Glaxosmithkline LLC v. Banner Pharmacaps, Inc. ( 2014 )

United States Court of Appeals
for the Federal Circuit
______________________
GLAXOSMITHKLINE LLC
(formerly known as SmithKline Beecham
Corporation),
Plaintiff-Appellee,
v.
BANNER PHARMACAPS, INC. AND
IMPAX LABORATORIES, INC.,
Defendants-Appellants,
AND
ROXANE LABORATORIES, INC.,
Defendant-Appellant,
AND
MYLAN INC. AND
MYLAN PHARMACEUTICALS INC.,
Defendants-Appellants,
AND
WATSON LABORATORIES, INC. FLORIDA,
Defendant-Appellant.
______________________
2013-1593, -1594, -1595, -1598
______________________
2 GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC.
Appeals from the United States District Court for the
District of Delaware in Nos. 11-CV-0046, 11-CV-0542 and
11-CV-0789, Judge Richard G. Andrews.
______________________
Decided: February 24, 2014
______________________
WILLIAM F. LEE, Wilmer Cutler Pickering Hale and
Dorr, LLP, of Boston, Massachusetts, argued for plaintiff-
appellee. With him on the brief were LISA J. PIROZZOLO
and SARAH R. FRAZIER, of Boston, Massachusetts;
WILLIAM G. MCELWAIN, THOMAS G. SAUNDERS and
MATTHEW GUARNIERI, of Washington, DC; and
CHRISTOPHER R. NOYES, of New York, New York.
DEANNE E. MAYNARD, Morrison & Foerster, LLP, of
Washington, DC, argued for all defendants-appellants.
With her on the brief for defendants-appellants Banner
Pharmacaps, Inc., et al., were MARC A. HEARRON, of
Washington, DC and PARISA JORJANI, of San Francisco,
California. Of counsel on the brief were C. KYLE
MUSGROVE and MICHAEL M. SHEN, Haynes and Boone,
LLP, of Washington, DC. On the brief for Roxane Labora-
tories, Inc. were KENNETH G. SCHULER and MARC N.
ZUBICK, Latham & Watkins LLP, of Chicago, Illinois; and
DARRYLL H. STEENSMA, of San Diego, California. On the
brief for Watson Laboratories, Inc. – Florida were GARY E.
HOOD and MARK T. DEMING, Polsinelli, PC, of Chicago,
Illinois. On the brief for Mylan Inc., et al. were JAMES H.
WALLACE, JR., MARK A. PACELLA, and LUCY M. STARK,
Wiley Rein, LLP, of Washington, DC.
______________________
Before O’MALLEY, WALLACH, and TARANTO, Circuit
Judges.
GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC. 3
TARANTO, Circuit Judge.
Plaintiff GlaxoSmithKline LLC (“GSK”) sued Banner
Pharmacaps, Inc., Impax Laboratories, Inc., Roxane
Laboratories, Inc., Mylan Inc., Mylan Pharmaceuticals,
Inc., and Watson Laboratories, Inc.–Florida (collectively,
“Defendants”). Invoking 35 U.S.C. § 271(e)(2), GSK
alleged that drug products containing the molecule dutas-
teride that Defendants propose to market fall within
claims of U.S. Patent No. 5,565,467, which covers dutas-
teride and its pharmaceutically acceptable solvates. All
Defendants stipulated to infringement, which is no longer
an issue, but alleged that the asserted claims were invalid
for anticipation, lack of utility, lack of enablement, and
inadequacy of the written description. After a three-day
bench trial, the district court issued an opinion concluding
that Defendants did not prove the asserted claims invalid.
GlaxoSmithKline LLC v. Banner Pharmacaps, Inc., No.
11-CV-046, 2013 WL 4082232 (D. Del. Aug. 9, 2013).
Defendants appeal the rejection of their written-
description challenge. Their appeal presents only one
contention—that “solvate” is not adequately described,
whether construed as Defendants urge or as the district
court construed it. We affirm, without resolving the
claim-construction dispute.
BACKGROUND
This case involves claims to the chemical compound
dutasteride and its pharmaceutically acceptable solvates.
Claim 1 of the ’467 patent, the only independent claim,
reads, “17β-N-(2,5-bis(Trifluoromethyl))phenylcarbamoyl-
4-aza-5α-androst-1-en-3-one or a pharmaceutically ac-
ceptable solvate thereof.” ’467 patent, col. 16, lines 4-6.
The parties agree that dutasteride is the molecule identi-
fied before “or a pharmaceutically acceptable solvate
thereof.” The other asserted claims all recite “[a] phar-
maceutical formulation comprising” the “compound of
claim 1,” subject to further restrictions having no effect on
4 GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC.
the issue presented here. See id. at col. 16, lines 7-20
(dependent claims 2 through 5).
Dutasteride “is useful in the treatment of androgen
responsive diseases.” ’467 patent, col. 10, lines 19-20.
Androgens are a class of hormones—with testosterone
“the major circulating androgen”—implicated in a number
of diseases, including “benign prostatic hyperplasia,
prostate cancer, acne, male pattern baldness and hir-
sutism.” Id. at col. 1, lines 18-19, 55-60. In some target
tissues, including prostate and skin tissue, testosterone
produces certain effects by first being converted to dihy-
drotestosterone. See id. at col. 1, lines 15-25. Dutasteride
inhibits the enzymes that catalyze the conversion and
thus mitigates some of testosterone’s physiological effects,
which is sometimes medically desirable. See id.
The asserted claims cover not only dutasteride, but
also any “pharmaceutically acceptable solvate thereof.” A
“solvate,” by definition, is something that originates in a
“solution,” which is a mixture of two substances: a “solute”
dissolved in a “solvent.” Salt water is a solution, in which
salt is the solute and water the solvent. A solvate is a
molecule (a) consisting of a complex made up of solute
molecules and solvent molecules (b) resulting from the
solution. The parties agree on that much, and also on the
proposition that, at least frequently, a solvate complex is
“crystalline,” a purely structural description referring to
the regular, periodic arrangement of the constituent
molecules or atoms. The parties disagree about whether
“solvate” (in the context of this patent) means only such
crystalline complexes—a dispute we need not resolve.
Dutasteride has been proven effective in treating be-
nign prostatic hyperplasia, otherwise known as enlarge-
ment of the prostate gland. GSK markets Avodart® and
Jalyn™, which contain dutasteride and are approved by
the Food and Drug Administration to treat symptoms of
benign prostatic hyperplasia. Each Defendant filed at
GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC. 5
least one Abbreviated New Drug Application under 21
U.S.C. § 355(j), seeking FDA approval to market a generic
version of Avodart® or Jalyn™. Each ANDA included a
certification under § 355(j)(2)(A) that the ’467 patent is
invalid, is unenforceable, or would not be infringed by
marketing of the proposed generic product. As authorized
by 35 U.S.C. § 271(e)(2), GSK responded by suing Defend-
ants for infringement of its ’467 patent.
The district court construed “pharmaceutically ac-
ceptable” to mean “[s]uitable for use when administered
to the recipient thereof as a pharmaceutical.” Claim
Construction Opinion at 8, GlaxoSmithKline LLC, No. 11-
CV-046 (D. Del. Nov. 15, 2012). The court also construed
“solvate” (of dutasteride), which is the claim term at issue
here. GSK and Defendants disagreed about whether the
term refers only to crystalline complexes of solute and
solvent molecules—that is, of dutasteride (the solute) and
some solvent—or, instead, also includes non-crystalline
complexes. GSK argued for the broader construction,
Defendants for the narrower. The district court acknowl-
edged Defendants’ “considerable extrinsic evidence” that,
in the pharmaceutical field, “solvate” is limited to crystal-
line complexes, no matter how created, but it concluded
that the specification of this particular patent “direct[ly]
contradict[s]” any such narrow usage. See id. at 7-8
(relying on ’467 patent, col. 3, line 58, through col. 4, line
12). The court construed a “solvate” of dutasteride to
mean
[a] complex formed by dutasteride with a solvent
in which dutasteride is reacted or from which it is
precipitated or crystallized.
Id. at 4. Despite potential confusion about the meaning of
this language, including about what “it” refers to, the
parties agree in interpreting the district court’s construc-
tion to refer to three processes of forming dutasteride
solvates—by a reaction of dutasteride with a solvent; by
6 GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC.
precipitation of a complex from a solution of dutasteride
and a solvent; by crystallization of a complex from a
solution of dutasteride and a solvent—with the resulting
complex not required to be crystalline.
Defendants stipulated to infringement and have not
raised any infringement issue on appeal (not even condi-
tionally, should we reverse the district court’s claim
construction in deciding the issue they do raise on ap-
peal). The only issue before us is Defendants’ invalidity
challenge asserting the inadequacy of the written descrip-
tion, a challenge that the district court rejected—along
with invalidity challenges asserting anticipation, lack of
utility, and lack of an enabling disclosure—after a three-
day bench trial held after the stipulation of infringement.
Defendants did not dispute that dutasteride is adequately
described: it is precisely identified by structure. Instead,
they argued that “solvates” of dutasteride, a limitation in
all asserted claims, lacked adequate support in the writ-
ten description. Specifically, Defendants argued that the
written description failed to describe the crystalline form
of solvate or, more generally, a wide enough range of the
solvates included in the district court’s construction,
which need not be crystalline and could be produced
through reaction, precipitation, or crystallization.
Addressing the adequacy of the written description,
the district court made various findings, some focused on
solvate formation and some on determining which solv-
ates were therapeutically effective. See GlaxoSmithKline
LLC v. Banner Pharmacaps, Inc., No. 11-CV-046, 2013
WL 4082232, at *2-3 (D. Del. Aug. 9, 2013) (findings of
fact). It found that dutasteride is “the key structural
feature of the solvate” and what “distinguish[es] the ’467
[p]atent from the prior art.” Id. at *2, 8. It found that
solvate formation “has been known in the art for over 100
years,” that dutasteride is a steroid, that “[s]teroids in
particular have been known to be prone to solvate for-
mation since 1983,” and that “the universe of solvents
GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC. 7
thought to be pharmaceutically acceptable was well-
known and relatively small.” Id. at *2, 6. The court noted
that “it [was] difficult or even impossible to predict
whether a particular solvate form will offer bioavailabil-
ity, at least prior to the solvate’s actual formation,” but
found that methods to determine the solubility of an
already formed solvate “were well-known and routine in
the art” and “could be done in less than a week.” Id. at
*6-7 (emphasis added).
The district court concluded that Defendants failed to
prove the inadequacy of the written description. Accord-
ing to the district court, “[t]here is no reason why a person
skilled in the art would not credit a patentee with posses-
sion of a solvate merely because the patentee did not
disclose solvates formed by each solvation pro-
cess,” i.e., reaction, precipitation, crystallization. Id. at
*5. The district court characterized Example 3D—which
describes dissolving dutasteride in liquid propylene
glycol, see ’467 patent, col. 15, lines 21-25—as identifying
a “reacted” solvate. Id. at *7-8. The court found the
example, in addition to what was known in the art, “suffi-
cient to meet the written description requirement.” Id.
The district court rejected not only Defendants’ writ-
ten-description challenge but also their remaining inva-
lidity arguments. In particular, based on extensive
findings of fact, the court concluded that the patent
enables a person of ordinary skill in the art to make and
to use the full range of the claimed molecules. Id. at *8-
13. Defendants do not appeal that ruling.
Defendants timely appealed, raising only a written-
description issue here. We have jurisdiction under 28
U.S.C. § 1295(a)(1).
DISCUSSION
This appeal presents a single issue: whether, under
what is now 35 U.S.C. § 112(a), the written description of
8 GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC.
the ’467 patent adequately supports the claims to “solv-
ates” of dutasteride. Adequacy of the written description
is a question of fact. Ariad Pharm., Inc. v. Eli Lilly & Co.,
598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). After a
bench trial, we review the district court’s findings of fact
for clear error. Pozen Inc. v. Par Pharm., Inc., 696 F.3d
1151, 1166 (Fed. Cir. 2012).
Defendants have presented a limited issue. Although
noting that the claimed solvates must be “pharmaceuti-
cally acceptable,” Defendants’ brief does not argue that,
even if the specification adequately describes “solvates,” it
inadequately describes the pharmaceutically acceptable
ones. There is no such contention, and there is no men-
tion of the “pharmaceutically acceptable” language, in the
statement of issues, in the (argument-summarizing)
introduction and statement of the case, in the summary of
the argument, or in any heading or subheading of the
argument section of the brief. The only argument actual-
ly developed in the brief is that there is no adequate
description of “solvates,” whether that term is limited to
crystalline structures (as Defendants argue) or covers
crystalline and non-crystalline structures, produced
through reaction with a solvent or precipitation or crystal-
lization from a solution (as the parties understand the
district court’s construction). We conclude that Defend-
ants have not properly presented any other contention in
this court, especially given the lack of elaboration on the
distinct issues that would be raised by a written-
description challenge to the phrase “pharmaceutically
acceptable.”
On the sole issue properly presented, we reject De-
fendants’ challenge. Under either the district court’s
claim construction or Defendants’ claim construction, the
claim term “solvate” refers to a molecular complex defined
by structure and by the process of creating it, not by what
the molecule does. Under the district court’s construction,
the structure is any complex of dutasteride and solvent,
GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC. 9
not necessarily a crystalline complex, resulting from any
of three processes: reaction with a solvent or precipitation
or crystallization from a solution. Under Defendants’
construction, the structure is a complex of dutasteride and
a solvent in which the arrangement is crystalline, result-
ing from crystallization out of a solution. In either event,
the written description, which presents materially the
same interpretive choice, describes the same class by
identifying a particular structure obtained by particular
processes. No matter which construction is adopted, the
term “solvate” involves no performance property (the
claimed compound need not perform an identified func-
tion or produce an identified result) and hence raises no
issue of insufficient structural, creation-process, or other
descriptions to support such a property. In this situation,
we affirm the district court’s finding that “solvate” is
adequately described, without needing to choose between
the offered constructions of “solvate.”
The Detailed Description provides a description by
structure and process of creation that matches the
claimed term, whichever construction is preferable. It
declares:
Those skilled in the art of organic chemistry will
appreciate that many organic compounds can
form complexes with solvents in which they are
reacted or from which they are precipitated or
crystallized. These complexes are known as “solv-
ates”. For example, a complex with water is
known as a “hydrate”. Solvates of [dutasteride]
are within the scope of the invention.
It will also be appreciated by those skilled in or-
ganic chemistry that many organic compounds
can exist in more than one crystalline form. For
example, crystalline form may vary from solvate
to solvate. Thus, all crystalline forms of [dutas-
teride] or the pharmaceutically acceptable solv-
10 GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC.
ates thereof are within the scope of the present
invention.
’467 patent, col. 3, line 58, through col. 4, line 12. That
language defines the claimed genus by two properties.
First, a solvate is a complex of dutasteride molecules and
solvent molecules, with dutasteride being, as the district
court found, “the key structural component.” Glax-
oSmithKline LLC, 2013 WL 4082232, at *2. Second, the
structure is one that is created by an identified process—
specifically, by dissolving dutasteride (the solute) in a
solvent. Just as they dispute the claim construction, the
parties dispute the precise meaning of this passage,
including whether the resulting complex must be crystal-
line and whether it must be produced by just one process
or any of three (crystallization only, or any of reaction,
precipitation, or crystallization). But under each side’s
construction and reading of the specification, the descrip-
tion matches the claim, and regardless of which side is
right, the description remains entirely based on structure
of the compound and its process of creation.
We have no precedent under which this two-condition
description, matching the claim scope, would be insuffi-
cient. To the contrary, this court has repeatedly “ex-
plained that an adequate written description requires a
precise definition, such as by structure, formula, chemical
name, physical properties, or other properties, of species
falling within the genus sufficient to distinguish the
genus from other materials.” Ariad, 598 F.3d at 1350
(emphasis added). Describing a complex of dutasteride
and solvent molecules is an identification of “structural
features commonly possessed by members of the genus
that distinguish them from others,” allowing one of skill
in the art to “visualize or recognize the identity of the
members of the genus.” Regents of the Univ. of California
v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997); cf.
Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d
1353, 1366-67 (Fed. Cir. 2011) (holding written descrip-
GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC. 11
tion inadequate “[g]iven the absence of information re-
garding structural characteristics of” the claimed genus).
The structural identification here is further narrowed by
requiring that the structure result from (one or any of
three) identified processes. On the (related, though
distinct) question of establishing conception, i.e., a defi-
nite and permanent idea of the complete and operative
invention, we have indicated that it can be enough to
identify a compound “by its method of preparation.”
Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1206
(Fed. Cir. 1991); see Fiers v. Revel, 984 F.2d 1164, 1169
(Fed. Cir. 1993); id. at 1171 (written-description analysis
referring to earlier conception analysis).
In this case, the claim is no broader in scope than the
written description: the above-quoted passage from the
written description matches the claim scope (whether
they are narrow or broad, as the parties dispute). It is
therefore quite different from the claims in Eli Lilly & Co.
v. Teva Pharmaceuticals USA, Inc., 619 F.3d 1329, 1344-
45 (Fed. Cir. 2010), where the claim covered particle sizes
before and after formulation into tablets, but the specifi-
cation addressed only pre-formulation size. Critically,
moreover, the claim term at issue, “solvate,” is not func-
tional: to be a “solvate,” a compound need not produce a
desired result or otherwise perform a certain function.
The claim term and its corresponding description, howev-
er broad, identify certain structures produced by certain
processes. We have not required more for an adequate
written description that matches claim scope. And we see
no basis for doing so in the present context, where “the
concept of solvation . . . has been known in the art for over
100 years” and “[s]teroids in particular [such as dutaster-
ide] have been known to be prone to solvate formation
since 1983,” GlaxoSmithKline LLC, 2013 WL 4082232, at
*2, 6, and it is now undisputed that the written descrip-
tion enables a person of skill in the art to make and use
the full claimed range of “solvates” of dutasteride.
12 GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC.
The claims in this case, not involving functional claim
language, do not present the fundamental difficulty
presented by the claims in virtually all of the precedents
on which Defendants rely. The claims in those cases used
functional language: they “cover[ed] any compound later
actually invented and determined to fall within the
claim’s functional boundaries”; such language may “mere-
ly recite a description of the problem to be solved [how to
produce a desired result] while claiming all solutions to
it.” Ariad, 598 F.3d at 1353. In the field of genetic inven-
tions, our precedents have addressed claims that seek to
distinguish members of the claimed genus by the shared
performance property of encoding a particular enzyme or
other product. See, e.g., Carnegie Mellon Univ. v. Hoff-
mann-La Roche Inc., 541 F.3d 1115, 1123-24 (Fed. Cir.
2008) (claiming “recombinant plasmids that contain a
DNA coding sequence that is broadly defined, and only by
its function, viz., encoding DNA polymerase I”); Eli Lilly,
119 F.3d at 1562-63 (claiming genetic material capable of
“encod[ing] insulin” or “coding for human proinsulin”);
Fiers, 984 F.2d at 1171 (claiming all DNA “that achieve[s]
a result without defining what means will do so”). In
other cases, the claimed performance property has been a
compound’s ability to inhibit the action of a particular
protein, see Ariad, 598 F.3d at 1340-41; Univ. of Rochester
v. G.D. Searle & Co., 358 F.3d 916, 918 (Fed. Cir. 2004), a
compound’s ability to inhibit a particular medical compli-
cation, see Boston Scientific Corp., 647 F.3d at 1364, or an
antibody’s ability to bind to a particular antigen, see
Noelle v. Lederman, 355 F.3d 1343, 1349-50 (Fed. Cir.
2004); In re Alonso, 545 F.3d 1015, 1018 (Fed. Cir. 2008).
Here, in contrast, under any of the parties’ preferred
claim constructions, “solvates” of dutasteride are not
distinguished by a particular performance property. The
claim term does not assert coverage of yet-unidentified
ways of achieving a desired result; it does not “attempt to
preempt the future before it has arrived.” Fiers, 984 F.2d
GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS, INC. 13
at 1171. This case thus sharply differs from those De-
fendants invoke. In the circumstances of this case, we
have no basis for reversing the district court’s finding that
the written description conveys to the relevant skilled
artisan that “the inventor[s] actually invented the inven-
tion claimed.” Ariad, 598 F.3d at 1351.
CONCLUSION
For the foregoing reasons, we affirm the district
court’s rejection of Defendants’ written-description chal-
lenge to the validity of the asserted claims of the ’467
patent.
AFFIRMED