Almirall, LLC v. Amneal Pharmaceuticals LLC

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

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).

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

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).

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

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-

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

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

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

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.

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

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