Wyeth LLC v. Astrazeneca Pharmaceuticals Lp, Astrazeneca Ab

United States Court of Appeals
for the Federal Circuit
______________________
WYETH LLC,
Plaintiff-Appellant
v.
ASTRAZENECA PHARMACEUTICALS LP,
ASTRAZENECA AB,
Defendants-Appellees
______________________
2024-2325
______________________
Appeal from the United States District Court for the
District of Delaware in No. 1:21-cv-01338-MFK, Judge
Matthew F. Kennelly.
______________________
Decided: July 9, 2026
______________________
J ENNIFER L. SWIZE, Jones Day, Washington, DC, ar-
gued for plaintiff-appellant. Also represented by ANTHONY
I NSOGNA, San Diego, CA; D ANIEL P AUL J OHNSON, Pitts-
burgh, PA; G ASPER LAROSA, New York, NY; MATTHEW J.
RUBENSTEIN, Minneapolis, MN; J ASON G. WINCHESTER ,
Chicago, IL.
CHRISTOPHER N EIL SIPES , Covington & Burling LLP,
Washington, DC, argued for defendants-appellees. Also
represented by ROBERT J ASON F OWLER, M EGAN P ATRICIA
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 2
K EANE, EINAR STOLE, ALEXANDER T RZECIAK, ASHLEY MARIE
WINKLER.
______________________
Before L OURIE, L INN, and HUGHES , Circuit Judges.
L OURIE, Circuit Judge.
Wyeth appeals from a final decision of the United
States District Court for the District of Delaware granting
judgment as a matter of law (“JMOL”) of invalidity of as-
serted claims 1, 3, and 9 of U.S. Patent 10,603,314
(“the ’314 patent”) and asserted claim 1 of U.S. Pa-
tent 10,596,162 (“the ’162 patent”) (together, “the asserted
patents”). Wyeth LLC v. Astrazeneca Pharms. LP, No. 21-
CV-1338, 2024 WL 3823006 (D. Del. Aug. 14, 2024) (“Deci-
sion”). For the following reasons, we affirm.
BACKGROUND
Wyeth’s ’314 and ’162 patents generally relate to meth-
ods of cancer treatment. Specifically, the asserted patents
claim methods of using irreversible inhibitors to treat “ge-
fitinib and/or erlotinib resistant” non-small cell lung cancer
(“NSCLC”). ’314 patent, Abstract. NSCLC is associated
with overactivity of the epidermal growth factor receptor
(“EGFR”), a receptor tyrosine kinase that regulates cell
growth and division. Id. at col. 2 ll. 1–3. Drugs used to
treat NSCLC—known as EGFR tyrosine kinase inhibitors
(“TKIs”)—bind to specific regions of EGFR and inhibit sig-
naling that would otherwise promote cancer cell growth.
Id. at col. 2 ll. 52–62.
Two TKIs, gefitinib and erlotinib (together, “g/e”),
showed promise in treating NSCLC. Gefitinib and erlo-
tinib are “reversible” inhibitors, meaning they form non-
covalent bonds with EGFR that dissociate over time. As a
result, “[a] significant limitation in using [reversible inhib-
itors such as g/e] is that recipients thereof may develop a
resistance to their therapeutic effects after they initially
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 3
respond to therapy, or they may not respond to EGFR-TKIs
to any measurable degree at all.” Id. at col 3 ll. 19–23; see
also id. at col. 7 ll. 57–63. The inventions of the asserted
patents seek to address this shortcoming through the use
of “irreversible” EGFR inhibitors. That is, the asserted pa-
tents claim a method for treating “g/e resistant NSCLC” by
using “irreversible” EGFR inhibitors that covalently bind
to a specific amino acid at a specific location of EGFR. Id.
at col. 3 ll. 43–49, col. 7 ll. 15–19. Specifically, exemplary
claim 1 of the ’314 patent recites:
1. A method for treating gefitinib and/or erlotinib
resistant non-small cell lung cancer in a patient in
need thereof, comprising administering daily to the
patient having gefitinib and/or erlotinib resistant
non-small cell lung cancer a pharmaceutical com-
position comprising a unit dosage of an irreversible
epidermal growth factor receptor (EGFR) inhibitor
that covalently binds to cysteine 773 residue in the
ligand-binding pocket of EGFR or cysteine 805 res-
idue in the ligand-binding pocket of erb-B2.
Id. at col. 35 ll. 52–60 (emphases added).
The specification discloses that the claimed “irreversi-
ble EGFR inhibitor may be any compound which binds to
cysteine 773 of EGFR (SEQ ID NO: 1).”1 Id. at col. 3 ll. 57–
59. It then describes, in total, three compounds (i.e., EKB-
569, HKl-357, and HKl-272) as examples of such EGFR in-
hibitors. Id. at col. 13 ll. 50–51. In describing the in vitro
experimentation involving these three compounds, the
specification states that the results “demonstrate[d] in-
creased killing of NSCLC cells harboring an EGFR muta-
tion.” Id. at col. 16 ll. 21–22.
1 The ’314 and ’162 patents’ specifications are mate-
rially the same, and we therefore cite the ’314 specification
as exemplary.
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 4
The specification also discloses that “[t]he therapeutic
compositions of this invention, e.g. irreversible EGFR in-
hibitors, are conventionally administered intravenously, as
by injection of a unit dose, for example.” Id. at col. 9 ll. 30–
32. It further states that the claimed “unit dosage” refers
to “physically discrete units suitable as unitary dosage for
the subject, each unit containing a predetermined quantity
of active material calculated to produce the desired thera-
peutic effect in association with the required diluents; i.e.,
carrier, or vehicle.” Id. at col. 9 ll. 33–38 (emphases added).
As it relates to the claimed requirements of “administering
[a unit dosage] daily to the patient,” id. at col. 35 ll. 52–60,
the specification explains that calculating a unit dosage to
achieve such therapeutic effect in a patient “depends on the
subject to be treated, capacity of the subject’s system to uti-
lize the active ingredient, and degree of therapeutic effect
desired,” id. at col. 9 ll. 42–46, in addition to “the particular
compound employed, the mode of administration and the
severity of the condition being treated,” id. at col. 8 ll. 55–
57.
Accounting for those variable factors, the specification
states that the “[p]recise amounts of active ingredient . . .
depend on the judgment of the practitioner and are pecu-
liar to each individual.” Id. at col. 9 ll. 44–46. In terms of
any additional guidance, the specification explains that a
“skilled artisan is aware of the effective dose for each pa-
tient,” id. at col. 8 ll. 57–58, and offering that, “in general,
satisfactory results are obtained when the compounds of
the invention are administered at a daily dosage of from
about 0.5 to about 1000 mg/kg of body weight,” and that the
“total daily dosage is projected to be from about 1 to 1000
mg, preferably from about 2 to 500 mg,” id. at col. 8 ll. 59–
66 (emphases added).
In September 2021, Wyeth filed a complaint in the dis-
trict court asserting that AstraZeneca induced infringe-
ment of the ’314 and ’162 patents based on marketing,
distribution, and sales of its irreversible EGFR inhibitor
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 5
Tagrisso (osimertinib). Decision, 2024 WL 3823006, at *2.
The district court construed several terms, including the
term “unit dosage.” See Puma Biotechnology, Inc. v. Astra-
zeneca Pharms. LP, No. 21-CV-1338, 2023 WL 2683559,
at *9 (D. Del. Mar. 29, 2023) (“Claim Construction Deci-
sion”). The court explained that the “claimed methods in-
volve administering daily a ‘unit dosage’ of an irreversible
EGFR inhibitor that covalently binds to a specific part of
the enzyme.” Id. at *1. The court identified that the spec-
ification “expressly define[d]” a “unit dos[age],” and ulti-
mately adopted that definition: “physically discrete units
suitable as unitary dosage for the subject, each unit con-
taining a predetermined quantity of active material calcu-
lated to produce the desired therapeutic effect in association
with the required diluents; i.e., carrier, or vehicle.” Id. at
*9 (quoting ’314 patent col. 9 ll. 33–38 (emphases added)).
The case proceeded and after a five-day trial, a jury
concluded that the asserted claims were not invalid and
that AstraZeneca induced infringement of the asserted
claims, awarding Wyeth $107,500,000 in damages. Deci-
sion, 2024 WL 3823006, at *3. AstraZeneca renewed its
motion for JMOL post-verdict and argued, in part, that no
reasonable jury could have found the asserted patents not
invalid. Id. at *1. As relevant on appeal, AstraZeneca ar-
gued that the asserted claims were invalid for lack of ena-
blement. Id. at *9. Specifically, it argued that “the patents
claim but do not enable treatment via a ‘unit dosage—i.e.,
a predetermined quantity of active material calculated to
produce the desired therapeutic effect.’” Id. (quoting ’314
patent col. 9 ll. 36–37). “In [AstraZeneca’s] view, identify-
ing the unit dosage for even just a single compound is
highly unpredictable and involves [a] tremendous amount
of work and experimentation.” Id. at *12 (cleaned up).
Moreover, it contended that even while the asserted pa-
tents identify “unit dosage” ranges of 1 to 1,000 mg and 2
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 6
to 500 mg, those ranges were too broad and provided insuf-
ficient guidance for a skilled artisan to determine a suita-
ble dosage. Id.
Wyeth disagreed and “argue[d] that the patents pro-
vide sufficient disclosure of ‘unit dosages’ that would
achieve the desire[d] therapeutic effect of interfering with
the EGFR pathway and killing cancer cells and that deter-
mining the dosage for any given irreversible EGFR inhibi-
tor would not require undue experimentation.” Id. It
added that AstraZeneca’s arguments sought to improperly
add clinical requirements of toxicity, safety, and efficacy,
which fall within the domain of FDA. Id. at *12–13.
The district court granted JMOL of invalidity for lack
of enablement of the asserted claims determining that no
reasonable jury could have found the asserted claims not
invalid. Id. at *15. At the outset of its analysis, the court
made clear that the asserted claims do not require “FDA
approval []or clinical effectiveness.” Id. at *13. At the same
time, it rejected Wyeth’s characterization that the asserted
patents merely “claim ‘a method for killing cancer cells,’ . . .
full stop.” Id. Rather, the district court explained that the
asserted patents claim a method of treating g/e resistant
NSCLC “in a patient” with “a unit dosage” that must be
“administer[ed] daily to the patient.” Id. (quoting ’314 pa-
tent col. 35 ll. 53–57). In other words, it concluded that the
claims do not require “ideal or optimal dos[ing]” as the FDA
requires but do require “that the ‘unit dosage’ ‘produce[s]
the desired therapeutic effect’ in a patient.” Id. (citing
Claim Construction Decision, 2023 WL 2683559, at *9 (em-
phasis added)).
The district court next turned to the evidence pre-
sented at trial. Id. at *13–14. It concluded that Astra-
Zeneca presented clear and convincing evidence that no
reasonable jury could have found that the asserted patents
enabled a skilled artisan to administer the claimed “unit
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 7
dosage” of the claimed irreversible EGFR inhibitor to a pa-
tient without undue experimentation. Id. at *14. The court
emphasized that (1) the specification disclosed no working
examples of unit dosages administered to patients, and
(2) AstraZeneca presented unrebutted evidence that some
disclosed dosage levels would be toxic, including doses re-
quired to achieve a therapeutic effect in patients. Id.
The district court relied on trial testimony of Wyeth’s
own experts agreeing that a therapeutic unit dosage in a
patient must avoid toxic doses, see J.A. 17548, and further
agreeing that the specification’s disclosed dosage ranges
exceed the maximum tolerated dose for two of the disclosed
compounds, see J.A. 17397–98, J.A. 17549, and potentially
the third, see J.A. 17563. See Decision, 2024 WL 3823006,
at *14. It also relied on testimony of the inventors of the
asserted patents who explained that, via a post-application
2008 Godin-Heymann publication, the “concentrations re-
quired in vitro may not be achievable in patients due to
drug toxicity.” J.A. 11804, 11807; see also J.A. 17397–98
(co-inventor Dr. Haber testifying that “[t]he concentrations
in the test tube are higher than those you can give to pa-
tients” and specifically agreeing that the drug concentra-
tions in the asserted patents were found to be “five times
higher” than what could be administered to patients).
In view of that evidence, the district court concluded
that the asserted patents “provide[d] ‘only a starting point,
a direction for future research’ that place[d] the burden on
a [skilled artisan] to conduct ‘an iterative, trial-and-error
approach to practice the claimed invention.’” Id. at *15
(quoting ALZA Corp. v. Andrx Pharms., LLC, 603 F.3d 935,
939–41 (Fed Cir. 2010)). It also explained that the experi-
mentation necessary to achieve a suitable unit dosage
would not be routine because the asserted patents lacked
guidance on how a skilled artisan could reliably screen
compounds to determine their therapeutic dosage ranges.
Id. In sum, the district court held “the asserted claims of
the ’314 and ’162 patents [ ] invalid for failure to meet the
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 8
enablement requirement of 35 U.S.C. § 112(a)” and
granted AstraZeneca’s motion for JMOL of invalidity. Id.
Wyeth timely appealed. We have jurisdiction under
28 U.S.C. § 1295(a)(1).
D ISCUSSION
Wyeth asks us to reinstate the jury verdict on the
ground that the district court erred in granting JMOL of
invalidity for lack of enablement of the asserted claims of
the ’314 and ’162 patents. It contends that the district
court improperly changed its construction of the term “unit
dosage” post-verdict by imposing additional clinical safety
and efficacy requirements. See Wyeth Op. Br. 24–26. It
also argues that the district court further erred by testing
its new and flawed construction against the jury’s verdict
in its enablement analysis, and that even if such construc-
tion were appropriate, its grant of JMOL of lack of enable-
ment fails on the evidence.2 See id. We disagree and
discuss each argument in turn.
I
We apply our own law with respect to patent law is-
sues. Midwest Indus., Inc. v. Karavan Trailers, Inc.,
175 F.3d 1356, 1359 (Fed. Cir. 1999) (en banc in relevant
part). For matters not unique to patent law, we apply the
law of the regional circuit, here, the Third Circuit. Versata
Software, Inc. v. Callidus Software, Inc., 780 F.3d 1134,
1136 (Fed. Cir. 2015) (applying Third Circuit law). The
Third Circuit reviews grants and denials of motions for
JMOL under Rule 50(b) de novo. Cordance Corp. v. Ama-
zon.com, Inc., 658 F.3d 1330, 1333 (Fed. Cir. 2011) (citing
2 Wyeth also appeals a second issue regarding pre-
patent-issuance damages and provisional rights under
35 U.S.C. § 154(d). Because we affirm the district court’s
grant of JMOL of invalidity, we do not reach that issue.
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 9
Lightning Lube, Inc. v. Witco Corp., 4 F.3d 1153, 1166 (3d
Cir. 1993)). Moreover, in the Third Circuit, “JMOL is
proper when after ‘viewing the evidence in the light most
favorable to the nonmovant and giving it the advantage of
every fair and reasonable inference, there is insufficient ev-
idence from which a jury reasonably could find’ for the non-
movant.” Id.
A
We first address claim construction. Wyeth contends
that the district court improperly imported clinical safety
and efficacy requirements into the claims because, in its
view, the claims require only that the “unit dosage” provide
the therapeutic effect of “inhibiting EGFR and killing can-
cer cells” full stop. Wyeth Op. Br. 24. It argues that be-
cause the claims do not include clinical-trial endpoints, a
grant of JMOL based on the importation of unclaimed
safety standards, or any consideration of “a safe unit dos-
age,” cannot be supported. Id. (citing United Therapeutics
Corp. v. Liquidia Techs., Inc., 74 F.4th 1360, 1369 (Fed.
Cir. 2023), cert. denied, 144 S. Ct. 873 (2024) (“Absent in-
corporation of safety and efficacy requirements in the
claims,” arguments “concerning the safety and efficacy of
treating . . . patients [are] not before us.”)). We disagree.
Wyeth mischaracterizes the claims and the district court’s
interpretation of those claims.
“We review claim construction based on intrinsic evi-
dence de novo and review any findings of fact regarding ex-
trinsic evidence for clear error.” Regeneron Pharms., Inc.
v. Mylan Pharms. Inc., 130 F.4th 1372, 1378 (Fed. Cir.
2025) (citation omitted). “Claim terms are generally given
their plain and ordinary meaning, which is the meaning
that one of ordinary skill in the art would ascribe to a term
when read in the context of the claims, specification, and
prosecution history.” Id. at 1378–79 (citing Phillips v.
AWH Corp., 415 F.3d 1303, 1313–17 (Fed. Cir. 2005)(en
banc)). Ultimately, “[t]he construction that stays true to
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 10
the claim language and most naturally aligns with the pa-
tent’s description of the invention will be, in the end, the
correct construction.” Phillips, 415 F.3d at 1316 (citation
omitted).
While Wyeth is correct that the claims do not require
FDA-type clinical safety or efficacy standards, it fails to ap-
preciate and give meaning to other relevant claim terms—
namely, that the claimed “unit dosage” must be “adminis-
ter[ed] daily” to a human “patient.” ’314 patent col. 35 ll.
53–57. Each of those terms should be afforded meaning.
See Merck & Co. v. Teva Pharms. USA, Inc., 395 F.3d 1364,
1372 (Fed. Cir. 2005) (“A claim construction that gives
meaning to all the terms of the claim is preferred over one
that does not do so.” (citations omitted)). Moreover, the dis-
trict court’s pre-trial construction of the term “unit dosage,”
which adopts the specification’s definition, is unchallenged.
Thus, “unit dosage” refers to “physically discrete units suit-
able as unitary dosage for the subject, each unit containing
a predetermined quantity of active material calculated to
produce the desired therapeutic effect in association with
the required diluents; i.e., carrier, or vehicle.” Claim Con-
struction Decision, 2023 WL 2683559, at *9 (emphases
added) (citing ’314 patent col. 9 ll. 34–38).
The claims therefore plainly require the daily admin-
istration of a unit dosage to a patient to achieve a thera-
peutic effect in treating g/e-resistant NSCLC, not merely
the identification of compounds capable of inhibiting EGFR
activity in vitro. That interpretation does not import any
FDA-type safety or efficacy requirements into the claims as
Wyeth contends. It simply gives operative meaning to the
claim language itself, which necessarily contemplates some
repeatable dosing regimen calculated to produce a thera-
peutic effect in a patient. In particular, the requirement
that a “unit dosage” must be “administer[ed] daily to the
patient” draws the claims beyond merely requiring “killing
cancer cells,” yet constrains them short of requiring full-
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 11
blown FDA-type clinical safety standards. See ’314 patent
col. 35 ll. 53–57.
The specification reinforces that plain reading of the
claims. Rather than describing dosage solely in terms of
whether a compound can kill cancer cells or inhibit EGFR
activity, the patent explains that calculating a therapeuti-
cally effective dosage “depends on the subject to be treated,
capacity of the subject’s system to utilize the active ingre-
dient, and degree of therapeutic effect desired.” ’314 patent
col. 9 ll. 42–44. The specification further recognizes that
the “[p]recise amounts of active ingredient . . . depend on
the judgment of the practitioner and are peculiar to each
individual.” Id. at col. 9 ll. 44–46. Together, these disclo-
sures support the interpretation that the claimed “unit dos-
age” contemplates a dosage regimen tailored for practical
administration to a human patient, not merely any concen-
tration capable of producing anti-cancer effects in vitro.
The district court therefore did not err in its claim con-
struction, nor its elaboration of that construction, post-ver-
dict. In fact, the court maintained on JMOL that “there is
no requirement that the asserted patents enable a ‘unit
dosage’ that is acceptable in terms of lacking side effects,
meeting the FDA’s safety criteria, having a particular level
of effectiveness against a patient’s cancer progression or
other clinical symptoms, or meeting any other criteria that
might make a drug an attractive option for a practicing cli-
nician.” Decision, 2024 WL 3823006, at *13. It also ex-
plained that the claims’ lack of FDA-type limitations does
not necessarily mean that the claims therefore provide no
meaningful limitations on dosing. See id. at *13–14. Thus,
the court simply reinforced its prior construction of the
claims, explaining that they require the administration of
a unit dosage “calculated to produce the desired therapeu-
tic effect” in a patient. See id. at *13. That the court, in
part, framed the bounds of this limitation in terms of “tox-
icity” concerns, see id. at *13–14, simply reflects a recogni-
tion that the requirement of “administering daily to the
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 12
patient” must have some operative meaning, i.e., a repeat-
able dosing regimen in human patients. It does not mean
that the claims require more particular FDA-type clinical
standards of safety or efficacy.
Finally, the district court did not improperly amend its
construction post-verdict, as Wyeth contends. See Wyeth
Op. Br. 25–26. Before and after trial, the court construed
the claims to require daily administration of a “unit dos-
age” “to produce the desired therapeutic effect” in a patient.
Compare Claim Construction Decision, 2023 WL 2683559,
at *9, with Decision, 2024 WL 3823006, at *13. The district
court’s “elaboration” on its construction of “unit dosage”
post-verdict was permissible to “clarif[y] what was inher-
ent in the construction.” Cordis Corp. v. Bos. Sci. Corp.,
658 F.3d 1347, 1356 (Fed. Cir. 2011).
We therefore find no error in the district court’s claim
construction nor its elaboration of that construction on
JMOL.
B
We next address enablement. Wyeth argues that the
district court erred in granting JMOL because, viewing the
evidence in the light most favorable to Wyeth, a reasonable
jury could have concluded that AstraZeneca failed to prove
by clear and convincing evidence that the asserted claims
require undue experimentation to determine a non-toxic or
non-fatal unit dosage for daily administration to a patient.
See Wyeth Op. Br. 37–45. We disagree. Wyeth mischarac-
terizes the district court’s analysis, and, regardless, the
specification fails to enable the claims as properly con-
strued.
“Enablement is a legal question based on underlying
factual determinations.” Vasudevan Software, Inc. v. Mi-
croStrategy, Inc., 782 F.3d 671, 684 (Fed. Cir. 2015) (cita-
tion omitted). The enablement requirement is satisfied
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 13
when the specification contains sufficient disclosure to per-
mit “a person of skill in the art to make and use the claimed
invention.” Id. (citing 35 U.S.C. § 112). In particular, “the
specification must enable the full scope of the invention as
defined by its claims.” Amgen Inc. v. Sanofi, 598 U.S. 594,
610 (2023) (emphasis added). In other words, “[t]he more
one claims, the more one must enable.” Id. And while some
experimentation is permissible, “the specification . . . must
teach those skilled in the art how to make and use the full
scope of the claimed invention without undue experimen-
tation.” Baxalta Inc. v. Genentech, Inc., 81 F.4th 1362,
1365 (Fed. Cir. 2023).(quoting MagSil Corp. v. Hitachi
Glob. Storage Techs., Inc., 687 F.3d 1377, 1380 (Fed. Cir.
2012)).
As discussed above, the claims require administering
an irreversible EGFR inhibitor daily in a functionally-de-
fined “unit dosage”—an amount calculated to produce a
therapeutic effect “in a patient.” See Claim Construction
Decision, 2023 WL 2683559, at *9 (citing ’314 patent col. 9
ll. 34–38). Moreover, the specification explains that the
claimed “irreversible EGFR inhibitor may be any com-
pound which binds to cysteine 773 of EGFR (SEQ ID NO:
1).” Id. at col. 3 ll. 57–59 (emphasis added). Thus, to enable
the claims, the specification must provide guidance to allow
a skilled artisan to determine a daily unit dosage calcu-
lated to produce a therapeutic effect in a patient across the
full scope of claimed compounds without undue experimen-
tation. See Baxalta, 81 F.4th at 1365. Specifically, in the
context of the asserted claims, the specification must pro-
vide some basis for translating information about the dis-
closed compounds’ in vitro activity into the claimed daily
dosing regimen “in a patient,” see ’314 patent col. 35 ll. 53–
55, rather than leaving that determination entirely to a
skilled artisan’s knowledge and experimentation. See Ide-
nix Pharms. LLC v. Gilead Scis. Inc., 941 F.3d 1149, 1159
(Fed. Cir. 2019) (“It is the specification, not the knowledge
of one skilled in the art, that must supply the novel aspects
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 14
of an invention in order to constitute adequate enable-
ment.” (quoting Genentech, Inc. v. Novo Nordisk A/S,
108 F.3d 1361, 1366 (Fed. Cir. 1997))).
Here, however, the specification leaves the determina-
tion of the claimed “unit dosage” entirely to the knowledge
of the skilled artisan. See ’314 patent col. 8 ll. 57–58 (“The
skilled artisan is aware of the effective dose for each pa-
tient.”). While the knowledge of one of ordinary skill may
play an important role in enablement, it may not provide
the only means to enable these specific claim limitations.
See Idenix, 941 F.3d at 1159. That is what a specification
of a patent must provide. See id. It is undisputed that the
specification provides no working examples of any unit dos-
age calculated to achieve a therapeutic effect and suitable
for daily administration in human patients. See Decision,
2024 WL 3823006, at *14. Instead, the specification iden-
tifies only three compounds as examples of preferred em-
bodiments: EKB-569, HKl-357, and HKl-272. Id. at col.
3 ll. 56–57, col. 13 ll. 50–51. With respect to those com-
pounds, the specification describes in vitro experimenta-
tion without any further description of (1) how to
extrapolate in vivo dosing from those in vitro results or
(2) any other teachings sufficient to allow a skilled artisan
to calculate a “unit dosage” as claimed. Those in vitro data
alone are insufficient to enable these claims. See, e.g.,
Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1217
(Fed. Cir. 1991) (“[T]he district court erred in accepting the
in vitro data as support for claims containing what has
been found to be an in vivo limitation.”).
Wyeth points to the asserted patents’ disclosure of
prior-art studies involving various irreversible EGFR in-
hibitors, as well as animal studies and later clinical expe-
rience, to argue that skilled artisans would have
understood that irreversible inhibitors could be adminis-
tered safely and could have determined appropriate dos-
ages without concern that patients would die. See Wyeth
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 15
Op. Br. 38–43. But that evidence does not answer the rel-
evant question. The issue is not whether skilled artisans
knew that some irreversible EGFR inhibitors could be ad-
ministered to patients, but whether the specification
teaches how to determine the claimed therapeutically ef-
fective daily “unit dosage” for the claimed compounds. See
Idenix, 941 F.3d at 1159. The specification provides no
such guidance, instead leaving dosage determination en-
tirely to the skilled artisan, which in effect requires exper-
imentation. See ’314 patent col. 8 ll. 57–58.
Although the specification recites dosage ranges, see id.
at col. 8 ll. 59–66, they are qualified as “general,” id. at col.
8 l. 63, and “projected,” id. at col. 8 l. 67, ranges, and the
specification provides no further explanation of how those
ranges were derived, how a skilled artisan would select
among them for a given compound, or how they relate to
the claimed unit dosage calculated to produce a therapeutic
effect in a patient. The patent thus identifies ranges of
“projected” daily unit dosage for administration to a pa-
tient, while leaving the skilled artisan to supply the critical
teachings necessary to achieve or validate that projection.
And while “a specification need not disclose what is well
known in the art,” that “oft-repeated statement is merely a
rule of supplementation, not a substitute for a basic ena-
bling disclosure.” Genentech, 108 F.3d at 1366. Thus,
where, as here, the specification omits critical guidance
needed to practice the claimed invention, requiring skilled
artisans to fill those gaps through their own experimenta-
tion, undue experimentation is required. See id.
Moreover, as the trial record shows, when applying the
dosage ranges disclosed to the three compounds disclosed,
at least two of those compounds––HKI-272 and EKB-569–
–are not compatible for use in patients because they far ex-
ceed the maximum tolerated dose in humans. J.A. 17397–
98; J.A. 17549. For instance, AstraZeneca presented unre-
butted evidence that, for those two compounds, all thera-
peutically effective dosage levels, across the disclosed
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 16
dosage ranges, would exceed the maximally tolerated dose
in humans. Decision, 2024 WL 3823006, at *14 (citing var-
ious trial testimony presented by AstraZeneca).
Indeed, not only did Wyeth fail to rebut the evidence on
those issues but its own experts agreed. For instance, Wy-
eth’s invalidity expert Dr. Hausheer agreed that when cal-
culating a unit dosage for a patient, a skilled artisan would
want to avoid toxic doses to achieve a therapeutic effect.
See J.A. 17548. Another Wyeth witness and co-inventor
Dr. Haber explained that the specification’s dosage ranges
far exceed the maximum tolerated dose threshold for at
least one of the three compounds identified in the asserted
patents (HKI-272) by a factor of more than “five.” J.A.
17397–98 (testifying that “[t]he concentrations in the test
tube are higher than those you can give to patients” and
agreeing that the drug concentrations in the asserted pa-
tents were “five times higher” than what could be adminis-
tered to patients); see also J.A. 11804, 11807 (inventors of
the asserted patents explaining in their 2008 Godin-Hey-
mann publication that the “concentrations required in vitro
may not be achievable in patients due to drug toxicity.”).
Wyeth’s experts further testified that the same is true for
compound EKB-569, and may also be true for compound
HKI-357. See J.A. 17549; 17563.
Such testimony reinforces the lack of guidance pro-
vided by the specification. It shows that the compounds,
described as preferred embodiments, cannot be adminis-
tered to a patient on a daily basis across the full scope of
the dosage ranges disclosed. Thus, a skilled artisan would,
at a minimum, be required to conduct further testing and
screening to determine whether a claimed irreversible
EGFR inhibitor can be dosed so as to not exceed any maxi-
mum tolerated dose threshold while still achieving a ther-
apeutic effect. While the fact that inoperative
embodiments are disclosed is not necessarily dispositive,
this evidence weighs heavily in favor of non-enablement.
See Atlas Powder Co. v. E.I. du Pont De Nemours & Co.,
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 17
750 F.2d 1569, 1576–77 (Fed. Cir. 1984) (“[I]f the number
of inoperative combinations becomes significant, and in ef-
fect forces one of ordinary skill in the art to experiment un-
duly in order to practice the claimed invention, the claims
might indeed be invalid.” (citation omitted)).
The specification also accentuates its own shortcom-
ings by describing the complexity and unpredictability of
dosing the claimed “second generation” inhibitors; it is not
as routine as Wyeth purports. See Oral Arg. at 3:46–50,
Appeal No. 24–2325, available at
https://www.cafc.uscourts.gov/oral-arguments/24-2325_05
072026.mp3 (Wyeth counsel claiming that “there is noth-
ing novel about the dosage range”); id. at 28:56–29:00 (Wy-
eth counsel arguing that the patents enable a skilled
artisan to “dos[e] at conventional ranges”); see also Wyeth
Op. Br. 39–43. The specification, however, reveals that de-
termining the claimed “unit dosage” to achieve a therapeu-
tic effect depends on several variable factors. It “depends
on the subject to be treated, capacity of the subject’s system
to utilize the active ingredient, and degree of therapeutic
effect desired,” id. at col. 9 ll. 42–46, in addition to “the par-
ticular compound employed, the mode of administration
and the severity of the condition being treated,” id. at col.
8 ll. 55–57. The specification therefore concludes that the
“[p]recise amounts of active ingredient required to be ad-
ministered depend on the judgment of the practitioner and
are peculiar to each individual.” Id. at col. 9 ll. 44–46.
Thus, the specification itself demonstrates that determin-
ing the claimed “unit dosage” is a complex and highly indi-
vidualized task, while at the same time failing to provide
the information and guidance necessary for a skilled arti-
san to perform that task without undue experimentation.
And where, as here, the prior art is complex and unpredict-
able, the specification must provide correspondingly
greater guidance. See Wyeth & Cordis Corp. v. Abbott
Labs., 720 F.3d 1380, 1386 (Fed. Cir. 2013) (claims not en-
abled where the specification provided only a starting point
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 18
for further research in an unpredictable field and required
extensive screening and experimentation to identify oper-
ative embodiments).
Wyeth argues that the district court imposed a non-le-
thality requirement that AstraZeneca never advanced and
that the evidence does not support. See Wyeth Op. Br. 36–
43. Wyeth, however, mischaracterizes the district court’s
analysis. Again, the district court did not hold that the
claims require proof that every claimed dosage be non-
toxic, non-lethal, or satisfy any freestanding FDA clinical
safety criteria. See Decision, 2024 WL 3823006, at *13.
Rather, the court recognized that the claims require the
daily administration of a “unit dosage” to a human patient
and concluded that the specification fails to teach a skilled
artisan how to determine such a dosage across the full
scope of the claims. Id. at *15 (“Here, the patents-in-suit
do not teach which unit dosages of compounds covered by
the claims could be administered daily to a patient and
which could not.”). Evidence concerning toxic or lethal dos-
ages was relevant not because the claims contain a toxicity
limitation, but because that evidence demonstrated that
the patents’ disclosures provide little guidance as to which
disclosed dosages, if any, are suitable for daily administra-
tion to a patient across the functionally claimed class of
compounds. Here, as discussed, without teaching how to
distinguish operative from inoperative embodiments, the
specification leaves that task to the skilled artisan. See
’314 patent col. 8 ll. 57–58. That is precisely the type of
undue experimentation that the enablement requirement
forbids. See ALZA Corp., 603 F.3d at 941 (“[One] cannot
simply rely on the knowledge of a person of ordinary skill
to serve as a substitute for the missing information in the
specification.”); see also id. at 943 (“Patent protection is
granted in return for an enabling disclosure of an inven-
tion, not for vague intimations of general ideas that may or
may not be workable.” (citation omitted)).
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WYETH LLC v. ASTRAZENECA PHARMACEUTICALS LP 19
We recognize that it is accepted practice in patent law
for one to be able to claim a method of treatment disclosing
a range of doses to be administered, without showing ac-
tual clinical data, and leaving it to the FDA to ensure that
approved products are safe and effective. See United Ther-
apeutics, 74 F.4th at 1369. The problem with these patents
is that, perhaps because of close prior art, their claims are
limited to dosage forms to be administered to patients, yet
they disclosed only a broad range of doses some of which
were shown to be toxic, and they disclosed no actual dos-
ages for any compound within the scope of the claims,
thereby leaving it to a practitioner of the claims to perform
undue experimentation.
In sum, we conclude that the district court did not err
in granting JMOL of invalidity of the asserted claims of the
’314 and ’162 patents due to a lack of enablement.
CONCLUSION
We have considered Wyeth’s remaining arguments but
find them unpersuasive. For the foregoing reasons, we af-
firm the grant of JMOL of invalidity.
AFFIRMED
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