UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`AMNEAL PHARMACEUTICALS LLC and AMNEAL
`PHARMACEUTICALS OF NEW YORK, LLC
`
`Petitioners
`
`v.
`
`ALLERGAN, INC.
`
`Patent Owner
`________________________
`
`Case: IPR2018-00608
`
`
`
`
`
`U.S. Patent No. 9,161,926
`________________________
`
`
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 9,161,926
`UNDER 35 U.S.C. §§ 311-319 AND 37 C.F.R. §§ 42.1-.80, 42.100-.123
`
`
`
`
`
`
`
`
`Mail Stop “PATENT BOARD”
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, Virginia 22313–1450
`
`

`

`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
`
`TABLE OF CONTENTS
`
`INTRODUCTION .......................................................................................... 1 
`
`GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)) ................................ 6 
`
`
`
`I. 
`
`II. 
`
`III. 
`
`PRECISE RELIEF REQUESTED AND SUPPORTING REASONS .......... 6 
`
`IV.  OVERVIEW OF LEVEL OF SKILL AND PRIOR ART ............................. 6 
`
`A.
`
` 
`
`B.
`
` 
`
`Person of ordinary skill in the art (“POSA”). ....................................... 6 
`
`Scope and content of the art before November 20, 2012. ..................... 8 
`
`1. 
`
`2. 
`
`3. 
`
`Dapsone was well known. .......................................................... 8 
`
`Topical dapsone compositions were well known and
`preferred to oral forms. .............................................................. 8 
`
`Petitioners’ grounds rely specifically on the following
`prior art publications. ............................................................... 13 
`
`(a)  Garrett (AMN1004) ....................................................... 13 
`
`(b)  Nadau-Fourcade (AMN1005) ........................................ 15 
`
`(c)  Bonacucina (AMN1015) ............................................... 16 
`
`V.  OVERVIEW OF THE ’926 PATENT ......................................................... 17 
`
`1. 
`
`2. 
`
`The Claims ............................................................................... 18 
`
`Prosecution history ................................................................... 18 
`
`VI.  CLAIM CONSTRUCTION ......................................................................... 20 
`
`VII. 
`
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b)) ................ 20 
`
`A.
`
`  GROUND 1: Claims 1-6 are obvious over Garrett in view of
`Nadau-Fourcade. ................................................................................. 21 
`
`1. 
`
`Claims 1 and 5 .......................................................................... 21 
`
`(a)  Garrett discloses a “topical pharmaceutical
`composition” of “about 7.5% w/w dapsone,”
`
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`“water,” and “about 30% w/w to about 40%
`w/w ethoxydiglycol” “wherein the composition
`does not comprise adapalene.” ...................................... 24 
`
`(b) 
`
`It would have been obvious to a POSA to
`substitute the acrylamide copolymer in Nadau-
`Fourcade for the thickening agent in Garrett. ................ 31 
`
`(c)  Using “about 4% w/w” of the acrylamide
`copolymer as recited in claim 5 would have
`been obvious. ................................................................. 35 
`
`(d) 
`
`The claimed components are well-known for
`use in topical compositions and therefore a
`POSA would have had a reasonable expectation
`of successfully combining them. ................................... 36 
`
`Claim 2 ..................................................................................... 38 
`
`Claim 3 ..................................................................................... 39 
`
`Claims 4 and 6 .......................................................................... 39 
`
`2. 
`
`3. 
`
`4. 
`
`B.
`
` 
`
`GROUND 2: Claims 1-6 are obvious over Garrett in view of
`Bonacucina. ......................................................................................... 40 
`
`1. 
`
`Claims 1 and 5 .......................................................................... 41 
`
`(a)  Garrett discloses a “topical pharmaceutical
`composition” of “about 7.5% w/w dapsone,”
`“water,” and “about 30% w/w to about 40%
`w/w ethoxydiglycol” “wherein the composition
`does not comprise adapalene.” ...................................... 43 
`
`(b)  A POSA would have had a reason to use a
`viscosity builder consisting of the claimed
`acrylamide
`in
`a
`7.5% w/w
`dapsone
`compositions. ................................................................. 45 
`
`(c) 
`
`The claimed “about 4% w/w” copolymer
`limitation of claim 5 would have been the
`product of routine optimization by a POSA. ................. 50 
`
`ii
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`(d) 
`
`The claimed components are well known for
`use in topical compositions and therefore a
`POSA would have had a reasonable expectation
`of successfully combining them. ................................... 51 
`
`Claim 2 ..................................................................................... 53 
`
`Claim 3 ..................................................................................... 53 
`
`Claims 4 and 6 .......................................................................... 54 
`
`2. 
`
`3. 
`
`4. 
`
`C.
`
` 
`
`There are no objective indicia that could overcome the
`strong obviousness showing here. ....................................................... 54 
`
`1. 
`
`2. 
`
`3. 
`
`Allergan’s “unexpected” compatibility and smaller
`particle sized would have been expected. ................................ 55 
`
`indicia of non-
`There are no other objective
`obviousness. ............................................................................. 61 
`
`The prior art did not teach away from combining the
`claimed components in the claimed amounts. ......................... 62 
`
`VIII.  THERE IS NO BASIS TO DENY THE PETITION UNDER 35 U.S.C. §
`325(D) ........................................................................................................... 62 
`
`IX.  CONCLUSION ............................................................................................. 63 
`
`X.  MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) ................................... 63 
`
`
`
`
`
`iii
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`

`

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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
`
`TABLE OF AUTHORITIES
`
`
`Federal Cases
`
`Abbott Labs. v. Andrx Pharm., Inc.,
`452 F.3d 1331 (Fed. Cir. 2006) .............................................................................. 7
`
`
`Amneal Pharms. v. Supernus Pharms.,
` IPR2013-00368, Paper 8 (P.T.A.B. Dec. 17, 2013) ............................................. 56
`
`Chef America, Inc. v. Lamb-Weston, Inc.,
`358 F.3d 1371 (Fed. Cir. 2004) ............................................................................ 20
`
`
`Conopco, Inc. v. Procter & Gamble Co.,
`IPR2013-00505, Paper 69 (P.T.A.B. Feb. 10, 2015) ........................................... 33
`
`
`Cuozzo Speed Techs., LLC v. Lee,
`136 S. Ct. 2131 (2016) ......................................................................................... 20
`
`
`DePuy Spine, Inc. v. Medtronic Sofamor Danek, Inc.,
`567 F.3d 1314 (Fed. Cir. 2009) ............................................................................ 62
`
`
`Galderma Labs., L.P. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) ...................................................................... passim
`
`
`Great Atl. & Pac. Tea Co. v. Supermarket Equip. Corp.,
`340 U.S. 147 (1950) ...................................................................................... 39, 53
`
`
`Hotchkiss v. Greenwood,
`52 U.S. 248 (1850) .......................................................................................... 1, 29
`
`
`In re Aller,
`220 F.2d 454 (C.C.P.A. 1955) .............................................................................. 28
`
`
`In re Applied Materials, Inc.,
`692 F.3d 1289 (Fed. Cir. 2012) ......................................................... 28, 36, 45, 51
`
`
`In re Boesch,
`617 F.2d 272 (C.C.P.A.1980) ............................................................ 29, 36, 45, 51
`
`iv
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`

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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
`
`
`
`In re Fout,
`675 F.2d 297 (C.C.P.A. 1982) .............................................................................. 33
`
`
`In re Geisler,
`116 F.3d 1465 (Fed. Cir. 1997) .................................................................... passim
`
`
`In re GPAC Inc.,
`57 F.3d 1573 (Fed. Cir. 1995) .............................................................................. 57
`
`
`In re Harris,
`409 F.3d 1339 (Fed. Cir. 2005) ..................................................................... 59, 61
`
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .................................................................... passim
`
`
`In re Woodruff,
`919 F.2d 1575 (Fed. Cir. 1990) .................................................................... passim
`
`
`Iron Grip Barbell Co., Inc. v. USA Sports, Inc.,
`392 F.3d 1317 (Fed. Cir. 2004) ............................................................................ 58
`
`
`KSR International Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ..................................................................................... passim
`
`
`Leapfrog Enterprises, Inc. v Fisher-Price Inc.,
`485 F.3d 1157 (Fed. Cir. 2007) ............................................................................ 56
`
`
`Medichem, S.A. v. Rolabo, S.L.,
`437 F.3d 1157 (Fed. Cir. 2006) ..................................................................... 36, 52
`
`
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) .............................................................................. 55
`
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007) ..................................................................... 36, 52
`
`
`Randall Mfg. v. Rea,
`733 F.3d 1355 (Fed. Cir. 2013) .............................................................................. 7
`
`
`
`v
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`

`

`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
`
`
`Senju Pharm. Co. v. Apotex, Inc.,
`717 F. Supp. 2d 404 (D. Del. 2010) ........................................................ 37, 38, 52
`
`
`Sud-Chemie, Inc. v. Multisorb Techs., Inc.,
`554 F.3d 1001 (Fed. Cir. 2009) ............................................................................ 30
`
`
`Federal Statutes
`
`35 U.S.C. § 103(a) .......................................................................................... 1, 6, 21
`
`35 U.S.C. § 325(d) ............................................................................................ 63, 64
`
`35 U.S.C. §§ 311-319 ................................................................................................ 6
`
`Federal Regulations
`
`37 C.F.R. § 42.10(a) ................................................................................................. 64
`
`37 C.F.R. § 42.10(b) ................................................................................................ 65
`
`37 C.F.R. § 42.100(b) .............................................................................................. 20
`
`37 C.F.R. § 42.104(a) ................................................................................................. 6
`
`37 C.F.R. § 42.104(b) .............................................................................................. 20
`
`37 C.F.R. § 42.106(a) ............................................................................................... 65
`
`37 C.F.R. § 42.24(a) ................................................................................................. 65
`
`37 C.F.R. § 42.63(e) ................................................................................................. 65
`
`37 C.F.R. § 42.8(a)(1) .............................................................................................. 64
`
`37 C.F.R. § 42.8(b)(1) .............................................................................................. 64
`
`37 C.F.R. § 42.8(b)(2) .............................................................................................. 64
`
`
`vi
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
`
`
`37 C.F.R. § 42.8(b)(3) .............................................................................................. 64
`
`37 C.F.R. § 42.8(b)(4) .............................................................................................. 64
`
`37 C.F.R. §§ 42.1-.80 ................................................................................................. 6
`
`37 C.F.R. §§ 42.100-42.123 ....................................................................................... 6
`
`
`
`vii
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`

`

`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
`
`INTRODUCTION
`
`
`
`I.
`
`Petitioners Amneal Pharmaceuticals LLC and Amneal Pharmaceuticals of
`
`New York, LLC (“Petitioners”) submit this Petition for Inter Partes Review
`
`(“IPR”) seeking cancellation of claims 1-6 of U.S. Patent No. 9,161,926
`
`(AMN1001) (“the ’926 patent), assigned to Allergan, Inc., (Patent Owner”), as
`
`unpatentable under pre-AIA 35 U.S.C. § 103(a).
`
`The commercial embodiment of the challenged claims is Aczone® 7.5%
`
`Gel, a topical aqueous gel formulation comprising dapsone as the active ingredient,
`
`sold by Patent Owner Allergan. But prior to developing the 7.5% formulation that
`
`is central to the challenged claims here, Allergan previously marketed and sold
`
`Aczone® Gel 5%, which qualifies as prior art to the ’926 patent, and shares many
`
`features of the allegedly “new” 7.5% formulation. Notably, when the prior art
`
`Aczone® Gel 5% lost patent protection, Allergan applied obvious and routine
`
`modifications to arrive at the successor 7.5% formulation as a means to extend its
`
`patent monopoly.
`
`These modifications are at most the work of a skilled laborer, not an
`
`inventor. See Hotchkiss v. Greenwood, 52 U.S. 248, 267 (1850) (finding claims
`
`unpatentable where “the improvement is the work of the skilful [sic] mechanic, not
`
`that of the inventor.”); KSR International Co. v. Teleflex Inc., 550 U.S. 398, 427
`
`(2007) (citing Hotchkiss, “[a]nd as progress beginning from higher levels of
`
`1
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`

`

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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`achievement is expected in the normal course, the results of ordinary innovation
`
`are not the subject of exclusive rights under the patent laws.”1). There is nothing
`
`innovative about these changes that would entitle Allergan to patent protection.
`
`During prosecution, the examiner repeatedly found the challenged claims
`
`obvious, but eventually allowed the claims to issue only after the introduction of
`
`alleged unexpected results evidence; however, the examiner never found any claim
`
`limitation to be missing from the prior art or not prima facie obvious. And for good
`
`reason: the ’926 patent claims merely recite a known active ingredient, combined
`
`with known and commonly used excipients, in amounts and concentrations that
`
`were well-known in the prior art for the claimed purpose.
`
`Collectively, the challenged claims recite a topical pharmaceutical
`
`composition of:
`
`
`
`
`
`about 7.5% w/w dapsone, a known drug at a known concentration;
`
`about 30% w/w to about 40% w/w of diethylene glycol monoethyl
`
`ether (“ethoxydiglycol”), a known preferred solubilizing agent at a
`
`known concentration;
`
`
`
`about 2% w/w to about 6% w/w of acrylamide/sodium
`
`
`1 Throughout this petition, all emphasis to quotation is added, except where
`
`otherwise indicated.
`
`2
`
`

`

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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
`
`acryloyldimethyl tautate copolymer (“acrylamide copolymer”), a
`
`known thickening agent described as preferred in the prior art for
`
`topical formulations at known concentrations;
`
`water, a well-known and commonly used solvent, which was used in
`
`prior art dapsone gel formulations; and
`
`wherein the composition does not include adapalene, a negative
`
`limitation that existed in various prior art teachings, including
`
`
`
`
`
`Aczone® Gel 5%.
`
`Accordingly, and as discussed below, the ’926 patent merely claims compositions
`
`of a known amount of dapsone combined with excipients previously known for use
`
`with dapsone in topical compositions, each excipient acting according to known
`
`functions in known concentrations. This is not inventive.
`
`This petition demonstrates that all six challenged claims of the ’926 patent
`
`are unpatentable as obvious under at least two separate and independent grounds:
`
`First, the challenged claims are unpatentable over Garrett in view of
`
`Nadau-Fourcade, Ground 1. Decades before the priority date, dapsone was a
`
`well-known medicament, and in fact was approved by the Food and Drug
`
`Administration (“FDA”) as a 5% gel for treating acne. The Garrett reference
`
`discloses topical dapsone compositions having 5% w/w to 10% w/w dapsone, and
`
`further teaches each and every limitation of the challenged claims, except the
`
`3
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`acrylamide copolymer thickening agent. Garrett, however, teaches the use of other
`
`thickening agents, identifying five of them that were accepted in the art:
`
`Carbopol®, Hypan®, Natrosol®, Klucel®, and Stabileze®.
`
`But, by 2012, a POSA would have known that Garrett’s thickening agents
`
`were interchangeable with the claimed acrylamide copolymer thickening agent in
`
`view of at least the teaching in the Nadau-Fourcade reference, which specifically
`
`teaches the claimed acrylamide copolymer as a “preferred” thickening agent for
`
`water insoluble drugs like dapsone.
`
`Second, the challenged claims also would have been obvious over Garrett
`
`in view of Bonacucina, Ground 2. Allergan’s predecessor product—the prior art
`
`Aczone® Gel 5%—was known to be “gritty with visible drug particles present.”
`
`(AMN1010, 9.) The prior art Aczone® Gel 5% used Carbopol® 980 as its
`
`thickening agent, and therefore topical dapsone compositions, like Garrett, that use
`
`Carbopol® would be expected to be gritty. Another known drawback of using
`
`Carbopol® 980 is that it required neutralization with a base (e.g., sodium
`
`hydroxide) to function as a thickening agent.
`
`As such, a POSA would have had a reason to modify Garrett to improve
`
`texture and feel. Combined with Garrett, the Bonacucina reference teaches that
`
`“Sepineo P 600 [a commercial grade of the claimed acrylamide copolymer] is a
`
`prime candidate for use in the formulation of gels and emulsion gels with
`
`4
`
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`

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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`rheological properties suitable for topical administration.” (AMN1015, 7.) The
`
`claimed acrylamide copolymer, in contrast to Carbopol® 980, was known to
`
`render topical formulations “stable and have a perfectly uniform appearance,” and
`
`be “very pleasant for the touch and spread on the skin.” Further, the claimed
`
`acrylamide copolymer did not require neutralization with a base, unlike Carbopol®
`
`980.
`
`Based on either Ground 1 or 2, all challenged claims would have been
`
`obvious. Notably, neither Garrett, nor Nadau-Fourcade, nor Bonacucina was
`
`before the examiner during prosecution. Had the examiner properly considered
`
`these references, the ’926 patent would not have issued. The grounds in this
`
`petition demonstrate that a POSA would have had reason to substitute the
`
`thickening agent taught in the dapsone composition of Garrett with the acrylamide
`
`copolymer taught in either Nauau-Fourcade or Bonacucina, for multiple and
`
`independent reasons, any of which compels finding obviousness. And because
`
`each component of the claimed composition had previously been shown in the art
`
`as acceptable for use in topical compositions (including the prior art Aczone® Gel
`
`5%), and further because each component was being used for its intended purpose
`
`and in its intended concentration, a POSA would have had a reasonable
`
`expectation of successfully arriving at the claimed composition.
`
`This is a textbook case of obviousness: “the combination of familiar
`
`5
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`

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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
`
`elements according to known methods is likely to be obvious when it does no more
`
`than yield predictable results.” KSR, 550 U.S. at 416.
`
`II. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a))
`Petitioners certify that the ’926 patent is available for IPR and that
`
`Petitioners are not barred or estopped from requesting IPR of any of the challenged
`
`claims.
`
`III. PRECISE RELIEF REQUESTED AND SUPPORTING REASONS
`The Office should institute IPR under 35 U.S.C. §§ 311-319 and 37 C.F.R.
`
`§§ 42.1-.80 and 42.100-42.123, and cancel claims 1-6 of the ’926 patent as
`
`unpatentable under pre-AIA 35 U.S.C. § 103(a). This Petition is accompanied and
`
`supported by the declaration of Dr. Bozena Michniak-Kohn, Ph.D. (AMN1002), an
`
`expert in the field of topical pharmaceutical compositions and topical drug delivery
`
`(AMN1002, ¶¶6-12); and the declaration of Dr. Elaine Gilmore, M.D., Ph.D
`
`(AMN1018), a practicing dermatologist and expert in the clinical use of topical
`
`compositions, including topical dapsone compositions. (AMN1018, ¶¶6-13).
`
`Petitioners’ detailed, full statement of the reasons for relief requested is provided,
`
`infra, at §VII.
`
`IV. OVERVIEW OF LEVEL OF SKILL AND PRIOR ART
`
`Person of ordinary skill in the art (“POSA”).
`A.
`A POSA is presumed to be aware of all pertinent art prior to November 20,
`
`2012, the earliest priority date to which the ’926 patent could be entitled. The
`
`6
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`POSA is presumed to think along conventional wisdom in the art, and is a person
`
`of ordinary creativity. See Abbott Labs. v. Andrx Pharm., Inc., 452 F.3d 1331,
`
`1336 (Fed. Cir. 2006) (stating that a person of ordinary skill possesses the
`
`“understandings and knowledge reflected in the prior art”); see also Randall Mfg.
`
`v. Rea, 733 F.3d 1355, 1362 (Fed. Cir. 2013) (“[T]he knowledge of [a person of
`
`ordinary skill in the art] is part of the store of public knowledge that must be
`
`consulted when considering whether a claimed invention would have been
`
`obvious”).
`
`Here, a POSA would draw upon the knowledge and experience of related
`
`disciplines of a multi-disciplinary team that might lie outside the POSA’s primary
`
`training. A POSA relevant to the ’926 patent would have the knowledge of both a
`
`formulator of topical pharmaceutical compositions and clinician with experience
`
`treating dermatological diseases. The formulator POSA would possess a Ph.D. or
`
`equivalent degree in pharmaceutics, chemistry or a related discipline such as
`
`pharmacology, who also has practical experience (at least two years) of
`
`formulating topical drug delivery products, or the POSA could possess a Bachelors
`
`or Masters degree in one of the preceding disciplines with a greater level (at least
`
`four years) of the same formulating experience. (AMN1002, ¶¶16-18). The clinical
`
`POSA would possess an M.D. with a board certification in dermatology with at
`
`least two years of experience in dermatology, or otherwise treating skin conditions.
`
`7
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`It is also possible that an M.D. without a certification in dermatology (i.e., a
`
`primary care physician, or a pediatrician) may qualify as a clinical POSA,
`
`assuming that they have more than two years of knowledge and experience treating
`
`skin conditions. (AMN1018, ¶¶19-21).
`
`B.
`
`
`
`Scope and content of the art before November 20, 2012.
`1.
`Dapsone is not a new compound. It was first synthesized in 1908, and has
`
`Dapsone was well known.
`
`been for decades “a well-known medicament possessing several beneficial
`
`medicinal activities.” (AMN1002, ¶20; AMN1007, [0002]; AMN1004, 2:7-10,
`
`9:28-30; AMN1018, ¶22). Orally administered dapsone had long been used to treat
`
`leprosy, but was also known to be an effective agent for treating skin diseases such
`
`as acne vulgaris and rosacea. (AMN1002, ¶20; AMN1007, [0031]; AMN1004,
`
`3:9-15; AMN1018, ¶24).
`
`2.
`
`Topical dapsone compositions were well known and
`preferred to oral forms.
`
`Like orally administered dapsone, topical dapsone compositions were known
`
`in the art and used to treat dermatological conditions such as acne and rosacea.
`
`(AMN1002, ¶21; AMN1004, 3:9-15; AMN1007, [0002]-[0007], AMN1033, 2).
`
`Indeed, before the priority date, FDA had approved a topical dapsone 5%
`
`formulation, marketed and sold by Patent Owner Allergan under the trade name
`
`Aczone® Gel 5%, which was the predecessor to the Aczone® 7.5% product that is
`
`8
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`the commercial embodiment of the challenged claims here. (AMN1002, ¶21;
`
`AMN1010; AMN1018, ¶26). Topical administration of dapsone was preferred
`
`because of the reduced likelihood of systemic side effects. (AMN1018, ¶¶27, 32,
`
`35; AMN1024, 123.)
`
`The prior art topical dapsone compositions shared various common features:
`
`First, the art taught using a solubilizing agent to address dapsone’s known
`
`insolubility in water and in oils, which rendered both aqueous and non-aqueous
`
`dapsone formulations difficult to formulate. (AMN1002, ¶23; AMN1007, [0004]-
`
`[0005]). The same references also provided the solution. (AMN1002, ¶23;
`
`AMN1007, [0004]-[0005]; AMN1004, 13:10-14:19). Organic solvents that would
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`either completely dissolve the dapsone in the composition, or enable the dapsone to
`
`dissolve in a water-solvent combination were common solubilizing agents.
`
`(AMN1002, ¶23; AMN1007, [0048-49]). Of all the possible solubilizing agents,
`
`the prior art favored one above others: ethoxydiglycol, which is recited in the
`
`challenged claims.
`
`By 2012, Garrett taught that ethoxydiglycol was one of two “preferred
`
`solvents for use in [] topically applied dermatological composition[s].”
`
`(AMN1002, ¶23; AMN1004, 14:13-14; AMN1007, [0055]-[0057]; AMN1010, 1).
`
`Consistent with the preference for ethoxydiglycol in dapsone compositions, the
`
`predecessor Aczone® Gel 5% successfully employed ethoxydiglycol as a
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`solubilizing agent. (AMN1002, ¶24; AMN1010, 1). Indeed, dapsone’s solubility in
`
`ethoxydiglycol was so well understood that a solubility curve had been established
`
`that correlated the amount of ethoxydiglycol needed to dissolve various amounts of
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`dapsone. (AMN1002, ¶25; AMN1009, 326-327).
`
`Second, dapsone compositions most often were water-based compositions.
`
`(AMN1002, ¶21; AMN1007, [0018]; AMN1004, 4:2-15; AMN1008, Abstract;
`
`AMN1016; AMN1010, 1). Indeed, several working formulations containing water
`
`were known by 2012. (AMN1007, [0018], [0086], [0093], [0100], [0109], [0111],
`
`[0118], [0127], [0134], [0142]; AMN1004, 4:2-15; AMN1010, 1). Accordingly,
`
`the prior art was replete with aqueous dapsone compositions, including those
`
`taught by both Lathrop and Garrett. Beyond that, artisans were well aware that the
`
`prior art Aczone® Gel 5% was water-based. (AMN1002, ¶21; AMN1010, 1).
`
`Third, dapsone compositions, like most topical compositions, utilized a
`
`preservative. Preservatives in topical formulations were used to inhibit growth of
`
`bacteria in the composition. (AMN1004, 13:26-33; AMN1028, 20-21).
`
`Preservatives thereby maintain the integrity of the compositional components,
`
`increase the shelf-life of the composition, and generally make the composition
`
`safer for use. (AMN1002, ¶29; AMN1028, 20-21). Prior art topical dapsone
`
`compositions were known to use methyl paraben—the preservative recited in the
`
`challenged claims—as the preservative. (AMN1002, ¶29; AMN1007, [0082];
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`AMN1004, 13:26-14:18). Unsurprisingly, methyl paraben had been successfully
`
`employed in the prior art 5% Aczone Gel already on the market in 2012.
`
`(AMN1002, ¶29; AMN1010, 1).
`
`Fourth, dapsone compositions often utilized a viscosity-increasing agent,
`
`also known as a “thickening agent.” (AMN1002, ¶26; AMN1004, 12:5-13:25;
`
`AMN1016, 4:7-19; AMN1008, [0004]). Viscosity increasing agents have a few
`
`primary functions. Viscosity-increasing agents, also called thickening agents or
`
`gelling agents, thicken the composition to impart a smooth texture and feel.
`
`(AMN1002, ¶26; AMN1007, [0009], [0068]; AMN1013, [0176], [0200]-[0202]).
`
`In addition, thickening agents disperse or suspend particles or globules.
`
`(AMN1002, ¶57; AMN1007, [009], [0068]; AMN1013, [0176], [200]-[202]).
`
`Although solubilizing agents, such as ethoxydiglycol, were used to enhance the
`
`dissolution of dapsone in topical compositions, it was known that complete
`
`dissolution was not always possible. (AMN1002, ¶23; AMN1004, 11:15-33;
`
`AMN1007, [0049]-[0051]). By 2012, it was well known that some portion of
`
`dapsone in a composition may not dissolve in the organic solvent, or that some
`
`portion of the dissolved dapsone would precipitate out of the dissolved state into
`
`the undissolved state. (AMN1007, [0049-50]; AMN1004, 3:20-4:24, 11:20-33).
`
`When not fully dissolved, dapsone manifests as solid particles in the composition.
`
`(AMN1007, [0049]; AMN1004, 9:8-14).
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`Artisans further understood that the ratio of dissolved to undissolved
`
`dapsone was important. (AMN1002, ¶22; AMN1004, 11:15-12:2). The dissolved
`
`dapsone crosses the stratum corneum of the epidermis and is absorbed into the
`
`lower layers of the skin. (AMN1004, Abstract). The undissolved dapsone, on the
`
`other hand, can either be delivered to and act on the upper layers of the skin, or act
`
`as a reservoir of slowly absorbed dapsone. (AMN1004, 11:15-27). However,
`
`because the undissolved dapsone was dispersed or suspended in the composition,
`
`artisans understood that the undissolved drug particles needed to be controlled to
`
`maintain homogeneity of the drug particles, i.e., to prevent aggregation and
`
`clumping of the drug particles. (AMN1002, ¶26; AMN1011, 3:7-12). Formulators
`
`by 2012 understood the need to avoid aggregation and clumping of the drug
`
`particles, not only because it might compromise the stability of the overall
`
`composition, but it could impair the clinical efficacy of the drug because larger
`
`drug particles dissolve or disperse more slowly due to their lower surface
`
`area:volume ratio when compared to smaller particles of a similar shape.
`
`(AMN1002, ¶26; AMN1008, [0004]).
`
`By 2012, one such thickening agent, crosslinked acrylic acid polymers sold
`
`under various Carbopol® trade names, was known for its use in dapsone
`
`compositions. (AMN1002, ¶27; AMN1007, [0079], [0093], [0100], [0109], [0118],
`
`[0134], [0142]; AMN1004, 13:3-25). Other thickening agents were known to be
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,926
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`interchangeable with Carbopol® and suitable for dapsone (and other water
`
`insoluble drugs), including, the acrylamide/sodium acryloyldimethyl taurate
`
`copolymer (referred here as “acrylamide copolymer” for simplicity) that is claimed
`
`in the ’926 patent, such as Simulgel® 600 and Sepineo® P 600. (AMN1005,
`
`47:12-32 – 48:1-7; AMN1004, 13:3-25; AMN1015, 1).
`
`3.
`
`Petitioners’ grounds rely specifically on the following prior
`art publications.
`(a) Garrett (AMN1004)
`International Patent Application Publication No. WO 2009/061298, “Topical
`
`Treatment With Dapsone in G6PD-Deficient Patients,” (“Garrett”) published on
`
`May 14, 2009, and qualifies as prior art under pre-AIA 35 U.S.C. § 102(b).
`
`Garrett teaches a “dermatological composition that is a semi-solid aqueous
`
`gel, wherein dapsone is dissolved in the gel such that the dapsone has the capacity
`
`to cross the stratum corneum layer of the epidermis, and wherein the composition
`
`also contains [some] dapsone in a microparticulate state that does not readily cross
`
`the stratum corneum of the epidermis.” (AMN1004, Abstract, 3:20-26; AMN1002,
`
`¶40). Garrett teaches treatments “directed to dermatological conditions and the
`
`treatment is provided by a topical dapsone composition.” (AMN1004, 3:10-15;
`
`AMN1018, ¶¶30-31).
`
`Garrett discloses compositions having about 5% w/w to 10% w/w dapsone,
`
`which encompasses the claimed 7.5% w/w amount. (AMN1004, 3:33-4:15).
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`Petition for Inter Partes Review of U.S. Patent No. 9,161,92