Case: 20-1747 Document: 79 Page: 1 Filed: 08/16/2021
United States Court of Appeals
for the Federal Circuit
______________________
TEVA PHARMACEUTICALS INTERNATIONAL
GMBH,
Appellant
v.
ELI LILLY AND COMPANY,
Appellee
ANDREW HIRSHFELD, PERFORMING THE
FUNCTIONS AND DUTIES OF THE UNDER
SECRETARY OF COMMERCE FOR
INTELLECTUAL PROPERTY AND DIRECTOR OF
THE UNITED STATES PATENT AND TRADEMARK
OFFICE,
Intervenor
______________________
2020-1747, 2020-1748, 2020-1750
______________________
Appeals from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in Nos. IPR2018-
01422, IPR2018-01423, IPR2018-01425.
______________________
Decided: August 16, 2021
______________________
WILLIAM M. JAY, Goodwin Procter LLP, Washington,
DC, argued for appellant. Also represented by ELAINE
BLAIS, EDWINA CLARKE, ALEXANDRA LU, Boston, MA;
Case: 20-1747 Document: 79 Page: 2 Filed: 08/16/2021
2 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
NATASHA ELISE DAUGHTREY, Los Angeles, CA; WILLIAM
MILLIKEN, DEBORAH STERLING, Sterne Kessler Goldstein &
Fox, PLLC, Washington, DC.
WILLIAM BARRETT RAICH, Finnegan, Henderson,
Farabow, Garrett & Dunner, LLP, Washington, DC, ar-
gued for appellee. Also represented by CHARLES COLLINS-
CHASE, PIER DEROO, ERIN SOMMERS, YIEYIE YANG; SANJAY
M. JIVRAJ, MARK STEWART, Eli Lilly and Company, Indian-
apolis, IN.
MONICA BARNES LATEEF, Office of the Solicitor, United
States Patent and Trademark Office, Alexandria, VA, for
intervenor. Also represented by THOMAS W. KRAUSE,
BRIAN RACILLA, FARHEENA YASMEEN RASHEED.
______________________
Before LOURIE, BRYSON, and O’MALLEY, Circuit Judges.
LOURIE, Circuit Judge.
Teva Pharmaceuticals International GmbH (“Teva”)
appeals from a combined final written decision of the U.S.
Patent and Trademark Office (“PTO”) Patent Trial and Ap-
peal Board (“Board”) holding that the claims of U.S. Pa-
tents 9,340,614 (“’614 patent”), 9,266,951 (“’951 patent”),
and 9,890,210 (“’210 patent”) are unpatentable because
they would have been obvious over the cited prior art. Eli
Lilly & Co. v. Teva Pharms. Int’l GmbH, Nos. IPR2018-
01422, IPR2018-01423, IPR2018-01425, 2020 WL 806932
(P.T.A.B. Feb. 18, 2020) (“Board Decision”). For the rea-
sons provided below, we affirm.
BACKGROUND
I. Patents
Teva owns the ’614, ’951, and ’210 patents (collectively,
the “challenged patents”) directed to humanized antago-
nist antibodies that target calcitonin gene-related peptide
Case: 20-1747 Document: 79 Page: 3 Filed: 08/16/2021
TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 3
(“CGRP”). CGRP is a 37-amino acid peptide that is “a neu-
rotransmitter in the central nervous system, and has been
shown to be a potent vasodilator in the periphery, where
CGRP-containing neurons are closely associated with blood
vessels.” ’614 patent, col. 1 ll. 49–53.
The challenged patents explain that “CGRP has been
noted for its possible connection to vasomotor symptoms,”
id. at col. 1 ll. 57–58, such as “all forms of vascular head-
ache, including migraines.” Id. at col 2 ll. 22–23. Although
at the time of the challenged patents the pathophysiology
of migraine was not well understood, dilation of blood ves-
sels was associated with and thought to exacerbate the
pain symptoms of migraine. Id. at col. 3 ll. 33–44. Thus,
even before the challenged patents, the possible connection
between CGRP as a vasodilator and the pathology of mi-
graine informed the development of treatments for mi-
graine that sought to restrict the activity of CGRP in the
body. For example:
Possible CGRP involvement in migraine has been
the basis for the development and testing of a num-
ber of compounds that inhibit release of CGRP
(e.g., sumatriptan), antagonize at the CGRP recep-
tor (e.g., dipeptide derivative BIBN4096BS
(Boe[]hringer Ingelheim); CGRP(8-37)), or interact
with one or more of receptor-associated proteins,
such as, receptor activity membrane protein
(RAMP) or receptor component protein (RCP), both
of which affect binding of CGRP to its receptors.
Id. at col. 2 ll. 32–40.
The challenged patents are directed to humanized an-
tibodies that antagonize CGRP and thus inhibit its activity
in the body by targeting and binding to the CGRP ligand
(as opposed to CGRP receptors). The written description
describes “anti-CGRP antagonist antibodies and methods
of using anti-CGRP antagonist antibodies for treating or
preventing vasomotor symptoms, such as headaches, such
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4 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
as migraine.” Id. at col. 3 ll. 55–63. For purposes of this
appeal, however, the claims at issue are directed to the an-
tibodies themselves. 1 Claim 1 in each patent is the only
independent claim:
1. A human or humanized monoclonal anti-
CGRP antagonist antibody that preferentially
binds to human α-CGRP as compared to amylin.
’614 patent, col. 101 ll. 32–34.
1. A human or humanized monoclonal anti-
CGRP antagonist antibody that (1) binds human α-
CGRP and (2) inhibits cyclic adenosine monophos-
phate (cAMP) activation in cells.
’951 patent, col. 99 ll. 21–23.
1. A humanized monoclonal anti-Calcitonin
Gene-Related Peptide (CGRP) antagonist anti-
body, comprising:
two human IgG heavy chains, each heavy
chain comprising three complementarity
determining regions (CDRs) and four
framework regions, wherein portions of the
two heavy chains together form an Fc re-
gion; and
two light chains, each light chain compris-
ing three CDRs and four framework re-
gions;
1 In contrast to the claims at issue in this case, which
are directed to the antibodies themselves, Teva also owns
related patents with claims directed to methods of treat-
ment comprising a step of administering such antibodies.
Those claims are at issue in Appeal Nos. 2020-1876, 2020-
1877, and 2020-1878.
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TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 5
wherein the CDRs impart to the antibody
specific binding to a CGRP consisting of
amino acid residues 1 to 37 of SEQ ID
NO:15 or SEQ ID NO:43.
’210 patent, col. 103 ll. 35–45. The differences between
these claims have not been argued as significant to these
appeals.
II. IPR Petitions and Prior Art
Eli Lilly and Company (“Lilly”) filed petitions for inter
partes review (“IPR”) of claims 1–7 and 15–20 of the ’614
patent, claims 1–6 and 14–19 of the ’951 patent, and claims
1–5 of the ’210 patent. Lilly asserted that each of the chal-
lenged claims would have been obvious over a combination
of prior art references that includes Tan, 2 Wimalawansa, 3
and Queen. 4
Tan is a publication describing an in vivo study in rats
using an anti-CGRP monoclonal antibody for immunob-
lockade. 5 The study investigated the anti-CGRP activity of
a full-length monoclonal antibody called “MAb C4.19” as
2 K.K.C. Tan et al., Calcitonin gene-related peptide
as an endogenous vasodilator: immunoblockade studies in
vivo with an anti-calcitonin gene-related peptide monoclo-
nal antibody and its Fab’ fragment, 89 CLINICAL SCI. 6,
565–73 (1995).
3 S.J. Wimalawansa, Calcitonin Gene-Related Pep-
tide and its Receptors: Molecular Genetics, Physiology,
Pathophysiology, and Therapeutic Potentials, 17
ENDOCRINE REVIEWS 5, 533–85 (1996).
4 U.S. Patent 6,180,370.
5 Tan defines “immunoblockade” as “the blockade of
the effects of a biological mediator by inhibition of its bind-
ing to specific receptors with antibodies directed against
the mediator.” J.A. 4996.
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6 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
well as its Fab’ fragment. 6 See J.A. 4995–5003. Tan de-
scribes the results of one experiment demonstrating that
both the full-length antibody and the Fab’ fragment suc-
cessfully achieved immunoblockade by inhibiting the ef-
fects of exogenously administered CGRP. See J.A. 4996–
97. Tan also describes the results of a second experiment
analyzing whether the antibody and its Fab’ fragment in-
hibit endogenous CGRP-induced blood flow after a pre-
scribed incubation period. J.A. 4999. The results
demonstrated that the Fab’ fragment effectively blocked
skin blood flow after a 30-minute incubation period. The
full-length antibody did not block skin blood flow after a
60-minute incubation, but a 2-hour incubation period and
higher dose resulted in a 16% block in skin blood flow. Id.
Tan posited that “much larger doses and longer distribu-
tion times are required for successful immunoblockade”
with the full-length antibody. J.A. 5001.
Wimalawansa is a review article that describes CGRP,
including the history of its discovery, its molecular genetics
and structure, its biological actions, and its therapeutic po-
tentials. See J.A. 6552–604. Most of Wimalawansa’s dis-
cussion focuses on the therapeutic potential of activating
CGRP in the body with CGRP agonists. See J.A. 6578–86.
Wimalawansa also includes a brief discussion, however, of
the therapeutic potential of CGRP antagonists, noting that
“[e]vidence is accumulating that inappropriate release of
CGRP is a potential causative factor in several diseases,
including migraine.” J.A. 6586–87. To treat such diseases,
Wimalawansa states that the “role of CGRP antagonists
and humanized monoclonal antibodies should be explored.”
See J.A. 6589.
Queen “relates generally to the combination of recom-
binant DNA and monoclonal antibody technologies for
6 A “Fab’ fragment” is the portion of an antibody that
binds to the target antigen.
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TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 7
developing novel therapeutic agents.” J.A. 5063 at col. 1
ll. 19–21. Specifically, Queen discloses a method of human-
izing antibodies to address traditional problems associated
with injecting monoclonal antibodies from donors (e.g.,
mice) into humans.
III. Board Decision
After a combined oral hearing in the three IPR proceed-
ings, the Board issued a combined final written decision
holding that the challenged claims in all three patents are
unpatentable as they would have been obvious over various
cited references. The Board first found that the prior art
disclosed or suggested each and every limitation of the
challenged claims. See Board Decision, 2020 WL 806932,
at *12–15. The Board then found that a skilled artisan
would have been motivated to combine the teachings of the
prior art, id. at *40–41, and would have had a reasonable
expectation of successfully achieving the claimed inven-
tion, id. at *43. Lastly, the Board addressed secondary con-
siderations of nonobviousness. Id. at *43–61.
Regarding the motivation to combine, the Board con-
sidered Lilly’s asserted reasons why a skilled artisan would
have been motivated to combine the teachings of the refer-
ences to make a humanized anti-CGRP antibody. Id.
at *16–27. The Board also considered Teva’s asserted
safety and efficacy concerns as potential reasons not to
make a humanized anti-CGRP antibody. Id. at *27–40. Af-
ter weighing the evidence, the Board found “that anti-
CGRP antagonist antibodies were well known in the art,
and that the art encouraged the development of humanized
anti-CGRP antibodies.” Id. at *40. The Board also found
“no evidence that making a humanized anti-CGRP antago-
nist antibody would raise any safety concerns sufficient to
discourage a person of ordinary skill in the art from making
a human or humanized anti-CGRP antagonist antibody.”
Id.
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8 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
In considering whether a skilled artisan would have
had a reasonable expectation of success, the Board specifi-
cally noted that the challenged claims in this case are di-
rected to humanized antibodies and do not recite any safety
or efficacy limitations. 7 Id. at *43. Accordingly, the Board
rejected Teva’s argument that Lilly was required to make
a showing that a skilled artisan would have had a reason-
able expectation of successfully using the claimed antibod-
ies in the treatment of any disease or condition. Id.
Finally, the Board found that Teva failed to establish
either a presumption of nexus or a direct showing of nexus
between the claims and the asserted secondary considera-
tions based on objective indicia of nonobviousness. Id.
at *49. For completeness, the Board also considered Teva’s
evidence relating to the secondary considerations but found
that it was entitled to little weight. Id. at *49–61.
IV. Teva’s Appeal
Teva appealed from the Board’s combined final written
decision with respect to each of the three challenged pa-
tents, and we consolidated the appeals. We have jurisdic-
tion under 28 U.S.C. § 1295(a)(4)(A).
Teva primarily challenged the Board’s decision on the
merits, including the legal and factual issues underlying
the Board’s decision regarding unpatentability. Addition-
ally, Teva summarily argued that the panel that issued the
Board’s final written decision in this case consisted of mem-
bers who were unconstitutionally appointed in violation of
the Appointments Clause. Teva purported to preserve that
challenge based on this court’s decision in Arthrex, Inc. v.
Smith & Nephew, Inc., 941 F.3d 1320 (Fed. Cir. 2019),
7 Notably, in contrast to the claims at issue here, the
claims at issue in Appeal Nos. 2020-1876, 2020-1877, and
2020-1878 recite methods of treatment using humanized
anti-CGRP antagonist antibodies.
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TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 9
vacated, 141 S. Ct. 1970 (2021), as well as the arguments
presented to the Supreme Court in the then-pending peti-
tion for a writ of certiorari in that case.
While Teva’s appeal was pending, the Supreme Court
decided United States v. Arthrex, Inc., 141 S. Ct. 1970
(2021). We stayed all deadlines and proceedings in this
case and ordered the parties to file supplemental briefs ex-
plaining how the case should proceed in light of the Su-
preme Court’s decision in Arthrex. On July 7, 2021, Teva
filed its supplemental brief, proposing that we should first
decide the merits of the appeal, and if we do not otherwise
reverse or remand we should then issue a limited remand
under Arthrex. On July 21, 2021, Lilly and the PTO filed
their supplemental briefs. The PTO argued that, because
Teva’s supplemental brief included a request for a limited
remand under Arthrex, we should immediately remand the
case without deciding the merits. In contrast, Lilly argued
that by asking us to decide the merits of the appeal, Teva
waived its opportunity for a limited remand under Arthrex.
We rejected Teva’s proposal and instead ordered Teva
to elect one of two options: (i) a request that we issue a re-
mand for the limited purpose of allowing Teva the oppor-
tunity to request Director rehearing of the final written
decision; or (ii) a waiver of its right to seek Director rehear-
ing of the final written decision. On July 28, 2021, Teva
filed its response indicating that it waives its right to a lim-
ited remand to seek rehearing by the Director. Accord-
ingly, we lifted the stay, and we now proceed to decide the
appeal on the merits.
DISCUSSION
We review the Board’s legal determinations de novo, In
re Elsner, 381 F.3d 1125, 1127 (Fed. Cir. 2004), but we re-
view the Board’s factual findings underlying those deter-
minations for substantial evidence, In re Gartside, 203 F.3d
1305, 1316 (Fed. Cir. 2000). A finding is supported by sub-
stantial evidence if a reasonable mind might accept the
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10 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
evidence as adequate to support the finding. Consol. Edi-
son Co. v. NLRB, 305 U.S. 197, 229 (1938).
We begin by briefly addressing the Board’s finding that
each limitation of the challenged claims was individually
taught by the prior art. See Board Decision, 2020 WL
806932, at *12–15. The challenged patents’ written de-
scription concedes that “[a]nti-CGRP antagonist antibodies
[we]re known in the art” and commercially available. See,
e.g., ’614 patent col. 26 ll. 13–17. Additionally, Tan dis-
closed and described use of an anti-CGRP antagonist anti-
body, see J.A. 4996, Wimalawansa proposed the use of
humanized anti-CGRP antibodies, see J.A. 6586, and
Queen described methods of humanizing monoclonal anti-
bodies, see J.A. 5004. The Board also noted that Teva did
not contest Lilly’s evidence regarding the additional limi-
tations in the independent claims, including that the prior
art antibodies preferentially bind to CGRP as compared to
amylin (’614 patent, claim 1), that blocking CGRP would
inhibit cAMP activation (’951 patent, claim 1), and that the
recited heavy and light chains are generic to IgG antibodies
and the recited sequence IDs correspond to CGRP (’210 pa-
tent, claim 1). Accordingly, the Board’s finding that the
prior art taught every element of the challenged claims is
supported by substantial evidence. Teva does not chal-
lenge that finding on appeal.
Teva raises three challenges to the Board’s decision.
First, Teva contends that the Board erred as a matter of
law in its motivation to combine analysis by deviating from
the motivation asserted by Lilly in its petitions for inter
partes review. Second, Teva contends that even under the
motivation to combine that the Board did analyze, substan-
tial evidence does not support the Board’s factual findings.
And third, Teva contends that the Board erred in its anal-
ysis of secondary considerations of nonobviousness. We ad-
dress each challenge in turn.
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TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 11
I
Teva first contends that the Board erred by relying on
a different motivation to combine from the one that Lilly
asserted in its petitions for inter partes review. According
to Teva, Lilly asserted that a skilled artisan would have
been motivated to combine the teachings of the references
to make a humanized anti-CGRP monoclonal antibody for
therapeutic use in humans, but the Board instead consid-
ered whether a skilled artisan would have been motivated
to make the antibody merely to study or use it. Teva insists
that by not requiring Lilly to support its therapeutic moti-
vation, the Board incorrectly discounted important safety
and efficacy concerns that would have been demotivating
factors—i.e., reasons why a skilled artisan would have been
motivated not to make a humanized anti-CGRP monoclo-
nal antibody.
Lilly responds that the Board relied on the same moti-
vation that was asserted in the petitions, and that a moti-
vation to study or use a humanized antibody to assess its
therapeutic potential is not meaningfully different from
what Teva has termed a “therapeutic motivation.” Lilly
further contends that the Board extensively relied on prior
art disclosures regarding the potential safety and efficacy
of anti-CGRP antagonist antibodies for the treatment of
migraines and other vasomotor symptoms. For example,
Lilly notes that the Board agreed with Lilly’s contention
that Wimalawansa suggests study of anti-CGRP antibod-
ies in migraine, and that substantial evidence demon-
strates that Tan’s use of anti-CGRP antibodies in
connection with skin vasodilation has relevance to treating
disease in humans. As further examples, Lilly points to the
Board’s reliance on at least four other prior art references
demonstrating the therapeutic potential of anti-CGRP an-
tibodies.
As an initial matter, we agree with Lilly that the Board
properly analyzed the motivation to combine that Lilly
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12 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
asserted in its IPR petitions. To be sure, the Board may
not “deviate from the grounds in the petition and raise its
own obviousness theory.” Sirona Dental Sys. GmbH v. In-
stitut Straumann AG, 892 F.3d 1349, 1356 (Fed. Cir. 2018).
But here, the Board upheld its mandate to “base its deci-
sion on arguments that were advanced by a party”—
namely, Lilly—“and to which the opposing party”—
namely, Teva—“was given a chance to respond.” In re Mag-
num Oil Tools Int’l, Ltd., 829 F.3d 1364, 1381 (Fed. Cir.
2016).
Lilly argued in its petition that a skilled artisan would
have been motivated to make the claimed humanized anti-
body for therapeutic use in humans. See, e.g., J.A. 829
(“Consequently, a POSA—with her ordinary creativity—
would have been motivated to combine [the prior art] to ob-
tain a humanized anti-CGRP antagonist antibody that
would be suitable for administration to humans . . . .” (em-
phasis added)). And that was precisely the motivation that
the Board found. Common sense and scientific reality dic-
tate that scientists do not “study or use” humanized anti-
bodies with an end goal of treating diseases in test tubes or
in rats. At bottom, the prior art supports a motivation to
humanize antibodies with the goal of treating human dis-
ease.
Teva’s argument about the Board’s alleged failure to
consider safety and efficacy concerns misses the mark. Be-
cause the claims are directed to humanized antibodies, the
question before the Board was whether a skilled artisan at
the time of the invention would have been motivated to
make the claimed humanized antibodies, not whether a
skilled artisan would have been motivated to use those an-
tibodies to treat human disease. Teva is, of course, correct
that the analysis must account for “reasons not to com-
bine,” which are facts relevant to the overall consideration
of obviousness. See, e.g., Arctic Cat Inc. v. Bombardier Rec.
Prods., 876 F.3d 1350, 1360 (Fed. Cir. 2017); see also id. at
1363 (“Evidence suggesting reasons to combine cannot be
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TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 13
viewed in a vacuum apart from evidence suggesting rea-
sons not to combine”). But, as it pertains to Teva’s argu-
ment about safety and efficacy concerns, the relevant
inquiry is not (as Teva suggests) whether the asserted con-
cerns would have presented a reason not to use the claimed
antibodies in human treatments. Rather, the relevant in-
quiry—which the Board extensively analyzed—is whether
those concerns would have dissuaded a skilled artisan from
making the claimed antibodies to study their therapeutic
potential in the first place.
As a factual matter, Teva is not correct in asserting
that the Board failed to consider whether a skilled artisan
would have expected the treatment to be unsafe or unsuc-
cessful. On the contrary, the Board extensively analyzed
Teva’s asserted safety and efficacy concerns, including
those associated with “blocking the CGRP pathway,” those
raised by “Tan and Wimalawansa,” those related to “mi-
graine and stroke,” and those based on “differences be-
tween blocking a CGRP receptor and an antibody against
the CGRP ligand.” See Board Decision, 2020 WL 806932,
at *27–40. After weighing evidence based on expert testi-
mony and numerous publications that the parties pre-
sented, the Board reached a factual finding that the safety
and efficacy concerns would not be “sufficient to discourage
a person of ordinary skill in the art from making a human
or humanized anti-CGRP antagonist antibody.” Id. at *40.
The Board specifically noted that Teva relied “heavily on
potential safety concerns based on the role of CGRP in the
body and general characteristics of antibodies in vivo,” and
that evidence was outweighed by Lilly’s reliance on “actual
studies of CGRP antagonists, including antibodies.” Id.
at *41. Thus, the Board concluded that “any alleged safety
concerns would not have deterred or discouraged the com-
bination of prior art teachings to achieve the invention of
the challenged claims.” Id.
For the foregoing reasons, we are not persuaded by
Teva’s contention that the Board deviated from Lilly’s
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14 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
asserted motivation to combine, and we disagree with
Teva’s assertion that the Board improperly discounted po-
tential safety and efficacy concerns associated with the
claimed invention. The Board properly considered the evi-
dence relevant to Lilly’s asserted motivation to combine.
II
As an alternative to its argument that the Board devi-
ated from Lilly’s asserted motivation to combine, Teva ar-
gues that the Board relied on unsupported interpretations
of isolated statements in the prior art to find a motivation
to study or use humanized anti-CGRP antibodies. For ex-
ample, Teva contends that the Board misinterpreted the
phrase “CGRP antagonists and humanized monoclonal an-
tibodies” in Wimalawansa as referring to antibodies that
target the CGRP ligand, even though, Teva asserts, a
skilled artisan would have understood that term as refer-
ring to the extremely specific receptor antagonists that are
the focus of Wimalawansa’s section on CGRP antagonism.
At best, Teva argues, Wimalawansa cautions that further
study is needed before CGRP antagonists could be evalu-
ated in humans. Regarding Tan, Teva emphasizes that the
full-length antibody was unsuccessful in achieving im-
munoblockade in rats, and Teva contends that Tan’s ex-
pression of optimism that its negative results could be
overcome does not support a motivation to further explore
the full-length antibody.
In response, Lilly argues that substantial evidence
supports a motivation to make the claimed antibody. Lilly
focuses on the disclosures of the references themselves, as
well as the interpretations of the references by expert wit-
nesses and contemporaneous prior art publications. Lilly
argues that the disclosures of Tan, Wimalawansa, and nu-
merous other prior art references would have motivated a
skilled artisan to make humanized anti-CGRP antibodies
with the goal of treating human disease.
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TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 15
We agree with Lilly that substantial evidence supports
a motivation to make a humanized anti-CGRP antibody to
study its therapeutic potential for use in treatment of hu-
man disease. Lilly identifies evidence that supports the
Board’s reasonable readings of each reference. For exam-
ple, Lilly points to the testimony of three separate experts
supporting the Board’s interpretation of Tan’s 16% re-
sponse as a trend toward anti-CGRP activity with the full-
length antibody, including the experts’ interpretation of
Tan’s optimism that longer distribution times and higher
concentrations would improve the response. See, e.g.,
J.A. 4716 (testimony of Dr. Alain Vasserot); J.A. 4605–07
(testimony of Dr. Andrew Charles); J.A. 9874–80 (testi-
mony of Dr. Joseph Balthasar). As for Wimalawansa, alt-
hough the expert witnesses differed regarding the phrase
“CGRP antagonists and humanized monoclonal antibod-
ies,” Lilly points to evidence of a contemporaneous prior art
publication that cited Wimalawansa to support the propo-
sition that the CGRP ligand is a target in migraine treat-
ment. See, e.g., J.A. 6429.
Unsurprisingly, Teva disagrees with the Board’s inter-
pretations of Tan and Wimalawansa. But what a piece of
prior art teaches presents a question of fact that is re-
viewed for substantial evidence. See, e.g., In re Warsaw
Orthopedic, Inc., 832 F.3d 1327, 1332 (Fed. Cir. 2016) (“An
examination of the scope and content of the prior art pro-
duces factual findings reviewed for substantial evidence.”
(citing Gartside, 203 F.3d at 1316)). When it comes to com-
peting interpretations of the teachings of prior art refer-
ences, we must uphold the principle that “[i]f two
‘inconsistent conclusions may reasonably be drawn from
the evidence in record, the PTAB’s decision to favor one
conclusion over the other is the epitome of a decision that
must be sustained upon review for substantial evidence.’”
Elbit Sys. of Am., LLC v. Thales Visionix, Inc., 881 F.3d
1354, 1356 (Fed. Cir. 2018) (internal brackets omitted)
(quoting In re Cree, Inc., 818 F.3d 694, 701 (Fed. Cir.
Case: 20-1747 Document: 79 Page: 16 Filed: 08/16/2021
16 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
2016)). Under this deferential standard of review, we can-
not replace the Board’s reasonable interpretation of refer-
ences with Teva’s interpretation. For the foregoing
reasons, we are not persuaded that the Board committed
reversible error with regard to its analysis of the motiva-
tion to combine the teachings of the prior art references.
III
Turning to the issue of secondary considerations of
nonobviousness, Teva’s primary evidence was based on two
commercial products—its own AJOVY® product and Lilly’s
Emgality® product—both of which are antibodies within
the scope of the challenged patent claims. Teva asserted
that both products have received industry-wide acclaim,
satisfied a long-felt need, achieved unexpected results,
faced industry skepticism, and achieved commercial suc-
cess. Teva also presented evidence of a license it entered
into with third parties AlderBio Holdings, LLC and Alder
Biopharmaceuticals, Inc. (collectively, “AlderBio”) that in-
cluded the challenged patents. The Board found that the
commercial products and the license lacked sufficient
nexus to the challenged claims. See Board Decision, 2020
WL 806932, at *49–50, 60–61.
Teva argues that the Board made two legal errors.
First, Teva argues that, in finding no presumption of nexus
between the claims and the secondary considerations based
on the commercial products, the Board misapplied this
court’s holding in Fox Factory, Inc. v. SRAM, LLC, 944 F.3d
1366 (Fed. Cir. 2019). Second, with regard to the AlderBio
license, Teva argues that the Board erred by focusing on
AlderBio’s products rather than the scope of the license.
We address each of Teva’s arguments below.
A
In considering the Board’s finding that Teva failed to
show a nexus between the challenged claims and the com-
mercial AJOVY® and Emgality® products, we begin with a
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TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 17
discussion of the nexus requirement. It is well-established
law that in order to accord substantial weight to secondary
considerations of nonobviousness, “the evidence of second-
ary considerations must have a ‘nexus’ to the claims, i.e.,
there must be ‘a legally and factually sufficient connection’
between the evidence and the patented invention.” Henny
Penny Corp. v. Frymaster LLC, 938 F.3d 1324, 1332 (Fed.
Cir. 2019) (quoting Demaco Corp. v. F. Von Langsdorff Li-
censing Ltd., 851 F.2d 1387, 1392 (Fed. Cir. 1988)). “The
patentee bears the burden of showing that a nexus ex-
ists . . . .” WMS Gaming Inc. v. Int’l Game Tech., 184 F.3d
1339, 1359 (Fed. Cir. 1999) (citing Cable Elec. Prods., Inc.
v. Genmark, Inc., 770 F.2d 1015, 1027 (Fed. Cir. 1985)). “To
determine whether the patentee has met that burden, we
consider the correspondence between the objective evi-
dence and the claim scope.” Henny Penny, 938 F.3d at
1332.
It has long been recognized that “a patentee is entitled
to a rebuttable presumption of nexus between the asserted
evidence of secondary considerations and a patent claim if
the patentee shows that the asserted evidence is tied to a
specific product and that the product ‘is the invention dis-
closed and claimed.’” Fox Factory, 944 F.3d at 1373 (quot-
ing Demaco, 851 F.2d at 1392). The presumption applies
“when the patentee shows that the asserted objective evi-
dence is tied to a specific product and that product ‘embod-
ies the claimed features, and is coextensive with them.’”
Polaris Indus., Inc. v. Arctic Cat, Inc., 882 F.3d 1056, 1072
(Fed. Cir. 2018) (quoting Brown & Williamson Tobacco
Corp. v. Philip Morris Inc., 229 F.3d 1120, 1130 (Fed. Cir.
2000)). “Conversely, ‘[w]hen the thing that is commercially
successful is not coextensive with the patented invention—
for example, if the patented invention is only a component
of a commercially successful machine or process,’ the pa-
tentee is not entitled to a presumption of nexus.” Fox Fac-
tory, 944 F.3d at 1373 (quoting Demaco, 851 F.2d at 1392).
Case: 20-1747 Document: 79 Page: 18 Filed: 08/16/2021
18 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
Much has been written discussing the “coextensive-
ness” requirement for the presumption of nexus, and in Fox
Factory we attempted to summarize the current state of
the law. We rejected attempts “to reduce the coextensive-
ness requirement to an inquiry into whether the patent
claims broadly cover the product that is the subject of the
evidence of secondary considerations.” Id. at 1377. Rather,
we explained, “the degree of correspondence between a
product and a patent claim falls along a spectrum.” Id.
at 1374. At one end of the spectrum lies “perfect or near
perfect correspondence,” and at the other end lies “no or
very little correspondence.” Id. “Although we do not re-
quire the patentee to prove perfect correspondence to meet
the coextensiveness requirement, what we do require is
that the patentee demonstrate that the product is essen-
tially the claimed invention.” Id. “Whether a product is
coextensive with the patented invention, and therefore
whether a presumption of nexus is appropriate in a given
case, is a question of fact.” Id. at 1373.
Bound up with the coextensiveness requirement is the
issue of “unclaimed features” in a commercial product,
which we also addressed in Fox Factory. “[W]e have never
held that the existence of one or more unclaimed features,
standing alone, means nexus may not be presumed.” Id.
at 1374. Indeed, like the coextensiveness requirement it-
self, the concept of unclaimed features is best viewed as
part of a spectrum. Toward one end of the spectrum, we
have said that “if the unclaimed features amount to noth-
ing more than additional insignificant features, presuming
nexus may nevertheless be appropriate.” Id. Toward the
other end of the spectrum, we have said that “[a] patent
claim is not coextensive with a product that includes a ‘crit-
ical’ unclaimed feature that is claimed by a different patent
and that materially impacts the product’s functionality.”
Id. at 1375.
In applying our Fox Factory holding in this case, the
Board stated that it “d[id] not understand Fox Factory to
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TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 19
be making a distinction between features that are ‘critical’
and features that ‘materially impact’ the functionality of
the product.” Board Decision, 2020 WL 806932, at *48. Ac-
cordingly, the Board concluded that in order to defeat a pre-
sumption of nexus, a patent challenger need only show that
an “unclaimed feature materially affects the functioning of
the product that is alleged to be coextensive with the
claim.” Id. Teva argues that this was a misinterpretation
of Fox Factory, and to the extent the Board announced a
bright-line rule that the presumption of nexus does not ap-
ply if any unclaimed feature materially affects the func-
tioning of a product that is alleged to be coextensive, we
agree with Teva that the Board erred. As Teva argues, un-
der such a rule the presumption of nexus would rarely, if
ever, attach because virtually every innovative product in-
evitably has some unclaimed feature that materially af-
fects its functionality. Such a rule would be unsound. For
example, a claim to a new and unobvious pharmaceutical
compound would surely have a nexus to the marketed fin-
ished product sold to consumers, although that finished
product will almost always contain excipients such as sol-
ubilizers, antioxidants, stabilizers, etc., that materially af-
fect its functionality. Such excipients should not
reasonably be found to destroy the nexus between the claim
and the product.
Our conclusion that the Board erred in its articulation
of the legal standard, however, does not end our inquiry
into whether a presumption of nexus applies in this case.
The presumption analysis requires the fact finder to con-
sider the unclaimed features of the stated products to de-
termine their level of significance and their impact on the
correspondence between the claim and the products. Fox
Factory, 944 F.3d at 1375. As we discuss further below,
despite its incorrect articulation of the law, the Board con-
ducted the necessary factual analysis of the unclaimed fea-
tures of the AJOVY® and Emgality® products and reached
the correct conclusion that no presumption of nexus applies
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20 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
in this case. Therefore, the Board’s error in articulating
the legal standard was harmless. See In re Watts, 354 F.3d
1362, 1369 (Fed. Cir. 2004) (“[T]he harmless error rule ap-
plies to appeals from the Board . . . .”).
As we turn to the Board’s factual analysis of the un-
claimed features, we emphasize that the question whether
the presumption of nexus applies in each case turns on the
nature of the claims and the specific facts. For example, in
Fox Factory the relevant comparison was between a struc-
turally claimed mechanical chainring and a product that
included an unclaimed “gap filling” feature that was “criti-
cal,” “claimed by a different patent,” “materially impact[ed]
the product’s functionality,” and led “to a chainring that
will retain a chain in even the worst conditions.” 944 F.3d
at 1375. Based on those facts, we determined that “no rea-
sonable fact finder could conclude, under the proper stand-
ard, that the X-Sync chainrings are coextensive with the
patent claims.” Id. at 1374–75.
We have also considered the coextensiveness require-
ment in chemical and biological cases that more closely re-
semble the technology at issue here. For example, in
Immunex Corp. v. Sandoz Inc., 964 F.3d 1049, 1067–68
(Fed. Cir. 2020), the patent claims recited the molecular
weight and amino acid sequence of the “protein” to which
they were directed. See U.S. Patent 8,063,182. There, we
held that “[n]exus is appropriately presumed in this case
where the court concluded that the claims are directed to
the active ingredient in Enbrel® and its method of manu-
facture.” Immunex, 964 F.3d at 1067. More generally, it is
hard not to imagine a presumption of nexus between a
structurally claimed genus of chemical compounds and a
commercial product that meets each claim limitation.
In contrast to the claims in Fox Factory and Immunex,
the antibodies in the claims at issue in this case are de-
scribed, not in terms of their structure, but rather in terms
of their function—in particular, their ability to bind to the
Case: 20-1747 Document: 79 Page: 21 Filed: 08/16/2021
TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 21
CGRP ligand. See ’614 patent, col. 101 ll. 32–34 (“1. A hu-
man or humanized monoclonal anti-CGRP antagonist an-
tibody that preferentially binds to human α-CGRP as
compared to amylin.”); see also ’951 patent, col. 99 ll. 21–23
(“1. . . . antibody that (1) binds to human α-CGRP and (2)
inhibits [cAMP] activation in cells”); ’210 patent, col. 103
ll. 35–45 (“1. . . . wherein the CDRs impart to the antibody
specific binding to a CGRP . . . .”). As we have recently
noted, functional claim language can lead to broad claims,
especially when there are no structural limitations to
clearly define the scope. See, e.g., Amgen Inc. v. Sanofi, 987
F.3d 1080, 1087 (Fed. Cir. 2021) (discussing claims with
“broad functional language”). 8 A claim to “anything that
works” hardly has a nexus to any particular product. Thus,
we reject the strained comparisons that the parties and the
Board have made between the facts of this case and the
facts in other cases dealing with the presumption of nexus.
Because the claims in this case have a broad scope due
to their lack of structural limitations, the unclaimed fea-
tures in the commercial products cited here are of particu-
lar importance to the coextensiveness analysis. The Board
considered how four such unclaimed features in the
AJOVY® and Emgality® antibodies affect the functionality
of the products—i.e., their ability to function as anti-CGRP
antagonist antibodies. For example, the Board found that,
although the claims do not recite amino acid sequences,
AJOVY® and Emgality® have specific sequences that criti-
cally affect binding affinity and inhibit the ability of the
antibodies to kill cells. See Board Decision, 2020 WL
806932, at *46–47. The Board also found that, although
8 While our Amgen decision considered breadth in
the context of the enablement requirement of 35 U.S.C.
§ 112, we see a similar problem here as we must consider
the breadth of functional claims to determine whether they
are coextensive with specific commercial products.
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22 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
the claims did not recite limitations regarding picomolar
binding affinity, full-length antibodies versus fragments,
or IgG antibody classes, all of those features are critical to
the ability of the AJOVY® and Emgality® antibodies to
function as humanized anti-CGRP antagonist antibodies.
See id. at *47–49. The Board’s factual findings regarding
unclaimed features are thus supported by substantial evi-
dence, and Teva has not shown otherwise.
Teva concedes that “at some point”—i.e., somewhere
along the coextensiveness spectrum that we described in
Fox Factory—“the differences between a product and a pa-
tent claim become so significant that nexus cannot be pre-
sumed.” See Teva Br. at 52. In view of the extremely broad
scope of the functionally claimed antibodies of the chal-
lenged claims and the unclaimed features that undisput-
edly materially affect how AJOVY® and Emgality® function
as humanized anti-CGRP antagonist antibodies, no rea-
sonable fact finder could conclude that that point has not
been crossed in this case. Thus, Teva has failed to show
that a presumption of nexus applies in this case. As Teva
does not appear to dispute the Board’s statement that the
presumption was the sole basis for its assertion of nexus,
see Board Decision, 2020 WL 806932, at *49, we conclude
that there is no nexus between the challenged claims and
the secondary considerations based on the AJOVY® and
Emgality® products.
B
We finally turn to Teva’s arguments based on the
AlderBio license. Teva argues that, while the law requires
a nexus between the challenged claims and the “licenses
themselves,” see In re Antor Media Corp., 689 F.3d 1282,
1293–94 (Fed. Cir. 2012) (citing In re GPAC Inc., 57 F.3d
1573, 1580 (Fed. Cir. 1995)), the Board erred by requiring
a direct nexus between the challenged claims and Alder-
Bio’s products.
Case: 20-1747 Document: 79 Page: 23 Filed: 08/16/2021
TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 23
Lilly responds that substantial evidence supports the
Board’s finding that Teva failed to show a connection be-
tween the broad AlderBio license and the challenged
claims. Lilly argues that Teva relied exclusively on the fact
that the three challenged patents were included among 188
licensed patents, without any meaningful analysis of the
economic reasons motivating the licensee. Moreover, Lilly
argues, because Teva’s witnesses conceded that the license
and royalty payments would continue unabated regardless
of the validity of the three challenged patents, the license
is not probative of the nonobviousness of the challenged pa-
tents.
We agree with Lilly that the Board’s conclusion that
the AlderBio license lacked nexus to the challenged claims
was supported by substantial evidence. The significance of
licensing a patent as a secondary consideration in enhanc-
ing the nonobviousness of an invention is that an independ-
ent party with an interest in being free of the patent has
chosen to respect it and pay a royalty under it rather than
litigate and invalidate it. Such action tends to support its
validity. Here, given that 188 patents were licensed, the
nexus between the license and the validity of any particu-
lar claim is rather tenuous to say the least. Thus, the
Board was correct to require that Teva show something
more than the mere existence of the license. See Sibia Neu-
rosciences, Inc. v. Cadus Pharm. Corp., 225 F.3d 1349, 1358
(Fed. Cir. 2000) (“[T]he mere existence of these licenses is
insufficient to overcome the conclusion of obvious-
ness . . . .”); see also Merck & Cie v. Gnosis S.p.A., 808 F.3d
829, 838 (Fed. Cir. 2015) (“It is therefore difficult to deter-
mine the extent to which the licensing agreement was a
result of the novel features in the [challenged] patent, as
opposed to the other patents involved.”).
Teva failed to show anything more than the existence
of the license. Teva did not present direct evidence that
AlderBio’s motivation for entering into the license was re-
lated to the validity or enforceability of the three
Case: 20-1747 Document: 79 Page: 24 Filed: 08/16/2021
24 TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY
challenged patents. In the absence of such evidence, we
cannot fault the Board for looking to the license’s “whereas”
clause to identify the purpose of the license, namely, the
development of AlderBio’s products. With that purpose in
mind, the Board reasonably considered whether Teva had
presented evidence of a relationship between the chal-
lenged claims and the development of such products. See
S. Ala. Med. Sci. Found. v. Gnosis, S.p.A., 808 F.3d 823,
827–28 (Fed. Cir. 2015) (holding that “evidence that the li-
censee ultimately manufactured a product that embodies
the claimed invention may be probative of a nexus between
the claimed invention and the licensing activity”). The
Board expressly found that Teva did not show “that any of
the challenged patents cover the Alder Product by a com-
parison of the [] product to the challenged claims.” Board
Decision, 2020 WL 806932, at *61.
Teva’s argument loses sight of the true purpose of the
nexus requirement, which is to consider whether “the fact-
finder can infer that the licensing ‘arose out of recognition
and acceptance of the subject matter claimed’ in the pa-
tent.” See S. Ala. Med., 809 F.3d at 827 (quoting GPAC, 57
F.3d at 1580). Teva instead hinges its arguments on subtle
differences between terms that have been used in our case
law—e.g., the “licensing activity” versus the licensee’s
“products.”
At bottom, the Board found that the relevant facts,
which are supported by substantial evidence, “minimize[d]
any nexus between the challenged claims and the AlderBio
License.” Board Decision, 2020 WL 806932, at *61. Ac-
cordingly, we hold that substantial evidence supports the
Board’s decision that there is a lack of nexus between the
challenged claims and the secondary consideration of li-
censing.
Case: 20-1747 Document: 79 Page: 25 Filed: 08/16/2021
TEVA PHARMACEUTICALS v. ELI LILLY AND COMPANY 25
CONCLUSION
We have considered Teva’s remaining arguments but
we find them unpersuasive. Accordingly, the Board’s deci-
sion is affirmed.
AFFIRMED