Hospira, Inc. v. Genentech, Inc.

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Trials@uspto.gov 	Paper 16
Tel: 571-272-7822 	Entered: July 27, 2017
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
HOSPIRA, INC.,
Petitioner,
v.
GENENTECH, INC.,
Patent Owner.
Case IPR2017-00739
Patent 7,892,549 B2
Before ZHENYU YANG, CHRISTOPHER G. PAULRAJ, and
ROBERT A. POLLOCK, Administrative Patent Judges.
POLLOCK, Administrative Patent Judge.
DECISION
Denying Institution of Inter Partes Review
35 U.S.C. § 325(d) and 37 C.F.R. § 42.108

IPR2017-00739
Patent 7,892,549 B2
I. 	INTRODUCTION
Hospira, Inc. (“Petitioner”)1 filed a Petition requesting an inter partes review
of claims 1–11 and 14–17 of U.S. Patent No. 7,892,549 B2 (Ex. 1101, “the ’549
patent”). Paper 1 (“Pet.”). Genentech, Inc. (“Patent Owner”) filed a Preliminary
Response to the Petition. Paper 8 (“Prelim. Resp.”). Based on the particular
circumstances of this case, we exercise our discretion under 35 U.S.C. § 325(d)
and 37 C.F.R. § 42.108 and do not institute an inter partes review of the
challenged claims.
A. 	Related Applications and Proceedings
In addition to this proceeding, Petitioner has challenged claims 1–17 of the
’549 Patent in IPR2017-00737. The ’549 Patent shares substantially the same
specification with U.S. Patent No. 7,846,441 B2 (“the ’441 Patent), and is related
as follows. The ’549 Patent issued from Application No. 10/356,824, filed
February 3, 2003 (“the ’824 Application”), which is a continuation of Application
No. 09/208,649, filed Dec. 10, 1998 (“the ’649 Application”), and claims benefit
of priority to Provisional Application No. 60/069,346, filed Dec. 12, 1997 (“the
’346 Provisional Application”). Ex. 1101, [21], [63], [60], 1:4–9. The ’441 Patent
issued from the ’649 Application and is presently the subject of IPR2017-00731.
Petitioner has also filed IPR2017-00804 and IPR2017-00805 involving the
claims of U.S. Patent Nos. 6,627,196 and 7,371,379, respectively. These two
patents are not in the chain of priority of the ’549 and ’441 Patents but relate to
subject matter similar to that at issue here. Petitioner also directs us to invalidation
and revocation proceedings involving European Patent EP 1,037,926, which also
1 Petitioner identifies Pfizer, Inc. as “the real party in interest for Petitioner.”
Paper 10, 2.
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Patent 7,892,549 B2
claims benefit of priority to the ’346 Provisional Application. See Pet. 1–2 (citing
Ex. 1104, 1126, and 1149).
B. 	The ’549 Patent and Relevant Background
According to the Specification, 25% to 30% of human breast cancer patients
overexpress a 185-kD transmembrane glycoprotein receptor (p185HER2), also
known as HER2 (human epidermal growth factor receptor-2) or ErbB2. Ex. 1101,
1:21–32, 5:16–21. These HER2-positive cancers are associated with poor
prognoses and resistance to many chemotherapeutic regimens including
anthracyclines (e.g., doxorubicin or epirubicin). Id. at 3:43–52, 4:11–12, 11:41–
45. Conversely, patients with HER2-positive cancers are three times more likely
to respond to treatment with taxanes than those with HER2 negative tumors. Id. at
3:52–56 (citing Baselga ’97 (Ex. 1107)).
Although “ErbB2 overexpression is commonly regarded as a predictor of
poor prognosis,” “a humanized version of the murine anti-ErbB2 antibody 4D5,
referred to as rhuMAb HER2 or HERCEPTIN® [or trastuzumab] has been
clinically active in patients with ErbB2-overexpressing metastatic breast cancers
that had received extensive prior anti-cancer therapy.” Ex. 1001, 3:35–61 (citing
Baselga ’96 (Ex. 1105)). Anti-ErbB2 4D5 antibodies also “enhance the activity of
paclitaxel (TAXOL®) and doxorubicin against breast cancer xenographs in nude
mice injected with BT-474 human breast adenocarcinoma cells, which express
high levels of HER2.” Id. at 3:56–61 (citing Baselga ’94 (Ex. 1106)).
According to the Specification,
The 	present 	invention 	concerns 	the 	treatment 	of 	disorders
characterized 	by 	overexpression 	of 	ErbB2, 	and 	is 	based 	on 	the
recognition that while treatment with anti-ErbB2 antibodies markedly
enhances the clinical benefit of the use of chemotherapeutic agents in
general, a syndrome of myocardial dysfunction that has been observed
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Patent 7,892,549 B2
as 	a 	side-effect 	of 	anthracycline 	derivatives 	is 	increased 	by 	the
administration of anti-ErbB2 antibodies.
Id. at 3:65–4:5.
The ’549 Patent thus relates to the treatment of breast cancers that
overexpress HER2/ErbB2 “comprising administering a therapeutically effective
amount[2] of a combination of an anti-ERbB2 antibody and a chemotherapeutic
agent other than an anthracycline derivative, e.g. doxorubicin or epirubicin, in the
absence of an anthracycline derivative, to the human patient.” Id. at 4:6–13. In
some embodiments, the anti-ERbB2 antibody of the combination is Herceptin and
the chemotherapeutic agent “is a taxoid, such as TAXOL® (paclitaxel) or a
TAXOL® derivative.” Id. at 4:23–25. The combination may further include one
or more additional anti-ErbB2 antibodies, “antibodies which bind to the EGFR . . .
ErbB3, ErbB4, or vascular endothelial factor (VEGF),” “one or more cytokines,”or
“a growth inhibitory agent.” Id. at 23:60–24:5, 25:20–34; see also id. at 11:4–40
(defining “chemotherapeutic agent” and “growth inhibitory agent”).
The ’549 Patent also provides an Example disclosing the conduct and results
of a clinical trial involving 469 women with metastatic HER2-positive breast
cancer Id. at 26:34–30:25. All patients were treated with one of two
chemotherapy regimens (CRx) designated either “AC” for anthracycline
(doxorubicin or epirubicin) and cyclophosphamide, or “T” for Taxol (paclitaxel).
See id. at 28:5–47; 29:13–30:12. Half of the patients were also treated with the
anti-ERbB2 antibody Herceptin, designated “H”. Id. The Specification discloses
2 The Specification defines a “therapeutically effective amount” of the combination
as “an amount having an antiproliferative effect,” which can be measured by
assessing the time to disease progression (TTP) or determining the response rates
(RR).” Id. at 10:41–50.
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Patent 7,892,549 B2
that “[a]t a median follow-up of 10.5 months, assessments of time to disease
progression (TTP in months) and response rates (RR) showed a significant
augmentation of the chemotherapeutic effect by HERCEPTIN®, without increase
in overall severe adverse events (AE).” Id. at 29:13–18. According to the
inventors:
These data indicate that the combination of anti-ErbB2 antibody
treatment with chemotherapy markedly increases the clinical benefit,
as assessed by response rates and the evaluation of disease progression.
However, due to the increased cardiac side-effects of doxorubicin or
epirubicin, 	the 	combined 	use 	of 	anthracyclines 	with 	anti-ErbB2
antibody therapy is contraindicated. 	The results, taking into account
risk and benefit, favor the combined treatment with HERCEPTIN® and
paclitaxel (TAXOL®).
Id. at 30:17–25.
C. 	Challenged Claims
Petitioner challenges claims 1–11 and 14–17. Pet. 4. Claims 1, 5, and 16
are independent. Claim 1 requires “administering a combination” of three
agents—an anti-ErbB2 antibody, a taxoid, and “a further growth inhibitory
agent”—”in an amount effective to extend the time to disease progression:”
1. 	A method for the treatment of a human patient with breast cancer
that 	overexpresses 	ErbB2 	receptor, 	comprising 	administering 	a
combination of an antibody that binds ErbB2, a taxoid, and a further
growth inhibitory agent to the human patient in an amount effective to
extend the time to disease progression in the human patient, wherein
the antibody binds to epitope 4D5 within the ErbB2 extracellular
domain sequence.
Independent claim 16 is similar to claim 1, but further includes a negative
limitation requiring the administration of the three agents “in the absence of an
anthracycline derivative.”
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Independent claim 5 is also similar to claim 1, but specifies that the taxoid is
paclitaxel. Depending from claims 1 and 5, respectively, claims 2 and 7 require
that the 4D5 anti-ErB2 antibody is humanized.
Claim 5 also differs from claims 1 and 16 in reciting a “further therapeutic
agent,” rather than the “further growth inhibitory agent” of claims 1 and 16.
Claims depending from claim 5 variously specify that this “further therapeutic
agent” is “another ErbB2 antibody, EGFR antibody, ErbB3 antibody, ErbB4
antibody, vascular endothelial growth factor (VEGF) antibody, cytokine, [or]
growth inhibitory agent” (claim 11; see claims 12–14)3, wherein the growth
inhibitory agent may be “a DNA alkylating agent” (claim 15).
D. 	The Asserted Prior Art and Grounds of Unpatentability
Petitioner asserts the following grounds of unpatentability (Pet. 4):
Ground 	Reference 	Basis 	Claims
1 	Nabholtz4 102(b) 	1–8, 10–11, and 14–17
2 	Leyland-Jones5 102(a) 	1–11 and 14–17
3 Claims 12 and 13, respectively, recite that the further therapeutic agent is
“another ErbB3 antibody” and “a vascular endothelial growth factor (VEGF)
antibody.” As set forth in section II(D), below, Petitioner does not assert that these
claims are unpatentable in this Petition.
4 Nabholtz et al., Results of Two Open-Label Multicentre Pilot Phase II Trials with
Herceptin® in Combination with Docetaxel and Platinum Salts (Cis- or
Carboplatin) (TCH) as Therapy for Advanced Breast Cancer In Women with
Tumors Over-Expressing HER2, 64(1) B REAST CANCER RESEARCH AND
TREATMENT 82 (Abstract 327) (2000). Ex. 1114.
5 Leyland-Jones et al., Phase III Comparative Study of Trastuzumab and Paclitaxel
With and Without Carboplatin in Patients with HER-2/neu Positive Advanced
Breast Cancer, 76(Suppl. 1) B REAST CANCER RESEARCH AND TREATMENT S37
(Abstract 35) (2002). Ex. 1150.
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Ground 	Reference 	Basis 	Claims
3 	Yardley6 102(a) 	1–11 and 14–17
Petitioner also relies on Ex. 1111, the declaration of its technical expert,
Allan Lipton, MD.
II. 	ANALYSIS
Petitioner challenges claims 1–11 and 14–17 as anticipated by one or more
of Nabholtz, Leyland-Jones, and Yardley. See Pet. 4, 24–55. Petitioner contends
that each of the asserted references qualifies as prior art under 35 U.S.C. § 102(a)
or (b) because the challenged claims are not entitled to an earlier priority date with
respect to the three-part combinations such that, “the date of the claimed invention
is no earlier than February 3, 2003 (the filing date of the ’549 patent’s claims).”
Id. at 19; see id. at 4–5, 15–19.
Patent Owner responds that, “[d]uring prosecution, the examiner determined
that the challenged claims are entitled to priority to the provisional application
filed on December 12, 1997, and therefore withdrew a rejection based upon the
same Nabholtz reference (Ex. 1114) that Petitioner asserts in Ground 1.” Prelim.
Resp. 1. Patent Owner argues that the Board should deny the instant Petition under
35 U.S.C. § 325(d) because “[t]he Patent Office has already decided the dispositive
issue for this petition” as neither Nabholtz nor the later-published Leyland-Jones
and Yardley references qualify as prior art with respect to the ’549 Patent. Id. For
the reasons that follow, we agree with Patent Owner.
6 Yardley et al., Final Results of the Minnie Pearl Cancer Research Network First-
Line Trial of Weekly Paclitaxel/Carboplatin/Trastuzumab in Metastatic Breast
Cancer, 76 (Suppl. 1) B REAST CANCER RESEARCH AND T REATMENT S113 (Abstract
439) (2002). Ex. 1153.
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Before addressing the details of parties’ arguments, we discuss the relevant
portions of the prosecution history.
A. Relevant Prosecution History.
As indicated in section I(B), above, the ’549 Patent issued from the ’824
Application, filed February 3, 2003, which is a continuation of the ’649
Application, filed Dec. 10, 1998. The ’649 Application claims benefit of priority
to the ’346 Provisional Application, filed Dec. 12, 1997. See e.g., Ex. 1101, 1:4–8.
The Specifications of both the ’649 Application and the ’346 Provisional
Application are substantially identical to that of the ’549 Patent. See, e.g., Prelim.
Resp. 3. Because Nabholtz, Leyland-Jones, and Yardley were published after the
filing date of the ’649 Application, we focus our attention on the disclosure of ’649
Application.
The inventors of the ’549 Patent first claimed the administration of a three-
part combination with the filing of the ’824 Application on February 3, 2003. Cf.
Ex. 1121, 45–46 and Ex. 1119-1, 47. Representative of those claims, claim 20 of
the ’824 Application recited “a combination of an antibody that binds ErbB2, a
taxoid and a further chemotherapeutic agent.” Id. at 47 (emphasis added).
In the first substantive office action, dated June 2, 2006, the Examiner
rejected these claims under 35 U.S.C. § 112, first paragraph, for lack of
enablement. Ex. 1119-5, 34, 38–41. According to the Examiner, “it does not
appear predictable that all antibodies that bind to Her–2/neu will predictably
increase the time to disease progression when combined with paclitaxel and a
further chemotherapeutic agent.” Id. at 39. Thus, according to the Examiner,
while the Specification is “enabling for methods comprising the administration of
Herceptin®, a taxoid and a further chemotherapeutic agent in amounts to extend
time to disease progression,” it “does not reasonably provide enablement for
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methods comprising the use or administration of all anti-Her-2/neu antibodies in
combination with a taxoid and a further chemotherapeutic agent.” Id. at 38–40; see
id. at 288.
In determining whether then-pending claim 20 and similar claims were
entitled to benefit of priority of an earlier-filed application, the Examiner stated:
The claims presently under examination are drawn to method
comprising the administration of an anti-erbB2 antibody, a taxoid and
a further chemotherapeutic agent. 	Parent application 09/208,649
provides support for the combination of a anti-erbB2 antibody and a
taxoid, and appears to provide support for the combination of an anti
erbB2 antibody and any chemotherapeutic agent and further a another
antibody that may bind to EGFR, ErbB3, ErbB4 or VEGF; or further a
cytokine or a growth inhibitory agent. 	However, the specific method
of combining an anti-ErbB2 antibody with a taxoid and a further
chemotherapeutic agent does not appear to have been contemplated, nor
the specific method of combining an anti-ErbB2 antibody with a taxoid
and carboplatin [as set forth in then-pending independent claim 32].
Id. at 41–42 (emphasis added). Based on this initial priority determination, the
Examiner rejected those claims under § 102(b) as anticipated by Nabholtz (Ex.
1114), which is the same invalidity theory as Ground I of the instant Petition. Id.
at 42; Pet. 4, 24–35.
In an amendment filed September 12, 2006, Applicants addressed the
enablement rejection by amending independent claims 20 and 32 to recite,
“wherein the antibody inhibits proliferation of human breast cancer cells that
overexpress ErbB2 receptor and induces antibody-dependent cellular cytotoxicity
(ADCC).” See Ex. 1119-5, 171, 174–178. In accordance with the Examiner’s
statement that “application 09/208,649 . . . appears to provide support for the
combination of an anti-erbB2 antibody and any chemotherapeutic agent and further
. . . a growth inhibitory agent,” Applicants also amended claim 20 to recite “a
combination of an antibody that binds ErbB2, a taxoid and a further growth
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inhibitory agent.” Id. at 41–42, 171, 174, 179 (emphasis added). Applicants
pointed to support for the latter amendment “at least on page 37, lines 9–18, page
35, lines 6–14, and page 16, lines 11–24” of the ’649 Specification.” Id. at 174.
The referenced passages recite:
A “growth inhibitory agent” when used herein refers to a compound
or composition which inhibits growth of a cell, especially an ErbB2
overexpressing cancer cell either in vitro or in vivo. Thus, the growth
inhibitory agent is one which significantly reduces the percentage of
ErbB2 overexpressing cells in S phase. Examples of growth inhibitory
agents include agents that block IE cell cycle progression (at a place
other than S phase), such as agents that induce G1 arrest and M-phase
arrest. Classical M-phase blockers include the vincas (vincristine and
vinblastine), TAXOL®, and topo II inhibitors such as doxorubicin,
epirubicin, daunorubicin, etoposide, and bleomycin. Those agents that
arrest G1 also spill over into S-phase arrest, for example, DNA
alkylating 	agents 	such 	as 	tamoxifen, 	prednisone, 	dacarbazine,
mechlorethamine, cisplatin, methotrexate, 5-fluorouracil, and ara-C . .
. .
Ex. 1121, 20 (16:11–24);
The formulation herein may also contain more than one active
compound as necessary for the particular indication being treated,
preferably those with complementary activities that do not adversely
affect each other. For example, it may be desirable to further provide
antibodies which bind to EGFR, ErbB2 (e.g. an antibody which binds
a different epitope on ErbB2), ErbB3, ErbB4, or vascular endothelial
factor (VEGF) in the one formulation. Alternatively, or in addition, the
composition may comprise a cytotoxic agent, cytokine or growth
inhibitory agent, provided that the cytotoxic agent is other than an
anthracycline 	derivative, 	e.g. 	doxorubicin, 	or 	epirubicin. 	Such
molecules are suitably present in combination in amounts that are
effective for the purpose intended.
id. at 39 (35:6–14); and
It may be desirable to also administer antibodies against other tumor
associated antigens, such as antibodies which bind to the EGFR, ErbB3,
ErbB4, or vascular endothelial factor (VEGF). 	Alternatively, or in
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addition, two or more anti-ErbB2 antibodies may be co-administered to
the patient. Sometimes, it may be beneficial to also administer one or
more cytokines to the patient. 	In a preferred embodiment, the ErbB2
antibody 	is 	co-administered 	with 	a 	growth 	inhibitory 	agent. 	For
example, the growth inhibitory agent may be administered first,
followed 	by 	the 	ErbB2 	antibody. 	However, 	simultaneous
administration or administration of the ErbB2 antibody first is also
contemplated. 	Suitable dosages for the growth inhibitory agent are
those presently used and may be lowered due to the combined action
(synergy) of the growth inhibitory agent and anti-ErbB2 antibody.
id. at 41 (37:9–18).
Applicants also argued that claim 32, directed to the specific 3-part
combination of “an antibody that binds ErbB2, a taxoid and carboplatin” was
supported in the ’649 Application at:
- 	Page 5, lines 4–5 referring to “chemotherapeutic regimens”
(emphasis added);
- 	Page 5, lines 14–17 stating that “treatment with anti-ErbB2
antibodies 	markedly 	enhances 	the 	clinical 	benefit 	of 	the 	use 	of
chemotherapeutic agents in general” (emphasis added);
- 	Page 37, line 2 which refers to “dosing schedules for such
chemotherapeutic agents” (emphasis added), “such chemotherapeutic
agents” being other than an anthracycline derivative (page 36, lines 26–
27) and including carboplatin and taxoids (page 16, lines 1–10) . . . .
Ex. 1119-5, 180; see Ex. 1121, 9 (5:4–5, 14–17), 41 (37:2). Applicants pointed to
additional support for the 3-part combination of anti-ErbB2 antibody, taxoid, and
carboplatin, at page 35, line 6 of the ’649 Specification, which provides support for
combining “more than one active compound.” Id.; see Ex. 1121, 39 (35:6).
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In a subsequent office action, dated September 11, 2007,7 the Examiner
maintained that claim 32, directed to a three-drug combination comprising
carboplatin, was not supported by the earlier applications; maintained the
enablement rejection of claims 20 and 32 because the Specification did not appear
to contemplate anti-ErbB2 antibodies other than based on the 4D5 epitope; and
further determined that the then-pending claims were not entitled to benefit of
priority because they were “drawn to methods of treating human patients with
breast cancer that expresses ErbB2 receptor, whereas the disclosures of the parent
applications teach the treatment of breast cancer that overexpresses ErbB2
receptor.” Ex. 1119-5, 286, 290–93 (emphasis added). Although the Examiner
determined that claim 20 was still not entitled to benefit of priority, she expressly
stated that “the specifications of the parent applications . . . generally teach[]
combining an anti-ErbB2 antibody with a taxoid and a further agent which is . . . a
growth inhibitory agent . . . .” See id. at 292–93.
On January 28, 2008, Applicants engaged in an Examiner interview,
wherein, according to the Examiner’s Interview Summary, the parties “[d]iscussed
proposed amendments and arguments, which appear to overcome rejections of
record under 112, first, 112, 2nd and 102(b).” Ex. 1119-6, 241. Shortly thereafter,
on February 8, 2008, Applicants submitted an amendment cancelling claims 1–33,
including claim 32 reciting the three-drug carboplatin combination, and amending
certain independent claims to recite methods “for the treatment of a human patient
with breast cancer that overexpresses ErbB2 receptor.” Ex. 1119-5, 303–304
(emphasis added). Upon entry of that amendment, then-pending claim 34 was
7 We note that although Petitioner relies on the Office Action dated December 5,
2006 (see Pet. 13–14), the Examiner vacated that Action in the September 11, 2007
Office Action. Ex. 1119-5, 288.
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identical to claim 1 of the ’549 patent. Cf. id. at 303, claim 34 with Ex. 1001,
claim 1.
Applicants also amended then-pending claim 38 to recite the three-part
combination of “an anti-ErbB2 antibody which binds to epitope 4D5 within the
ErbB2 extracellular domain sequence, a taxoid, and a further therapeutic agent.”
Ex, 1119-5, 303. With respect to support for the claimed “further therapeutic
agent” (as is recited in claim 16 of the ’549 Patent), Applicants cited
[P]age 37, lines 7-29 which provides support for the inclusion of a
genus of further therapeutic agents in addition to the anti-ErbB2
antibody and chemotherapeutic agent (e.g. the taxoid), such as another
ErbB2 antibody, EGFR antibody, ErbB3 antibody, ErbB4 antibody,
vascular endothelial growth factor (VEGF) antibody, cytokine, or
growth inhibitory agent.
Id. at 306; see also Ex. 1121, 40–41 (36:26–37:18) (corresponding passage from
’649 Application).
In response to the February 8, 2008 amendments, the Examiner withdrew all
rejections under 35 U.S.C. § 112, and determined that the then-pending claims
have priority to the ’346 Provisional Application (and, thus, to the substantially
identical ’649 Application). See Ex. 1119-6, 244–45. The Examiner then
withdrew the § 102(b) rejection over Nabholtz “in view of the amendment to the
claims so that now the claims have priority to parent application 60/069,346 (filed
12/12/1997).” Id. at 245.
The ’649 Patent ultimately issued after further arguments and amendments
not directly relevant this Decision. See e.g., Ex. 1119-7, 93 (Notice of
Allowability dated October 8, 2010).
B. 	The Parties’ Arguments
Petitioner argues that the ’739 Patent is not entitled to benefit of priority of
the ’649 Application because the challenged claims fail to satisfy the written
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description and enablement requirements of 35 U.S.C. § 112, first paragraph. See
Pet. 15–19. We address those contentions in turn.
a. 	Written Description
With respect to written description, Petitioner argues that, “[t]here is no
disclosure of any method of treatment in which the claimed three-drug
combination is administered.” Id. at 16. Patent Owner responds that during
prosecution leading to the issuance of the 549 Patent, Applicants
established priority for those claims based upon the parent application’s
specific disclosure of using growth inhibitory agents as part of the
present invention. 	(Ex. 1119-5 at 179 (citing Ex. 1121 at 20 (16:11
24), 39 (35:6-14), 41 (37:9-18).) 	Based upon that disclosure, the
examiner agreed that the claims reciting a combination with “a further
growth inhibitory agent” were supported by, and thus entitled to priority
to, the parent applications. (Ex. 1119-5 at 41; id. at 292-93; Ex. 1119
6 at 245.)
Prelim. Resp. 10–11; see also id. 11, n.3 (arguing that Applicant demonstrated
support for a three-part combination comprising a “further therapeutic agent”).
Having considered the Specification of the ’649 Application and the arguments
raised during prosecution, as discussed section II(B), above, Petitioner has not
presented any further evidence in this proceeding that would persuade us to reach a
conclusion different from the Examiner’s position that the challenged claims are
adequately disclosed in the priority document.
b. 	Enablement
Petitioner further argues that the challenged method claims involving the
three-drug combinations are not entitled to benefit of priority because the earlier
applications do not disclose clinical results demonstrating that the use of those
combinations were enabled. See Pet. 17–19; Ex. 1111 ¶¶ 53–55. Petitioner argues
that Applicant’s statement to the Examiner “that ‘data from clinical trials of the
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combination are needed to demonstrate that they can be usefully combined,’”
flatly contradicts Patent Owner’s position that the ’649 Application and ’346
Provisional Application adequately disclose the claimed invention. Pet. 17–18
(citing Ex. 1119-5, 308–09). We do not find Petitioner’s argument persuasive. As
an initial matter, Petition fails to address the “Wands” factors in its enablement
analysis. See In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
Moreover, considered in context, we read the thrust of Applicants’ argument
as indicating that clinical trials were necessary to establish that anti-ErbB2
antibodies could be efficaciously combined with known chemotherapies—as was
demonstrated in the ’549 Patent’s Example. See Ex. 1101, 29:12–30:25 (showing
response rates and time to disease progression for combinations of anti-ErbB2
antibodies with either anthracycline and cyclophosphamide (AC) or taxol (T). In
particular, the passage Petitioner cites derives from Applicants’ argument that the
Perez reference teaches that, although
both ‘paclitaxel and carboplatin have significant single-agent activity’
. . . only their ongoing trial of the combination [] would ‘answer the
question of the potential role of this combination.’ 	In other words,
Perez supports the notion that even if individual agents are known for
cancer therapy, data from clinical trials of the combination are needed
to demonstrate that they can be usefully combined. Moreover, even if
Perez provides an invitation to experiment with the combination of
paclitaxel/carboplatin, this would not have provided a reasonable
prediction as to the efficacy of a biologic such as rhuMAb HER2 with
chemotherapy, such as a taxoid, particularly given the state of the art at
the filing date at which time no biologic had been approved in the US
for therapy of a solid tumor, such as breast cancer.
Ex. 1119-5, 308–309. In that same Response, Applicants also argued that Baselga
1996 “did not reveal whether the addition of rhuMAb HER2 antibody to
chemotherapy could extend TTP in patients compared to antibody or
chemotherapy alone.” Ex. 1119-5, 308. We also note that as of the filing date of
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the ’649 Application, the combination of paclitaxel and another platinum-based
chemotherapeutic (cisplatin) was known to be effective in the treatment of
metastatic breast cancer. See Ex. 1125; Ex. 1111 ¶¶ 29–30, 73; see also copending
IPR2017-00739, Paper 1 at 16–17 (Petitioner’s arguments that “[d]rug
combinations, generally, including two- and three-agent combinations, were
routinely used to fight cancer, including breast cancer,” and that “the combination
of paclitaxel with cisplatin was also known to be synergistic”).
Accordingly, we agree with Patent Owner that Applicants’ argument was
intended to “support[] the patentability of the pending claims, not that the results of
clinical trials were necessary to render obvious the claimed three-drug
combination.” See Prelim. Resp. 12.
Petitioner also argues that “to obtain earlier priority for claims directed to an
‘effective’ use of a cancer drug treatment, the inventor must ‘provide experimental
proof that his invention could be effective in treating cancer.’” Pet. 18–19 (citing
Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1324 (Fed. Cir. 2005).
We do not read Rasmusson so broadly. The Court in Rasmusson noted that,“[t]he
Board found that a person of ordinary skill in the art would not have believed that
finasteride was effective in treating prostate cancer simply because finasteride was
known to be a selective 5αR inhibitor. . . . because the anti-tumor effects shown by
published experiments involving multi-active 5αR inhibitors could be attributable
to contaminating activities having no relation to 5αR inhibition.” 413 F.3d at
1324. Moreover, “Rasmusson did not make any contrary showing that a person of
ordinary skill . . . would have recognized that a selective 5αR inhibitor . . . would
have been effective in treating prostate cancer. Id. Accordingly, in order to obtain
an earlier priority date, “Rasmusson needed to provide experimental proof that his
invention could be effective in treating cancer.” Id.
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In comparison to Rasmusson, the present case is not so lacking in evidence.
As discussed in section I(B), above, the ’649 Application presents clinical results
demonstrating the effectiveness of 2-part combinations comprising anti-ErbB2
antibodies and various chemotherapeutic agents, including paclitaxel. In addition,
Petitioner admits in a co-pending Petition involving the same patent, that multi-
drug combinations of chemotherapy agents were routinely used to treat breast
cancer. See IPR2017-00739, Paper 1 at 17.8
For these reasons, we find the instant case distinguishable from Rasmusson
and, based on the facts before us, find that it not unreasonable to infer that
“determining an effective amount of a three drug combination is a matter of routine
experimentation within the general knowledge and skill set of a POSITA.” See Ex.
1111 ¶ 52. Accordingly, we determine that Petitioner has not shown that the
challenged claims are not entitled the benefit of priority to earlier applications due
to lack of enablement.
C. Section 325(d)
Institution of an inter partes review is discretionary. See Harmonic Inc. v.
Avid Tech., Inc., 815 F.3d 1356, 1367 (Fed. Cir. 2016) (explaining that under
§ 314(a), “the PTO is permitted, but never compelled, to institute an IPR
proceeding”). Accordingly, our rules provide that “the Board may authorize the
review to proceed” or “deny some or all grounds for unpatentability for some or all
of the challenged claims.” 37 C.F.R. § 42.108(a), (b). Our discretionary
8 We further note that “Petitioner’s priority analysis does not cite or discuss the
Wands factors, or otherwise analyze whether the disclosure of the provisional
application would have required undue experimentation by a person of ordinary
skill trying to make and use the invention.” See Prelim. Resp. 15 (citing Pet. 16–
19; Ex. 1111 ¶¶ 53–55).
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Patent 7,892,549 B2
determination of whether to institute review is guided, in part, by 35 U.S.C. §
325(d), which states, in relevant part:
MULTIPLE PROCEEDINGS -- . . . In determining whether to institute
or order a proceeding under this chapter, chapter 30, or chapter 31, the
Director may take into account whether, and reject the petition or
request because, the same or substantially the same prior art or
arguments previously were presented to the Office.
35 U.S.C. § 325(d).
Our discretion under § 325(d) involves a balance between several competing
interests. See Neil Ziegman, N.P.Z., Inc. v. Stephens, Case IPR2015-01860, slip
op. at 12–13 (PTAB Feb. 24, 2016) (Paper 11) (“While petitioners may have sound
reasons for raising art or arguments similar to those previously considered by the
Office, the Board weighs petitioners’ desires to be heard against the interests of
patent owners, who seek to avoid harassment and enjoy quiet title to their rights.”)
(citing H. Rep. No. 112-98, pt. 1, at 48 (2011)). “On the one hand, there are the
interests in conserving the resources of the Office and granting patent owners
repose on issues and prior art that have been considered previously.” Fox Factory,
Inc. v. SRAM, LLC, Case IPR2016-01876, slip op. 7 (PTAB Apr. 3, 2017) (Paper
8). “On the other hand, there are the interests of giving petitioners the opportunity
to be heard and correcting any errors by the Office in allowing a patent—in the
case of an inter partes review—over prior art patents and printed publications.” Id.
As discussed in section II(B), above, the Examiner considered fully the
written description and enablement issues underlying Applicant’s claim to priority
in allowing the claims to issue, and Petitioner has not presented new evidence or
arguments that would convince us that the Examiner’s determination was
unreasonable. The Examiner’s decision to withdraw the rejection under 35 U.S.C.
§ 102(b) over Nabholtz was expressly predicated on that priority determination,
which removed Nabholtz as prior art. In Ground I of this Petition, Petitioner also
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Patent 7,892,549 B2
asserts that the claims are unpatentable under § 102(b) over Nabholtz, thus raising
“the same or substantially the same prior art or arguments previously [] presented
to the Office” as contemplated under 35 U.S.C. § 325(d). Under the circumstances
of this case, we exercise our discretion under § 325(d) and decline to institute inter
partes review based on Ground I.
Because the priority determination with respect to Nabholtz is dispositive
with respect to whether the later-published Leyland-Jones and Yardley references
qualify as prior art, we likewise exercise our discretion under § 325(d) and decline
to institute inter partes review based on Grounds II and III.
III. 	ORDER
In consideration of the foregoing, it is ORDERED that the Petition is
denied, and no trial is instituted.
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Patent 7,892,549 B2
PETITIONER:
Amanda Hollis
Stefan Miller
Karen Younkins
KIRKLAND & ELLIS LLP
Amanda.hollis@kirkland.com
dichromik@gmail.com
Karen.younkins@kirkland.com
PATENT OWNER:
David Cavanaugh
Owen Allen
WILMER CUTLER PICKERING HALE AND DORR LLP
David.cavanaugh@wilmerhale.com
Owen.allen@wilmerhale.com
Adam Brausa
DURIE TANGRI LLP
abrausa@durietangri.com
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