# United States **Court of Appeals**  **for the Federal Circuit**

______________________
GLAXOSMITHKLINE LLC (formerly known as SmithKline Beecham Corporation ), Plaintiff

- Appellee,

v.

BANNER PHARMACAPS, I NC. AND IMPAX LABORATORIES, INC., Defendants

- Appellants,

AND

ROXANE LABORATORIES, INC., Defendant

- Appellant,

AND

MYLAN INC. AND MYLAN PHARMACEUTICAL S INC., Defendants

- Appellants,

AND

WATSON LABORATORIES, INC. FLORIDA, Defendant -A ppellant.

______________________

2013

- 1593,

- 1594,

- 1595,

- 1598

______________________GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 2

Appeals from the United States District Court for the District of Delaware in No s. 11

- CV

- 0046, 11

- CV

- 0542 and 11

- CV

- 0789, Judge Richard G. Andrews.

______________________
Decided: February 2 4 , 2014

______________________

W ILLIAM F. L EE , Wilmer Cutler Pickering Hale and Dorr, LLP, of Boston, Massachusetts, argued for plaintiff

appellee. With him on the brief were L ISA J. P IROZZOLO and S ARAH R. F RAZIER , of Boston, Massachusetts; W ILLIAM G. M C E LWAIN , T HOMAS G. S AUNDERS and M ATTHEW G UARNIERI , of Washington, DC; and C HRISTOPHER R. N OYES , of New York, New York.

D EANNE E. M AYNARD , Morrison & Foerster, LLP, of Washington, DC, argued for all defendan ts

- appellants. With her on the brief for defendants

- appellants Banner Pharmacaps, Inc., et al., were M ARC A. H EARRON , of Washington, DC and P ARISA J ORJANI , of San Francisco, California . Of counsel on the brief were C. K YLE M USGROVE and M ICHAEL M. S HEN , H aynes and Boone, LLP, of Washington, DC

. O n the brief for Roxa n e Labor atories, Inc. were K ENNETH G. S CHULER and M ARC N. Z UBICK , Latham & Watkins LLP, of Chicago, Illinois ; and D ARRYL L H. S TEENSMA , of San Diego, California

. On the brief for Watson Laboratories, Inc. – Florida were G ARY E. H OOD and M ARK T. D EMING , Polsinelli, PC, of Chicago, Illinois . On the brief for Mylan Inc., et al. were J AMES H. W ALLACE , J R ., M ARK A. P ACELLA , and L UCY M. S TARK , Wiley Rein, LLP, of Washin gton, DC

.

______________________
Before O’M ALLEY , W ALLACH , and T ARANTO , Circuit Judges.GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 3

T ARANTO , Circuit Judge

. Plaintiff GlaxoSmithKline LLC (“GSK”) sued Banner Pharmacaps, Inc., Impax Laboratories, Inc., R oxane Laboratories, Inc., Mylan Inc., Mylan Ph armaceuticals, Inc., and Wat son Laboratories, Inc.

– Florida (collectively,

“ Defendants ”) . Invoking 35 U.S.C. § 271(e)(2)

, GSK alleged that drug products containing the molecule duta steride that Defendants propose to market fall within claims of U.S. Patent No. 5, 565,467 , which covers duta steride and its pharmaceutically acceptable solvate s. All Defend ants 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 , 2 013 WL 4082232 (D. Del. Aug. 9, 2013)

. Defenda nts appeal the rejection of their written

description challenge

. Their appeal presents only one contention—t hat “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.

B ACKGROUND
This case involves claims to the chemical compound dutasteride and its pharmaceutically acceptable solvate s. 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 a cceptable solvate thereof. ” ’467 patent, col. 16, lines 4 -6

. The parties agree that dutasteride is the molecule ident ified before “or a pharmaceutically acceptable solvate thereof.” The other asserted claims all recite “[a] pha rmaceutical formulation comprising” the “compound of claim 1 ,” subject to further restrictions having no e ffect onGLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 4

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 hi rsutism.” Id . at col. 1, lines 18

- 19 , 55

- 60

. In some target tissues, including prostate and skin tissue, testosterone produces certain effect s by first being converted to dih ydrotestosterone. See id. at col. 1, lines 15

- 25. Dutasteride inhibits the enzymes that cata lyze the conversion and thus mitigat es 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” diss olved 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 f requently, 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 wheth er “solvate” (in the context of this patent) means only such crystalline complexes

— a dispute we need not resol ve

. Dutasteride has been proven effective in treat ing benign prostatic hyperplasia , otherwise known as enlarg ement of the prostate gland

. GSK markets Avodart® and JalynTM, which contain dutasteride and are approved by the Food and Drug Administration to treat symptoms of benign prostatic hyperplasia. Each Defendant filed atGLAXOSMITHKLINE 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 JalynTM. 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 a uthorized by 35 U.S.C. § 271(e)(2), GSK responded by suing Defen dants for infringement of its ’467 patent

. The district court construed “ phar maceutically a cceptable ” to mean “[s]uitable for use when administered to the recipient thereof as a pharmaceuti cal.” C laim 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. G SK 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 acknow ledged Defendants’ “considerable extrinsic evidence” that, in the pharmaceutical field, “solvate” is limited to crysta lline complexes, no matter how created, but it concluded that the specification of this particular patent “direct [ly] contradic t[ s] ” any such narrow usage. See id. at 7 -8 (relying on ’467 p atent, col. 3, line 58, t hrough 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 fro m which it is precipi tated or crystallized.

Id. at 4. Despite potential confusion about the meaning of this language, including about what “it” refers to, t he
pa rties agree in interpreting the district court’s construction to refer to three processes of forming dutasteride solvates— by a reaction of dutasteride with a solvent; byGLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 6

precipitation of a complex from a solution of dutasteride and a solvent; by crystallization of a complex from a solution of dutasteride and a s olvent— with the resulting complex not required to be crystalline

. Defendants stipulated to infringement and have not raised any infringement issue on appeal ( not even cond itional ly, should we reverse the district court’s claim construction in deciding the issue they do raise on a ppeal )

. The only issue before us is Defendants’ invalidity challenge asserting the in adequa cy of the written descri ption, a challenge that the district court rejected

— along with invalidity challenges asserting anticipation, lack o f utility, and lack of an enabling disclosure

— after a three

day bench trial held after the stipulation of infringe ment. 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 claim s , lacked adequate support in the wri tten 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 solvate s 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 sol vates were therapeutically effective. See GlaxoSmithKline LLC v. Banner Pharmacaps, Inc., No. 11

- CV

- 046, 2013 WL 4082232, at *2 -3 (D. Del. Aug. 9, 20 13) (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 fo rmation since 1983,” and that “the universe of solventsGLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 7

thought to be pharmaceutically acceptable was well

known and relatively small.” Id. at * 2, 6. T he court noted that “it [was] difficult or even impossible to predict whether a particular solvate form will offer bioavailabi lity , 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)

. Th e district court concluded that Defendants failed to prove the inadequacy of the written description

. According to the d istrict court, “[t]here is no reason why a person skilled in the art would not credit a patentee with posse ssion of a solvate merely because the patentee did not disclose solvates formed by each solvation pr ocess,” i.e.

, reaction, precipitation, crystalliz ation. 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 addi tion to what was known in the art, “ sufficient to meet the written description requirement .” Id.

The district court rejected not only Defendants’ wri tten- description challenge but also their remaining inv ali d ity arguments . I n 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 appea led, raising only a written

description issue here. We have jurisdiction under 28 U.S.C. § 1295(a)(1)

. D ISCUSSION This appeal presents a single issue: whether , under what is now 35 U.S.C. § 112(a), the written description ofGLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 8

the ’467 patent adequately su pports the claims to “ sol vate s” of duta s teride. 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 finding s 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 “pharmaceut ica l ly accepta ble,” Defendants’ brief does not argue that, even if the specification adequately describes “solvates,” it i nadequately describe s the pharmaceutically acceptable ones. There is no such contention, and there is no me ntion of the “pharmaceutically acceptable” language, in the
stat ement 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 actua lly developed in t he 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 crysta llization from a s ol ution (as the parties understand the district court’s construction)

. We conclude that Defen dants 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 wr itten

description challenge to the phrase “pharmaceutically acceptable.”

On the sole issue properly presented, we reject D efendants’ 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 sol ution . Under Defendants’
construct ion, the structure is a complex of dutasteride and a solvent in which the arrangement is crystalline , resul ting from crystallization out of a solution. In either event, the written descrip tion, which presents materially the same interpretive choice, descr ibes the same class by identify ing a particular structure obtained by particular
process es. No matter which construction is adopted, the term “solvate” involves no performance property ( the claimed compo und need not perform an identified fun ction or produce an identified result) and hence raises no issue of insufficient structural

, creation

- process , or other description s 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 “ sol vates”

. For example, a co mplex with wate r is known as a “hydrate”

. Solvates of [dutasteride] are within the scope of the invention.
It will also be appreciated by those skilled in o rganic 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 [duta ste r ide] or the pharmaceutically acceptable sol v-GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 10

ates thereof are within the scope of the present invention. ’467 patent, col. 3, line 58, through col. 4, line 12. That language d efines the claimed genus by two properties

. First, a solvate i s a complex of dutasteride molecules and solvent molecules , with dutasteride being, as the district court found, “the key structural component.” Gla xoSmithKline LLC

, 2013 WL 4082232

, at * 2. Second, the
structure is one that is created by an identified process

—
s pecifically, 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 whethe r the resulting complex must be crysta lline 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 descri ption matches the claim, and regardless of which side is right, the description remains entirely based on structure of the compo und and its process of creation.
We have no precedent under which t h is two

- condition description , matching the cl aim scope, would be in sufficient

. To the contrary, this court has r epeatedly “ e xplained 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 “struc tural 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 descri p-GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 11

tion inadequate “[g]iven the absence of information r egarding structural characteristics of ” the claimed genus). The str uctural identification here is further narrowed by requir ing that the structure result from (one or any of three) identified process es. On the (related , though distinct ) question of establishing conception, i.e. , a definite 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 match es the claim scope (whether they are narrow or broad, as the parties di spute)

. 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 specification addressed only pre

- formulation size. Critically, moreover, t he claim term at issue , “solvate,” is not fun ctional: to be a “solvate,” a compound need not produce a desired result or oth erwise perform a certain function. The claim term and its corresponding description, howe ver 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 , w here “the concept of solvation .

. . has been known in the art for over 100 years ” and “[s] teroids in particular [such as dutaste ride] 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 descri ption enables a person of skill in the art to make and use the full claimed range of “solvates” of dutasteride.GLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 12

T he claims in t his case , not involving functiona l claim language, do not pres ent 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 d eter mined to fall within the claim’ s functional boundaries ” ; such language may “merely 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 inve ntions, our precedents have addressed claims that seek to distinguish members of the claimed genus by the shared performance property of e ncoding a par ticular enzyme or other product

. See , e.g., Carnegie Mellon Univ. v. Hoffmann

- 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 capa ble of “encod[ing] insulin” or “coding for human proinsulin”); Fiers , 984 F.2d at 1171 ( claiming all D NA “ that achieve [s] a result without defining what means will do so ”). In other cases, the claimed performance property has been a

c ompound ’ 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 compl ication, see Boston Scientific Corp. , 647 F.3d at 1364
, or an antibod y’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 distinguish ed 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.2dGLAXOSMITHKLINE LLC v. BANNER PHARMACAPS , INC

. 13

at 1171

. This case thus sharply differs from those D efendants invoke. In the circumstances of this case, w e 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 inve ntion claimed .” Ariad

, 598 F.3d at 1351.

C ONCLUSION For the foregoing reasons, we affirm th e district court’s rejection of Defendants ’ written

- description cha llenge to the validity of the asserted claims of the ’467 patent.

AFFIRMED