprising. (i) a deletion or functional
inactivation of an endogenous B-galactosidase gene,“ “culturing said bacterium in the presence of
lactose,” and “retrieving a fucosylated oligosaccharide form said bacterium or from a culture
supernatant of said bacterium" (‘O18patent at cl. l).
I therefore find the record supports Glycosyn‘s claimed investment amount in research and
development with a nexus to the claims ofthe ‘O13 patent, with certain exceptions. In the same
way that Software subscriptions were adjusted using the labor allocation percentages, and
equipment investment more reasonably should have been (‘discussed above), l find Glycosyn's
laboratory research and development supplies should be as well. Glycosytfs witness does not
sufficiently make clear that every item listed in the purchase records, CX-0093C through CK
DUQSC,was solely for 2’-FL development work (see CX-0093C at Q62‘),which is important given
I09
the clear recognitionthatonly. of scientists’time in 20]’?and] in 2018 was relatedto 2’
FL (see CIB at 130-131). When that allocation is applied, the record supports a research and
developmentinvestmentwitha nexusto theclaimsof the ’Ol8patentof_ as in the
below tables:
‘Z See FN 10.
1’ See FN 6.
llO
Finally, Jennewein makes an overall claim, seemingly against all of Glycosyrfs
investments, that “Glycosyn was no longer involved in that research at the time the Amended
Complaint was filed, and had already moved to other projects” such that “Glycosyn cannot rely on
R&D that was discontinued at the time of filing its Amended Complaint in support of domestic
industry.“ (RIB at 143.) Jcnnewcin contends “[p]ast expenditures may only be used to support a
domestic industry claim if the complainant ‘is continuing to make qualifying investments at the
time the complaint is filed.” (id. (citing Television Sets, Television Receivers, Tefei-isifonTuners,
and Comporients The:-eofi lnv. No. 337-TA-910, Comm'n Op. at 68 (Oct. 30. 2015) (“Television
Sets"); Marina, LLC v. Mr’! Trade Comm ’n, 716 F.3d 596, 601 n.6 (Fed. Cir. 20l3)).)
I do not agree. Jenneweitfs sole support for this alleged cessation of activity is a line from
a Glyeosyn witness’s deposition, which does not support the argument. (See R_lBat 143 (citing
.lX-0020C at 151:20-1523).) There, the witness testified, “Q. And for the second half 0f2018.
whatdo you expectwill be the allocationsof the employeesfor 2~FL-7 A. I think
there’s still, at least a (JX-0020C at
I51 :20-152:3.) l find additional evidence shows Glycosyn continues to make qualifying
investments in2‘-FL. Forexample, thesame witness testified th
“to continue the research in 2’-FL"
(1-lr’gTr. at 44:20-45: 13), and Glycosyrfs records show it continued with 2’-FL fermentation runs
throughout 2018 (see CX-OOOZCat Q1 13).
B. “Significant” or “Substantial”
The next step in the evaluation of domestic industry is to determine if the investment
amounts identified above are “significant,” as in subsections (A) and (B), or “substantial,” as in
subsection (C). The most recent precedential decision by the Court of Appeals For the Federal
lll
Circuit addressing this determination is Leia, which restated law applicable to a number of issues
surrounding the economic prong of domestic industry. See 786 F.3d at S83-85. In particular, the
Federal Circuit held that the statutory tenns ‘“significant’ and ‘substantial’ refer to an increase in
quantity, or to a benchmark in numbers” and “[a]n ‘investment in plant and equipment’ therefore
is characterized quantitatively, r'.e.,by the amount of money invested in the plant and equipment.“
Lela, 786 F.3d at 883. Continuing. the Federal Circuit held that: “[a]ll ofthe foregoing requires a
quantitative analysis in order to determine whether there is a ‘significant’ increase or attribution
by virtue of the claimant’s asserted commercial activity in the United States.” Id. In short.
“Qualitative factors cannot compensate for quantitative data that indicate insignificant investment
and employment." Id. at 885.
I find GIycosyn’s investments in plant, equipment. and labor are “significant.” Glyeosyn
conducts virtually all of its research and development in the United States, and has provided
records showingits foreignexpensesconstitutea de minimi.s- in travel costs. (CX-0003C
at Q64.) Whencomparedagainstthis- Glycosyn’sdomesticfacility,equipment,and labor
investment Of_ 2 ill facilities, - inequipment,_ in
labor) must provide a “‘significant’ increase or attribution" of value to its 2’-FL development
under the rubric set by Leia. 786 F.3d at 883. There is simply no other source but domestic activity
to credit.
Moreover, the record shows Glycosyn’s investment with respect to 2’-FL is significant
even unto itself. A Glycosyn witness testified, using profit and loss schedules, that its Company
wideoperatingexpensesovertherelevanttimeperiodtotal_ (CX-0003Cat Q67,68;
CX-0088C.)l havenotroubleconcludingGlycosyn’s_ inZFFLfacility,equipment,
and labor cost is a significant portion of this company-wide investment. For the same reasons, I
H2
concludeGlycosyn‘s— inresearchanddevelopmentcostswitha nexusto theclaims
of the ‘O18patent are "substantial."
Jennewein‘s dispute over significance. and substantiality, is mainly that “the roughly.
I Glycosyncontends it investedin a domestic industry for the ‘O18patent since 2015 pales
in comparisonto the— at least,investmentFrieslandCarnpinahas made for its 2’-FL
production facility-” (RIB at 141 (citing l-1r’gTr. at 46:13-16).) Vtfhilcthis may be true, I
disagree that this inter-company comparison is more indicative of significance (or lack thereof)
than, for example, a comparison of Glyc0syn’s domestic versus foreign expenditures. It is also
important to consider that the domestic industry article in question is not the 2’-FL which
Frics1andCampina will produce, but the 2’-FL produced by Glycosyn in the United States under
the methods of the ’018 patent. (See CIB at I5, 92 (citing CX-0059C; C-X-0131C; CX-0064C).)
It cannot be reasonably disputed that G1ycosyn’s investments have significantly contributed, in a
quantitative sense, to that production.
Jennewein also argues “[e]ven taken in their totality, the whole of Glycosyrfs investments
and employmentare _ Any investmentsand employmentthat would relate to
exploitationof the ‘O18patentare_ and Glycosynhas not offeredany contextfor
concluding that those investments would be ‘significant’ or “substantial,” (Id. at 144.) To the
contrary, - isnota trivialamountandGlycosyn offeredeachofthequantitative
contexts discussed above—oomparison to its company-wide operating expenses and comparison
lo foreign expenditures. (CIB at 135-136, 139-140.)
Accordingly, I find Glycosyn satisfies the economic prong of domestic industry under each
ofsubsections (A), (B), and (C).
113
VI. CONCLUSIONS OF LAW
l. The Commission has in rem jurisdiction over the Accused Product, 2‘-FL.
2. The importation or sale requirement of Section 33'? is satisfied.
3. Glycosyn has been shown to practice claims 1-3, 5, 8, 10-14, 18, 22, and 24-28 of
U.S. Patent No. 9,970,013.
4. Glycosyn has not been shown to practice claims 9 or 23 of the ‘O18patent.
5. The domestic industry requirement is satisfied with respect to the ’0l8 patent.
6. Jennewein directly infringes claims 1-3, 5, 8, 10, 12, 18, and 24-28 of the ‘O18
patent.
7. Jennewein does not infringe claim 23 of the ‘O18patent.
3. No claims ofthe ‘0lS patent have been shown to be invalid under 35 U.S.C. § 103.
9. No claims ofthe ‘O18patent have been shown to be invalid under 35 U.S.C. § 1I2.
I0. The ‘O18patent has not been shown to be unenforceable.
11. There is a violation of Section 337 with respect to the ’0l 8 patent.
VII. RECOMMENDED DETERMINATION ON REMEDY AND BOND
The Commission's Rules provide that subsequent to an initial determination on the
question of violation of section 337 of the Tariff Act of 1930, as amended, 19 U.S.C. § 1337, the
administrative law judge shall issue a recommended determination concerning the appropriate
remedy in the event that the Commission finds a violation of section 337, and the amount ofbond
to be posted by respondent during Presidential review of the Commission action under section
3375). See 19 C.F.R. § 210.-42(a)(l)(ii).
The Commission has broad discretion in selecting the form, scope, and extent of the
remedy in a section 337 proceeding. Viscofim, SA. v. In! '1 Trade Comm ’n, 787 F.2d 544, 543
(Fed. Cir. 1986). Under Section 337(d)(l), if the Commission determines as a result of an
investigation that there is a violation of section 337, the Commission is authorized to enter either
l 14
a limited or a general exclusion order. 19 U.S.C. § 133'?(d)(l). A limited exclusion order instructs
the U.S. Customs and Border Protection (“CBP”) to exclude from entry all articles that are covered
by the patent at issue and that originate from a named respondent in the investigation. A general
exclusion order instructs the CBP to exclude irom entry all articles that are covered by the patent
at issue, without regard to source. Certain Purple Protective Gloves, luv. No. 337-TA~5OD,
Com1n’n Op. at 5 (Dec. 22, 2004). Under section 337(t')(1), the Commission may issue a cease
and desist order in addition to, or instead of, an exclusion order. 19 U.S.C. § 1337(i)(1). The
Commission generally issues a cease and desist order directed to a domestic respondent when there
is a “commercially significant“ amount of infringing, imported product in the United States that
could be Sold, thereby undercutting the remedy provided by an exclusion order. See Certain
Crystoflirte Cejodroril Monoliydrote, lnv. No. 337-TA-293, USITC Pub. 2391, Cornm‘n Op. on
Remedy, the Public Interest and Bonding at 37-42 (June 1991); Certoin Coiiderisens,Parts Thereof
and Prods. Containing Some, IrichzdingAir Conditiorters for Automobiles, Inv. No. 337-TA-334
(Remand), Comm’n Op. at 26-23, 1997 WL 817767, at *1 1-12 (U.S.l.T.C. Sept. 10, 1997).
Additionally, during the 60-clay period of Presidential review under 19 U.S.C. § 1337(j),
“articles directed to be excluded from entry under subsection (d) . . . shall . . . be.entitled to entry
under bond prescribed by the Secretary in an amount determined by the Commission to be
sufficient to protect the complainant from any injury." See 19 U.S.C. § 133'/(i)(3). "The
Commission typically sets the bond based on the price differential between the imported infringing
product and the domestic industry article or based on a reasonable royalty. However, where the
available pricing or royalty information is inadequate, the bond may be set at one hundred ( IOU)
percent of the entered value of the infringing product." Certain Industrial Automation Systems
and Components Thereof Including Control Systems, Controllers, Visuotization Hardware,
I15
Motioit and Motor Control Systenis, Networking Equipment, SafetjvDevices, and Power Supplies,
lnv. No, 337-TA-1074, Comnftl Op. at 13 (Apr. 23, 2019) (“Azttomation .S:vsterns")(public
version) (citation omitted).
Section 337 also mandates consideration of the effect of exclusion on (1) public health and
welfare; (2) competitive conditions in the U.S. economy; (3) U.S. production of articles that are
like or directly competitive with the articles subject to the investigation; and (4) U.S. consumers.
19 U.S.C. § l337(d)(l). By publication in the Federal Register, the Commission has instructed
me “to take evidence or other inforrnation and hear arguments from the parties and other interested
persons with respect to the public interest in this investigation, as appropriate, and provide the
Commission with findings of fact and a recommended determination on this issue, which shall be
limited to the statutory public interest factors set forth in 19 U.S.C. 1337(_d)(1),(f)(1), (g)(1).” S3
Fed. Reg. 28.865 (June 21, 2018).
A. LIMITED EXCLUSION ORDER
Should a violation be found, Glycosyn seeks a limited exclusion order “against the subject
article, 2‘-FL.” (CIB at 147.) Glycosyn argues against any carve-out for 2'-FL made by any
particular strain number in light of a general reluctance from the Commission to identify model
numbers in exclusion orders (id. at 148 (citations omitted)) and the record evidence showing the
only strain Jennewein actually uses to create imported 2’-FL is its #1540 strain (id. (citing, inter
aha, RX-0337C at Q71, 75, 131-132; CX-0215C at 7)). The Staff agrees with Glycosyn here.
(SRB at 40-41.)
Similarly, Glycosyn argues against a certification provision based on its view that there is
no other strain “that docs not infringe the ‘O18Patent, that is sufficiently fixed in design (and with
regulatory approval) for sale to the United States market for foodst|1ffs.“ (Id. at 149 (citing Certain
116
Self-Cleaning Litter Boxes and Components Thereofl lnv. No. 337-TA-625, Cornm’n Op. at 59
[60] (Apr. 28, 2009_)).) Glycosyn also argues Jennewein is most likely incapable of so certifying.
(See CRB at 7 I-72.) If a certification is used, Glycosyn insists that Jennewein should nonetheless
be prohibited from importing 2’-FL for use in foodstuffs until “all necessary regulatory approval"
has been granted (id.), and that Glyeosyn should be afforded rights to audit Jennewein‘s production
facilities (id. at 151]). The Staff does not agree with the above proposals. [SRB at 41-42.)
Jennewein seeks a carve-out from a limited exclusion order for its TTFL12 strain for
reasons of non-infringement, as well as a certification provision. (RIB at 144-145.) Jenneweiri
argues that the process nature of the patent at issue, the ’0l8 patent, is not grounds to refuse a
certification provision. (Id. at 145 (citing Certain Salinornvciir Biomass & Prepmwtions
Containing Same Recommended Determination on Remedy & Bonding, Inv. No. 337-TA-370
(Dec. 13, 1995); Certain Acfd—Washed Denim Garments and Accessories, Including Jeans,
Jackets", Bogs and Skirts, lnv. No. 337—TA-324, Cornrn’n Op. at 22-23 (Aug. 14, 1992)).)
Jertnewein contends it is capable of providing such information. (Id. (citing Hr"g Tr. at 3148:10
2 1).) Jennewein also challenges G1ycosyn’s premise that any regulatory approval is needed at all
before 2’-FL from additional bacterial strains can be imported or sold (RRB at 71-74) and argues
the requested audit rights are inappropriate on a number of grounds (id. at 75).
As determined above, a violation of Section 337 has taken place, and 1 therefore
recommend to the Commission that a limited exclusion should issue according to statute. 19
U.S.C. § l337(d)( 1). As to those positions taken by Glycosyn on additional provisions for the
exclusion order, I do not agree. Glycosyn’s requested audit rights are without precedent and its
request for prohibitions on importation tmtil regulatory approvals have been met intrudes on the
Food and Drug AdIninistration’s authority—in addition to placing an inordinate burden on the
117
Commission. l do not recommend the Commission include either provision in any limited
exclusion order.
Certification presents a difficult question. The record evidence shows that 2‘-FL produced
by a first process is essentially indistinguishable from 2’-FL produced by another. (See, e.g., Hr‘g
Tr. at 350120-351:2: RX-0406C at Q60; CX-0002C at Ql2l; JX-0011 at l45:l5-I8 (“Q. Once
Jennewein’s 2’-FL is in powder form, is there any way to ~ to determine, using that powder, which
strain was used to produce that 2‘-FL? A. No.”).) As the ‘O18patent is strictly a method patent.
this creates two problems. First, there is no way for Customs and Border Patrol to discern on their
own whether Z‘-FL was rnadc by an infringing process or not. Second, there is likely no way for
Glyeosyn to ascertain for itself whether Jennewein violates any exclusion order from importation
records alone. (See CPB at 147-l48 (describing knowledge gained through GRAS submission).)
And Jennewcin’s ability to import 2‘-FL (or any “fucosylated oligosaccharidc”) made under a non
infringing process rnust be maintained as well.
Accordingly, l see some son of certification provision necessary, with certain heightened
requirements. l therefore recommend the Commission include a certification provision, wherein
said certification is required to state with particularity the grounds of non-infringement of the
imported oligosaccharide and be accompanied by sufficient corroborating evidence of the type
provided in discovery in this investigation.
B. BOND
Regarding bond during the presidential review period. the parties have stipulated to a 5%
bond on Jet1newein's 2’-FL during the 60-day-Presidential review period. (CIB at 150 (citing JX
D007);RIB at I45.) This is a reasonable amount to protect Glycosyn from hann during the review
H8
period. Accordingly, l recommend the Commission set a bond in the amount of 5% of entered
value.
C. PUBLIC INTEREST
Regarding the statutory public interest factors, Glycosyn contends there is no evidence of
any significant adverse effects from an exclusion order. (CIB at 140-147.) Regarding health and
welfare, Glycosyn argues “the evidence does not show that any of the infant formula products on
the make ed-av
— (CIBat 140-141 (citingHr’gTr.at26:23-22:21, 31:5-33121; ex-0001c
at Q37-50, 57-58; RX-0406C at Q86).) Thus, as oftoday, Glycosyn adds, .Iennewein’s 2’-FL “is
not essential to the health and safety of babies in the United States, or necessary for any important
public health or welfare need . . . (Id. at 141.) Regarding competitive conditions, Glycosyn
notes that “infant formula supplemented with 2‘-FL [1was introduced to the market only recently"
(id. at 143 (citing, inter ufia, JX-0010C at 30:1-23 (“It is very difficult to make any forecasts at
this early stage about possible sales figures because it’s a completely new product.”))) and ofthe
many infant formula products available, only a few contain small amounts of 2‘-FL (see id. at I43
I44). Glycosyn also identifies “numerous alternative, non-infringing 2'-FL producers that can step
in and replace the excluded products, such as GlycosynfFrieslandCampina. DuPont/Inbiose.
Glycorn, and eventually, BASF.” (Id. at I46.) The Staff agrees with Glycosyn on these points.
(SIB at 127-134.)
Jennewein emphasizes 2’-FL‘s “critical role[]" in infant development and the benefits of
including it in infant formula, keeping in mind that Jennewein was the first and is the only company
selling 2‘-FL in the U.S. (RIB at I36-137 (citing RX-0358C at Q188).) Jennewein asserts that
“Glycosyn makes no competitive products that could replace .Iennewein’s 2‘-FL if it were
I19
excluded from the US" lid. at 137 (citing, inter cilia, Hr’g Tr. at 57:1-4, 57:22-5813)), and
“Glycosyn provided no evidence that alternate suppliers can replace Jeru1ewein‘s 2‘-FL in a
commercially reasonable time or in sufficient quantities" (id. at 138).
Based on the record, I do not find the requested limited exclusion order would meaningfully
impact public health and welfare, competitive conditions, domestic production of articles, or U.S.
consumers. While it is clear that the purpose of providing 2’-FL in infant formula is to improve
public health, the evidence shows that the otherwise well-established market has only recently
begun including 2’-FL into its products, The
U.S. public is therefore not dependent on such products, as ofyet. Moreover, assuming Jennewein
is the only supplier of 2‘-FL to the U.S. market, then all infant formula manufacturers or vendors
in the U.S. will be affected cqually—along with the consumers who purchase those formula
products. To the extent these entities wish to continue using 2‘-FL in their formula, the Staff, in
particular, has persuasively shown that the demand can be met by competitors. (See SIB at I29
l3l (citing, infer cilia. RX-0327C at 25; CX-0009; CX-OOIl), 132; SRB at 43-44.)
Accordingly, it is my recommended determination that issuance of a remedial order in this
investigation would not be contrary to the public interest.
I20
VIII. INITIAL DETERMINATION AND ORDER
Based on the foregoing, Mit is my Initial Determination that there is a violation of Section
337 ofthe Taritt‘ Act of 1930, as amended, I9 U.S.C. § 1337, in the importation into the United
States, the sale for importation, or the sale within the United States after importation of certain
human milk oligosaccharides and methods of producing the same, in connection with the asserted
claims ofU.S. Patent No. 9,970,018.
Fnrthefinore, it is my determination that a domestic industry in the United States exists that
practices or exploits the asserted patent.
The undersigned hereby certifies to the Commission this lnitial Detennmation, together
with the Record of the hearing in this investigation consisting of the following: the transcript of
the evidentiary hearing, with appropriate corrections as may hereafter be ordered; and the exhibits
accepted into evidence in this investigation as listed in the appendices hereto. '5
Pursuant to I9 C.F.R. § 2l0.42(h), this Initial Determination shall become the
determination of the Commission unless a party files a petition for review pursuant to 19 C.F.R.
§ 2 l0.43(a) or the Commission, pursuant to 19 C.F.R. § 210.44, orders on its own motion a review
of the Initial Determination or certain issues therein.
H The failure to discuss any matter raised by the parties or any portion of the Record herein
does not indicate that said matter was not considered. Rather, any such rnalter(s) or portion(s) of
the Record has/have been determined to be irrelevant, immaterial or meritless. Arguments made
on brief which were otherwise unsupported by Record evidence or legal precedent have been
accorded no weight.
'5 The pleadings of the parties filed with the Secretary need not be certified as they are already
in the C‘ornmission’spossession in accordance with Commission rules.
I2l
Confidentialig Notice:
This [nitial Determination is being issued as confidential, and a public version will be
issued pursuant to Commission Rule 2lO.5(f). Within seven (7) days of the date of this [nitial
Determination, the parties shall jointly submit; (1) a proposed public version of this opinion with
any proposed rcdactions bracketed in red; and (2) a written justification for any proposed
redactions specifically explaining why the piece of information sought to be redacted is
confidential and why disclosure of the information would be likely to cause substantial hami or
likely to have the effect of impairing the Commissioifs ability to obtain such information as is
necessary to perform its statutory functions.“
SO ORDERED.
1?;
. L_
D//U
tamcron Elliot V if if C
Administrative Law Judge
5° Under Commission Rules 210.5 and 20l.6(a)_.confidential business information includes:
information which concerns or relates to the trade secrets, processes, operations, style of works, or
apparatus, or to the production, sales, shipments, purchases, transfers, identification of customers,
inventories, or amount or source of any income, profits, losses, or expenditures of any person,
firm, partnership, corporation, or other organization, or other infomiation of commercial value, the
disclosure of which is likely to have the effect of either impairing the Commission's ability to
obtain such information as is necessary to perform its statutory functions, or causing substantial
harm to the competitive position of the person, firm, partnership, corporation. or other organization
from which the information was obtained, unless the Commission is required by law to disclose
such information. See 19 C-.F.R,§ 20l.6(a). Thus, to constitute confidential business information
the disclosure of the infomiation sought to be designated confidential must likely have the effect
of either: (I) impairing the Commission’s ability to obtain such infomiation as is necessary to
perform its statutory functions; or (2) causing substantial harm to the competitive position of the
person, firm, partnership, corporation, or other organization from which the information was
obtained.
122
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND
METHODS OF PRODUCING THE SAME
INV. NO. 337-TA-1120
PUBLIC CERTIFICATE OF SERVICE
l, Lisa R. Barton, hereby certify that the attached INITIAL DETERMINATION has been
served by hand upon the Commission Investigative Attorney, Lisa Murray, Esq. and the
following parties as indicated, on
UET B 3 2919 .
Lisa R. Bartdn, Secretary O
U.S. lntemational Trade Commission
500 E Street SW, Room 112A
Washington, D.C. 20436
FOR COMPLAINANT GLYCOSYN LLC
Michael C. Newman, Esq. ( ) Via Hand Delivery
MINTZ LEVIN COHN FERRIS GLOVSKY ( /5 ExpressDelivery
AND POPEO PC y( ) Via First Class Mail
One Financial Center ( ) Other;
Boston, MA. 02111
FOR RESPONDENT .]ENNEWEIN BIOTECHNOLOGIE GmbH
Gary M. Hnath, Esq. Via Hand Delivery
MAYER BROWN, LLP Express Delivery
1999 K Street, NW Via First Class Mail
Washington, DC 20006 Other:
UNITED STATES INTERNATIONAL TRADE COMMISSION
Washington, D.C.
In the Matter of
CERTAIN HUMAN MILK
OLIGOSACCHARIDES AND METHODS
OF PRODUCING THE SAME
Inv. No. 337-TA-1120
ORDER NO. 22: CONSTRUING THE TERMS OF THE ASSERTED CLAIMS OF
THE PATENTS AT ISSUE
(December 18, 2018)
TABLE OF CONTENTS
I. INTRODUCTION ................................................................................................................. 1
IL IN GENERAL ........................................................................................................................ 1
III. RELEVANT LAW ................................................................................................................2
IV. LEVEL OF ORDINARY SKILL .......................................................................................... 6
V. THE ASSERTED PATENTS ................................................................................................ 7
A. The '230 Patent ..........................................................................................................7
B. The '018 Patent .......................................................................................................... 9
VI. CLAIM CONSTRUCTION ................................................................................................. 12
A. Construction of the Agreed-Upon Claim Terms ...................................................... 12
B. Construction of the Disputed Claim Terms ............................................................. 13
1. "P-galactosidase activity comprises between 0.05 and [200 units I 5 units I 4
units/ 3 units/ 2 units]" ............................................................................... 13
2. "functional . . . p-galactosidase gene" ......................................................... 23
3. "wild type" ................................................................................................... 29
I. INTRODUCTION
This Investigation was instituted by the Commission on June 21, 2018 to determine whether
certain human milk oligosaccharides and methods of producing the same infringe U.S. Patent Nos.
9,453,230 (the "'230 patent") and 9,970,018 (the '"018 patent"). See 83 Fed. Reg. 28865-6 (June
21, 2018). The Complainant is Glycosyn LLC ("Glycosyn"). The Respondent is Jennewein
Biotechnologie GmbH ("Jennewein") (altogether, ''the Parties").
Pursuant to Ground Rule 8, a Markman hearing was held October 16, 2018 regarding the
interpretation of the certain terms of the patents at issue. Prior to the hearing, the Parties and the
Commission Investigative Staff ("Staff') filed initial and amended joint claim construction charts
setting forth a limited set of terms to be construed. The Parties and the Staff also filed initial and
reply claim construction briefs, wherein each party offered its construction for the claim terms in
dispute, along with support for its proposed interpretation. 1 At the beginning of the hearing, the
Parties indicated one of the claim terms in dispute, "promotor-less," would not construction due to
withdrawal of the relevant claims by Glycosyn. See Hr'g Tr. at 4:13-5:3.
Il. IN GENERAL
The claim terms construed in this Order are done so for the purposes of this section 337
Investigation. Those terms not in dispute need not be construed. See Vanderlande Indus. Nederland
1 For convenience, the briefs and amended chart submitted by the Parties are referred to hereafter
as:
CIMB Comolainant's Initial Markman Brief
CRMB Comolainant's Reply Markman Brief
RIMB Respondents' Initial Markman Brief
Resoondents' Reply Markman Brief
SIMB Staffs Initial Markman Brief
SRMB Staffs Reply Markman Brief
JC Amended Joint Claim Construction Chart
Hr'g Tr. Markman hearing transcript
BV v. Int 'l Trade Comm 'n, 366 F.3d 1311, 1323 (Fed. Cir. 2004) (noting that the administrative law
judge need only construe disputed claim terms).
ID. RELEVANT LAW
"An infringement analysis entails two steps. The first step is determining the meaning and
scope of the patent claims asserted to be infringed. The second step is comparing the properly
construed claims to the device accused of infringing." Markman v. Westview Instruments, Inc., 52
F.3d 967, 976 (Fed. Cir. 1995) (en bane) (internal citations omitted), affd, 517 U.S. 370 (1996).
Claim construction is a "matter of law exclusively for the court." Id. at 970-71. "The construction
of claims is simply a way of elaborating the normally terse claim language in order to understand
and explain, but not to change, the scope of the claims." Embrex, Inc. v. Serv. Eng'g Corp., 216
F.3d 1343, 1347 (Fed. Cir. 2000).
Claim construction focuses on the intrinsic evidence, which consists of the claims
themselves, the specification, and the prosecution history. See Phillips v. AWH Corp., 415 F.3d
1303, 1314 (Fed. Cir. 2005) (en bane); see also Markman, 52 F.3d at 979. As the Federal Circuit
in Phillips explained, courts must analyze each of these components to determine the "ordinary and
customary meaning of a claim term" as understood by a person of ordinary skill in art at the time of
the invention. 415 F.3d at 1313. "Such intrinsic evidence is the most significant source of the
legally operative meaning of disputed claim language." Bell All. Network Servs. , Inc. v. Covad
Commc'ns Grp., Inc., 262 F.3d 1258, 1267 (Fed. Cir. 2001).
"It is a 'bedrock principle' of patent law that 'the claims of a patent define the invention to
which the patentee is entitled the right to exclude."' Phillips, 415 F.3d at 1312 (quotinglnnova/Pure
Water, Inc. v. Safari Water Filtration Sys. , Inc., 381 F.3d 1111, 1115 (Fed. Cir. 2004)). "Quite apart
from the written description and the prosecution history, the claims themselves provide substantial
guidance as to the meaning of particular claims terms." Id. at 1314; see also Interactive Gift
2
Express, Inc. v. Compuserve Inc., 256 F.3d 1323, 1331 (Fed. Cir. 2001) ("In construing claims,the
analytical focus must begin and remain centered on the language of the claims themselves, for it is
that language that the patentee chose to use to 'particularly point [] out and distinctly claim [] the
subject matter which the patentee regards as his invention."). The context in which a term is used
in an asserted claim can be "highly instructive." Phillips, 415 F.3d at 1314. Additionally, other
claims in the same patent, asserted or unasserted, may also provide guidance as to the meaning of a
claim term. Id. "Courts do not rewrite claims; instead, we give effect to the terms chosen by the
patentee." K-2 Corp. v. Salomon SA., 191 F.3d 1356, 1364 (Fed. Cir. 1999).
The specification "is always highly relevant to the claim construction analysis. Usually it is
dispositive; it is the single best guide to the meaning of a disputed term." Id. at 1315 (quoting
Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996)). "[T]he specification
may reveal a special definition given to a claim term by the patentee that differs from the meaning
it would otherwise possess. In such cases, the inventor's lexicography governs." Id. at 1316. "In
other cases, the specification may reveal an intentional disclaimer, or disavowal,of claim scope by
the inventor." Id. As a general rule, however, the particular examples or embodiments discussed
in the specification are not to be read into the claims as limitations. Id. at 1323. In the end,"[t]he
construction that stays true to the claim language and most naturally aligns with the patent's
description of the invention will be ... the correct construction." Id. at 1316 (quoting Renishaw PLC
v. Marposs Societa' per Azioni, 158 F.3d 1243, 1250 (Fed. Cir. 1998)).
In addition to the claims and the specification, the prosecution history should be examined,
ifin evidence. Id. at 1317; see Liebel-Flarsheim Co. v. Medrad, Inc., 358 F.3d 898,913 (Fed. Cir.
2004). The prosecution history can "often inform the meaning of the claim language by
demonstrating how the inventor understood the invention and whether the inventor limited the
invention in the course of prosecution, making the claim scope narrower than it would otherwise
3
be." Phillips, 415 F.3d at 1317; see Chimie v. PPG Indus. Inc. , 402 F.3d 1371, 1384 (Fed. Cir.
2005) ("The purpose of consulting the prosecution history in construing a claim is to exclude any
interpretation that was disclaimed during prosecution.").
When the intrinsic evidence does not establish the meaning of a claim, then extrinsic
evidence (i.e.,all evidence external to the patent and the prosecution history, including dictionaries,
inventor testimony, expert testimony, and learned treatises) may be considered. Phillips, 415 F.3d
at 1317. Extrinsic evidence is generally viewed as less reliable than the patent itself and its
prosecution history in determining how to define claim terms. Id. "The court may receive extrinsic
evidence to educate itself about the invention and the relevant technology,but the court may not use
extrinsic evidence to arrive at a claim construction that is clearly at odds with the construction
mandated by the intrinsic evidence." Elkay Mfg. Co. v. Ebco Mfg. Co., 192 F .3d 973,977 (Fed. Cir.
1999).
If, after a review of the intrinsic and extrinsic evidence, a claim term remains ambiguous,
the claim should be construed so as to maintain its validity. Phillips, 415 F.3d at 1327. Claims,
however,cannot be judicially rewritten in order to fulfill the axiom of preserving their validity. See
Rhine v. Casio, Inc., 183 F.3d 1342, 1345 (Fed. Cir. 1999). Thus,"if the only claim construction
that is consistent with the claim's language and the written description renders the claim invalid,
then the axiom does not apply and the claim is simply invalid." Id.
The construction of a claim term is generally guided by its ordinary meaning. However,
courts may deviate from the ordinary meaning when: (1) "the intrinsic evidence shows that the
patentee distinguished that term from prior art on the basis of a particular embodiment, expressly
disclaimed subject matter, or described a particular embodiment as important to the invention;" or
(2) "the patentee acted as his own lexicographer and clearly set forth a definition of the disputed
claim term in either the specification or prosecution history." Edwards Lifesciences LLC v. Cook
4
Inc., 582 F.3d 1322, 1329 (Fed. Cir. 2009); see also GE Lighting Sols., LLC v. AgiLight, Inc., 750
F.3d 1304, 1309 (Fed. Cir. 2014) ("the specification and prosecution history only compel departure
from the plain meaning in two instances: lexicography and disavowal."); Omega Eng'g, Inc, v.
Raytek Corp., 334 F.3d 1314, 1324 (Fed. Cir. 2003) ("[W]here the patentee has unequivocally
disavowed a certain meaning to obtain his patent, the doctrine of prosecution disclaimer attaches
and narrows the ordinary meaning of the claim congruent with the scope of the surrender."); Rheox,
Inc. v. Entact, Inc., 276 F.3d 1319, 1325 (Fed. Cir. 2002) ("The prosecution history limits the
interpretation of claim terms so as to exclude any interpretation that was disclaimed during
prosecution."). Nevertheless, there is a "heavy presumption that a claim term carries its ordinary
and customary meaning." CCS Fitness, Inc. v. Brunswick Corp., 288 F.3d 1359, 1366 (Fed. Cir.
2002) (citations omitted). The standard for deviating from the plain and ordinary meaning is
"exacting" and requires "a clear and unmistakable disclaimer." Thorner v. Sony Computer Entm 't
Am. LLC, 669 F.3d 1362, 1366-67 (Fed. Cir. 2012); see Epistar Corp. v. Int'/ Trade Comm 'n, 566
F.3d 1321, 1334 (Fed. Cir. 2009) (requiring "expressions of manifest exclusion or restriction,
representing a clear disavowal of claim scope" to deviate from the ordinary meaning) ( citation
omitted). As the Federal Circuit has explained, "[w]e do not read limitations from the specification
into claims; we do not redefine words. Only the patentee can do that." Thorner, 669 F.3d at 1366.
A claim must also be definite. Pursuant to 35 U.S.C. § 112, second paragraph: "The
specification shall conclude with one or more claims particularly pointing out and distinctly
claiming the subject matter which the applicant regards as his invention." 35 U.S.C.§ 112, � 2. In
Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120 (2014), the Supreme Court held that§
112, � 2 requires "that a patent's claims, viewed in light of the specification and prosecution history
inform those skilled in the art about the scope of the invention with reasonable certainty." Id. at
2129. A claim is required to "provide objective boundaries for those of skill in the art," and a claim
5
term is indefinite if it "might mean several different things and no informed and confident choice is
among the contending definitions." Interval Licensing LLC v. AOL, Inc. , 766 F.3d 1364, 1371 (Fed.
Cir. 2014). A patent claim that is indefinite is invalid 35 U.S.C.§ 282(b)(3)(A).
Courts are not required to construe every claim limitation of an asserted patent. See 02
Micro Intern. Ltd. v. Beyond Innovation Technology Co., 521 F.3d 1351, 1362 (Fed. Cir. 2008)
(citations omitted). Rather, "claim construction is a matter of resolution of disputed meanings and
technical scope, to clarify and when necessary to explain what the patentee covered by the claims,
for use in the determination of infringement." Id. at 1362 (quoting U.S. Surgical Corp. v. Ethicon,
Inc., 103 F.3d 1554, 1568 (Fed. Cir. 1997)); see also Embrex, 216 F.3d at 1347 ("The construction
of claims is simply a way of elaborating the normally terse claim language in order to understand
and explain, but not to change, the scope of the claims.") (citation omitted). In addition, "[a)
determination that a claim term 'needs no construction' or has the 'plain and ordinary meaning' may
be inadequate when a term has more than one 'ordinary' meaning or when reliance on a term's
'ordinary' meaning does not resolve the parties' dispute." 02 Micro, 521 F.3d at 1361. Claim
construction, however, is not an "obligatory exercise in redundancy." U.S. Surgical Corp., 103 F.3d
at 1568. "[M]erely rephrasing or paraphrasing the plain language of a claim by substituting
synonyms does not represent genuine claim construction." C.R. Bard, Inc. v. U.S. Surgical Corp.,
388 F.3d 858, 863 (Fed. Cir. 2004).
IV. LEVEL OF ORDINARY SKILL
In its opening brief, Glycosyn contends, for both asserted patents:
[A] person of ordinary skill in the art for the purposes of this case
would typically have a Ph.D in molecular biology, biochemistry, or
chemical engineering, or an equivalent field, and 1-2 years of
experience working with E. coli bacteria or related systems. Or such
a person could have a lower level degree (e.g., a M.A.) in a slmila.r
field to those listed above, but a greater amount of .relevant working
6
experience ( e.g., 5-6 years of experience working with £. Coli bacteria
or related systems).
(CIMB at 17 (citing CIMB, Ex. 4 at ,r 24).)
In its opening brief, Jennewein contends, for both asserted patents:
(RlMB at 14.)
[T]he person of ordinary skill in the field of the Asserted Patents is a
person having a Ph.D. in molecular biology, biochemistry, biological
or chemical engineering, or an equivalent field, and 1-2 years of
experience working with E. coli bacteria or related systems. Or a
person having a lower level degree (e.g., a M.A.) in a similar field to
those listed above, but a greater amount of relevant working
experience ( e.g., 5-6 years of experience working with E. Coli
bacteria or related systems).
These proposed levels of skill are nearly identical, and the Staff indicates agreement with
them. (SIMB at 9.) Accordingly, the undersigned finds that one of ordinary skill in the art would
have (1) a Ph.D in molecular biology, biochemistry, or chemical engineering, or an equivalent field,
and 1-2 years of experience working with E. coli bacteria or related systems, or (2) a lower level
degree (e.g., a M.A.) in a similar field to those listed above, but a greater amount ofrelevant working
experience (e.g., 5-6 years of experience working with E. coli bacteria or related systems).
V. THE ASSERTED PATENTS
A. The '230 Patent
The '230 patent, entitled "Biosynthesis of Human Milk Oligosaccharides in Engineered
Bacteria," issued on September 27, 2016 to Massimo Merighi, John M. McCoy, and Matthew Ian
Heidtman. The '230 patent is assigned on its face to Glycosyn LLC. The '230 patent generally
relates to "compositions and methods for producing purified oligosaccharides, in particular certain
fucosylated and/or sialylated oligosaccharides that are typically found in human milk." ('230 patent
at Abstract.) In particular:
The method for producing a fucosylated oligosaccharide in a
bacterium comprises the following steps: providing a bacterium that
7
comprises a functional p-galactosidase gene, an exogenous
fucosyltransferase gene, a GDP-fucose synthesis pathway, and a
functional lactose permease gene; culturing the bacterium in the
presence of lactose; and retrieving a fucosylated oligosaccharide from
the bacterium or from a culture supernatant of the bacterium.
(Id. at I :48-55.)
The '230 patent has 40 claims. As of the date of this order, claims 2 1 , 22, 27, 32, 34-38 are
asserted in this Investigation. The asserted claims read as follows (with the first instance of the
agreed-upon terms in italics and the first instance of the disputed terms highlighted in bold):
2 1 . A method for producing a fucosylated oligosaccharide in a bacterium, comprising
providing an E. coli bacterium, said bacterium comprising a deletion or functional
inactivation of the endogenous p-galactosidase gene; a functional exogenous wild type P
galactosidase gene inserted into an endogenous gene such that the resultant bacterium
comprises a low level of p-galactosidase activity, wherein said p-galactosidase activity
comprises between 0.05 and 200 units; an exogenous lactose-accepting fucosyltransferase
gene comprising an a.(1,2) fucosyltransferase gene, an a.(1,3) fucosyltransferase gene, or an
a.(1 ,4) fucosyltransferase gene; an inactivating mutation in an endogenous colanic acid
synthesis gene, wherein said colanic acid synthesis gene comprises an E. coli wcaJ, wzxC,
wcaD, wza, wzb, or wzc gene; and a functional lactose permease gene, wherein said lactose
permease gene comprises E. coli lacY; culturing said bacterium in the presence of lactose;
and retrieving a fucosylated oligosaccharide from said bacterium or from a culture
supernatant of said bacterium.
22. The method of claim 21, wherein said P-galactosidase gene inserted into an endogenous gene
comprises an E. coli lacZ gene.
8
27. The method of claim 21, wherein said bacterium accumulates an increased intracellular
lactose pool, wherein said increased intracellular lactose pool is at least 10% more than the
levels in a wild type bacterium.
32. The method of claim 21, wherein said lactose permease gene is an exogenous lactose
permease gene.
34. The method of claim 21, wherein said fucosylated oligosaccharide is 2'-fucosyllactose, 3-
fucosyllactose, or lactodifucotetraose.
35. The method of claim 21, wherein said low level of P-galactosidase activity comprises
between 0.05 and 5 units.
36. The method of claim 21, wherein said low level of P-galactosidase activity comprises
between 0.05 and 4 units.
3 7. The method of claim 21, wherein said low level of p-galactosidase activity comprises
between 0.05 and 3 units.
3 8. The method of claim 21, wherein said low level of �-galactosidase activity comprises
between 0.05 and 2 units.
B. The '018 Patent
The '018 patent, entitled "Biosynthesis of Human Mille Oligosaccharides in Engineered
Bacteria," issued on May 15, 2018 to Massimo Merighi, John M. McCoy, and Matthew Ian
Heidtman. The '018 patent is assigned on its face to Glycosyn LLC, and recorded as a continuation
of continuation of a divisional application from the application which became the '230 patent.
The '018 patent generally relates to "compositions and methods for engineering bacteria to produce
fucosylated oligosaccharides, and the use thereof in the prevention or treatment of infection." ('O 18
patent at Abstract.) In particular:
9
The method for producing a fucosylated oligosaccharide in a
bacterium comprises the following steps: providing a bacterium that
comprises a functional p-galactosidase gene, an exogenous
fucosyltransferase gene, a GDP-fucose synthesis pathway, and a
functional lactose perrnease gene; culturing the bacterium in the
presence oflactose; and retrieving a fucosylated oligosaccharide from
the bacterium or from a culture supernatant of the bacterium.
(Id. at 1:53-60.)
The '018 patent has 28 claims. As of the date of this order, claims 1-5, 8, 10, 12, 18, 20, 21,
23-28 are asserted in this Investigation. The asserted claims read as follows (with the first instance
of the agreed-upon terms in italics and the first instance of the disputed terms highlighted in bold):
1. A method for producing a fucosylated oligosaccharide in a bacterium, comprising providing
an isolated E. coli bacterium comprising, (i) a deletion or functional inactivation of an
endogenous p-galactosidase gene; (ii) an exogenous functional P-galactosidase gene
comprising a detectable level of p-galactosidase activity that is reduced compared to that of
a wild-type E. coli bacterium, wherein the level of (i-galactosidase activity comprises
between 0.05 and 200 units; (iii) an inactivating mutation in a colanic acid synthesis gene;
and (iv) an exogenous lactose-accepting fucosyltransferase gene; culturing said bacterium
in the presence oflactose; and retrieving a fucosylated oligosaccharide from said bacterium
or from a culture supernatant of said bacterium.
2. The method of claim 1, wherein said colanic acid synthesis gene comprises an E. coli wcaJ,
wzxC, wcaD, wza, wzb, or wzc gene.
3. The method of claim 2, wherein said colanic acid synthesis gene comprises a wcaJ gene.
4. The method of claim 1, wherein the bacterium comprises an increased intracellular
guanosine diphosphate (GDP)-fucose level, wherein the increased intracellular GDP-fucose
level is at least 10% more than the level of GDP-fucose in a wild-type bacterium.
10
5. The method of claim 1, wherein said exogenous lactose-accepting fucosyltransferase gene
encodes a.(1,2) fucosyltransferase and/or a(l ,3) fucosyltransferase.
8. The method of claim 1, wherein said exogenous functional �-galactosidase gene comprises
an E. coli lacZ gene.
10. The method of claim 1, wherein said bacterium further comprises a functional lactose
permease gene.
12. The method of claim 10, wherein said lactose permease gene comprises an E. coli lacY gene.
18. The method of claim 1, wherein the level of p-galactosidase activity comprises between
0.05 and 5 units.
20. The method of claim 1, wherein said bacterium comprises an increased intracellular lactose
level, wherein the increased intracellular lactose level is at least 10% more than the level in
a wild-type bacterium.
21. The method of claim 1, wherein said exogenous functional p-galactosidase gene is an E.
coli lacZ gene lacking an operably linked promoter, and said colanic acid synthesis gene
comprises an E. coli weal, wzxC, wcaD, wza, wzb, or wzc gene.
23. The method of claim 1, wherein said exogenous functional p-galactosidase gene is inserted
into an endogenous gene.
24. The method of claim I , wherein said exogenous functional p-galactosidase gene comprises
a recombinant �-galactosidase gene engineered to produce a detectable level of �
galactosidase activity that is reduced compared to the level of �-galactosidase activity in a
wild-type E. coli bacterium.
25. The method of claim 24, wherein the level of p-galactosidase activity comprises between
0.05 and 5 units.
11
26. The method of claim 1, wherein the level of fl-galactosidase activity comprises between
0.05 and 4 units.
27. The method of claim 1, wherein the level of fl-galactosidase activity comprises between
0.05 and 3 units.
28. The method of claim 1, wherein the level of fl-galactosidase activity comprises between
0.05 and 2 units.
VI. CLAIM CONSTRUCTION
A. Construction of the Agreed-Upon Claim Terms
Prior to the Markman hearing, the Parties reached agreement regarding the construction of
five terms:
Claim Term
"providing"
"in the presence of lactose"
"exogeneous"
"colonic acid synthesis gene"
Relevant Claims
'230 patent claim 2 1
'018 patent claim 1
'230 patent claim 21
'018 patent claim 1
'230 patent claims 21, 32
'018 patent claims 1, 5, 8, 21,
23, 24
'230 patent claim 21
'018 patent claims 1-3, 2 1
12
Agreed Construction
A) plain and ordinary
meaning:
plain and ordinary meaning,
i.e., furnishing, supplying,
making available, or
preparing.
A) plain and ordinary
meaning:
plain and ordinary meaning,
i.e., lactose is available to the
bacterium
A) plain and ordinary
meaning:
plain and ordinary meaning,
i.e., originating outside an
organism, tissue, or cell
(BJ patentee as lexicographer:
By 'colanic acid synthesis
gene' is meant a gene
involved in a sequence of
reactions,
usually controlled and
catalyzed by enzymes that
result Ill the synthesis of
colanic acid.
"E. coli lacZ gene" '230 patent claim 22 A) plain and ordinary
meaning:
'01 8 patent claims 8, 21
plain and ordinary meaning,
i.e., a structural gene that
encodes the �-galactosidase
protein and is part of the lac
operon in the DNA of E. coli
(JC at 4.)
B. Construction of the Disputed Claim Terms
1. "P-galactosidase activity comprises between 0.05 and (200 units / 5 units / 4
units / 3 units / 2 units]"
The Parties disagree on the proper claim construction and have proposed the following
constructions:
Relevant Glycosyn Jennewein Staff
Claims
'230 patent (B) patentee as INDEFINITE: (B) patentee as
claims lexicographer: This term is not lexicographer &
2 1 , 35-38 �-galactosidase activity amenable to (C) disavowal of scope
IS defmition with �-galactosidase activity
'018 patent measurable at between reasonable is
claims 1, exactly 0.05 and exactly certainty to one of measurable at between
18, 25-28 [200/5/4/3/2] Miller ordinary exactly 0.05 and exactly
Units, skill in the art, and is [200/5/4/3/2] Miller
as defined in Miller, therefore indefinite under Units,
J.H., 35 U.S.C. 1 1 2. as defined in Miller,
Experiments in In the alternative, to the J.H.,
Molecular extent that the Experiments in
Genetics (Cold Spring Commission Molecular
Harbor Lab. 1 972) at finds the term is not Genetics (Cold Spring
352-355 indefinite and requires Harbor Lab. 1 972) at
construction, Respondent 352-355
proposes the following
construction:
(A) plain and ordinary
meaning;
(B) patentee as
lexicoJ!rapher &
1 3
(CJ disavowal ofscope
"�-galactosidase activity
between exactly 0.05 and
exactly [200 units/5
units/ 4
units/3 units/2 units] at
substantially all times
during culturing of the
bacterium and retrieval
of
the fucosylated
oligosaccharide, when
measured according to
the
assay procedures
described
in J.H. Miller,
"Experiment
48," Experiments in
Molecular Genetics,
Cold
Spring Harbor, NY
(1972)
352-355."
(JC at 2-3.)
In its opening brief, Glycosyn argues this term is not indefinite. (CIMB at 1 8.) Glycosyn
explains that "P-galactosidase is an enzyme that catalyzes the cleavage of �-galactosidase (i.e.,
sugars such as lactose) into two parts" and is well-known in the art. (Id. (citing Prather Deel. (CIMB,
Ex. 4) at ,r 34).) Glycosyn continues, "[t]he 'activity' of an enzyme is a measure of its ability to
convert a certain amount of 'substrate' per unit time" (id. at 19 (citing Prather Deel. at ,r 43)) and
"[o]ne of the tests that measures the activity of �-galactosidase, the 'Miller assay,' which reports
activity in 'Miller units,' was developed almost 50 years ago (id. (citing CIMB, Ex. 5)). Glycosyn
alleges this is "a well-described, uncomplicated procedure." (Id. (citing Prather Deel. at ,r 46).)
Glycosyn then goes on to describe the details of the Miller test. (See id. at 20, 21-22.)
Thus, reasons Glycosyn, a person of ordinary skill in the art reading the specification and
claims of the asserted patents would understand that "units" as used in the claims refers to "Miller
14
units." (Id. at 20-21 (citing, inter alia, '230 patent at 7:26-33; '018 patent at 7:30-37).) Glycosyn
argues that modifications of the Miller test are permitted and do not take away from a person of
ordinary skill's understanding that they have performed the so-named protocol. (Id. at 22 (citing
Prather Deel. at ,r 47).) Glycosyn contends, accordingly, that "[b]oth Complainant and Respondent
have been able to perform the Miller assay on their respective cultures of bacteria that produce P
galactosidase to measure ' measurable' amounts of p-galactosidase activity." (Id. (citing CIMB, Ex.
7 at 12, 33-34, 36-37; CIMB, Ex. 8).)
With this understanding, Glycosyn argues that "P-galactosidase activity comprises between
0.005 and [200 units/5 units/4 units/3 units/2 units]" should be afforded its plain and ordinary
meaning" as defined by the specifications of the '230 and '018 patents. (Id. at 23 (citing '230 patent
at 7:26-33; '018 patent at 7:30-37).) Glycosyn criticizes Jennewein's construction for "insert[ing]
a temporal limitation that is found nowhere in the claim, specification, or prosecution history." (Id.
(citing 3M Innovative Props. Co. v. Tredegar Corp., 725 F.3d 1315, 1333 (Fed. Cir. 2013)).)
Glycosyn argues "[t]he '230 and '018 patents do not specify when the claimed p-galactosidase
activity range must be measured, or for how long the claimed range must be achieved. That is
because these parameters do not matter for purposes of the claimed invention." (Id. at 24-25
(discussing '230 patent at 5:65-6:7, 7:33-41, 9:32-44, 18:23-32; Prather Deel. ,r 50).) Rather,
according to Glycosyn:
[T]he claimed p-galactosidase activity ranges merely need be present
at times useful for the production of 2'-FL. See Prather Deel. at ,r 51.
This could be at the very beginning when the bacterium is being
constructed (for "phenotypic marking of desirable genetic loci during
construction of host cell backgrounds"); it could be later during the
fermentation of the bacteria ("for detection of cell lysis due to
undesired bacteriophage contaminations in fermentation processes");
or it could be even later at the end of the fermentation process ("for
the facile removal of undesired residual lactose at the end of
fermentations"). Id.
15
(Id. at 25.)
ln its reply brief, Glycosyn argues there is no merit to Jennewein's contention that
"comprises," as used in the claim and in connection to the claimed numerical activity range, renders
the limitation meaningless under the intrinsic evidence and settled law. (See CRMB at 2 (referring
to RIMB at 15).) Glycosyn contends "as noted by Staff, the sue of the term 'comprises' in this
context allows for the possibility that ' the action of the P-galactosidase enzyme may also have other,
unrecited effects' beyond the claimed p-galactosidase activity between 0.05 and 200 units;" and
therefore, the term is sufficiently definite. (Id. at 3 (citing Prather Deel. at ,r 50).) Glycosyn
considers Jennewein's claim of indefiniteness (for failure to define when the P-galactosidase activity
must be present) as the flip side of Jennewein's use of a temporal requirement in its alternate
construction. (Id. (referring to RIMB at 16, 21-22).) Glycosyn argues both sides represent improper
interpretations under settled law and the teachings of the specification. (Id. at 3-4 (citing, inter alia,
3M Innovative Props., 725 F.3d at 1 333; Broadcom Corp. v. Emu/ex Corp., 732 F.3d 1325, 1333
(Fed. Cir. 2013); Bell Commc'ns Research v. Vita/ink Commc'ns Corp., 5 5 F.3d 615, 622-23 (Fed.
Cir. 1995); '230 patent at 7:33-41; Prather Deel. at ,r 5 1); see generally id. at 6-7.)
Further, with respect to any ambiguity in how to implement the Miller test, Glycosyn
highlights that principle which states "when a claim does specify a method of measurement, its
omission of details about bow to implement the method will not invalidate the claim if a person of
ordinary skill in the art could infer the details from industry standards or professional judgment."
(Id. at 5 (citing, inter a/ia, Abbot/ GmbH & Co., KG v. Cenocor Ortho Biotech, Inc., 870 F. Supp.
2d 206, 230 (D. Mass. 2012)).) Glycosyn argues, through its expert declaration, that a person of
ordinary skill could do exactly that. (Id. (citing Prather Deel. at ,r 46-47).)
In its opening brief, Jennewein argues that "[t]his term fails to inform with reasonable
certainty to one of ordinary skill in the art the proper scope of the claims, and is therefore indefinite
1 6
under 35 U.S.C.§ 112, if2." (RJMB at 15.) Jennewein reasons that because the range is preceded
by "comprises," an open-ended or unbounded term, "it is hopelessly unclear whether the inventors
intended that P-galactosidase activity would be limited to the claimed range, or not." (Id. at 15; see
RRMB at 2-3 ("The term comprises defines the range of p-galactosidase activity allowed, not the
action of p-galactosidase.").) Jennewein adds "the term 'activity' in the context of the claims is not
amenable to definition with reasonable certainty to one of ordinary skill in the art. Neither the
claims nor the specification define at what point this activity must be present." (R1MB at 16; see
RRMB at 4.) Jennewein explains:
Complainant apparently contends that a process falls within the scope
of the claim if there is activity in the claimed range for any amount of
time, even if only a small percentage, and that the range can be
exceeded during the remaining time. That cannot be correct. Should
activity greatly exceed 200 units during most of fermentation, 2'-FL
may not be produced. High level p-galactosidase activity is contrary
to the purpose of the invention, at least because it could destroy the
intracellular lactose pool and prevent 2'-FL production. Exh. 1, '230
Patent at 7:26-41. Furthermore, low level p-galactosidase activity is a
key distinction between the invention and the Samain patent. Exh. 9,
Confidential Deposition Transcript of John McCoy ("McCoy"), Sept.
10, 2018 at 286:1 1-291: 10. A skilled artisan therefore would not be
able to determine the claim's scope with reasonable certainty.
(RIMB at 16.) Jennewein further argues that different methods for measuring the claimed "Miller
units" "may lead to inconsistent results," causing further indefiniteness. (See id. at 17-18 (citing
Dow Chem. Co. v. Nova Chemicals Corp. (Canada), 803 F.3d 620, 630 (Fed. Cir. 2015)); see RRMB
at 4-5.) Should the undersigned not determine the term is indefinite, Jennewein argues the claimed
range must be strict in light of the prosecution history of the asserted patents (see RIMB at 18-20
(discussing RIMB, Exs. 6, 7)), must be measured using the assay procedures in Miller, and the range
must be satisfied "at substantially all times during culturing of the bacterium and retrieval of the
fucosylated oligosaccharide . . . ." (Id. at 21.) Jennewein argues this is so because:
17
Should the P-galactosidase activity fall outside of this low range, one
of two failures could occur. When the activity is too high, the lactose
feedstock will be destroyed before 2'-FL is finished being
constructed. Id. at 7:33-35. But when the activity is too low, the
residual lactose in the fermentation broth will not be destroyed in the
retrieval step, rendering it impractical to retrieve 2'-FL from the
culture, particularly at a commercial scale. See id. at 33-41.
(Id. at 22; see RRMB at 7 ("If Complainant's broad interpretation is adopted, the claims would have
no limit on at what point, or for how long, p-galactosidase activity must be present during production
and purification of 2'-FL"), 8-9 (citing inventor testimony), 10 ("Complainant's construction
therefore allows activity that is contrary to the expressed purposes of the invention explained above
- producing 2'-FL and allowing its facile purification from lactose").)
Further, in its reply brief, Jennewein emphasizes that should the term not be indefinite, "units
must be measured according to the assay procedures in Miller." (RRMB at 5.) Jennewein faults
Glycosyn for "want[ing] to adopt part of the Miller assay - the method for calculating units - but
not the express description of how the assay should be performed." (Id. at 6.) Jennewein argues
"[d]uring the prosecution of the '230 patent, the patentee made clear that units of P-galactosidase
activity must be measured according to the assay procedures in Miller" (id. at 6 (citing RIMB, Ex.
6)) and so Glycosyn is now judicially estopped from arguing otherwise now (id. at 7 (citing Typhoon
Touch Techs. , Inc. v. Dell, Inc., 659 F.3d 1376, 1381 (Fed. Cir. 2011); Omega Eng'g. , Inc. v. Raytek
Corp., 334 F.3d 1314, 1323-24 (Fed. Cir. 2003)).)
In its opening brief, and with respect to indefiniteness, the Staff observes "[t]he term
'comprising' is specifically defined in the patent specification" which "simply provides that the
claimed method may include 'additional, unrecited elements or method steps."' (SIMB at 15-16
(citing '230 patent at 11:43-48); SRMB at 2-3.) The Staff argues one of ordinary skill would
understand the use of "comprises" functions to "not exclude the possibility that the action of the P
galactosidase enzyme may also have other, unrecited effects" and "would easily be able to discern
18
the bounds of the invention with reasonable certainty, based on the exact numerical ranges claimed."
(Id. at 16 (citing Nautilus, 134 S. Ct. at 2124).) The Staff further disputes the propriety of imposing
a "at substantially all times . . ." requirement into the construction under the legal principle that an
accused product which sometimes, but not always, practices a claim still practices the claim. (Id. at
16-17 (citing Broadcom Corp. v. Emu/ex Corp., 732 F.3d 1 325, 1333 (Fed. Cir. 2013)).)
In its reply brief, the Staff addresses Jennewein's additional grounds for indefiniteness and
continues to disagree. Regarding the impact of "activity," the Staff faults Jennewein for "not
explain[ing] why one of ordinary skill in the art would be unable to understand what 'P-galactosidase
activity' is without first knowing when that activity occurs" primarily because the definition of
"activity" is agreed (''the process of cleaving the disaccharide lactose into glucose and galactose, as
performed by the intracellular P-galactosidase enzyme") and "does not change depending on when
the activity occurs." (Id. at 3 (citing SIMB, Ex. 7 at 343).) The Staff reasons:
If a p-galactosidase enzyme cleaves lactose at any point during a
process, then there has been "P-galactosidase activity." If that activity
is measurable at between 0.05 and 200 Miller units at any point in the
process, then at that point it is within the scope of the invention
disclosed in claim 1 of the '230 Patent and claim 1 of the '018 Patent.
See SBr. exh. 2 ('230 Patent) at 123:67; SBr. exh. 3 ('018 Patent) at
1 11:49-50. The Staff submits that one of ordinary skill in the art
would be able to discern "with reasonable certainty" whether the level
of p-galactosidase activity at any given point in a process is within the
scope of the invention. See Nautilus, Inc. v. Biosig Instruments, Inc.,
134 S. Ct. 2120, 2124 (2014).
(Id.) Regarding Jennewein's assertion that different Miller tests will produce different results, the
Staff argues "[t]he more reasonable interpretation of the text is that Miller is describing two
interchangeable variations of the Miller assay, either of which would yield the same results.
Respondent has cited no evidence that this is incorrect." (Id. at 4.) For similar reasons to those
discussed above, the Staff does not agree with any of the additional limitations Jennewein places
into its alternative proposed construction. (See id. at 5-6.) The Staff also argues Jennewein's
19
construction tries to limit the scope of the invention to the most efficient embodiment of the claim,
which is improper. (Id. at 6 (citing Linear Tech. Corp. v. International Trade Comm 'n, 566 F.3d
1049, 1058 (Fed. Cir. 2009); Liebel-Flarsheim Co. v. Medrad, Inc., 358 F.3d 898, 906 (Fed. Cir.
2004); RF Delaware, Inc. v. Pacific Keystone Techs., Inc., 326 F.3d 1255, 1263 (Fed. Cir. 2003)).)
Upon review of the evidence, the undersigned finds Jennewein has not shown by clear and
convincing evidence that the term is indefinite. In particular, Jennewein's argument that "persons
of ordinary skill in the art could not know whether they infringe the claims with reasonable certainty
if they had a p-galactosidase activity outside of the recited range" (RJMB at 15-16; see RIMB, Ex.
4 at ,i,r 39-41) is not persuasive. If a person of ordinary skill can know when their P-galactosidase
activity falls outside of the recited range, then they can also know if that activity was within the
recited range-which would exactly inform them of whether they infringe or not. Moreover,
Jennewein's contention that a person of ordinary skill would not understand with reasonable
certainty what the range means or how to measure it (see RIMB at 17-18; RRMB at 4-5 (discussing
different methodologies of testing and "natural and man-made variations")) is undercut by
Jennewein's own expert. For example, while that expert opines "Miller describes two alternative
method steps to conduct the assay" and "[o]ne measurement is likely to profuse [sic] higher values
on that count and other factors in the assay may act in different directions," that expert also makes
predictions on the practical drawbacks of p-galactosidase activity falling above or below the claimed
range with9ut reference to which technique is employed and under what conditions:
12. Should P-gaJactosidase activity not fall within the claimed range
during the entire process of producing 2' -FL, several problems would
anse.
13. Higher levels of P-gaJactosidase activity would destroy lactose
faster than a cell could covert lactose to 2'-FL. P-gaJactosidase
activity above 200 units dUiing fermentation would likely eliminate
or greatly inhibit a cell's ability to produce 2'-FL. Resp. Br., Exh. 6
4/7I16 Declaration of John McCoy.
20
14. On the other hand, p-galactosidase activity below 0.05 units
would likely make purification of 2 '-FL impractical, particularly at
commercial scale. This is because 2' -FL and lactose are difficult to
separate from each other. p-galactosidase destroys lactose that
remains after 2'-FL production is complete, allowing for easier
purification of2'-FL from the culture medium. Too low of a level P
galactosidase activity during [sic] would therefore lose this important
benefit of destroying residual lactose in the cell culture after 2'-FL
syntheses was complete.
(RRMB, Ex. A at ,r,r 12-14.) Further, the undersigned finds Glycosyn's expert more persuasive on
this issue. Glycosyn's expert states clearly:
Miller assays are conducted in hundreds of labs across the world to
this day. Any person of ordinary skill in the art at the time of the
invention would not only be familiar with the Miller assay, but also
would be able to follow it as its methodology is very clearly described
in Miller's 1972 textbook.
A person of ordinary skill in the art at the time of the invention would
understand that there is flexibility contained within the procedure of
the Miller assay, and that scientists routinely modify procedures of
assays to better fit within their research needs.
(CIMB, Ex. 4 at ,r 46.) Jennewein's expert, on the other hand, paradoxically argues both of "[a]
person of ordinary skill in the art understood in 2011 that certain factors can alter the data obtained
using the Miller assay, which would result in incorrect readings of P-galactosidase" (RIMB, Ex. 4
at ,r 45) and "[a]n ordinary scientist would not know how the activity would change with
alterations in these parameters, and could not predict if his process would infringe the claimed P
galactosidase activity based on these variations" (id. at ,r 50).
With respect to the timing or duration of the activity within the claimed range, the claims'
failure to "specify whether the activity must remain at a low level throughout the claimed process
steps of culturing and retrieving or only during part of those steps, and if so, what part of those
steps" (RIMB at 16; see RRMB at 4), the undersigned does not find this results in an indefinite
claim. Rather, it results in a broad claim which is met when P-galactosidase activity falls within the
2 1
claimed range at some point. This is perfectly compatible with the principle that "[a]n accused
product that sometimes, but not always, embodies a claimed method nonetheless infringes." Bell
Commc 'ns, 5 5 F.3d at 622-23.
Turning to Jennewein's alternate construction, the undersigned declines to include "at
substantially all times during culturing of the bacterium and retrieval of the fucosylated
oligosaccharide" in the construction. Jennewein argues this added temporal requirement is needed
to "resolv[e] the claim's ambiguity" (RRMB at 7), but as discussed above, the claim is not
ambiguous as to when the claimed activity range must be met- it need only be met at some point
in time. Jennewein also argues the temporal requirement is needed for the invention to have its
beneficial effects (see RlMB at 22; RRMB at 8-10) but none of the patent specification excerpts
cited by Jennewein for support suggest this dependency (see '230 patent at 5: 13-18, 5:47-6:8, 7:18-
41, 9:28-44, 18:19-31).
Further, while Glycosyn and the Staff do not address it, the undersigned finds no reason to
read "when measured according to the assay procedures described in [the Miller textbook)" into the
claim. To the extent the use of this assay is implied or required when one of ordinary skill is
measuring activity in Miller Units (see RRMB at 5), then it is already present through the claim's
explicit recitation of Miller Units. Jennewein's argument that "[d]uring the prosecution of the '230
patent, the patentee made clear that units of P-galactosidase activity must be measured according to
the assay procedures in Miller" (RRMB at 6 (emphasis added)) is completely unsupported by the
prosecution history excerpt cited (RIMB, Ex. 6 at 6/4/14 Reply and Amendment at 11-12) where
the patentee simply noted the assay is widely known. This was in no way a clear and unmistakable
disclaimer to avoid rejection under Thorner, 669 F.3d at 1366-67.
Accordingly, "P-galactosidase activity comprises between 0.05 and [200 units/ 5 units/ 4
units/ 3 units/ 2 units]" is hereby not found to be indeimite and construed as "fl-galactosidase
22
activity is measurable at between exactly 0.05 and exactly [200/5/4/3/2) Miller Units, as defined
in Miller, J.H., Experiments in Molecular Genetics (Cold Spring Harbor Lab. 1972) at 352-
355."
2. "functional . . . IJ-galactosidase gene"
The Parties disagree on the proper claim construction and have proposed the following
constructions:
Relevant
Claims
'230 Patent
claim 21
'018 Patent
claims 1,
21, 23, 24
(JC at 3.)
Glycosyn
(A) plain and ordinary
meaning:
plain and ordinary
meaning, i.e., a gene
involved in producing a
working p-galactosidase
e e.
Jennewein
(A) plain and ordinary
meaning:
plain and ordinary
meaning, i.e., "a gene
that encodes a full-length
working
- alactosidase e e"
Staff
(A) plain and ordinary
meaning:
plain and ordinary
meaning, i.e., a gene
that encodes a working
p-galactosidase enzyme
For this limitation, the Parties' constructions differ very narrowly. In its opening brief,
Glycosyn explains "[i]t appears the parties all agree that a working P-galactosidase enzyme is a P
galactosidase enzyme that has the ability to cleave the glycosidic bond between galactose and
glucose." (CIMB at 27.) Glycosyn argues, however, that Jennewein's construction involving "full
length" is improper on technical grounds because "[w]ith regard to the enzyme produced from tbe
lacZ gene, 'a full-length working P-galactosidase enzyme' does not exist."' (Jd. at 28 (citing Prather
Deel. at ,r 41).) Glycosyn contends the claim term is deliberately broad as to whether p-galactosidase
enzyme needs to be produced by a single full-length gene or multiple genes and "[t]here is nothing
in the patents that places any significance on having a single gene produce a 'full-length' P
galactosidase enzyme, and nothing in the patent that expressly limits the 'functional . . . P
galactosidase gene' to a single 'full-length' gene." (Id. at 28.) Further, Glycosyn contends "[a]
person of ordinary skill in the art at the time of the invention would have readily understood that
23
this low-level p-galactosidase activity could have been equally achieved by inserting a full-length
lacZ gene, or by inserting complementary lacZa or lacZQ P-galactosidase genes. (Id. at 28-29
(citing Prather Deel. at 1 38-42).)
Essentially, according to Glycosyn, "[t]he claims are not even limited to lacZ, but instead
include any p-galactosidase gene (of which lacZ is the [sic] only one type)." (Id. at 29.) Glycosyn
argues this is shown through principles of claim differentiation, where lacZ is expressly claimed in
other dependent claims as the recited "P-galactosidase gene." (See id. (citing Phillips, 415 F.3d at
1314-1315); see also CR.MB at 9-10 ("if the dependent claim term 'E. coli lacZ gene' means 'E.
coli lacZ gene that encodes a full-length enzyme,' as Respondent suggests, then the independent
claim would necessarily be broader and would not contain the additional 'full length' limitation."))
With this understanding, Glycosyn adds that there is no meaningful dif ference between its
construction and the Staffs and "the term 'encoding' is just another way of saying 'involved in
producing.'" (CIMB at 30 (citing CIMB, Ex. 4 at 1 33).)
In its reply brief, Glycosyn argues that Jennewein's arguments on whether a fragment of a
P-galactosidase gene can be considered a "functional" gene are belied by Jennewein's technical
documents. (See CR.MB at 8 (citing CR.MB, Ex. 15 at 16967).) Glycosyn argues one such document
is "far better evidence of what a person of ordinary skill in the art would have understood was meant
by a 'functional gene' than any litigation-inspired constructions presented by Jennewein now." (/d. )
Lastly, Glycosyn argues that the specification's identification of only "full-length" p-galactosidase
genes (lacZ and lac4) cannot limit the claims as that would be improper act of limiting the claims
to the specification (see id. at 10 (citing Phillips, 415 F. 3d at 1323)); and, contrary to Staffs
argument, it is not true that the only way to obtain a working enzyme is to encode a "full-length"
enzyme. (See id. at 10-1 1 (discussing SIMB at 18-19).) Glycosyn suggests the Staff confuses the
claim term "functional" as describing the enzyme as opposed to the gene. (Id. at 11.)
24
In its opening brief, Jennewein identifies the issue as "whether a proper construction should
[] clarify that the p-galactosidase gene must 'encode' a 'full-length' working enzyme." (RIMB at
23.) Jennewein argues the claims themselves and the patents' specifications plainly answer this
question in the affirmative. (Id. ; see id. at 24 (discussing '230 patent at els. 2, 22; '018 patent at els.
8, 24).) Jennewein also points to its expert's declaration to support "a P-galactosidase gene would
be understood by those of ordinary skill in the art to encode for the full-length P-galactosidase
protein from its start codon to the termination codon, and would not encode merely a fragment of it.
. . . A skilled artisan intending to cover a gene fragment would not have used use [sic] the word
'gene' alone. Instead the skilled artisan would have used 'fragment' or its equivalent to describe
the gene." (Id. at 24 (citing RIMB, Ex. 4 at ,r 26-28).) Jennewein adds that "[t]he specification of
the Asserted Patents teaches only two specific P-galactosidase genes, lacZ and lac4, both of which
encode a full-length, working p-galactosidase in a different species of bacteria (E. coli and K. lactis,
respectively)." (Id. at 25 (citing '230 patent at 2:65-67, 7:34-35).)
On technical grounds, Jennewein explains:
However, a fragment of the p-galactosidase gene does not encode the
p -galactosidase enzyme, but rather only a fragment of the P
galactosidase enzyme. Moreover, a "functional p-galactosidase gene"
must encode a functional P-galactosidase enzyme, i.e. a "working P
galactosidase enzyme," as the parties agree. In contrast, a gene that
does not encode a working P-galactosidase enzyme-for example a
fragment of a P-galactosidase gene that encodes only a non-working
fragment of the enzyme-would not be a "functional P-galactosidase
gene." Ex. 4, Stephanopoulos at ,r,r 26-28.
(Id. at 23.) Jennewein also explains, with respect to the fragments associated with the technique
known as alpha complementation:
When expressed separately, each fragment produces a portion of the
Lacz protein, but neither portion has p-galactosidase activity alone.
Id. When lacZa and lacZw are simultaneously expressed in the san1e
cell, their portions of the Lacz protein assemble into one of the four
subunits of the Lacz P-galactosidase enzyme. Id. Assembly with the
25
remaining three subunits into a homotetramer results in a functional
�-galactosidase enzyme that has �-galactosidase activity. Id
(RRMB at 12-13.)
Further, in its reply brief, Jennewein argues "[t]here is no support in the intrinsic evidence
for Complainant's tortured reading of the claim language" and agrees with the Staff that Glycosyn's
construction creates new ambiguities. (RRMB at 10 (citing SIMB at 18).) Jennewein generally
disputes that a gene "involved in producing," as in Glycosyn's construction, is interchangeable with
a gene that "encodes." (See id at 11-12 (citing, inter alia, RRMB, Ex. [A] at 11 6-7; RRMB, Ex. D
at 257-258).) Jennewein also alleges it is improper for Glycosyn to rely on Jennewein's accused
process to define the claim term. (See id at 13-14 (citing NeoMagic Corp. v. Trident Microsystems,
Inc., 287 F.3d 1062, 1074 (Fed. Cir. 2002)).)
With that said, Jennewein finds the Staff's construction amenable in light of the Staff's
argument that the term "functional . . . p-galactosidase gene" would not be met by a gene that
produces that enzyme only when another undefined gene or gene segment is simultaneously
produced. (See id. at 11.)
In its opening brief, the Staff understands Glycosyn's construction to cover "any gene that
is involved in producing such an enzyme, even if the gene can only do so in conjunction with other
genes." (SIMB at 17.) The Staff argues this presents problems for partial genes and whether they
are "functional" or not, as "[i]nfringement would depend on the presence or absence of 'other
segments' that are not identified anywhere in the claim language, in the specification, or in the
prosecution history." (Id. at 18; SRMB at 10.) On the other hand, the Staff finds Jennewein's
construction acceptable except for the "full-length" tenn. (See SIMB at 18-19.) The Staff
summarizes, "what is important in the context of the asserted patents is whether the gene in question
encodes an enzyme that successfully performs its function." (Id. at 19.)
26
In its reply brief, the Staff argues the claim language "a functional promoter-less P
galactosidase gene inserted into an endogenous gene such that the resultant bacterium comprises a
low level of p-galactosidase activity," when read in context, "indicates that the P-galactosidase gene
must be fully 'functional' at the time it is inserted into an endogenous gene." (SRMB at 8.) This,
according to the Staff, contradicts Glycosyn's construction. (Id )
Upon review of the evidence, the undersigned frrst emphasizes that claim terms are not to
be construed in light of the accused device. "[T]his court has repeatedly stated that a court must
construe claims without considering the implications of covering a particular product or process."
SmithKline Beecham Corp. v. Apotex Corp., 703 F.3d 1331, 1339 (Fed. Cir. 2005) (citing
NeoMagic., 287 F.3d at 1074 ("It is well settled that claims may not be construed by reference to
the accused device.")); SRI Int'! v. Matsushita Elec. Corp. ofAm., 775 F.2d l 107, 1118 (Fed. Cir.
1985) ("It is only after the claims have been construed without reference to the accused device that
the claims, as so construed, are applied to the accused device to determine infringement.")
Much of the parties' briefing involves argument over whether a technique known as "u
cornplementation" would fall under the scope of this term. (See CIMB at 26-27, 28-29; CRMB at
7-9, 10 ("There is no dispute that Respondent's E. coli strain produces a working P-galactosidase
enzyme."), 11; RIMB at 24; RRMB at 12-14 (citing NeoMagic, 287 F.3d at 1074); SRMB at 7-1 0.)
This technique is not discussed in the asserted patents. (See generally '230 patent; 'O 18 patent.)
Rather, it became clear at the Markman hearing, on the public record, that a-complementation is
related to Jennewein's accused products in this Investigation. (See, e.g., Hr' g Tr. at 64:5-19, 65: 10-
17, 69:4-10 ("this then means that there is no infringement of any claims of the asserted patents . . .
. ").)
27
Thus, the undersigned finds that briefing and argument which concerns whether or not a
complementation falls within the scope of or is covered by "functional . . . P-galactosidase gene" is
not persuasive.
Moving on, the Parties' primary dispute is whether a "functional . . . P-galactosidase gene"
can be any gene that is involved in the production of the p-galactosidase enzyme, as in Glycosyn's
construction, or whether it must be a gene that encodes that enzyme, as in the Jennewein and the
Staff's. Jennewein's construction also uses the term "full-length" to describe a functional enzyme
(see, e.g., RIMB at 25 ("A P-galactosidase enzyme would not be functional unless it is full-length
or substantially full-length, for only those contain enough of the P-galactosidase structure that is
responsible for producing enzymatic activity.")), but the undersigned finds this descriptor is
misplaced given the term to be construed is "functional . . . P-galactosidase gene" and not "functional
P-galactosidase enzyme." Indeed, Jennewein acknowledges that "full-length" is not critical to its
proposed construction. (See RIMB at 27 (noting "full-length" is implicit in the Staff's construction
which omits "full-length.").)
The undersigned finds Jennewein and the Staffs construction more persuasive. The asserted
patents do not specifically explain what is meant when the modifier "P-galactosidase" is placed
before the word "gene," which is what the present dispute turns on. Thus, consideration of extrinsic
evidence is appropriate; and the Parties' experts' explanations of "gene" resolves the issue.
Glycosyn's expert explains "[a] gene is a sequence of DNA that contains the molecular
'code' for producing functional biological molecules, such as proteins." (CIMB, Ex. 4 at ,r 32.)
Jennewein's expert similarly explains, "[w]hen ordinary scientists read the term 'gene,' they think
of the nucleotide (DNA) sequence encoding the amino acid sequence of the an entire protein."
(RIMB, Ex. 4 at ,r 26.) These explanations are consistent and are hereby adopted. Further consistent
are both of Glycoysn's and Jennewein's constructions in their interpretation of "P-galactosidase" in
28
"P-galactosidase gene" to mean the creation or production of the enzyme P-galactosidase.
Additionally, no party contends that anything other than the plain and ordinary meaning should
apply to this term. (See, e.g., CIMB at 25 (table).)
Thus, in light of the experts' statements and the parties' constructions, the undersigned finds
the plain and ordinary meaning of "functional . . . P-galactosidase gene" is simply "a functional
sequence of DNA that encodes p-galactosidase."
While Glycosyn's expert also states "to say that a gene 'encodes' a working enzyme is to
say that it is 'involved in producing' a working enzyme" (id., Ex. 4 at 1 33), Jennewein's expert
squarely takes the opposition position, "[o]rdinary scientists generally do not describe a gene as
merely being 'involved' in producing a protein like p-galactosidase. They normally say a gene
'encodes' P-galactosidase" (RIMB, Ex. 4 at 1 25). The undersigned finds Jennewein's expert more
persuasive in light of the very particular and detailed nature of this art, and notes that Glycosyn
provides no other evidence beyond its expert's opinion to support its "involved in producing"
interpretation.
Accordingly, "functional . . . p-galactosidase gene" is hereby construed as "a functional
sequence of DNA that encodes �-galactosidase."
3. "wild type"
The Parties disagree on the proper claim construction and have proposed the following
constructions:
Relevant Glycosyn Jennewein Staff
Claims
'230 Patent (A) plain and ordinary (A) plain and ordinary (A) plain and ordinary
claims 21, 27 meaning: meaning: meaning:
plain and ordinary plain and ordinary plain and ordinary
'018 Patent meaning, i.e., the meaning, i.e., "the form meaning, i.e., the
claims 1, phenotype most most commonly found in phenotype most
4, 20, 24 commonly found in nature" commonly found in
nature nature
29
(JC at 3-4.)
For this limitation, the Parties' dispute is also narrow. Glycosyn argues "[t]hroughout the
claims and the specification, the term 'wild type' is used to compare observable traits of the E. coli
organism as compared to the modified E. coli organism described in the claims." (CIMB at 34-35
(citing '230 patent at els. 2, 8, 21, 27; '0 18 patent at els. 1, 4, 20, 24); see id at 35 (citing '230 patent
at 5:6-18, 6:42-46, 16:43-49; '018 patent at 5:6-18, 6:42-46, 16:43-49).) Glycosyn reasons:
The picture is clear: every time the term "wild type" is used in the
patent claims, it is used in relation to observable traits of the E. coli
organism. Such observable traits are referred to by persons of
ordinary kill [sic] in the art as "phenotype." They are not a "form," as
Respondent contends.
(Id. at 35.) Glycosyn argues it and the Staffs proposed construction "comports with how a person
of ordinary skill in the art would understand the term 'wild type' at the time of the invention. . . .
This also aligns with dictionaries commonly used by people of ordinary skill in the art in question
at the time of the invention." (Id. at 35-36 (citing Prather Deel. at � 36; CIMB, Ex. 13 at 68993-
68997).) In its reply brief, Glycosyn contends Jennewein admits "phenotype is defined in term of
observable traits or observable characteristics" and "wild-type is used in the patents to describe a
phenotype." (CRMB at 14 (citing RIMB at 31).) To the extent Jennewein argues the existence of
"wild-type" genotypes, in addition to phenotypes, Glycosyn urges the use of "form" in Jennewein's
construction "does not capture this" and "adds complexity and confusion, and leaves the definition
of wild-type less apparent and subject to further interpretation." (Id.)
In its opening brief, Jennewein highlights that '" [w]ild-type' appears in two contexts in the
Asserted Patents: 'wild-type gene' and 'wild-type bacterium"' and argues its own construction
"embraces the clear, plain meaning in both contexts: the form most commonly found in nature."
(RIMB at 29-30.) Jennewein points out the '230 patent's recitation of both phenotype and genotype
(id. at 30 (citing '230 patent at 18: 19-23)) and extrinsic textbook evidence that defines "phenotype"
30
as "distinct from its genotype" (id. (citing RIMB, Ex. 10 at 08, G-13)). Jennewein swnmarizes,
"[g]enes have both a phenotype and a genotype, and there is no reason to include one and exclude
the other from the plain meaning of 'wild-type"' and a person of ordinary skill would understand
"wild-type" is not limited to phenotype of a gene. (Id. (citing RI.MB, Ex. 11 at 977, 1232; RIMB,
Ex. I O at 342).)
Regarding a phenotype as an "observable" characteristic or trait, Jennewein contends "[a]
gene would not have an 'observable' trait or characteristic-that would be the gene's product, not
the gene itself." (Id. at 3 1 (citation omitted).) Further, Jennewein reasons "[a]lthough a wild-type
bacterium could have the same phenotype as a genetically engineered bacterium, in that case the
bacterium would no longer be considered a 'wild type."' (Id. (citing RIMB, Ex. 4 at ,r 56).) Thus,
Jennewein explains, "[t]he term 'wild-type' qualifies the thing that appears after it-here, either or
a gene or bacteria" and "neither a 'gene' nor a 'bacteria' is a phenotype, and the claim needs no such
additional requirement." (Id. at 32.)
In its reply brief, Jennewein asserts "[t]he parties agree that a ' wild-type' is the form as it
exists in nature. A key aspect of this natural state of 'wild-type' is that it is unchanged by man."
(RRMB at 18 (citing RIMB, Ex. 4 at ,r,r 55-56; CIMB, Ex. 13); see id. at 20-21 (citing SIMB, Ex.
10 at 2370).) Jennewein contends the construction from Glycosyn and the Staff "eliminates this
'natural' aspect of 'wild-type' and would include man-made mutants." (Id. at 18-19.) Jennewein
continues to add that discussions in the patent specifications of "levels of activity in a wild-type
gene or bacterium does not mean that the gene or bacterium is limited to its phenotype" (id. at 19
(citing RRMB, Ex. A at ,r 18)) and "[n]either the claims nor the specification define a wild-type
gene as being synonymous with wild-type activity" (id.).
In its opening brief, the Staff points to extrinsic dictionary evidence which defines "wild
type" as a phenotype, and other extrinsic dictionary evidence which defines the same as a genotype
31
or phenotype. (S1MB at 22 (discussing SIMB, Exs. 10, 11).) The Staff explains it prefers using
"phenotype," as in Glycosyn's construction, over "form/' as in Jennewein's construction, because
"it is a slightly more accurate reflection of the manner in which the term 'wild-type' is used in the
asserted patents." (Id. at 22-23.) The Staff reasons:
Both patents are focused on the behavior of the engineered organisms,
specifically on their ability to produce human milk oligosaccharides
such as 2'-FL, rather than on the specific molecular makeup of the
organisms' genetic structure. In other words, they are focused on the
modified E. coli bacterium's phenotype rather than its genotype. The
Staffs proposed construction reflects this fact.
(Id. at 23 (emphasis in original).) In its reply brief, the Staff repeats "the focus of both asserted
patents is on the behavior of the engineered organism, specifically on its ability to produce human
milk oligosaccharides such as 2'-FL, as well as the effect of the behavior of the specific facZ gene
on the organism's ability to produce 2'-FL." (SRMB at 15 (emphasis in original).) The Staff
continues, "(a)ny genotype of a functional promoter-less p-galactosidase gene will do, so long as it
has the effect of causing a low level of P-galactosidase activity. In other words, it is the effect of
the gene on the bacterium, and not its physical structure, that is important." (Id. ) Thus, the Staff
concludes phenotype is the proper interpretation of "wild-type." (Id. at 16.) The Staff also faults
Jennewein's comparison of phenotypes between man-made and wild organisms as unsupported by
Jennewein's cited expert declaration. (See SRMB at 16-17 (discussing RIMB, Ex. 4 at ,r,r 56, 58).)
Upon review of the evidence, the undersigned finds Jennewein's construction is more
accurate. The claims of a patent are the starting point for claim construction. Interactive Gift
Express, 256 F.3d at 1331. The claims of the asserted patents use "wild type'' or "wild-type" as
descriptors in two distinct contexts-for both a gene (see '230 patent at els. 2, 5, 21, 24) and for a
bacterium as a whole (see '230 patent at els. 8, 27; '018 patent at els. 1, 4, 20, 24). More specifically,
"wild type" is used in the context of a gene which is inserted into another gene ('230 patent at els.
32
2, 5, 21, 24) and then also in the context of comparing observable traits between two bacteria ('230
patent at els. 8, 27; '018 patent at els. 1 , 4, 20, 24.)
Jennewein's construction is consistent with both of these contexts-the "wild type" gene or
bacterium is the "form" or "type" of the gene or bacterium "most commonly found in nature." It is
this type of the gene which is inserted into another gene (see '230 patent at els. 2, 5, 21, 24) and the
type of bacteria which is compared to the bacterium of the invention (see '230 patent at els. 8,
27; '018 patent at els. 1, 4, 20, 24). Jennewein's construction is further consistent with those portions
of the patent specification which refer to "wild-type" in the contexts of a "coding sequence"
(see '230 patent at 12:64-67 ("DNA fragment carrying . . . a wild-type E. coli lacZ+ coding
sequence")) and "wild-type copy of the lacZ (p-galactosidase) gene" (id at 16:43-47) or "supplying
a wild-type thyA gene" (id at 16:63-65).
Glycosyn and the Staff's construction, interpreting "wild-type" as a "phenotype" is arguably
consistent in the context of comparing organisms with observable traits, but not in the gene context
where there is no observable trait, or "phenotype" under comparison as, for example, in the
following claims:
2. The method of claim 1, wherein the functional promoter-less P
galactosidase gene inserted into an endogenous gene comprises an
exogenous wild type E. coli lacZ gene.
5. The method of claim 1. , wherein said bacterium comprises a
functional promoter-less wild-type E. coli lacz+gene inserted into an
endogenous Ion gene.
24. The method of claim 21, wherein said bacterium comprises a
functional, wild-type, promoter-Jess E. coli lacz+gene inserted into an
endogenous Ion gene.
('230 patent at els. 2, 5, 24.)
Every claim term is presumed to have meaning. Innova/Pure Water, 381 F.3d at 1119
("While not an absolute rule, all claim terms are presumed to have meaning in a claim."). To have
33
meaning in these claims, "wild type" must refer to something other than "phenotype." Glycosyn
and the Staff's construction is thus too narrow. Indeed, as demonstrated by these claims, Glycosyn
is incorrect when it argues "[t]he picture is clear: every time the term 'wild type' is used in the patent
claims, it is used in relation to observable traits of the E. coli organism." (CIMB at 35.)
Further, the balance of the extrinsic evidence supports Jennewein's broad construction.
While the dictionary definition cited by Glycosyn does link "wild type" to phenotype, it does so in
the context of a "wild type" as a "member[] of a species." (CIMB, Ex. 13.) Genes are not members
of a species and as noted above, the asserted patents use "wild type" in the contexts of both overall
organisms and genes themselves. Glycosyn's definition, is therefore oflesser probative value. The
Staff's cited dictionary definition linking "wild-type" to phenotype is of similar little value as it too
is in the context of a member of a species-"the phenotype that is characteristic of most of the
members of the species occurring naturally and contrasting with the phenotype of a mutant." (SIME,
Ex. 11.) The Staff's rationale for including "phenotype" in its construction likewise comes from
the viewpoint of the overall organism. (See, e.g., SIMB at 23 ("In other words, [the patents] are
focused on the modified E. coli bacterium's phenotype rather than its genotype. The Staffs
proposed construction reflects this fact."); SRMB at 15 ("the Staff maintains that the focus of both
asserted patents is on the behavior of the engineered organism . . . .")).
On the other band, the Staff's second cited dictionary definition defines "wild type" in the
proper context-that of genetic material-and states "the standard gene, or the standard genotype
or phenotype of an individual, that is found in a wild or natural population [or] a form that is
arbitrarily designated as such." (SIMB, Ex. 10.) Jennewein's cited dictionary definitions also define
"wild type" in the proper context. A fil'st definition defines "wild-type gene" as "the form of a gene
[allele] normally found in nature" (RIMB, Ex. 11 at 977, 1232) and second definition states "the
34
' normal, norunutant form of a macromolecule, cell or organism"' (RIMB, Ex. 1 0 at 342 (emphasis
added)).
Thus, the undersigned finds those dictionary definitions directed to "wild type" genes, or
other macromolecules, to be of higher probative value than those directed to "wild type" organisms.
As those gene-specific definitions do not link "wild type" to phenotype, a construction not limited
to phenotype is warranted.
Regarding expert testimony as extrinsic evidence, the undersigned finds Glycosyn's expert
to be completely conclusory on this issue, stating only "[a] person of ordinary skill in the art at the
time of the invention would understand that 'wild type' as used in the claims and specifications of
the Asserted Patents refers to the phenotype most commonly found in nature." (CIMB, Ex. 4 at ,r
36.) Jennewein's expert provides a more persuasive and reasoned justification for his opinion to the
contrary. (See RIMB, Ex. 4 at ,r,r 55-66; RRMB, Ex. A at ,r,r 16-19.) The undersigned also finds,
however, no particular reason to use the word "form" in place of ''type" as in Jennewein's
construction either.
Accordingly, "wild-type" or "wild type" is hereby simply construed as "the type most
commonly found in nature."
SO ORDERED.
Chief Administrative Law Judge
35
CERTAIN HUMAN MILK OLIGOSACCHARIDES AND
METHODS OF PRODUCING THE SAME
INV. NO. 337-TA-1120
PUBLIC CERTIFICATE OF SERVICE
I, Lisa R. Barton, hereby certify that the attached Order No. 22 has been served by hand upon
the Commission Invest�ative aiti111ley, Lisa Murray, Esq. and the following parties as
indicated, on DE1.; 1 8 ZUla
FOR COMPLAINANT GLYCOSYN LLC
Michael C. Newman, Esq.
MINTZ LEVIN COHN FERRIS GLOVSKY
AND POPE O PC
One Financial Center
Boston, MA. 021 1 1
� � �
Lisa R. Barton, Secretary
U.S. International Trade Commission
500 E Street SW, Room 1 1 2A
Washington, D.C. 20436
( ) Via Hand Delivery
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( ) Other:
FOR RESPONDENT JENNEWEIN BIOTECHNOLOGIE GmbH
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