Pfizer Inc. v. Teva Pharmaceuticals USA, Inc. ( 2014 )

NOTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
PFIZER INC., WARNER-LAMBERT COMPANY LLC,
AND C.P. PHARMACEUTICALS INTERNATIONAL
C.V.,
Plaintiffs-Appellees,
AND
NORTHWESTERN UNIVERSITY,
Plaintiff-Appellee,
v.
TEVA PHARMACEUTICALS USA, INC. AND
TEVA PHARMACEUTICAL INDUSTRIES, LTD.,
Defendants-Appellants,
AND
LUPIN, LTD. AND LUPIN PHARMACEUTICALS,
INC.,
Defendants-Appellants,
AND
ACTAVIS, INC. AND ACTAVIS ELIZABETH, LLC,
Defendants-Appellants,
AND
COBALT LABORATORIES, INC. AND
2 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
COBALT PHARMACEUTICALS, INC.,
Defendants-Appellants,
AND
SUN PHARMA GLOBAL, INC.,
SUN PHARMACEUTICAL INDUSTRIES, LTD.,
AND SUN PHARMACEUTICAL INDUSTRIES, INC.,
Defendants-Appellants,
AND
WOCKHARDT LIMITED AND WOCKHARDT USA,
LLC,
Defendants-Appellants,
AND
ALPHAPHARM PTY. LTD. AND
MYLAN PHARMACEUTICALS, INC.,
Defendants-Appellants.
______________________
2012-1576, -1601, -1602, -1603, -1604, -1605, -1607
______________________
Appeals from the United States District Court for the
District of Delaware in Nos. 09-CV-0307, 09-CV-0308, 09-
CV-0309, 09-CV-0310, 03-CV-0311, 09-CV-0312, 09-CV-
0313, 09-CV-0315 and 10-CV-0853, Chief Judge Gregory
M. Sleet.
______________________
Decided: February 6, 2014
______________________
DIMITRIOS T. DRIVAS, White & Case LLP, of New
York, New York, argued for plaintiffs-appellees Pfizer
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 3
Inc., et al. With him on the brief were JEFFREY J. OELKE,
ADAM GAHTAN, BRENDAN G. WOODARD, ROBERT E.
COUNIHAN, and RYAN P. JOHNSON, for plaintiffs-appellees,
Pfizer Inc., et al. Of counsel on the brief were KEVIN M.
FLOWERS, MATTHEW C. NIELSEN and MARK H.
IZRAELEWICZ, Marshall, Gerstein & Borun, LLP, of Chica-
go, Illinois, for plaintiff-appellee Northwestern Universi-
ty.
JAMES F. HURST, Winston & Strawn, LLP, of Chicago,
Illinois, argued for defendants-appellants Sun Pharma
Global, Inc., et al. Of counsel was GEOFFREY P. EATON, of
Washington, DC.
TIMOTHY H. KRATZ, McGuireWoods LLP, of Atlanta,
Georgia, argued for defendants-appellants Alphapharm
Pty. Ltd., et al. With him on the brief were ROBERT L.
FLORENCE and GEORGE J. BARRY, III. With him on the
brief for defendants-appellants Cobalt Laboratories, Inc.,
et al. were E. ANTHONY FIGG, JOSEPH A. HYNDS, R.
ELIZABETH BRENNER-LEIFER and CHRISTINA NICHOLE
GIFFORD, Rothwell, Figg, Ernst & Manbeck, P.C., of
Washington, DC; for defendants-appellants Actavis, Inc.,
et al. were FRANCIS H. MORRISON, III, and JONATHAN A.
HARRIS, Axinn, Veltrop & Harkrider LLP, of Hartford,
Connecticut; for defendants-appellants, Teva Pharmaceu-
ticals USA, Inc., et al. were JAMES GALBRAITH, ANTONY
PFEFFER, MATTHEW C. RUEDY, and LINNEA P. CIPRIANO,
Kenyon & Kenyon, LLP, of New York, New York; for
defendants-appellants Lupin Ltd., et al. were ROBERT F.
GREEN, CARYN C. BORG-BREEN, CHRISTOPHER T. GRIFFITH,
ELIZABETH M. CROMPTON, Leydig, Voit & Mayer Ltd., of
Chicago, Illinois; for defendants-appellants Wockhardt
Limited, et al. were JOSEPH M. REISMAN, JAY R.
DESHMUKH, and THOMAS P. KRZEMINSKI, Knobbe, Mar-
tens, Olson & Bear, LLP, of San Diego, California.
_____________________
4 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
Before RADER, Chief Judge, PROST and MOORE, Circuit
Judges.
PROST, Circuit Judge.
Defendants-Appellants Teva Pharmaceuticals USA,
Inc.; Teva Pharmaceutical Industries, Ltd.; Lupin, Ltd.;
Lupin Pharmaceuticals, Inc.; Actavis, Inc.; Actavis Eliza-
beth, LLC; Cobalt Laboratories, Inc.; Cobalt Pharmaceu-
ticals, Inc.; Sun Pharma Global, Inc.; Sun Pharmaceutical
Industries, Ltd.; Sun Pharmaceutical Industries, Inc.;
Wockhardt Ltd.; Wockhardt USA, LLC; Alphapharm Pty.
Ltd.; and Mylan Pharmaceuticals, Inc. (collectively,
“Appellants”) appeal from a final judgment of the United
States District Court for the District of Delaware that
found various claims of the asserted patents 1 infringed
and from the court’s holdings regarding enablement, 2
written description, 3 and obviousness. Pfizer Inc. v. Teva
Pharm. USA, Inc., 882 F. Supp. 2d 643, 732 (D. Del. 2012)
(“District Court Opinion”).
Because we agree with the district court’s claim con-
struction, we affirm the finding of infringement. We also
hold that challenged claim 2 of the ’819 patent is not
invalid for lack of enablement, insufficient written de-
1 The asserted patents are: U.S. Patent Nos. 6,197,
819 (“’819 patent”); 5,563,175 (“’175 patent”); 6,001,876
(“’876 patent”); and U.S. Reissue Patent No. 41,920
(“RE ’920 patent”), which is a reissue of the ’876 patent.
2 Defendants-Appellants Sun Pharma Global, Inc.;
Sun Pharmaceutical Industries, Ltd.; and Sun Pharma-
ceutical Industries, Inc. (collectively, “Sun”) do not join
the other Appellants in challenging the district court’s
enablement determination.
3 Sun, alone among the Appellants, asserted a writ-
ten description invalidity defense below and now chal-
lenges the district court’s finding on appeal.
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 5
scription, or obviousness. Accordingly, we affirm the
judgment of the district court.
BACKGROUND
Plaintiffs-Appellees Pfizer Inc., CP Pharmaceuticals
International C.V., Warner-Lambert Company LLC, and
Northwestern University (collectively, “Appellees”) sued
each of the Appellants under 35 U.S.C. § 271(e)(2)(A) after
they submitted Abbreviated New Drug Applications
(“ANDAs”) to the U.S. Food and Drug Administration
(“FDA”) seeking approval to market a generic version of
Lyrica®, a prescription drug for treating seizures and
certain types of pain. Although Appellees asserted four
patents against Appellants below, only two patents,
the ’819 and the RE ’920 patent, are relevant on appeal.
Due to its claim scope and the breadth of the injunction
entered, the disposition of this appeal rests entirely on a
single claim: claim 2 of the ’819 patent. 4
The broadest in scope of the asserted claims, claim 2
recites: “4-amino-3-(2-methylpropyl) butanoic acid, or a
pharmaceutically acceptable salt thereof.” ’819 patent col.
4 Prior to the bench trial, the parties stipulated
that, to the extent the district court finds claim 2 to be
valid and enforceable, the Appellants’ respective ANDAs
are covered by the claim under the court’s claim construc-
tion and the proposed products infringe. District Court
Opinion, at 662-63. Likewise, on appeal, the parties
agree that Appellants’ entire case is predicated upon
claim 2, i.e., the other issues are moot and Appellants lose
the appeal if we affirm the district court’s findings with
respect to claim 2. Oral Argument at 2:41-4:24, 16:50-
17:09 available at http://oralarguments.cafc.uscourts.gov/
default.aspx?fl=2012-1576.mp3. Accordingly, we limit
our review of the district court’s findings and determina-
tions to claim 2.
6 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
27 ll. 32-33. The district court construed the term “4-
amino-3-(2-methylpropyl) butanoic acid” 5 to mean “the
chemical compound 4-amino-3-(2-methylpropyl) butanoic
acid,” without limitation as to stereochemical form. 6
Pfizer Inc. v. Teva Pharm. USA, Inc., No. 09-CV-307 (D.
Del. Oct. 13, 2010), ECF No. 100 (“Markman Order”).
5 4-amino-3-(2-methylpropyl) butanoic acid is also
known in the chemical nomenclature as 3-isobutylGABA.
6 Stereochemical form refers to the three-
dimensional structure of molecules. In organic chemistry,
stereoisomers are compounds with the same molecular
formula or atomic composition, but different spatial
arrangements. Enantiomers are a pair of stereoisomers
that are non-superimposable mirror images of each other
and often have distinct physical properties. Enantiomeric
pairs include compounds that have one or more stereogen-
ic centers, i.e., carbon atoms with four non-identical
substituent atoms or groups of atoms. These compounds
are thus said to be chiral.
To distinguish between different enantiomers of the
same compound, chemists use various naming conven-
tions. Enantiomers are called optical isomers because
they rotate plane-polarized light in a particular direction.
If the light rotates clockwise, then that enantiomer is
labeled (+); its counterpart will rotate the light counter-
clockwise and is labeled (-). A different nomenclature
labels each stereogenic center (R) or (S) according to a set
of scientific rules. A racemate (or racemic mixture) is an
equal mixture of two enantiomers and therefore is not
optically active (i.e., will not rotate plane-polarized light
in either direction because its constituent enantiomeric
pairs cancel one another out). Racemates are typically
designated (R, S) because they are comprised of both R-
enantiomers and S-enantiomers.
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 7
Pregabalin, the active ingredient in Lyrica®, is the S-
enantiomer of 3-isobutylGABA. 7 It is specifically dis-
closed by claim 1 of the ’819 patent as “[a] compound of
the formula S-(+)-4-amino-3-(2-methypropyl) butanoic
acid as a single optical isomer.” ’819 patent col. 27 ll. 29-
31. The district court construed the claim to mean “4-
amino-3-(2-methylpropyl) butanoic acid in the single S-(+)
isomer form only, free of the R-(-) isomer form.” Markman
Order, at 1.
After a bench trial in the consolidated Hatch-Waxman
action, the district court held, inter alia, that claim 2 is
not invalid for lack of enablement, insufficient written
description, or obviousness. District Court Opinion, at
732. Because the Appellants stipulated to infringement,
the court thereafter enjoined them from commercially
manufacturing, using, offering for sale, or selling their
proposed products prior to December 30, 2018—the expi-
ration date of the ’819 patent after the FDA’s extension of
its term under 35 U.S.C. § 156. See id. at 656, 730, 732.
This appeal followed. We have jurisdiction under 28
U.S.C. § 1295(a)(1).
7 In pharmacology, often only one enantiomer of a
chemical compound is responsible for certain desired
therapeutic effects, while the other enantiomer is less
effective or inactive. This well-known phenomenon is
attributable to the distinct physical structures of enanti-
omers. With respect to 3-isobutylGABA, the S-
enantiomer is the pharmaceutically useful stereoisomer
for the treatment of seizures and pain, while the R-
enantiomer is less potent.
8 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
DISCUSSION
I. CLAIM CONSTRUCTION AND INFRINGEMENT
Claim construction is an issue of law that we review
de novo. Cybor Corp. v. FAS Techs., Inc., 138 F.3d 1448,
1454-55 (Fed. Cir. 1998) (en banc). In construing a claim
term, we look at the term’s plain and ordinary meaning as
understood by a person of ordinary skill in the art. Phil-
lips v. AWH Corp., 415 F.3d 1303, 1313 (Fed. Cir. 2005)
(en banc). There are two exceptions to this general rule:
(1) when a patentee sets out a definition and acts as her
own lexicographer, or (2) when the patentee disavows the
full scope of a claim term either in the specification or
during prosecution. Thorner v. Sony Computer Entm’t
Am., LLC, 669 F.3d 1362, 1365 (Fed. Cir. 2012). The
subsequent infringement analysis is reviewed for clear
error after a bench trial. Alza Corp. v. Mylan Labs., Inc.,
464 F.3d 1286, 1289 (Fed. Cir. 2006).
Appellants argue that the district court erred in con-
struing claim 2 of the ’819 patent to cover 3-
isobutylGABA generally. They contend that the proper
construction of claim 2 is that it covers only racemic (i.e.,
a 50:50 mixture of S- and R-enantiomers of) 3-
isobutylGABA. Appellants contend that the patent speci-
fication, prosecution history, and applicant declarations
submitted to the U.S. Patent and Trademark Office
(“PTO”) support a narrower construction of the claimed
compound as a racemic mixture. Finally, they argue that
because their proposed products contain non-racemic
mixtures, they do not infringe.
Appellees counter that a narrower construction would
ignore the plain, clear, and specific language of the claim,
which places no limitation on the claimed chiral com-
pound. Appellees submit that the patentee’s inclusion of
test results of the compound’s racemate in the specifica-
tion, juxtaposed with the lack of a racemic limitation in
the claim language, demonstrates the patentee’s intent
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 9
not to limit the compound being claimed to its racemate.
Appellees also point out that at trial, Appellants’ own
expert admitted that claim 2 covers “3-isobutylGABA in
any isomeric form,” that is, “the form is not defined.” J.A.
20658.
We perceive no error in the district court’s construc-
tion. The plain language of the claim does not include the
narrowing limitation that the Appellants desire. The
patent specification discusses 4-amino-3-(2-methylpropyl)
butanoic acid as the “preferred compound” generally and
without regard to its stereochemistry. See, e.g., ’819
patent col. 3 ll. 65-67. The specification makes clear that
the patentee expressly used the word “racemate,” “race-
mic,” or its standard prefix (R, S) to refer to the chiral
compound’s racemate. See, e.g., ’819 patent col. 7 l. 39,
col. 9 l. 25, col. 13 l. 23. Likewise, the patentee used
standard prefixes (R) or (S) to designate a particular
enantiomer of the compound. See, e.g., ’819 patent col. 4
ll. 7-15, col. 5 ll. 34-40, col. 7 l. 39, col. 13 l. 24. Because
the patentee included no such references or prefixes in
claim 2, it should not be so limited.
Appellants also note that Tables 1 and 2 in the speci-
fication report test results pertaining only to the com-
pound’s racemate, but not other mixtures with differing
enantiomeric compositions. See ’819 patent tables 1, 2.
Appellants contend that this limited association of the
subject matter of claim 2 with only racemic 3-
isobutylGABA warrants a narrower construction. We
disagree. Absent a clear disavowal or lexicographic
definition in the specification or the prosecution history,
the reporting of test results limited to a racemate does not
warrant importing a racemic limitation into claim 2.
Moreover, rather than listing 3-isobutylGABA in Tables 1
and 2 without specifying its form, the patentee used the
prefix (R, S) to specify that the compound being tested
was a racemic mixture. Contrary to Appellants’ sugges-
tion, the patentee’s use of the prefix in the tables demon-
10 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
strates that it knew how to specify racemic 3-
isobutylGABA as distinguished from the compound gen-
erally and chose not to do so in claim 2.
Indeed, the district court correctly observed in its
claim construction order that “when the patentee identi-
fied the racemate in the specification, it used a prefix
(R, S) that does not appear in the disputed claim.”
Markman Order, at 1 n.2. The court also correctly noted
that the prosecution history cited to by the Appellants
also “does not evince a disclaimer of non-racemic forms,”
id., to warrant departure from the general rules of claim
construction. There is no basis elsewhere in the intrinsic
record to support Appellants’ suggestion that the absence
of an (R) or (S) prefix in claim 2 specifically signals the
racemate, rather than the compound without limitation
as to stereochemical form or composition. Accordingly, we
affirm the district court’s construction.
Because claim 2 was correctly construed to include 3-
isobutylGABA regardless of its enantiomeric forms and
infringement was stipulated to by the Appellants under
this construction, we also affirm the finding of infringe-
ment.
II. ENABLEMENT
Enablement is a question of law that we review with-
out deference, based on underlying factual inquiries that
we review for clear error after a bench trial. Cephalon,
Inc. v. Watson Pharm., Inc., 707 F.3d 1330, 1336 (Fed.
Cir. 2013). To be enabling under 35 U.S.C. § 112(a), a
patent’s specification must describe the invention and the
manner and process of making and using it, in such full,
clear, concise, and exact terms, as to allow any person
skilled in the art “to make and use the full scope of the
claimed invention without undue experimentation.”
MagSil Corp. v. Hitachi Global Storage Techs., Inc., 687
F.3d 1377, 1380 (Fed. Cir. 2012) (internal quotation
marks omitted).
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 11
The ’819 patent, issued on March 6, 2001, claims pri-
ority to U.S. Patent Application Serial No. 07/618,692
(“’692 application”), which was filed on November 27,
1990. ’819 patent col. 1 ll. 6-12. The district court held
that, based on its construction, claim 2 is sufficiently
enabled by the ’692 application because “a person of skill
in the art could have relied upon [the] application’s disclo-
sure to prepare 3-isobutylGABA . . . [with] no more than
routine experimentation.” District Court Opinion, at 655.
Appellants 8 contend that because claim 2 was con-
strued to cover all compositions of 3-isobutylGABA,
without limitation as to isomeric form, to be sufficiently
enabling the ’692 application must teach a skilled artisan
how to prepare every conceivable mixture of 3-
isobutylGABA’s enantiomers. Although the parent appli-
cation acknowledges that hundreds of permutations of
non-racemic mixtures of 3-isobutylGABA exist, see J.A.
3010-13, Appellants assert that it fails to disclose how to
prepare them. Appellants also contend that the ’692
application provides nothing more than boilerplate lan-
guage pointing to unspecified prior art as the basis for
making the claimed invention, and fails to disclose the
required starting materials, reaction conditions, and other
working examples.
We are not persuaded by Appellants’ arguments.
First, there is no requirement that a specification must
“disclose what is routine and well known in the art.”
Genentech, Inc. v. Novo Nordisk A/S, 108 F.3d 1361, 1366
(Fed. Cir. 1997). Second, as the district court found, there
is no dispute in the record that the co-inventors of the ’819
patent were the first to create and claim the chemical
compound 3-isobutylGABA. District Court Opinion, at
8 Reference to Appellants in this section does not
include Sun, who does not join the other Appellants in
challenging the district court’s enablement determination.
12 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
689. It is also undisputed that the parent application
discloses the method for synthesizing the compound and
states that the compound’s “enantiomers may be prepared
or isolated by methods already well known in the art.”
J.A. 3012-14. The district court found support for this
fact in the prior art, the prosecution history, and witness-
es’ trial testimonies. See District Court Opinion, at 683-
87; see also J.A. 3012-14, 21196-203, 21168-69, 21172-80,
20622-24, 21205-06. The court also acknowledged that
the same conclusion was reached by the PTO Examiner,
who withdrew an enablement rejection on that very basis
during prosecution of the patent. District Court Opinion,
at 689 n.41.
In view of the finding that enantiomer separation
methods are well-known and routine to a person of ordi-
nary skill, we agree with the district court that the inven-
tors were not required to provide a detailed recipe for
preparing every conceivable permutation of the compound
they invented to be entitled to a claim covering that
compound. Where a claim has been construed to cover a
chemical compound, the specification is not deficient
merely because it does not disclose how to prepare a
particular form or mixture—among hundreds of possible
permutations—of that compound. See In re Hogan, 559
F.2d 595, 606 (CCPA 1977) (noting that requiring such
specific disclosures would “impose an impossible burden
on inventors”).
Instead, claim 2 satisfies the requirements under
§ 112(a) because the ’692 application’s disclosure, coupled
with the methods for synthesis and resolution that were
found to be well-known and routine in the art, is suffi-
ciently enabling. The district court’s legal determination
of enablement was not incorrect. Its factual findings are
not clearly erroneous. We therefore affirm the determina-
tion that claim 2 is not invalid for lack of enablement.
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 13
III. WRITTEN DESCRIPTION
Compliance with the written description requirement
is a question of fact reviewed for clear error following a
bench trial. Lampi Corp. v. Am. Power Prods., 228 F.3d
1365, 1378 (Fed. Cir. 2002). A party alleging that a
patent is invalid for lack of written description has the
burden of establishing by clear and convincing evidence
that a patent disclosure does not reasonably convey to a
skilled artisan that the inventor was in possession of the
claimed invention at the time of the patent application.
See Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336,
1351 (Fed. Cir. 2010) (en banc).
The district court found claim 2 of the ’819 patent not
invalid for lack of written description. The court found
the ’692 application to have expressly claimed 3-
isobutylGABA in both racemic and non-racemic mixtures,
and detailed the inventor’s method for synthesizing the
compound. District Court Opinion, at 702. The court also
found the parent application to have included seven
claims specifically directed to the compound or its use in
pharmaceutical compositions or methods of treatment, as
well as repeatedly identified it as the preferred embodi-
ment of the invention. Id. The court noted the testimony
of the other Appellants’ enablement expert in which he
admitted that “chemists would understand what the
disclosure” in the ’692 application meant, id., as well as
Sun’s dearth of evidence at trial, before concluding that
the application’s descriptions were more than sufficient to
meet the written description standard. Id.
Sun alone presses a written description argument on
appeal. First, Sun argues that although the ’692 applica-
tion discloses a chemical synthesis method for the race-
mate of 3-isobutylGABA, see J.A. 21263-64, 20768, it
discloses nothing towards the isolation of the enantio-
mers, even though claim 2 of the ’819 patent has been
construed to encompass all forms of the compound.
14 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
Second, according to Sun, despite the patentee describing
the separation of the racemate (i.e., isolation of the enan-
tiomers) as anything but routine in later applications, at
the time of the ’692 application, both inventors readily
admitted that they had not yet separated the racemic
mixture to obtain a purified enantiomer. See J.A. 20814-
18. Taken together, Sun contends, these facts establish
that the inventors had not actually invented 3-
isobutylGABA in all of its forms in 1990.
Sun’s position on written description is surprisingly
similar to the other Appellants’ position on enablement.
Sun conflates the disclosure requirement for claim 2 with
that for claim 1: it argues that because the inventors had
not sufficiently described the narrower claim 1 (to pre-
bagalin) they could not have sufficiently described the
broader claim 2 (to 3-isobutylGABA).
But written description does not require inventors, at
the time of their application for a patent, to reduce to
practice and be in physical possession of every species
(e.g., the S-enantiomer of 3-isobutylGABA) of a genus (3-
isobutylGABA) claim. For claims to a chemical com-
pound, an application satisfies the written description
requirement when it details “relevant identifying charac-
teristics” such that the compound can be distinguished
from other compounds. In re Wallach, 378 F.3d 1330,
1333, 1335 (Fed. Cir. 2004). Here, the ’692 application
not only disclosed the structure of 3-isobutylGABA as the
preferred embodiment of the invention, see J.A. 3018-19,
20764:11-14, 3011, but also set forth in vitro and in vivo
data for the compound, J.A. 3025-29, 20766:19-21, and
described a method of synthesizing the compound, J.A.
3012-14, 20900. As the district court correctly found, such
a description is sufficient for persons of ordinary skill in
the art to recognize that the inventor invented what is
claimed. Union Oil Co. of Cal. v. Atl. Richfield Co., 208
F.3d 989, 997 (Fed. Cir. 2000)
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 15
We therefore affirm the finding that the ’692 applica-
tion provided an adequate written description for claim 2
under § 112(a).
IV. OBVIOUSNESS
The determination of obviousness is a legal conclusion
based on underlying facts. Allergan, Inc. v. Sandoz Inc.,
726 F.3d 1286, 1290-91 (Fed. Cir. 2013). After a bench
trial, we review the district court’s factual findings for
clear error and its conclusions of law de novo. Honeywell
Int’l, Inc. v. United States, 609 F.3d 1292, 1297 (Fed. Cir.
2010). A patent claim is invalid for obviousness if “the
differences between the claimed invention and the prior
art are such that the claimed invention as a whole would
have been obvious before the effective filing date of the
claimed invention to a person having ordinary skill in the
art to which the claimed invention pertains.” 35 U.S.C.
§ 103. The “underlying factual considerations in an
obviousness analysis include the scope and content of the
prior art, the differences between the prior art and the
claimed invention, the level of ordinary skill in the art,
and any relevant secondary considerations[,]” which
include “commercial success, long-felt but unsolved needs,
failure of others, and unexpected results.” Allergan, 726
F.3d at 1290-91 (citations omitted). Patent invalidity
must be established by clear and convincing evidence.
Microsoft Corp. v. i4i Ltd. P’ship, 131 S. Ct. 2238, 2242
(2011).
The district court concluded that the evidence pre-
sented by Appellants at trial was insufficient to render
claim 2 invalid under § 103. The district court held that
claim 2 would not have been obvious in view of the three
prior art references cited by Appellants: U.S. Patent No.
4,322,440 (“Fish”), U.S. Patent No. 5,051,448 (“Shash-
oua”), and a 1962 article published at pages 598 through
603 in the Bulletin de la Société Chimique de France
(“Colonge”). It found that these references did not teach
16 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
skilled artisans to select 3-isobutylGABA for its anticon-
vulsant activity. District Court Opinion, at 667. Specifi-
cally, the court found that Appellants provided neither
“information detailing what [chemical] structures were
important for anticonvulsant activity [research] in 1990”
nor “teachings from the Colonge, Fish, and Shashoua
references, which, individually or combined, would have
directed one skilled in the art” to arrive at the claimed
invention, i.e., to substitute alkyl groups 9 at GABA’s 3-
position. 10 Id. The court also determined that various
secondary considerations—namely, unexpected results,
long felt but unmet need, commercial success, and indus-
try recognition—strongly supported the conclusion of
nonobviousness. Id. at 667-72.
Appellants contend on appeal that the district court
clearly erred in failing to make the following findings: (1)
Fish, Shashoua, and Colonge taught that 3-
isopropylGABA and other homologous compounds may
have anticonvulsant activity; (2) one of ordinary skill in
the art would have expected 3-isobutylGABA to have
anticonvulsant activity due to its structural similarities to
3-isopropylGABA; and (3) gabapentin, a 3-alkylGABA
compound in the prior art with demonstrated anticonvul-
sant efficacy, provided a motivation for persons skilled in
the art to try other alkyl substituents at GABA’s 3-
position.
9 An alkyl group is a carbon chain of varying length
and orientation. Isobutyl is a four-carbon alkyl group
with a specific carbon configuration. There are potential-
ly infinite alkyl groups.
10 GABA stands for “gamma aminobutyric acid,”
which is a neurotransmitter that can cause seizures when
its levels in the brain are abnormally low. GABA has a
four-carbon structural backbone. The term “3-position”
refers to the third carbon on GABA’s backbone.
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 17
According to the district court and Appellees, Appel-
lants failed to make an obviousness case because the
evidence presented at trial was too sparse. We agree.
Whether a new chemical compound would have been
prima facie obvious over particular prior art compounds
follows a two-part inquiry under our precedent. First, the
court determines whether a chemist of ordinary skill in
the art would have selected the asserted prior art com-
pound as a lead compound, or starting point, for further
development. Eisai Co. v. Dr. Reddy’s Labs., Ltd., 533
F.3d 1353, 1359 (Fed. Cir. 2008). A lead compound is a
compound in the prior art that would be “most promising
to modify in order to improve upon its activity and obtain
a compound with better activity.” Takeda Chem. Indus.,
Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed.
Cir. 2007). The selection analysis may be guided by
evidence of the compound’s pertinent properties, such as
chemical activity or potency. See Eli Lilly & Co. v. Zenith
Goldline Pharm., Inc., 471 F.3d 1369, 1378 (Fed. Cir.
2006). Mere structural similarity between a prior art
compound and the claimed compound does not inform the
lead compound selection. Otsuka Pharm. Co. v. Sandoz
Inc., 678 F.3d 1280, 1292 (Fed. Cir. 2012); see Daichii
Sankyo Co. v. Matrix Labs., Ltd., 619 F.3d 1346, 1354
(Fed. Cir. 2010).
On the selection of a lead compound, the district court
found that the Appellants “did not point to any evidence
in the prior art indicating that a particular compound or
class of compounds, including alkyl-substituted GABA
analogs . . . would improve anti-seizure treatment.”
District Court Opinion, at 667. We agree that the record
contains scant evidence that either gabapentin or 3-
isopropylGABA would have been selected as a lead com-
pound.
With respect to gabapentin, no evidence in the record
firmly situates gabapentin in the prior art or otherwise
18 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
supports its selection as a lead compound. At most,
Appellants established that gabapentin was being tested
for its anticonvulsant effect contemporaneously with 3-
isobutylGABA, see J.A. 20849, but there is no testimony
establishing its being tested prior to the discovery of 3-
isobutylGABA. Appellants note that Appellees’ expert
admitted that by 1990, gabapentin had entered Phase III
clinical trials, see J.A. 20982-83, but no testimony indi-
cates that the trials or results therefrom had been dis-
closed publicly by then.
Further, there is no evidence in the record of motiva-
tion for a skilled artisan to modify gabapentin for further
anticonvulsant research. Appellees submit that Appel-
lants have failed to provide the most basic details about
gabapentin, such as a discussion of its advantages over
other compounds, biological or other data, or mechanism
of action—any of which would have aided the selection
analysis. Instead, Appellants chose to emphasize that
gabapentin was a solid choice for a skilled artisan based
on its structural similarity to pregabalin, a fact the speci-
fication of the ’819 patent acknowledged. See ’819 patent
col. 13 ll. 12-16. A patent challenger, however, must
demonstrate the selection of a lead compound based on its
“promising useful properties,” not a hindsight-driven
search for structurally similar compounds. Daichii, 619
F.3d at 1354.
Record evidence supporting 3-isopropylGABA’s candi-
dacy as a lead compound is just as meager. Appellants
suggest that the disclosure of 3-isopropylGABA in the
Fish, Shashoua, and Colonge references would have
directed a skilled artisan to modify other substituent
groups at GABA’s 3-position. The district court found,
however, that Appellants failed to make the case for why
3-isopropylGABA would have been selected for further
research in the first place, because the record lacks any
explanation for “what structures were important for
anticonvulsant activity[.]” District Court Opinion, at 667.
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 19
Indeed, nothing in the Fish, Shashoua, and Colonge
references single out 3-isopropylGABA, among the other
compounds within the references’ broad disclosures, as a
promising compound to modify due to its anticonvulsant
effect. In addition, these references fail to identify a lead
compound because they disclose nothing concrete about 3-
isopropylGABA or its mechanisms of action, including
whether it has anticonvulsive properties. See Daiichi, 619
F.3d at 1352 (requiring a lead compound to have proper-
ties that are similar to or improvable by the new com-
pound). Therefore, the district court did not clearly err
when it concluded that “the evidence [Appellants] pre-
sented is insufficient to show clearly and convincingly
that skilled artisans would have known to select 3-
isobutylGABA in November 1990 based simply on the fact
that it is a homologous compound” to 3-isopropylGABA.
District Court Opinion, at 666-67.
Proof of obviousness of a chemical compound “clearly
depends on a preliminary finding that one of ordinary
skill in the art would have selected [a particular prior art
compound] as a lead compound.” Takeda, 492 F.3d at
1357. The second step of the obviousness analysis re-
quires a showing that the prior art would have taught a
skilled artisan to make “specific molecular modifications”
to a lead compound so that the claimed compound may be
made with a reasonable expectation of success. Id. at
1356-57.
Beyond Appellants’ failure to establish a lead com-
pound as a threshold, the record also supports the district
court’s finding that Appellants failed to identify the
teachings required in the second step of the inquiry.
According to Appellants, the disclosures in Fish, Shash-
oua, and Colonge would have taught a skilled artisan to
modify “lower alkyl substitutes”—which includes isobu-
tyl—at GABA’s 3-position to achieve 3-isobutylGABA.
However, it is quite evident that the Fish, Shashoua, and
Colonge references together disclosed trillions of com-
20 PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC.
pounds without calling out alkyl groups in particular or
singling out isobutyl specifically. As the district court
correctly found, the Appellants “did not point to any
evidence in the prior art indicating that a particular
compound or class of compounds” nor “identify any teach-
ings as of the filing date that would have directed a
skilled artisan to substitute [at GABA’s 3-position] with
an isobutyl group, as opposed to any other alkyl group[.]”
District Court Opinion, at 667. Indeed, a vague sugges-
tion in the prior art pointing to a broad class of com-
pounds, without any teaching particularly identifying
isobutyl among the millions of potential compounds, is not
a teaching of “specific molecular modifications” required
by our precedent. Takeda, 492 F.3d at 1356. Finally, the
district court found Appellees to have credibly established
that anticonvulsant drug discovery in 1990 was “compli-
cated,” “unpredictable,” and “largely conducted through
trial and error.” District Court Opinion, at 667. This
finding would have precluded any argument by Appel-
lants that there would have been a “reasonable expecta-
tion of success” to achieve an anticonvulsant in 3-
isobutylGABA even if Appellants were able to establish
that the prior art taught the substitution of isobutyl at
GABA’s 3-position.
The district court did not err in finding that Appel-
lants failed to establish that gabapentin or 3-
isopropylGABA would have been selected as lead com-
pounds, or that Appellants failed to set forth evidence
identifying the necessary teachings for a skilled artisan to
modify alkyl groups at GABA’s 3-position to improve
anticonvulsant activity. Because we agree with the
district court that the Appellants failed to prove that
claim 2 would have been prima facie obvious over the
asserted prior art compounds, we need not address the
court’s findings regarding secondary considerations of
nonobviousness. See Otsuka, 678 F.3d at 1296.
PFIZER INC. v. TEVA PHARMACEUTICALS USA, INC. 21
CONCLUSION
We have considered the Appellants’ remaining argu-
ments and do not find them to be persuasive. We hold
that the district court did not err in its conclusion that
claim 2 of the ’819 patent has been infringed, and that
Appellants failed to prove that the claim is not enabled,
insufficiently described, or obvious. Based on the forego-
ing, the parties’ arguments with respect to the other
patent claims are moot. Accordingly, we affirm the dis-
trict court’s judgments of infringement and no invalidity.
AFFIRMED