`
`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.
`
`ALMIRALL, LLC
`Patent Owner.
`
`
`Case IPR2018-00608
`Patent No. 9,161,926 B2
`
`PATENT OWNER’S SUR-REPLY
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`IPR2018-00608
`Patent Owner’s Sur-Reply
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`TABLE OF CONTENTS
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`Page
`
`I.
`
`INTRODUCTION ............................................................................................... 1
`
`II. PETITIONER DOES NOT DISPUTE THE PROPER CONSTRUCTION
`OF “DAPSONE” IN THE ʼ926 PATENT .......................................................... 3
`
`III. PETITIONER FAILS TO SHOW ITS ASSERTED ART RENDERS
`OBVIOUS THE CHALLENGED CLAIMS OF THE ʼ926 PATENT ............... 6
`
`A. Petitioner Fails to Show Motivation to Develop a New Dapsone
`Formulation ............................................................................................... 6
`
`B. Petitioner Fails to Show Motivation in Garrett to Use an Increased
`Dapsone Concentration of 7.5% ............................................................... 7
`
`C. Petitioner Does Not Dispute that Garrett Provides No Motivation or
`Teaching to Use Acrylamide/Sodium Acryloyldimethyl Taurate
`Copolymer as the Polymeric Viscosity Builder ...................................... 10
`
`D. Petitioner Does Not Dispute that Garrett Provides No Motivation or
`Teaching to Exclude Adapalene.............................................................. 10
`
`E. Petitioner Fails to Show that the Asserted Art Discloses the Claimed
`About 2% w/w to About 6% w/w of a Polymeric Viscosity Builder
`Consisting of Acrylamide/Sodium Acryloyldimethyl Taurate
`Copolymer ............................................................................................... 11
`
`F. Petitioner Fails to Show Motivation to Combine ................................... 17
`
`1. Petitioner Fails to Show Motivation to Combine Garrett and
`Nadau-Fourcade (Ground 1) .......................................................... 17
`
`2. Petitioner Fails to Show Motivation to Combine Garrett and
`Bonacucina (Ground 2) .................................................................. 19
`
`IV. CONCLUSION .................................................................................................. 20
`
`
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`ii
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`IPR2018-00608
`Patent Owner’s Sur-Reply
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`TABLE OF AUTHORITIES
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`Page(s)
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`CASES
`Almirall LLC v. Taro Pharm. Indus. Ltd.,
`No. 1:17-cv-00663-JRB-SRF (D. Del. June 1, 2017) .......................................... 2
`
`Markman v. Westview Instruments, Inc.,
`52 F.3d 967 (Fed. Cir. 1995) (en banc) .............................................................. 15
`
`Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp.,
`831 F.3d 1350 (Fed. Cir. 2016) .......................................................................... 14
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) .......................................................................... 16
`
`Shire Dev., LLC v. Watson Pharm., Inc.,
`848 F.3d 981 (Fed. Cir. 2017) ............................................................................ 14
`
`Thorner v. Sony Computer Entm’t Am. LLC,
`669 F.3d 1362 (Fed. Cir. 2012) ............................................................................ 3
`
`Upsher-Smith Labs., Inc. v. Pamlab, L.L.C.,
`412 F.3d 1319 (Fed. Cir. 2005) .................................................................... 10, 11
`
`Vitronics Corp. v. Conceptronic, Inc.,
`90 F.3d 1576 (Fed. Cir. 1996) ............................................................................ 15
`
`STATUTES
`
`35 U.S.C. § 312(a) ..................................................................................................... 8
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`
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`iii
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`IPR2018-00608
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`PATENT OWNER’S EXHIBIT LIST
`
`Exhibit No.
`
`Description
`
`2001
`
`2002
`
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`
`Patent Assignment Agreement dated October 10, 2018
`
`Hagan declaration in support of pro hac vice application
`
`Declaration of Professsor Alexander M. Klibanov
`
`Curriculum Vitae for Professor Alexander M. Klibanov
`
`International Patent Application Publication No. WO
`2011/014627 (“Ahluwalia”)
`
`International Patent Application Publication No. WO
`2009/108147 (“Garrett I”)
`
`International Patent Application Publication No. WO
`2010/105052 (“Hani”)
`
`U.S. Patent No. 4,829,058 (“Seydel I”)
`
`U.S. Patent No. 4,912,112 (“Seydel II”)
`
`Wayback Machine Results for David Pascoe, Aczone Fails to
`Impress for Rosacea, Rosacea Support Group (July 23, 2012),
`available at https://rosacea-support.org/aczone-fails-to-
`impress-for-rosacea.html
`
`S. Puavilai et al., “Incidence of anemia in leprosy patients
`treated with dapsone,” J. Med. Assoc. Thailand 67(7): 404-407
`(1984) (“Puavilai”)
`
`iv
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`IPR2018-00608
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`Exhibit No.
`
`2012
`
`2013
`
`2014
`
`2015
`
`2016
`
`2017
`
`2018
`
`2019
`
`2020
`
`2021
`
`Description
`
`World Health Organization Alert No. 117, Antimalarial
`chlorproguanil-dapsone (LapDap™) withdrawn following
`demonstration of post-treatment haemolytic anaemia in G6PD
`deficient patients in a Phase III trial of chlorproguanil-
`dapsone-artesunate (Dacart™) versus artemether-lumefantrine
`(Coartem®) and confirmation of findings in a comparative trial
`of LapDap™ versus Dacart™ (Mar. 4, 2008)
`
`MaryAnn Steiner, “Dapsone Topical Gel for Acne,” J. Pharm.
`Soc. Wisc. 12(6): 67–71 (2009) (“Steiner”)
`
`ACZONETM Gel, 5% Prescribing Information (2008) (“2008
`Aczone 5% PI”)
`
`Robert Lott et al., “Medication adherence among acne
`patients: A review.” J. Cosmetic Dermatology 9: 160–166
`(2010) (“Lott”)
`
`Kirk A. James et al., “Emerging drugs for acne,” Expert Opin.
`Emerging Drugs 14(4): 649–659 (2009) (“James I”)
`
`Barry Coutinho, “Dapsone (Aczone) 5% Gel for the Treatment
`of Acne,” American Family Physician (Dec. 2010)
`(“Coutinho”)
`
`Food and Drug Administration Inactive Ingredient Database
`(September, 2012)
`
`H.C. Korting & C. Schöllmann, “Current topical and systemic
`approaches to treatment of rosacea,” JEADV 23: 876–882
`(2009) (“Korting”)
`
`European Commission’s Scientific Committee on Consumer
`Safety, Opinion on Diethylene Glycol Monoethyl Ether
`(DEGEE) (2010)
`
`Food and Drug Administration Inactive Ingredient Database
`(December, 2012)
`
`v
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`Exhibit No.
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`Description
`
`2022
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`2023
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`2024
`
`2025
`
`2026
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`2027
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`2028
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`2029
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`2030
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`2031
`
`2032
`
`Declaration of Julie Harper, M.D.
`
`Curriculum Vitae of Julie Harper, M.D.
`
`John Kraft & Anatoli Freiman, Management of acne,
`183 Canadian Med. Assoc. J. E430–E435 (2011) (“Kraft”)
`
`Meghan I. Dubina & Alan B. Fleisher Jr., Interaction of
`Topical Sulfacetamide and Topical Dapsone with Benzoyl
`Peroxide, 145 JAMA Dermatology 1027–1029 (2009)
`(“Dubina”)
`
`Stephen Titus & Joshua Hodge, Diagnosis and Treatment of
`Acne, 86 Am. Family Physician 734–740 (2012) (“Titus”)
`
`John S. Strauss, Biology of the Sebaceous Gland and the
`Pathophysiology of Acne Vulgaris, in Pathophysiology of
`Dermatologic Diseases, Second Edition, N. A. Soter and H.
`Baden eds., McGraw-Hill, New York 195–210 (1991)
`(“Strauss”)
`
`William D. James, Acne, 352 New Eng. J. Medicine
`1463–1472 (2005) (“James II”)
`
`Ayumi Naito et al., Topical retinoids for acne vulgaris
`(Protocol), 3 The Cochrane Library (John Wiley & Sons
`2008) (“Naito”)
`
`Physicians’ Desk Reference 2967–2969 (2011) (excerpt)
`
`Physicians’ Desk Reference 2765–2767 (2012) (excerpt)
`
`Gabriella Fabbrocini et al., Resveratrol-Containing Gel for the
`Treatment of Acne Vulgaris, 12 Am. J. of Clinical
`Dermatology 131–141 (2011) (“Fabbrocini”)
`
`vi
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`Exhibit No.
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`Description
`
`2033
`
`2034
`
`2035
`
`2036
`
`2037
`
`2038
`
`2039
`
`2040
`
`2041
`
`James Q. Del Rosso, The Use of Sodium Sulfacetamide
`10%-Sulfur 5% Emollient Foam in the Treatment of Acne
`Vulgaris, 2 J. Clinical and Aesthetic Dermatology 26–29
`(2009) (“Del Rosso”)
`
`Janusz Marcinkiewicz et al., Topical taurine bromamine, a
`new candidate in the treatment of moderate inflammatory acne
`vulgaris—A pilot study, 18 Eur J. Dermatology 433–439
`(2008) (“Marcinkiewicz”)
`
`Yuko Takenaka et al., Glycolic acid chemical peeling
`improves inflammatory acne eruptions through its inhibitory
`and bactericidal effects on Propionibacterium acnes, 39 J.
`Dermatology 350–354 (2012) (“Takenaka”)
`
`P. Marazzi et al., Clinical evaluation of Double Strength
`IsotrexinTM versus Benzamycin® in the topical treatment of
`mild to moderate acne vulgaris, 13 Journal of Dermatological
`Treatment 111–117 (2002) (“Marazzi”)
`
`N. Kellett et al., Conjoint analysis: a novel, rigorous tool for
`determining patient preferences for topical antibiotic
`treatment for acne. A randomized controlled trial, 154 British
`Journal of Dermatology 524–532 (2006) (“Kellett”)
`
`Frank C. Powell, Rosacea, 352 New Eng. J. Med. 793–803
`(2005) (“Powell”)
`
`Aczone 7.5% PI (“Aczone 7.5% PI”)
`
`Dina Anderson, Finding a Place for Topical Anti-
`inflammatory Acne Therapy, Practical Dermatology 17–18
`(July 2009) (“Anderson”)
`
`Michael Ghods et al., The Role of Dapsone Gel in the Acne
`Armamentarium, The Dermatologist (June 10, 2010), available
`at https://www.the-dermatologist.com/content/role-dapsone-
`gel-acne-armamentarium (“Ghods”)
`
`vii
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`Exhibit No.
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`Description
`
`2042
`
`2043
`
`2044
`
`2045
`
`2046
`
`2047
`
`2048
`
`2049
`
`2050
`
`David Pascoe, Aczone Fails to Impress for Rosacea, Rosacea
`Support Group (July 23, 2012), available at https://rosacea-
`support.org/aczone-fails-to-impress-for-rosacea.html
`(“Pascoe”)
`
`Clinical Study Report—ACZ ROS 01, A phase II,
`randomized, partial-blind, parallel-group, active- and vehicle-
`controlled, multicenter study of the safety and efficacy of
`Aczone™ (dapsone) Gel, 5% in subjects with papulopustular
`rosacea, QLT Inc. (Feb. 5, 2007)
`
`AZC ROS 01 Web Results Summary, A phase II, randomized,
`partial-blind, parallel-group, active- and vehicle-controlled,
`multicenter study of the safety and efficacy of Aczone™
`(dapsone) Gel, 5% in subjects with papulopustular rosacea,
`available at http://www.allerganclinicaltrials.com/
`pdfs/medical_aesthetics/Results_Web_PostingACZ-ROS-
`01.pdf
`
`Otto H. Mills et al., Comparing 2.5%, 5%, and 10% Benzoyl
`Peroxide on Inflammatory Acne Vulgaris, 25 Int’l J.
`Dermatology 664–667 (1986) (“Mills”)
`
`John V. Ashurst et al., Pathophysiological Mechanisms,
`Diagnosis, and Management of Dapsone-Induced
`Methemoglobinemia, 110 J. Am. Osteopathic Assoc. 16–20
`(2010) (“Ashurst”)
`
`J.S. Chun et al., Dapsone hypersensitivity syndrome with
`circulating 190-kDA and 230-kDA autoantibodies, 34 Clinical
`and Experimental Dermatology e798–e801 (2009) (“Chun”)
`
`U.S. Patent Publication No. 2011/0135584 (“Mallard”)
`
`U.S. Patent Publication No. 2011/0003894 (“Louis”)
`
`NDA 21-794 FDA approval letter (July 7, 2005)
`
`viii
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`Exhibit No.
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`Description
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`NDA 21-794 FDA approval letter (March 14, 2008)
`
`Deposition of Elaine S. Gilmore, M.D., Ph.D., taken
`November 16, 2018
`
`Deposition of Bozena B. Michniak-Kohn, Ph.D., taken
`November 20, 2018
`
`U.S. Patent No. 9,517,219
`
`2051
`
`2052
`
`2053
`
`2054
`
`
`
`
`
`
`
`
`
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`IPR2018-00608
`Patent Owner’s Sur-Reply
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`I.
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`INTRODUCTION
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`Petitioner’s Reply fails to remedy the deficiencies in its Petition. Petitioner
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`has not shown that a person of ordinary skill in the art would have been motivated
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`to formulate a novel topical pharmaceutical formulation using dapsone. Nor has
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`Petitioner provided credible evidence of any such motivation to do so in Garrett, or
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`of any motivation provided by Garrett to increase the concentration of dapsone
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`above 5%. And Petitioner has not shown any motivation or teaching to exclude
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`adapalene, as in the asserted claims. If Petitioner has shown anything, it is only the
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`hindsight underlying its proposition that a skilled artisan would have been
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`motivated to combine Garrett with either Nadau-Fourcade or Bonacucina.
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`Petitioner has, moreover, failed entirely to make a showing that the claimed
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`polymeric viscosity builder is disclosed in any of its asserted art. Positioned
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`without a reasonable response, Petitioner resorts to an attenuated argument that
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`“consisting of” instead means “comprising.” But Petitioner cannot overcome the
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`exceptionally strong presumption that the patentee’s choice of “consisting of” has
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`meaning, and requires a polymeric viscosity builder that consists only of A/SA
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`copolymer, and nothing else, in the claimed concentrations. As Petitioner presents
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`no evidence regarding how much A/SA copolymer is present in the Sepineo P 600
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`disclosed in Bonacucina and Nadau-Fourcade, even if it could show all of the other
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`elements and motivation to combine, Petitioner has not met its burden to present a
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`IPR2018-00608
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`prima facie case of obviousness. See 37 C.F.R. § 42.104(b)(4) (“The petition must
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`specify where each element of the claim is found in the prior art patents or printed
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`publications relied upon.”).
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`Petitioner attempts to newly orient the Board’s attention by alleging that
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`Almirall has taken inconsistent positions before the Delaware District Court and in
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`this proceeding. These are not the facts. The litigation before the Delaware
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`District Court concerned the presumptively distinct U.S. Patent No. 9,517,219
`
`(“the ʼ219 patent”)—not the ʼ926 patent at issue in this proceeding. See
`
`Complaint, Almirall LLC v. Taro Pharm. Indus. Ltd., No. 1:17-cv-00663-JRB-SRF
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`(D. Del. June 1, 2017). The claims of the ʼ219 patent are not the same as the
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`claims of the ʼ926 patent. Ignoring all other differences, the ʼ219 patent claims
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`require various concentrations of “a polymeric viscosity builder comprising
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`acrylamide/sodium acryloyldimethyl taurate copolymer.” Ex. 2054 at 15:39–
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`16:40. The claims at issue here, on the other hand, require “a polymeric viscosity
`
`builder consisting of acrylamide/sodium acryloyldimethyl taurate copolymer.” Ex.
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`1001 at 15:20–16:24. Almirall’s positions regarding a non-party’s infringement of
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`claims reciting a fundamentally distinct composition are irrelevant—and are
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`certainly neither inconsistent nor misrepresentations.
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`Petitioner also resorts to disparaging Almirall’s expert, Dr. Julie Harper. See
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`Reply at 5 n.3 (alleging that Dr. Harper received payment from Allergan for
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`“promotional activities for ACZONE® Gel 5%”). As Dr. Harper explained,
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`Petitioner’s counsel’s repeated description of her activities as “promotional” was
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`incorrect: “Not to promote it. I don’t do that. That’s not my job. To educate
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`people about the data that goes with this and its potential mechanism of action.”
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`Ex. 1049 at 115:24–116:14. Petitioner’s mischaracterization of Dr. Harper’s
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`activities serve no consequential end in this proceeding.
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`As Petitioner has failed to show, by a preponderance of the evidence, that
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`the ʼ926 patent is obvious over either Garrett and Nadau-Fourcade or Garrett and
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`Bonacucina, Patent Owner respectfully requests that this Board confirm the
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`patentability of claims 1–6 of the ʼ926 patent.
`
`II.
`
`PETITIONER DOES NOT DISPUTE THE PROPER
`CONSTRUCTION OF “DAPSONE” IN THE ʼ926 PATENT
`
`A patentee acts as his own lexicographer when he “clearly set[s] forth a
`
`definition of the disputed claim term.” Thorner v. Sony Computer Entm’t Am.
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`LLC, 669 F.3d 1362, 1365 (Fed. Cir. 2012) (quoting CCS Fitness, Inc. v.
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`Brunswick Corp., 288 F.3d 1359, 1366 (Fed. Cir. 2002)). Petitioner fails to point
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`to any portion of the specification or other intrinsic evidence to rebut Almirall’s
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`evidence that the patentee acted as his own lexicographer here. The ʼ926
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`specification explicitly and clearly sets forth the definition of “dapsone” as “4,4′-
`
`diaminodiphenyl sulfone.” Ex. 1001 at 2:6–7. That there are other, synonymous
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`names that may also describe the compound with that particular chemical structure
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`is irrelevant. Regardless, Petitioner does not dispute that “dapsone,” as used in the
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`claims of the ʼ926 patent, refers only to the specific chemical compound 4,4′-
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`diaminodiphenyl sulfone.
`
`Rather, Petitioner’s dispute appears to regard the definition of “dapsone”
`
`used in Petitioner’s primary obviousness reference, Garrett. That is irrelevant,
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`apart from being disingenuous. Petitioner admits that Garrett’s definition of
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`“dapsone” includes “three categories of compounds.” Reply at 9 (citing Ex. 1004
`
`at 8:18–27). Indeed, Garrett provides this definition in a section titled
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`“Definitions.” Ex. 1004 at 8:10, 8:18–27. These three categories are: (1) the
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`chemical compound defined as “dapsone” in the ʼ926 patent (with various ways of
`
`naming that compound), (2) chemical compounds with “similar chemical
`
`structures and thus similar therapeutic potential” to that compound, and (3)
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`chemical compounds “that have similar therapeutic potential, but are not as closely
`
`related by chemical structure” to that compound. Ex. 1004 at 8:18–22 (“As used
`
`herein, “dapsone” refers to the chemical compound dapsone having the chemical
`
`formula C12H12N2O2S as well as bis(4-aminophenyl)sulfone, 4[],4’-
`
`diaminodiphenyl sulfone and it hydrates, 4,4′-sulfonylbisbenzeneamine, 4,4′-
`
`sulfonyldianiline, diaphenylsulfone, dapsone analogs, and dapsone related
`
`compounds.” (emphases added)). As Dr. Kilbanov explained, two of those
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`categories—“dapsone analogs” and “dapsone derivatives”—each contain a vast
`
`number of distinct chemical compounds. See Ex. 2003 ¶¶ 82–85; id. ¶ 83
`
`(describing a few of the “many hundreds of distinct chemical compounds” that
`
`make up one sub-part of “dapsone analogs,” per the definition in Garrett); id. ¶ 84
`
`(providing an example of a “dapsone related compound” under the definition
`
`provided in Garrett, and explaining why that example encompasses “hundreds, if
`
`not thousands, of compounds” depending on the substituent’s identity and
`
`location); Ex. 1058 at 63:15–65:5. Petitioner does not, and cannot, dispute that
`
`two of the three categories contained within Garrett’s definition of “dapsone”
`
`comprise a legion of chemical compounds.
`
`Petitioner argues that as 4,4′-diaminodiphenyl sulfone is “the only
`
`compound in an FDA-approved product discussed in Garrett, a person of ordinary
`
`skill in the art person of ordinary skill in the art would understand that Garrett’s
`
`5% to 10% range applies to it.” Reply at 9. This argument is unavailing on its
`
`own and duplicitous in context of the Grounds as a whole. As Garrett defines
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`“dapsone” to include three categories totaling thousands of chemical compounds, a
`
`person of ordinary skill in the art would understand the range of “dapsone”
`
`concentrations disclosed in Garrett—unless otherwise stated—to refer to thousands
`
`of compounds. The only examples in Garrett referring to an FDA-approved
`
`product specifically identify “Aczone™ gel, 5%.” Ex. 1004 at 10:5–25, 11:1–4,
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`5
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`and Example 1 (23:4–38:25). That is, the only time Garrett discusses an FDA-
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`approved product, it refers only to a concentration of 5%. A person of ordinary
`
`skill in the art would understand all references to “dapsone” that do not specify
`
`otherwise—including each instance to the range of 5% to 10% dapsone—to refer
`
`instead to “dapsone” as defined by Garrett. Ex. 1058 at 65:15–66:4.
`
`III. PETITIONER FAILS TO SHOW THE ASSERTED ART RENDERS
`OBVIOUS THE CHALLENGED CLAIMS OF THE ʼ926 PATENT
`A.
`
`Petitioner Fails to Show Motivation to Develop a New Dapsone
`Formulation
`
`Almirall does not contest that the ACZONE® gel, 5% formulation has some
`
`level of effectiveness—it was, after all, approved by the FDA. But that approval
`
`alone does not provide motivation to create a new topical pharmaceutical dapsone
`
`composition. Amneal does not—and cannot—dispute that dapsone is, at best, a
`
`second-choice option for treatment of acne, and that there were numerous more
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`effective choices for new formulations. Reply at 5 (referring to topical dapsone gel
`
`as a “second-line” treatment).1 Petitioner skates over the lack of design need or
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`market pressure for a different dapsone topical composition by repeatedly stating
`
`
`1 Petitioner also refers to dapsone as “a known topically-administered treatment for
`
`. . . rosacea,” Reply at 6, but this is disingenuous. Dapsone has never been
`
`approved as a treatment for rosacea. Ex. 2022 ¶¶ 83–84.
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`6
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`that Garret discloses a range of dapsone concentrations—which does not close this
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`gap in Petitioner’s argument.
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`B.
`
`Petitioner Fails to Show Motivation in Garrett to Use an
`Increased Dapsone Concentration of 7.5%
`
`Petitioner also fails to show that, assuming a person of ordinary skill in the
`
`art was motivated to create a new dapsone formulation, she would have been
`
`motivated to increase the concentration specifically to 7.5%. Petitioner instead
`
`merely grasps at the statement in Garrett that its formulations are typically applied
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`“once or twice daily,” asserting a new argument: that the knowledge that the
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`commercial ACZONE® gel, 5% product is approved for twice-daily application
`
`would provide motivation to increase dapsone to a precise concentration for once-
`
`daily application. Reply at 14–15. Petitioner provides no basis for its assertion
`
`that a person of ordinary skill in the art, reading Garrett, would understand that
`
`increasing the dapsone concentration would reduce the dosing regimen. See, e.g,
`
`Ex.1018 ¶ 43 (Dr. Gilmore opining that a “reduced daily dose” does not meet a
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`“long-felt need”); Ex. 1004 at 23:8–12 (explaining that the frequency of the dosing
`
`should depend on the severity of the affliction); Ex. 2049 at 149:23–150:10 (Dr.
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`Harper noting only a general preference for once-daily products). Indeed, both
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`parties’ expert dermatologists testified that they prescribe the ACZONE® gel, 5%
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`product for once daily use. Ex. 2052 at 27:12–18 (Dr. Gilmore); Ex. 1049 at
`
`7
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`99:12–100:7 (Dr. Harper, testifying that she has often prescribed the 5% dapsone
`
`product once daily in order to simultaneously treat with another product that uses a
`
`different mechanism of action, and to “simplify the regimen”).
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`Moreover, Petitioner’s new argument, dependent on the ACZONE® gel, 5%
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`product’s prescribing information, is improper. Petitioner had full opportunity to
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`select the art it needed for its petition, and should have included relevant art in its
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`obviousness combination. 35 U.S.C. § 312(a). It does not now get to attempt to
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`compensate for the deficiencies of its asserted art by raising new arguments
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`requiring support of other art not part of its asserted grounds.
`
`Petitioner also argues for the first time that “the amount of dapsone was a
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`result-effective variable” based on the desired modification of reservoir capacity of
`
`undissolved dapsone. Reply at 15 (emphasis added).2 But Petitioner provides no
`
`explanation of why or how this is results-effective. And Dr. Michniak-Kohn
`
`admitted that the amount of undissolved dapsone is dependent not just on one
`
`variable, but on the entire formulation. Ex. 2053 at 158:2–159:4.
`
`
`2 Petitioner incorrectly asserts that Almirall did not dispute that multiple claimed
`
`elements were “results-effective variables.” See Reply at 13, 23, 26–27. The only
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`element Petitioner asserted was “result effective” in its Petition was the 30% to
`
`40% DGME. Petition at 28.
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`8
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`IPR2018-00608
`Patent Owner’s Sur-Reply
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`Petitioner acknowledges the risks associated with dapsone administration.
`
`Reply at 13–14. Petitioner does not dispute that those risks were serious, including
`
`hemolytic anemia. See PO Response at 42; Ex. 2022 ¶¶ 159-162. Nor does
`
`Petitioner dispute that Garrett did not attempt to determine the safety of a 7.5%
`
`dapsone formulation. See PO Response at 42. Petitioner’s characterization of
`
`Garrett’s disclosure is misleading: Garrett disclosed that “[i]n some preferred
`
`embodiments, the method of treatment does not induce hemolytic anemia” or
`
`“induce adverse hematologic events.” Ex. 1004 at 6:5–8. Garrett showed that for
`
`one preferred embodiment—5% dapsone—treatment with the formulation did not
`
`induce clinical signs of hemolytic anemia. Id. at 39:16–19. But Garrett did not
`
`include any data or even speculation regarding any other concentrations of
`
`dapsone. Petitioner resorts to citing the label for the ACZONE® gel, 7.5%
`
`formulation—a document dated after the ʼ926 patent issued—to claim that an
`
`“expected” exposure level from 7.5% dapsone applied topically was less than that
`
`of an oral dose. Reply at 14 (citing Ex. 2039 at 5). But that 2016 document does
`
`not negate the risks in increasing dapsone concentration that a POSA would have
`
`understood were present as of 2012. Petitioner fails, moreover, to rebut that person
`
`of ordinary skill in the art would have understood that increasing the amount of
`
`dapsone would not necessarily result in a commensurate increase in therapeutic
`
`benefit. See PO Response at 43; Ex. 2022 ¶ 158. Petitioner fails to demonstrate
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`9
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`IPR2018-00608
`Patent Owner’s Sur-Reply
`
`why a person of ordinary skill in the art would have been motivated to conceive of
`
`exactly 7.5% dapsone.
`
`C.
`
`Petitioner Does Not Dispute that Garrett Provides No Motivation
`or Teaching to Use Acrylamide/Sodium Acryloyldimethyl Taurate
`Copolymer as the Polymeric Viscosity Builder
`
`Petitioner does not dispute that Garrett discloses numerous polymeric
`
`viscosity builders. See PO Response at 46. Nor does Petitioner deny that only
`
`hindsight reconstruction of the challenged claims can explain a turn from the
`
`polymeric viscosity builders disclosed in Garrett—including the only polymeric
`
`viscosity builder in the sole topical dapsone formulation then available—to instead
`
`use the undisclosed acrylamide/sodium acryloyldimethyl taurate (“A/SA”)
`
`copolymer. The Petition record reflects no known problem3 with the polymeric
`
`viscosity builder of the commercial ACZONE® gel, 5% formulation, carbomer.
`
`D.
`
`Petitioner Does Not Dispute that Garrett Provides No Motivation
`or Teaching to Exclude Adapalene
`
`Petitioner argues that because adapalene is not disclosed in Garrett, Garrett
`
`must disclose its exclusion from the claims. Reply at 18–19. Its reliance on
`
`
`3 Petitioner points again to carbomer’s neutralization requirement. Reply at 26.
`
`But that an ingredient must be added properly is true of any ingredient in a
`
`pharmaceutical composition, and does not render it a problem. See Ex. 2003
`
`¶ 201.
`
`10
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`IPR2018-00608
`Patent Owner’s Sur-Reply
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`Upsher-Smith Laboratories, Inc. v. Pamlab, L.L.C. is misplaced. 412 F.3d 1319
`
`(Fed. Cir. 2005). In Upsher-Smith, the Federal Circuit held that express disclosure
`
`of embodiments containing an element, along with an indication that the element
`
`was “optional,” anticipates a claim expressly excluding that element. Id. at 1320–
`
`22. But those are not the facts here. Garrett does not disclose a single embodiment
`
`with retinoids, and does not disclose adapalene at all. See generally Ex. 1004.
`
`There is no suggestion in Garrett that the composition could include adapalene.
`
`Therefore, Garrett’s lack of contemplation of adapalene is not enough to render
`
`obvious its express exclusion. C.f. Upsher-Smith, 412 F.3d at 1322. Petitioner can
`
`point to no reason disclosed in Garrett to exclude adapalene.
`
`E.
`
`Petitioner Fails to Show that the Asserted Art Discloses the
`Claimed About 2% w/w to About 6% w/w of a Polymeric
`Viscosity Builder Consisting of Acrylamide/Sodium
`Acryloyldimethyl Taurate Copolymer
`
`Petitioner argues that Sepineo P 600, in the concentrations disclosed in
`
`Nadau-Fourcade and Bonacucina, meet the claimed limitation regarding a
`
`polymeric viscosity builder. To do so, Petitioner blatantly ignores a fundamental
`
`rule of patent claims: that “consisting of” denotes a closed term.
`
`Petitioner argues that although Sepineo P 600 is a polymeric viscosity
`
`builder, some of it components are not. But Petitioner cites no evidence that
`
`supports its claim that isohexadecane and polysorbate 80, as used in Sepineo P
`
`11
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`IPR2018-00608
`Patent Owner’s Sur-Reply
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`600, are not part of the polymeric viscosity builder contemplated by the ʼ926
`
`patent. Reply at 10–11. To the contrary, the material cited by Petitioner confirms
`
`that the entirety of Sepineo P 600 is the polymeric viscosity builder. Ex. 1050 ¶ 61
`
`(citing Ex. 1001 at 5:35–38, which provides an exemplary embodiment of a
`
`polymeric viscosity builder that explicitly includes, inter alia, isohexadecane and
`
`polysorbate 80); Ex. 1015 at 1–2 (noting the importance of isohexadecane and
`
`polysorbate 80 to the viscoelastic behavior of Sepineo P 600 gels).
`
`Indeed, in the very next paragraph, Petitioner points to the very portion of
`
`the specification making clear that an exemplary polymeric viscosity builder
`
`contemplated by the ʼ926 patent contains not only A/SA copolymer, but also other
`
`ingredients, including isohexadecane and polysorbate 80. Reply at 11 (citing Ex.
`
`1001 at 5:35–38 (“In some embodiments, the polymeric viscosity builder is an
`
`acrylamide/sodium acryloyldimethyltaurate copolymer, and further includes
`
`isohexadecane, sorbitan oleate, water, and Polysorbate 80.” (emphasis added))).
`
`Petitioner cannot have it both ways—that the isohexadecane and polysorbate 80
`
`components of Sepineo P 600 are not polymeric viscosity builders, but that they do
`
`contribute to the claimed concentration of polymeric viscosity builder of the ʼ926
`
`patent.
`
`Petitioner offers no evidence of how much A/SA copolymer is present in
`
`Sepineo P 600, and, therefore, how much is disclosed in the Bonacucina and
`
`12
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`IPR2018-00608
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`Nadau-Fourcade references. Indeed, Petitioner’s expert admitted that she has no
`
`idea of the concentration of A/SA copolymer itself. See Ex. 2053 at 196:9–17
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`(Dr. Michniak-Kohn testifying that she was not “asked to research that”); id. at
`
`197:3–198:15 (Dr. Michniak-Kohn testifying that she does not know the
`
`concentration of acrylamide/sodium acryloyldimethyl taurate copolymer in the
`
`Sepineo P 600 gels disclosed in the Bonacucina reference). Petitioner does not
`
`even suggest how much Sepineo P 600 would be required to achieve the claimed
`
`concentration of about 2% to about 6% w/w (claim 1) or about 4% (claims 3 and 5)
`
`of a polymeric viscosity builder consisting of A/SA copolymer. Indeed, Petitioner
`
`offers no evidence, or even so much as a supposition, as to the concentration of
`
`A/SA copolymer in the compositions disclosed in Bonacucina or Nadau-Fourcade.
`
`Without any evidence of the concentration of A/SA copolymer in Sepineo P 600,
`
`Petitioner cannot show that any reference disclosing Sepineo P 600 discloses the
`
`claimed concentrations of A/SA copolymer. Petitioner thus fails to show how
`
`either Bonacucina or Nadau-Fourcade disclose the polymeric viscosity builder as
`
`claimed. Even were that tortuous argument meritorious, Petitioner waived it by
`
`failing to make it in the Petition. See 37 C.F.R. § 42.23(b).
`
`In an attempt to compensate for this failing, Petitioner instead argues a
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`convoluted and improper construction for the claimed “polymeric viscosity builder
`
`consisting of acrylamide/sodium acryloyldimethyl taurate copolymer” as follows:
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`13
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`IPR2018-00608
`Patent Owner’s Sur-Reply
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`(1) there is a “nexus” between Dr. Warner’s declaration and the claims; (2) the
`
`description of an embodiment in the specification contemplates the polymeric
`
`viscosity builder including more than just A/SA copolymer; and (3) because of the
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`Warner declaration and the described embodiment, “consisting of” really means
`
`“comprising”. Reply at 10–12.4
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`It is black letter law that “consisting of” claim language is closed, and
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`excludes unrecited elements. Multilayer Stretch Cling Film Holdings, Inc. v. Berry
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`Plastics C
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