Case: 20-2331 Document: 80 Page: 1 Filed: 03/14/2022
`
`
`
`United States Court of Appeals
`for the Federal Circuit
`______________________
`
`ALMIRALL, LLC,
`Appellant
`
`v.
`
`AMNEAL PHARMACEUTICALS LLC, AMNEAL
`PHARMACEUTICALS OF NEW YORK, LLC,
`Appellees
`
`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
`______________________
`
`2020-2331
`______________________
`
`Appeal from the United States Patent and Trademark
`Office, Patent Trial and Appeal Board in Nos. IPR2019-
`00207, IPR2019-01095.
`______________________
`
`Decided: March 14, 2022
`______________________
`
`JAMES TRAINOR, Fenwick & West LLP, New York, NY,
`argued for appellant. Also represented by ADAM GAHTAN,
`RICHARD SHEA; ELIZABETH B. HAGAN, Seattle, WA.
`
`

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`ALMIRALL, LLC v. AMNEAL PHARMACEUTICALS LLC
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`
` DENNIES VARUGHESE, Sterne Kessler Goldstein & Fox,
`PLLC, Washington, DC, argued for appellees. Also repre-
`sented by KRISTINA CAGGIANO KELLY, ADAM LAROCK.
`
` ROBERT J. MCMANUS, Office of the Solicitor, United
`States Patent and Trademark Office, Alexandria, VA, for
`intervenor. Also represented by BENJAMIN T. HICKMAN,
`THOMAS W. KRAUSE, FARHEENA YASMEEN RASHEED.
` ______________________
`
`Before LOURIE, CHEN, and CUNNINGHAM, Circuit Judges.
`LOURIE, Circuit Judge.
`Almirall, LLC (“Almirall”) appeals from the final writ-
`ten decision of the U.S. Patent and Trademark Office Pa-
`tent Trial and Appeal Board (the “Board”) holding that
`claims 1–8 of U.S. Patent 9,517,219 (the “’219 patent”)
`would have been obvious over the cited prior art at the time
`the alleged invention was made.1 See Amneal Pharms.
`LLC v. Almirall, LLC, No. IPR2019-00207, 2020 WL
`2833274 (P.T.A.B. May 29, 2020) (“Decision”). For the rea-
`sons provided below, we affirm.
`BACKGROUND
`Almirall owns the ’219 patent, which relates to meth-
`ods of treating acne or rosacea with dapsone formulations
`that include an acrylamide/sodium acryloyldimethyl tau-
`rate copolymer (“A/SA”) thickening agent and the solvent
`diethylene glycol monoethyl ether (“DGME”). Dapsone can
`be used for treating various dermatological conditions.
`
`1 Because the challenged claims of the ’219 patent
`have an effective filing date before March 16, 2013, we ap-
`ply the version of 35 U.S.C. § 103 in effect before the adop-
`tion of the Leahy-Smith America Invents Act (“AIA”), Pub.
`L. No. 112-29, 125 Stat. 284 (2011).
`
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`’219 patent, col. 1 ll. 19–23. DGME allows compositions to
`be prepared with increased solubilized concentrations of
`dapsone. Id. at col. 2 ll. 48–50. A polymeric viscosity
`builder such as an A/SA agent can minimize the intensity
`of yellowing of the composition. Id. at col. 2, ll. 54–61. It
`can also influence dapsone crystallization by reducing the
`particle size and minimizing a gritty feel upon application.
`See id.
`Adapalene is a compound used for treating dermatolog-
`ical conditions, sometimes in combination with dapsone.
`See Decision at *18. The ’219 patent includes 62 general-
`ized composition embodiments, ’219 patent, col. 6 l. 58–
`col. 12 l. 40, and eight specific example formulations, id. at
`col. 12 l. 42–col. 15 l. 33. Several of the examples are de-
`scribed as including adapalene.
`Independent claims 1 and 6 read as follows:
`1. A method for treating a dermatological condition
`selected from the group consisting of acne vulgaris
`and rosacea comprising administering to a subject
`having the dermatological condition selected from
`the group consisting of acne vulgaris and rosacea a
`topical pharmaceutical composition comprising:
`about 7.5% w/w dapsone;
`about 30% w/w to about 40% w/w diethylene glycol
`monoethyl ether;
`about 2% w/w to about 6% w/w of a polymeric
`viscosity builder comprising acrylamide/so-
`dium acryloyldimethyl taurate copolymer;
`and
`water;
`wherein the topical pharmaceutical composi-
`tion does not comprise adapalene.
`Id. at col. 15 l. 40–col. 16 l. 13 (emphases added).
`
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`ALMIRALL, LLC v. AMNEAL PHARMACEUTICALS LLC
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`6. A method for treating a dermatological condition
`selected from the group consisting of acne vulgaris
`and rosacea comprising administering to a subject
`having the dermatological condition selected from
`the group consisting of acne vulgaris and rosacea a
`topical pharmaceutical composition comprising:
`about 7.5% w/w dapsone;
`about 30% w/w diethylene glycol monoethyl ether;
`about 4% w/w of a polymeric viscosity builder
`comprising acrylamide/sodium acryloyldime-
`thyl taurate copolymer; and
`water;
`wherein the topical pharmaceutical composi-
`tion does not comprise adapalene.
`Id. at col. 16 ll. 23–36 (emphases added).
`Amneal filed a petition for inter partes review of
`claims 1–8 of the ’219 patent. J.A. 120. Amneal argued
`that claims 1–8 would have been obvious over Int’l Patent
`Pub. WO 2009/061298 (“Garrett”) and Int’l Patent Pub.
`WO 2010/072958 (“Nadau-Fourcade”). J.A. 117–18. Am-
`neal also argued that claims 1–8 would have been obvious
`over Garrett and a publication titled “Characterization and
`Stability of Emulsion Gels Based on Acrylamide/Sodium
`Acryloyldimethyl Taurate Copolymer” (“Bonacucina”).2 Id.
`Garrett describes topical dapsone treatments for treat-
`ing dermatological conditions including acne and rosacea.
`Garrett states that the dapsone may exist in “a micropar-
`ticulate form, a dissolved form, or both.” J.A. 1475. Garrett
`
`2 Giulia Bonacucina, et al., Characterization and
`Stability of Emulsion Gels Based on Acrylamide/Sodium
`Acryloyldimethyl Taurate Copolymer, 10(2) AAPS
`PHARMSCITECH 368–75 (2009).
`
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`does not disclose any formulations that include adapalene.
`For example, Garrett identifies a commercial product,
`Aczone®, that lacks adapalene. J.A. 1482.
`Garrett’s formulations include thickening agents. J.A.
`1486. Garrett describes suitable thickening agents as in-
`cluding polymer thickeners such as hydrophilic gelling
`agents used in the cosmetic and pharmaceutical industries.
`J.A. 1485. Garrett explains that a gelling agent preferably
`comprises between about 0.2% to about 4% by weight of the
`composition. Id. Garrett identifies Carbopol® as a pre-
`ferred thickening agent. Id. Carbopol® is one of numerous
`cross-linked acrylic acid polymers that are given the name
`“carbomer.” Id. Garrett’s preferred compositional weight
`percent range for Carbopol® is between about 0.5% to
`about 2%.
`Garrett discloses a preferred embodiment that “in-
`cludes about 0.5% to 4.0% carbomer . . .; about 53.8% to
`84.2% water; about 10% to 30% ethoxydiglycol [i.e.,
`DGME]; about 0.2% methylparaben; about 5% to 10% dap-
`sone in a microparticulate and dissolved state; and about
`0.1% to 2% sodium hydroxide solution.” Decision at *5 (cit-
`ing J.A. 1476). But Garrett also contemplates adjustments
`for optimization. “The relative percentages for each of the
`reagents used . . . may vary depending upon the desired
`strength of the target formulation, gel viscosity, and the
`desired ratio of microparticulate to dissolved dapsone. Un-
`less otherwise designated, all reagents listed . . . are com-
`monly known by one of ordinary skill in the art and are
`commercially available from pharmaceutical or cosmetic
`excipient suppliers.” Id. at *6 (citing J.A. 1490, 1495).
`Nadau-Fourcade describes topical pharmaceutical
`compositions with a water-sensitive active pharmaceutical
`ingredient in dissolved form. J.A. 1529. The compositions
`are for dermatologic use for conditions including acne and
`rosacea. J.A. 1578. Nadau-Fourcade’s compositions may
`include a hydrophilic gelling agent. J.A. 1574. Nadau-
`
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`ALMIRALL, LLC v. AMNEAL PHARMACEUTICALS LLC
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`Fourcade lists exemplary thickeners including carbomers
`(e.g., Carbopol® products) and A/SA agents (e.g., Sepineo®
`or Simulgel® products) in a range of concentrations, but
`preferentially ranging from 0.01% to 5%. J.A. 1574–75.
`Two formulations shown in Examples 6 and 13 utilize sim-
`ilar components but different gelling agents. J.A. 1587,
`1589 (containing carbomer 0.1% and Simulgel® 600 0.20%,
`respectively).
`Bonacucina presents research on Sepineo® P 600, a
`concentrated dispersion of acrylamide/sodium acrylo-
`yldimethyl taurate copolymer in isohexadecane. J.A. 1688.
`Bonacucina reports that Sepineo® P 600 has self-gelling
`and thickening properties that are effective for topical ad-
`ministration. J.A. 1688–89 (explaining that “the possibil-
`ity of obtaining stiff and stable gelled phases with this
`polymer makes it a good candidate for the formulation of
`emulsion gels”). Testing revealed that Sepineo® P 600
`“thickens and gels well, a property that depends strongly
`on polymer concentration.” J.A. 1694. Bonacucina’s gels
`included a Sepineo® P 600 concentration of 0.5% to 5%.
`J.A. 1694; see also J.A. 1690 (Table I, showing examples
`with 0.5%, 1%, 3%, and 5% (w/w) Sepineo®).
`Relevant to this appeal, the Board’s decision hinged on
`whether a person of ordinary skill in the art would have
`found it obvious to substitute an A/SA agent taught by
`Nadau-Fourcade or Bonacucina for the carbomer gelling
`agent in Garrett’s formulations to arrive at the claimed
`composition. See Decision at *16. Garrett does not teach
`using an A/SA agent as its polymeric viscosity builder. Id.
`Instead, Garrett identifies five other preferred gelling
`agents, including Carbopol®. J.A. 1485.
`First, the Board determined that Garrett and Nadau-
`Fourcade in combination teach or suggest every claim lim-
`itation and that a person of ordinary skill in the art would
`have been motivated, with a reasonable expectation of suc-
`cess, to incorporate Nadau-Fourcade’s A/SA gelling agent
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`into Garrett’s dapsone formulations. Id. at *30. Specifi-
`cally, the Board determined that it would have been obvi-
`ous to substitute Nadau-Fourcade’s Sepineo® for Garrett’s
`Carbopol®. Id. at *16. The Board found that the class of
`hydrophilic gelling agents and the specific examples in the
`concentrations disclosed in Garrett overlap with the gelling
`agents taught by Nadau-Fourcade. Id. Nadau-Fourcade
`pairs Carbopol® and Sepineo® in a small set of especially
`preferred gelling agents. Id. at *17. The Board also relied
`on expert testimony explaining that a person of skill would
`have been able to immediately appreciate that Carbopol®
`and Sepineo® “perform the same function and are inter-
`changeable” and that “such a substitution was routine and
`predictable because such thickening agents were known for
`use in topical compositions with water insoluble drugs.” Id.
`Second, the Board determined that Garrett and
`Bonacucina in combination also teach or suggest every
`claim limitation and that a person of ordinary skill in the
`art would have been motivated, with a reasonable expecta-
`tion of success, to incorporate Bonacucina’s A/SA gelling
`agent into Garrett’s dapsone formulations. Id. at *30. Spe-
`cifically, the Board determined that it would have been ob-
`vious to substitute Bonacucina’s Sepineo® for Garrett’s
`Carbopol®. Id. at *20.
`The Board found that a person of ordinary skill would
`have had good reasons to pursue a replacement for Carbo-
`pol®. The Board relied on expert testimony that Garrett’s
`Carbopol® was known to have drawbacks, for example, re-
`quiring neutralization to achieve maximum viscosity and
`producing grittiness and possible agglomeration. Id. at
`*21. The Board also credited expert testimony in finding
`that Sepineo®’s advantages would have motivated a person
`of skill to replace Carbopol® with Sepineo®. For example,
`Sepineo® is self-gelling, is pre-neutralized, and reduces
`grittiness. Id.
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`ALMIRALL, LLC v. AMNEAL PHARMACEUTICALS LLC
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`The Board also found that a skilled artisan would have
`had a reasonable expectation of successfully replacing Gar-
`rett’s gelling agents with Bonacucina’s Sepineo®, in the
`same amounts, to arrive at the composition recited in the
`claims. Id. The Board determined that overlapping ranges
`support the conclusion that a person of ordinary skill in the
`art would have been expected to successfully replace Car-
`bopol® with equal amounts of Sepineo® in Garrett’s formu-
`lations. Id. The Board concluded that replacing Garrett’s
`Carbopol® with Bonacucina’s Sepineo® would have been a
`mere substitution of one gelling agent for another known
`in the field, and that each component of the Garrett-
`Bonacucina combination, once Sepineo® was substituted
`for Carbopol®, was used for the same function it is known
`to perform. Id.
`The Board also agreed with Amneal that Garrett
`teaches the negative adapalene claim limitation. Id. at
`*18. The Board found that “there is ample evidence of rec-
`ord supporting the conclusion that Garrett’s dapsone for-
`mulations for treating acne neither inherently included nor
`implicitly required adapalene.” Id. at *25. The Board ex-
`plained that “it is not Garrett’s mere silence as to the pres-
`ence of adapalene, but its disclosure of complete dapsone
`formulations to treat acne in its absence that suggests that
`adapalene is not included in Garrett’s formulations.” Id. at
`*18. The Board noted that “the commercial Aczone® 5%
`product referenced in Garrett did not include adapalene.”
`Id. Relying on Garrett’s teachings and expert testimony,
`the Board determined that Almirall failed to show that a
`person of ordinary skill in the art would have viewed
`adapalene as included in Garrett’s dapsone formulations.
`Id.
`The Board ultimately concluded that Amneal demon-
`strated by a preponderance of the evidence that claims 1–
`8 of the ’219 patent are unpatentable. Id. at *33. Almirall
`appealed.
` We have
`jurisdiction under 28 U.S.C.
`§ 1295(a)(4)(A).
`
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`DISCUSSION
`Almirall raises two challenges on appeal. First, Almi-
`rall contends that the Board erred in presuming obvious-
`ness based on overlapping ranges. Second, Almirall argues
`that the Board’s obviousness determinations were unsup-
`ported by substantial evidence.
`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 ev-
`idence as adequate to support the finding. Consol. Edison
`Co. v. NLRB, 305 U.S. 197, 229 (1938).
`I
`We first consider Almirall’s challenge to the Board’s de-
`termination that “Garrett discloses a range for each of the
`various components of the composition that either fully en-
`compasses or overlaps/abuts the ranges and amounts for
`those components recited in the challenged claims, and this
`is sufficient to create a presumption of obviousness as to
`the claimed amounts.” Decision at *14.
`Almirall argues that the Board erred in presuming ob-
`viousness based on overlapping ranges because no single
`reference discloses all of the claimed ranges. First, Almi-
`rall argues that Garrett’s ranges for its polymeric viscosity
`builders do not create a presumption of obviousness be-
`cause Garrett only discloses ranges for carbomer thicken-
`ers, not A/SA thickeners as claimed. Second, Almirall
`argues that the Board erred by looking to the overlapping
`range for the A/SA element in Nadau-Fourcade and
`Bonacucina to provide that missing limitation. Almirall
`argues that Nadau-Fourcade and Bonacucina cannot be
`used in combination with Garrett to establish a presump-
`tion of obviousness because the presumption applies only
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`when a single reference discloses all claimed ranges. See
`Appellant’s Br. 27–28 (citing Iron Grip Barbell Co. v. USA
`Sports, Inc., 392 F.3d 1317 (Fed. Cir. 2004)).
`Amneal responds that the Board did not err in applying
`a presumption of obviousness of overlapping ranges. First,
`Amneal argues that Garrett’s disclosure of carbomer thick-
`ener ranges is sufficient to support the rejection because
`disclosure of the precise, claimed composition is not neces-
`sary to show obviousness. Citing Valeant and Anacor, Am-
`neal asserts that ranges for structurally and functionally
`similar compounds can establish a prima facie case of obvi-
`ousness. See Appellee’s Br. 24–26 (citing Valeant Pharms
`Int’l Inc. v. Mylan Pharms Inc., 955 F.3d 25 (Fed. Cir.
`2020); Anacor Pharms., Inc. v. Iancu, 889 F.3d 1372 (Fed.
`Cir. 2018)). Second, Amneal argues that the Board did not
`err in looking to Nadau-Fourcade and Bonacucina because
`the obviousness inquiry is flexible and does not require
`that all elements be shown in a single reference.
`“A prima facie case of obviousness typically exists when
`the ranges of a claimed composition overlap the ranges dis-
`closed in the prior art.” In re Peterson, 315 F.3d 1325, 1329
`(Fed. Cir. 2003) (citing In re Geisler, 116 F.3d 1465, 1469
`(Fed. Cir. 1997)); see also E.I. du Pont de Nemours & Co. v.
`Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018); Iron
`Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322
`(Fed. Cir. 2004). “The point of our overlapping range cases
`is that, in the absence of evidence indicating that there is
`something special or critical about the claimed range, an
`overlap suffices to show that the claimed range was dis-
`closed in—and therefore obvious in light of—the prior art.”
`E.I. du Pont, 904 F.3d at 1008. A presumption of obvious-
`ness does not shift the burden of persuasion to the patentee
`to prove nonobviousness, but a presumption establishes
`that, “absent a reason to conclude otherwise, a factfinder is
`justified in concluding that a disclosed range does just
`that—discloses the entire range.” Id.
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`We agree with Amneal that the Board did not err in
`applying a presumption of obviousness of overlapping
`ranges. The Board’s decision sets forth factual findings of
`similarity between carbomers and A/SA agents that sup-
`port its conclusion that “Garrett discloses a range for each
`of the various components of the composition that either
`fully encompasses or overlaps/abuts the ranges and
`amounts for those components recited in the challenged
`claims, and this is sufficient to create a presumption of ob-
`viousness as to the claimed amounts.” Decision at *14. For
`example, Amneal’s expert explained that Garrett’s gelling
`agents and Nadau-Fourcade’s gelling agents have overlap-
`ping characteristics. Id. at *17. The Board also credited
`expert testimony that a person of ordinary skill in the art
`would have been able to immediately appreciate that the
`carbomers and A/SA agents at issue perform the same
`function and are interchangeable. Id. Moreover, there was
`no evidence that A/SA agents would have different interac-
`tions with the other ingredients of the compositions rela-
`tive to carbomer. Indeed, the Board credited expert
`testimony that a skilled artisan “would not have expected
`any incompatibilities in substituting” the gelling agents.
`Id. Thus, the Board found that Garrett’s gelling agents and
`A/SA agents are “used in very similar concentrations for
`similar formulations.” Id.
`The Board also found that the presumption was not
`overcome because Almirall’s evidence of unexpected results
`and failure of others was unpersuasive. We find those con-
`clusions supported by substantial evidence.
`But even if we agreed with Almirall that the presump-
`tion does not apply in this case, the outcome would be the
`same. Ultimately, despite Almirall’s attempts to argue
`otherwise, this case does not depend on overlapping
`ranges. It is simply a case of substituting one known gel-
`ling agent for another. Each may be effective at a different
`concentration in different formulations, but that is just a
`
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`property of the particular known material, subject to con-
`ventional experimentation.
`It is undisputed that Nadau-Fourcade and Bonacucina
`each separately disclose an A/SA thickener within the
`claimed range. As further discussed below, despite deter-
`mining that there was a presumption of obviousness, the
`Board also analyzed whether a person of ordinary skill in
`the art would have been motivated to combine Garrett with
`Nadau-Fourcade or Bonacucina to arrive at the claims with
`a reasonable expectation of success.
`II
`We therefore next consider Almirall’s arguments that
`the Board erred in determining that claims 1–8 would have
`been
`obvious
`over Garrett and Nadau-Fourcade
`(Ground 1), as well as over Garrett and Bonacucina
`(Ground 2).
`As a preliminary matter relevant to both obviousness
`grounds, Almirall argues that the Board failed to account
`for the negative adapalene claim limitation. Almirall ar-
`gues that although Garrett does not indicate that any of its
`formulations include adapalene, more is needed for a dis-
`closure of a negative claim limitation. Amneal responds
`that substantial evidence supports the Board’s finding that
`Garrett effectively teaches the negative adapalene claim
`limitation.
`We agree with Amneal. Almirall’s argument is con-
`trary to our precedent. “[A] reference need not state a fea-
`ture’s absence in order to disclose a negative limitation.”
`AC Techs., S.A. v. Amazon.com, Inc., 912 F.3d 1358, 1367
`(Fed. Cir. 2019). Instead, it was reasonable for the Board
`to find that, in the context of Garrett, a skilled artisan
`would recognize that the reference discloses a complete for-
`mulation—excluding the possibility of an additional active
`ingredient. See, e.g., Novartis Pharms. Corp. v. Accord
`Healthcare, Inc., 21 F.4th 1362, 1373 (Fed. Cir. 2022)
`
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`(recognizing that for negative limitations, “the disclosure
`must be read from the perspective of a person of skill in the
`art”). It is undisputed that Garrett discloses dapsone for-
`mulations that lack adapalene. The Board thus did not err
`in concluding that Garrett discloses the negative adapa-
`lene claim limitation.
`Ground 1: Garrett and Nadau-Fourcade
`Almirall argues that the Board’s holding that claims 1–
`8 would have been obvious over Garrett and Nadau-Four-
`cade was unsupported by substantial evidence.
`First, we consider Almirall’s argument that the Board
`failed to require evidence of a motivation to combine Gar-
`rett with Nadau-Fourcade. The presence or absence of a
`motivation to combine references in an obviousness deter-
`mination is a question of fact. See In re Gartside, 203 F.3d
`at 1316. Almirall argues that the Board erred by substi-
`tuting the alleged interchangeability of Sepineo® and Car-
`bopol® for evidence of a motivation to combine Nadau-
`Fourcade with Garrett. Amneal responds that the Board
`properly placed the burden on Amneal to show that the
`prior art provided reasons to combine the references.
`The record amply supports the Board’s conclusion that
`a person of ordinary skill in the art would have been moti-
`vated to replace Garrett’s gelling agent with an A/SA copol-
`ymer. The Board relied on prior art and expert testimony
`in determining that a person of ordinary skill would have
`recognized Carbopol® and Sepineo® as closely related gel-
`ling agents that could be interchangeably used in dapsone
`formulations in the same concentration range. The Board
`did not rely on a conclusory rationale of “design choice” as
`sufficient to find that a skilled artisan would have com-
`bined the references; on the contrary, it reviewed the con-
`text-specific evidence for the soundness of Amneal’s
`rationale. In explaining why a person of ordinary skill
`would have made the choice to use an A/SA copolymer, the
`Board relied on Garrett and Nadau-Fourcade’s teachings
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`as well as expert testimony. For example, the Board cred-
`ited Amneal’s expert’s testimony that “such a substitution
`was routine and predictable because such thickening
`agents were known for use in topical compositions with wa-
`ter insoluble drugs” and that a person of ordinary skill
`“would not have expected any incompatibilities.” Decision
`at *17.
`We conclude that the Board’s rationale for the combi-
`nation was sufficient to support its obviousness determina-
`tion. The Board noted that Garrett explicitly states that
`“[p]olymer thickeners that may be used include those
`known to one skilled in the art, such as hydrophilic and
`hydroalcoholic gelling agents frequently used in the cos-
`metic and pharmaceutical industries.” Id. (citing J.A.
`1485). The record demonstrates that A/SA copolymers
`would have been predictable design choices that a person
`of ordinary skill would have considered for development of
`topical dapsone formulations. See KSR Int’l Co. v. Teleflex
`Inc., 550 U.S. 398, 421 (2007) (“When there is a design need
`or market pressure to solve a problem and there are a finite
`number of identified, predictable solutions, a person of or-
`dinary skill has good reason to pursue the known options
`within his or her technical grasp.”); id. at 416 (“[W]hen a
`patent claims a structure already known in the prior art
`that is altered by the mere substitution of one element for
`another known in the field, the combination must do more
`than yield a predictable result.”); id. at 417 (“If a person of
`ordinary skill can implement a predictable variation, § 103
`likely bars its patentability.”).
`Second, we consider Almirall’s argument that a person
`of ordinary skill would not have had a reasonable expecta-
`tion of success in incorporating Nadau-Fourcade’s A/SA co-
`polymer into Garrett’s formulations. Almirall argues that
`the evidence fails to show that Sepineo® and Carbopol®
`are interchangeable. Almirall asserts that a person of or-
`dinary skill could not substitute an A/SA copolymer at the
`same amount and concentration as a carbomer. Almirall
`
`

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`Case: 20-2331 Document: 80 Page: 15 Filed: 03/14/2022
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`ALMIRALL, LLC v. AMNEAL PHARMACEUTICALS LLC
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`15
`
`contends that Nadau-Fourcade’s Examples 6 and 13
`demonstrate that different formulations require different
`thickeners at different concentrations. Amneal counters
`that the Board relied on expert testimony in correctly de-
`termining that Nadau-Fourcade teaches that Sepineo® is
`interchangeable with Carbopol® as a gelling agent in topi-
`cal pharmaceutical formulations containing water-insolu-
`ble drugs.
`We agree with Amneal. A finding of a reasonable ex-
`pectation of success does not require absolute predictability
`of success. See OSI Pharms., LLC v. Apotex Inc., 939 F.3d
`1375, 1385 (Fed. Cir. 2019). The Board’s reasonable expec-
`tation of success analysis is supported by substantial evi-
`dence. The Board credited Amneal’s expert’s testimony
`that a person of ordinary skill would have understood that
`use of Nadau-Fourcade’s A/SA gelling agents in Garrett’s
`formulation would have been routine and predictable be-
`cause the agents were known for use in topical composi-
`tions with water insoluble drugs. Furthermore, the Board
`found that a person of ordinary skill would not have ex-
`pected any incompatibilities. The Board analyzed the rec-
`ord evidence and found that Carbopol® and Sepineo® were
`recognized to be interchangeable and equivalent gelling
`agents that could be used in topical formulations contain-
`ing dapsone, and that they could be used in the same con-
`centration range. We are therefore not persuaded that the
`Board erred in analyzing the evidence provided by Amneal
`and its impact on whether a skilled artisan would have had
`a reasonable expectation of success in combining these
`prior art teachings to achieve the claimed invention.
`Ground 2: Garrett and Bonacucina
`Almirall argues that the Board’s holding that claims 1–
`8 would have been obvious over Garrett and Bonacucina
`was unsupported by substantial evidence.
`First, we consider Almirall’s argument that Amneal
`failed to provide evidence of a motivation to combine
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`Case: 20-2331 Document: 80 Page: 16 Filed: 03/14/2022
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`16
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`ALMIRALL, LLC v. AMNEAL PHARMACEUTICALS LLC
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`Garrett with Bonacucina. Almirall argues that Bonacucina
`does not suggest which active pharmaceutical ingredients
`or excipients may be compatible with Sepineo®. Almirall
`contends that mitigating grittiness and eliminating a neu-
`tralization step were not motivating factors, because grit-
`tiness was not a concern for Garrett’s formulations and
`that A/SA copolymers still require neutralization. Amneal
`counters that the Board relied on expert testimony in cor-
`rectly determining that a person of ordinary skill would
`have been motivated to use Bonacucina’s A/SA copolymer
`because of its advantages.
`We agree with Amneal that the Board’s analysis was
`supported by substantial evidence. The evidence supports
`the finding that dapsone compositions with carbomer could
`be gritty and require neutralization. Bonacucina teaches
`that Sepineo®, in contrast, forms stiff and stable composi-
`tions and is pre-neutralized. We find no error in the
`Board’s determination that Bonacucina suggests Sepineo®
`as a gelling agent for topical applications like Garrett’s
`dapsone formulations.
`Second, we consider Almirall’s argument that a person
`of ordinary skill would not have had a reasonable expecta-
`tion of success in incorporating Bonacucina’s A/SA copoly-
`mers into Garrett’s formulations. Almirall argues that
`Bonacucina fails to suggest that Sepineo® could success-
`fully replace a carbomer in any formulation. Amneal coun-
`ters that the Board relied on expert testimony in correctly
`determining that a person of ordinary skill would have had
`a reasonable expectation of success because Bonacucina
`taught using Sepineo® at overlapping concentrations and
`because carbomers had known drawbacks which were re-
`solved by Sepineo®.
`We again agree with Amneal. The Board’s reasonable
`expectation of success analysis was supported by substan-
`tial evidence. The Board found that “[t]he reasonable ex-
`pectation of success for using Sepineo[®] as a gelling agent
`
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`Case: 20-2331 Document: 80 Page: 17 Filed: 03/14/2022
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`ALMIRALL, LLC v. AMNEAL PHARMACEUTICALS LLC
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`17
`
`in Garrett’s dapsone formulations stems from the fact that
`Sepineo[®] was a well-known gelling agent that had been
`successfully used for other similar topical formulations.”
`Decision at *27. We are not persuaded that the Board erred
`in analyzing the evidence provided by Amneal and its im-
`pact on whether a skilled artisan would have had a reason-
`able expectation of success in combining these prior art
`teachings to achieve the claimed invention.
`CONCLUSION
`We have considered Almirall’s remaining arguments,
`but we find them unpersuasive. The Board’s decision was
`supported by substantial evidence and not erroneous as a
`matter of law. For the foregoing reasons, the decision of
`the Board is affirmed.
`
`AFFIRMED
`
`