Court Opinion

ID: 6323378
Source: CourtListenerOpinion
Date Created: 2022-03-15 16:01:48.898855+00
Date Added: 2024-06-11T09:21:36.426681
License: Public Domain

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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 2              ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC

    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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 ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC               3

 ’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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 4              ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC

     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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 ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC              5

 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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 6              ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC

 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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 ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC             7

 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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 8              ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC

     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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 ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC              9

                         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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 10             ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC

 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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 ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC             11

     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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 12             ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC

 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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 ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC             13

 (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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 14             ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC

 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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 ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC             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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 16             ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC

 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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 ALMIRALL, LLC   v. AMNEAL PHARMACEUTICALS LLC           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