Almirall, LLC v. Amneal Pharmaceuticals LLC

• Court: Court of Appeals for the Federal Circuit
• Decided: March 14, 2022
• Docket: 20-2331
• Status: Published

Opinion

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. Case: 20-2331 Document: 80 Page: 2 Filed: 03/14/2022

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). Case: 20-2331 Document: 80 Page: 3 Filed: 03/14/2022

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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). Case: 20-2331 Document: 80 Page: 4 Filed: 03/14/2022

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). Case: 20-2331 Document: 80 Page: 5 Filed: 03/14/2022

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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- Case: 20-2331 Document: 80 Page: 6 Filed: 03/14/2022

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 Case: 20-2331 Document: 80 Page: 7 Filed: 03/14/2022

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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. Case: 20-2331 Document: 80 Page: 8 Filed: 03/14/2022

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). Case: 20-2331 Document: 80 Page: 9 Filed: 03/14/2022

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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 Case: 20-2331 Document: 80 Page: 10 Filed: 03/14/2022

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. Case: 20-2331 Document: 80 Page: 11 Filed: 03/14/2022

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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 Case: 20-2331 Document: 80 Page: 12 Filed: 03/14/2022

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) Case: 20-2331 Document: 80 Page: 13 Filed: 03/14/2022

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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 Case: 20-2331 Document: 80 Page: 14 Filed: 03/14/2022

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 Case: 20-2331 Document: 80 Page: 15 Filed: 03/14/2022

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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 Case: 20-2331 Document: 80 Page: 16 Filed: 03/14/2022

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 Case: 20-2331 Document: 80 Page: 17 Filed: 03/14/2022

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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