Petition for Inter Partes Review of USPN 8,129,431
`
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`__________________
`
`INNOPHARMA LICENSING, INC., INNOPHARMA LICENSING LLC,
`INNOPHARMA INC., INNOPHARMA LLC,
`MYLAN PHARMACEUTICALS INC., and MYLAN INC.
`Petitioner,
`
`v .
`
`SENJU PHARMACEUTICAL CO., LTD., BAUSCH & LOMB, INC., and
`BAUSCH & LOMB PHARMA HOLDINGS CORP.
`Patent Owner.
`
`U.S. Patent No. 8,129,431 to Sawa et al.
`Issue Date: March 6, 2012
`Title: Aqueous Liquid Preparation Containing 2-Amino-3-(4-
`bromobenzoyl) Phenylacetic Acid
`__________________
`
`Inter Partes Review No.: IPR2015-00903
`__________________
`
`Petition for Inter Partes Review of U.S. Patent No. 8,129,431
`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, VA 22313-1450
`
`
`
`
`
`

`

`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION ........................................................................................... 1
`
`II. OVERVIEW .................................................................................................... 1
`
`A.
`
`B.
`
`The ‘431 Patent ..................................................................................... 3
`
`The Scope and Content of the Prior Art ................................................ 4
`
`1.
`
`2.
`
`Aqueous Ophthalmic Preparations of Bromfenac ...................... 4
`
`Tyloxapol and Related Surfactants in NSAID Aqueous
`
`Ophthalmic Preparations ............................................................. 5
`
`C.
`
`The Differences Between the Challenged Claims and the Prior
`Art .......................................................................................................... 6
`
`III. STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL
`STATEMENTS ............................................................................................... 9
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) ...................................... 9
`
`A.
`
`Each Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) .........................10
`
`B. Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) ............................11
`
`1.
`
`2.
`
`Judicial Matters .........................................................................11
`
`Administrative Matters .............................................................12
`
`C. Designation of Lead and Back-Up Counsel (37 C.F.R. §
`42.8(b)(3)) ...........................................................................................14
`
`D. Notice of Service Information (37 C.F.R. § 42.8(b)(4)) .....................14
`
`
`
`ii
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`Petition for Inter Partes Review of USPN 8,129,431
`
`
`V.
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(a)) ..........................................14
`
`VI. THE ‘431 PATENT AND CLAIM CONSTRUCTION ...............................15
`
`VII. PERSON OF SKILL IN THE ART (“POSA”) & STATE OF THE
`ART ...............................................................................................................16
`
`VIII. IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b)) .................19
`
`A.
`
`Independent Claims 1 and 18 ..............................................................20
`
`1.
`
`Ogawa in View of Sallmann .....................................................20
`
`B. Dependent Claims 2-17 and 19-22 ......................................................36
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Claims 2-6, 11-17, and 19-22 – sodium salt of bromfenac ......36
`
`Claims 3, 4, 6, 12, 13, and 20 – bromfenac concentration .......38
`
`Claims 5 and 22.........................................................................39
`
`Claims 11, 15-17, and 21 ..........................................................40
`
`Claims 3-5 and 11 – tyloxapol concentration range .................42
`
`Claims 6, 15-17, and 20-22 – tyloxapol concentration .............44
`
`Claims 12-14 – tyloxapol concentration ...................................47
`
`Claims 7-10, 13, 14, 16 and 17- additives ................................48
`
`Claims 9 and 10 - pH ................................................................50
`
`C. Objective Indicia of Nonobviousness .................................................50
`
`1.
`
`2.
`
`No Unexpected Results Over the Closest Prior Art. .................51
`
`Other Objective Indicia .............................................................53
`
`
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`iii
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`Petition for Inter Partes Review of USPN 8,129,431
`
`IX. CONCLUSION ..............................................................................................55
`
`CERTIFICATION OF SERVICE ON PATENT OWNER....................................... 1
`
`
`
`
`
`iv
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`Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`TABLE OF AUTHORITIES
`
`Page(s)
`
`
`CASES
`
`Amneal Pharmaceuticals, LLC v. Supernus Pharmaceuticals, Inc., IPR2013-
`00368, Paper 8 (December 17, 2013) ................................................................. 51
`
`Chapman v. Casner,
`315 Fed. App’x 294 (Fed. Cir. 2009) ..................................................... 38, 42, 50
`
`Ecolab, Inc. v. FMC Corp.,
`569 F.3d 1335 (Fed. Cir. 2009) .......................................................................... 15
`
`Friskit, Inc. v. Real Networks, Inc.,
`306 F. App’x 610 (Fed. Cir. 2009) ..................................................................... 53
`
`Galderma Labs., L.P., v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) .......................................................... 39, 41, 42, 48
`
`In re Aller,
`220 F.2d 456 ................................................................................................. 41, 47
`
`In re De Blauwe,
`736 F.2d 699 (Fed. Cir. 1984) ............................................................................ 51
`
`In re Malagari,
`499 F.2d 1297,1303 (C.C.P.A. 1974) ................................................................ 50
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) ........................................................ 41, 48, 50, 52
`
`In re Woodruff,
`919 F.2d 1575 (Fed.Cir. 1990) ..................................................................... 43, 50
`
`Iron Grip Barbell Co., Inc., v. USA Sports, Inc.,
`392 F.3d 1317 (Fed. Cir. 2004) .......................................................................... 39
`
`KSR International Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) ............................................................................ 2, 16, 26, 36
`
`
`
`v
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`

`

`Petition for Inter Partes Review of USPN 8,129,431
`
`
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) ............................................................................ 50
`
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006) .......................................................................... 53
`
`Purdue Pharma Prods. L.P. v. Par Pharm., Inc.,
`377 Fed App’x 978 (Fed. Cir. 2010) .................................................................. 54
`
`Sakraida v. AG Pro, Inc.,
`425 U.S. 273 (1976) ............................................................................................ 26
`
`Sinclair & Carroll Co., v. Interchemical Corp.,
`325 U.S. 327 (1945) ........................................................................................... 24
`
`Stratoflex, Inc. v. Aeroquip Corp.,
`713 F.2d 1530 (Fed. Cir. 1983) .................................................................... 53, 54
`
`Sundance, Inc. v. DeMonte Fabricating Ltd.,
`550 F.3d 1356 (Fed Cir. 2008) ....................................................................... 7, 29
`
`Tokai Corp. v. Eason Enters., Inc.,
`632 F.3d 1358 (Fed. Cir. 2011) .......................................................................... 54
`
`Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC,
`683 F.3d 1356 (Fed. Cir. 2012) .............................................................. 26, 30, 33
`
`STATUTES
`
`35 U.S.C. § 102(b) ................................................................................................... 20
`
`35 U.S.C. § 103 .................................................................................................... 1, 19
`
`35 U.S.C. § 112 .................................................................................................passim
`
`35 U.S.C. § 315(a)(1) ............................................................................................... 10
`
`REGULATIONS
`
`37 C.F.R. § 42.6(d) .................................................................................................. 19
`
`37 C.F.R. § 42.8(a)(1) .............................................................................................. 10
`
`37 C.F.R. § 42.8(b)(1) .............................................................................................. 10
`
`
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`vi
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`Petition for Inter Partes Review of USPN 8,129,431
`
`37 C.F.R. § 42.8(b)(2) .............................................................................................. 11
`
`37 C.F.R. § 42.8(b)(3) .............................................................................................. 14
`
`37 C.F.R. § 42.8(b)(4) .............................................................................................. 14
`
`37 C.F.R. § 42.10(b) .................................................................................................. 9
`
`37 C.F.R. § 42.22(a) ................................................................................................. 14
`
`37 C.F.R. § 42.63(e) ................................................................................................... 9
`
`37 C.F.R. § 42.100(b) .............................................................................................. 15
`
`37 C.F.R. § 42.104(a) ................................................................................................. 9
`
`37 C.F.R. § 42.104(b) .............................................................................................. 19
`
`37 C.F.R. § 42.106(a) ................................................................................................. 9
`
`
`
`vii
`
`

`

`Petition for Inter Partes Review of USPN 8,129,431
`
`
`Petitioner’s Exhibit List
`
`
`Exhibit #
`
`Description
`
`1001
`
`1002
`
`1003
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`1011
`
`Sawa et al., U.S. Patent No. 8,129,431 B2, “Aqueous Liquid
`Preparation Containing 2-Amino-3-(4-Bromobenzoyl) Phenylacetic
`Acid”
`
`Certified English translation of Hara, Yoshiyuki , “Bromfenac sodium
`hydrate,” Clinics & Drug Therapy 19:1014-1015 (2002)
`
`Declaration of Paul A. Laskar, Ph.D.
`Ogawa et al., U.S. Patent No. 4,910,225 “Locally Administrable
`Therapeutic Composition for Inflammatory Disease”
`
`Desai et al., U.S. Patent No. 5,603,929, “Preserved Ophthalmic Drug
`Compositions Containing
`Polymeric Quaternary Ammonium
`Compounds”
`
`Desai, et al., U.S. Patent No. 5,558,876, “Topical Ophthalmic Acidic
`Drug Formulations”
`
`Certified English translation of “Bromfenac sodium hydrate” in the
`Japanese Pharmacopoeia 2001 Edition: 27-29, Yakuji Nippo Limited
`(2001)
`
`FDA approved “BROMDAYTM (bromfenac ophthalmic solution,
`.09%) Product Label,” U.S. Approval: March 24, 2005, ISTA
`Pharmaceuticals, Inc.
`
`Sallmann et al., U.S. Patent No. 6,107,343, “Ophthalmic And Aural
`Compositions Containing Diclofenac Potassium”
`
`Guttman et al., “Solubilization of Anti-inflammatory steroids by
`Aqueous Solutions of Triton-WR-1339,” Journal of Pharmaceutical
`Sciences 50: 305-307 (1961)
`
`Fu et al., Australian Patent No. AU-B-22042/88, “Preservative System
`For Ophthalmic Formulations”
`
`
`
`viii
`
`

`

`1012
`
`1013
`
`1014
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Yasueda et al., U.S. Patent No. 6,274,609, “Aqueous Liquid
`Pharmaceutical Composition Containing as Main Component
`Benzopyran Derivative”
`
`“Orange Book: Approved Drug Products with Therapeutic
`Equivalence Evaluations,” Appl. No. N203168, U.S. FDA, accessed at
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?
`Appl_No=203168&Product_No=001&table1=OB_Rx
`
`“Orange Book: Approved Drug Products with Therapeutic Equivalence
`Evaluations,” Appl. No. N203168, Active Ingredient Bromfenac Sodium,
`accessed
`at
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?App
`l_No=203168&TABLE1=OB_Rx, last accessed on February 14, 2014
`
`1015
`
`Reserved
`
`1016
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`Kapin, et al., International Patent No. WO 2002/13804, “Method For
`Treating Angiogenesis-Related Disorders Using Benzoyl Phenylacetic
`Acid”
`
`Flach, Allan., “Topical Nonsteroidal Antiinflammatory Drugs for
`Ophthalmic Uses,” Ophthalmic NSAIDS: 77-83 (1996)
`
`Prince, S., et al., “Analysis of benzalkonium chloride and its homologs:
`HPLC versus HPCE,” Journal of Pharmaceutical and Biomedical
`Analysis 19: 877-882, Elsevier Science B.V., Netherlands (1999)
`
`Bergamini et al., U.S. Patent No. 5,597,560, “Diclofenac And
`Tobramycin Formulations For Ophthalmic And Otis Topical use”
`
`Wong, Michelle, International Patent No. WO 94/15597, “Ophthalmic
`Compositions Comprising Benzyllauryldimethylammonium Chloride”
`(filed January 11, 1993); issued July 21, 1994)
`
`Reddy, Indra K., Ocular Therapeutics and Drug Delivery: A Multi-
`Disciplinary Approach: 42-43, 390 (1996)
`
`
`
`ix
`
`

`

`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Story, M., et al., European Patent No. 0274870, “Micelles containing a
`non-steroidal antiinflammatory compound” (filed December 12, 1987;
`issued July 7, 1988)
`
`“Borax (Sodium tetraborate),” Biochemicals and Reagents: 175, Sigma-
`Aldrich (2000-2001)
`
`Schott, H., “Comparing the Surface Chemical Properties and the Effect
`of Salts on the Cloud Point of a Conventional Nonionic Surfactant,
`Octoxynol 9 (Triton X-100), and of Its Oligomer, Tyloxapol (Triton WR-
`1339),” Journal of Colloid and Interface Science 205: 496-502 (1998)
`
`Regev, O., et al., “Aggregation Behavior of Tyloxapol, a Nonionic
`Surfactant Oligomer, in Aqueous Solution,” Journal of Colloid and
`Interface Science 210: 8-17 (1999)
`
`Aviv, H., International Patent No. WO 94/05298, “Submicron
`Emulsions as Ocular Drug Delivery Vehicles”
`
`Gennaro, A., “Boric Acid,” Remington: The Science and Practice of
`Pharmacy 20: 1041, University of Sciences, United States (2000)
`
`Wade, A., and Weller, P., “Edetic Acid,” and “Sodium Metabisulfite,”
`Handbook of Pharmaceutical Excipients 2: 176-179, 451-453, American
`Pharmaceutical Association, United States (1994)
`
`Selected pages from the file history of U.S. Patent No. 8,129,431, March
`28, 2005 Amendment.
`
`"DuractTM," Physician’s Desk Reference 52:3035-3037 (1998)
`
`"monohydrate," Webster’s New World Dictionary of the American
`Language: 920, New World Dictionaries / Simon and Schuster (1980)
`
`"Voltaren," Orange Book: Approved Drug Products with Therapeutic
`Equivalence Evaluations, Appl. No. N020037, U.S. FDA, accessed at
`http://www.accessdata.fda.gov/scripts/cder/ob/docs/obdetail.cfm?Appl
`No=020037&TABLE1=OB Rx
`
`
`
`x
`
`

`

`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Yanni et al., U.S. Patent No. 5,475,034, "Topically Administrable
`Compositions Containing 3-Benzoylphenylacetic Acid Derivatives for
`Treatment of Ophthalmic Inflammatory Disorders"
`
`"ISTA Pharmaceuticals Submits New Drug Application for Xibrom™
`QD (once-daily), News Release, ISTA Pharmaceuticals (December 20,
`2007)
`"Acular®" and "Azopt™," Physician’s Desk Reference 54: 486-487,
`491-492 (2000)
`
`Doughty, M., "Medicines Update for optical practitioners- Part 11.,"
`Optician 5853 (223), (2002)
`
`Fan, T., "Determination of Benzalkonium Chloride in Ophthalmic
`Solutions Containing Tyloxapol by Solid-Phase Extraction and
`Reversed-Phase High-Performance Liquid Chromatography," Journal of
`Pharmaceutical Sciences 82 (11): 1172-1174, American Pharmaceutical
`Association, United States (1993)
`
`Guy et al., U.S. Patent No. 5,540,930, "Suspension of Loteprednol
`Etabonate for Ear, Eye, or Nose Treatment" (filed October 25, 1993;
`issued July 30, 1996)
`
`(loteprednol etabonate ophthalmic
`"ALREX™
`FDA approved
`suspension) 0.2% Product Label," U.S. Approval: 1998, Bausch &
`Lomb Pharmaceuticals
`
`FDA approved "LOTEMAX™ (loteprednol etabonate ophthalmic
`suspension) 0.5% Product Label," U.S. Approval: 1998, Bausch &
`Lomb Pharmaceuticals
`
`"TOBRADEX®" Physician’s Desk Reference 54: 490 (2000)
`
`"Alomide® 0.1%" Physician’s Desk Reference 50: 469 (1996)
`
`Kawabata et al., Canadian Patent No. CA 2 383 971 A1, "Prophylactic
`and Therapeutic Medicaments for Ophthalmic Uses"
`
`Johnson, R., et al., U.S. Patent No. 2,880,130, "Anti-Inflammatory
`Steroid Solutions"
`
`
`
`xi
`
`

`

`Petition for Inter Partes Review of USPN 8,129,431
`
`Johnson, R., et al., U.S. Patent No. 2,880,138, "Anti-Inflammatory
`Steroid Solutions"
`
`Patani, G., et al., "Bioisoterism: A Rational Approach in Drug Design,"
`Chem. Rev. 96: 3147-3176 (1996)
`
`Ostrovskii, V.A., et al., "Acid-base properties of 5-substituted
`tetrazoles," Chemistry of Heterocyclic Compounds 17: 412-416 (1981)
`
`FDA approved "XIBROM™ (bromfenac ophthalmic solution, .09%)
`Product Label," ISTA Pharmaceuticals, Inc.
`
`Senju Pharmaceutical Co., Ltd. Press Releases, "The approval of
`BRONUCK® (bromfenac sodium hydrate ophthalmic solution) as an
`import drug
`in China," http://www.senju.co.jp/,
`accessed
`at
`http://www.senju.co.jp/english/news/__icsFiles/afieldfile/2009/11/1
`8/2009111814br.pdf, published November 17, 2009, 1 page
`
`FDA approved "PROLENSA™ (bromfenac ophthalmic solution,
`0.07%) Product Label," U.S. Approval: April 5, 2013, Bausch & Lomb
`Incorporated
`The United States Pharmacopeia 24: The National Formulary 19: 1809-
`1813, 1864-1866, The United States Pharmacopeial Convention, Inc.
`(1999)
`
`Ali, et al., U.S. Patent No. 6,071,904, "Process for Manufacturing
`Ophthalmic Suspensions"
`
`Curriculum Vitae of Paul A. Laskar, Ph.D.
`
`xii
`
`1045
`
`1046
`
`1047
`
`1048
`
`1049
`
`1050
`
`1051
`
`1052
`
`1053
`
`
`
`
`
`
`

`

`Petition for Inter Partes Review of USPN 8,129,431
`
`
`I.
`
`INTRODUCTION
`
`InnoPharma Licensing, Inc., InnoPharma Licensing LLC, InnoPharma Inc.,
`
`InnoPharma LLC, Mylan Pharmaceuticals Inc., and Mylan Inc. (collectively,
`
`“Petitioner”) petition for Inter Partes Review (“IPR”), seeking cancellation of
`
`claims 1-22 (“challenged claims”) of U.S. Patent No. 8,129,431 to Sawa et al.
`
`(“the ’431 patent”) (EX1001), which is owned by Senju Pharmaceutical Co., Ltd.
`
`(“Senju” or “patent owner”).
`
`II. OVERVIEW
`
`The Board has already issued its Decision Instituting Inter Partes Review
`
`(“Decision”) on all challenged claims of the ’431 patent on the same grounds
`
`raised herein. Metrics, Inc. v. Senju Pharmaceutical Co., Ltd., IPR2014-01041
`
`(Paper 19). In its Decision, the Board found that Petitioner Metrics, Inc. had
`
`demonstrated a reasonable likelihood that claims 1-22 of the ’431 patent are
`
`unpatentable for failing to satisfy the nonobviousness requirement of 35 U.S.C. §
`
`103. Id. The Board instituted IPR of the challenged claims on two separate
`
`grounds:
`
`•
`
`•
`
`
`
`Claims 1-5, 7-14, and 18-19 as obvious over Ogawa and Sallmann under 35
`
`U.S.C. § 103; and
`
`Claims 6, 15-17, and 20-22 as obvious over Ogawa, Sallmann, and Fu under
`
`35 U.S.C. § 103.
`
`1
`
`

`

`Petition for Inter Partes Review of USPN 8,129,431
`
`Id. at Paper 19, pg. 20. Petitioner hereby files its own petition on the same grounds
`
`and concurrently seeks to join the instituted IPR proceedings on these challenged
`
`claims.
`
`The challenged claims all are directed to an aqueous formulation of
`
`bromfenac (a non-steroidal anti-inflammatory drug (“NSAID”)) with tyloxapol (a
`
`non-ionic surfactant). At the relevant time, tyloxapol was a known non-ionic
`
`surfactant in aqueous formulations of NSAIDs while bromfenac was a known
`
`NSAID previously formulated with another non-ionic surfactant, polysorbate 80.
`
`Thus, the purported inventors of the aqueous preparations of the challenged claims
`
`simply switched tyloxapol for polysorbate 80 (both well-known non-ionic
`
`surfactants). Or, viewed another way, the purported inventors of the challenged
`
`claims of the ’431 patent merely switched bromfenac for diclofenac (both well-
`
`known structurally similar NSAIDs). Swapping known alternatives from the prior
`
`art, according to their known functions to achieve predictable results, is not
`
`innovation. See, e.g., KSR International Co. v. Teleflex Inc., 550 U.S. 398, 416
`
`(2007) (“[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.”).
`
`
`
`2
`
`

`

`Petition for Inter Partes Review of USPN 8,129,431
`
`
`A. The ’431 Patent
`
`The challenged claims of the ’431 patent are directed to aqueous liquid
`
`preparations for ophthalmic administration. Claim 1 is reproduced below:
`
`1. An aqueous liquid preparation consisting essentially of the
`
`following two components, wherein the first component is 2-amino-3-
`
`(4-bromobenzoyl)-phenylaceticacid
`
`or
`
`a
`
`pharmacologically
`
`acceptable salt thereof or a hydrate thereof, wherein the hydrate is at
`
`least one selected from a 1/2 hydrate, 1 hydrate, and 3/2 hydrate and
`
`the second component is tyloxapol, wherein said liquid preparation is
`
`formulated for ophthalmic administration, and wherein when a
`
`quaternary ammonium compound
`
`is
`
`included
`
`in said
`
`liquid
`
`preparation, the quaternary ammonium compound is benzalkonium
`
`chloride.
`(EX1001, 11:66-12:101) (emphasis added).
`
`In pertinent part, claim 1 is directed to an aqueous liquid preparation for
`
`ophthalmic administration consisting essentially of just two components: (1)
`
`bromfenac (or its salts and hydrates); and (2) tyloxapol.2
`
`1 Citations are as
`
`follows: X:YY-ZZ
`
`(col:lines; patent); X:Y:Z
`
`(page:col:para; journal article); X:Y (page:para; journal article).
`
`2 Claim 1 recites that “when a quaternary ammonium compound is
`
`included,” then it is benzalkonium chloride (“BAC”). (EX1001, 12:6-7) (emphasis
`
`added). Thus, BAC is an optional component of the aqueous liquid preparation of
`
`
`
`
`
`3
`
`

`

`Petition for Inter Partes Review of USPN 8,129,431
`
`In the context of the ’431 patent, the “consisting essentially of” transitional
`
`phrase is construed to mean that the claimed ophthalmic formulations may include
`
`additional unrecited ingredients provided they do not materially affect the stability
`
`of the formulation “within a pH range giving no irritation to eyes, and change of
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`the [bromfenac] over time can be inhibited, and ... when the aqueous solution
`
`contains a preservative, deterioration in the preservative effect of said preservative
`
`can be inhibited for a long period of time.” (EX1001, 2:34-47, Abstract). The
`
`’431 patent specification expressly allows for other ingredients to be present in the
`
`formulation, including a preservative, buffer, thickener, stabilizer, chelating agent,
`
`and pH controlling agent, or an additional active ingredient. (EX1001, claims 7
`
`and 8, 6:42-44).
`
`B.
`
`The Scope and Content of the Prior Art
`
`1.
`
`Aqueous Ophthalmic Preparations of Bromfenac
`
`Bromfenac, like diclofenac and ketorolac, was a well-known NSAID useful
`
`for treating inflammation in the eye. (EX1002, 2:1:2; EX10033, ¶¶ 27-29). Each
`
`
`claim 1, since claim 1 also encompasses preparations “when a quaternary
`
`ammonium compound is not included.”
`
`3 This Petition is accompanied by the Declaration of Paul A. Laskar, Ph.D.
`
`(Laskar Dec. (EX1003)).
`
`
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`4
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`Petition for Inter Partes Review of USPN 8,129,431
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`of bromfenac, diclofenac, and ketorolac are in the class of NSAIDs possessing a
`
`carboxylic acid group (-COOH) and, as discussed below, this class of NSAIDs was
`
`known to interact with benzalkonium chloride (“BAC”) in aqueous ophthalmic
`
`formulations in a way that weakens the preservative efficacy of BAC. (EX1003,
`
`¶¶ 27-29). By January 21, 2003, bromfenac had been formulated with BAC along
`
`with non-ionic surfactants in aqueous preparations for ophthalmic delivery.
`
`The Ogawa patent (EX1004) described an aqueous ophthalmic formulation
`
`containing (1) bromfenac, (2) polysorbate 80, and (3) BAC. (EX1004, 9:5-10:19;
`
`see also Hara (EX1002), the Desai patents (EX1005 and EX1006), BRONUCK
`
`Japanese Pharmacopeia (EX1007), and BROMDAY Prescribing Information
`
`(EX1008)).
`
`2.
`
`Tyloxapol and Related Surfactants in NSAID Aqueous
`Ophthalmic Preparations
`
`By January 21, 2003, tyloxapol and related alkylaryl polyether surfactants
`
`were well-known non-ionic surfactants formulated in the prior art with NSAIDs.
`
`For example, Sallmann described liquid ophthalmic formulations containing (1)
`
`diclofenac sodium (an NSAID), (2) tyloxapol surfactant, and (3) BAC. (EX1009,
`
`8:1-15).
`
`Tyloxapol, like polysorbate 80, was successfully used to stabilize aqueous
`
`ophthalmic formulations as early as the 1960s. (EX1009, 8:1-15; EX1010,
`
`306:2:2-4; EX1003, ¶¶ 32, 34-37, 39). Notably, the prior art taught that tyloxapol
`
`
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`5
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`Petition for Inter Partes Review of USPN 8,129,431
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`was effective in stabilizing NSAIDs, like bromfenac. (EX1003, ¶ 37; EX1016,
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`6:8- 9, 8:13-22, Formulation 3; EX1011). The prior art also disclosed examples
`
`where tyloxapol is a preferred non-ionic surfactant for use in ophthalmic
`
`formulations containing acidic NSAIDs, like bromfenac (EX1009, 4:62; EX1003,
`
`¶¶ 34, 39, 56), and where tyloxapol was superior to polysorbate 80 as a surfactant
`
`in aqueous liquid formulations of an acidic compound. (EX1012, 7:20-43). In the
`
`prior art, a finite number of non-ionic surfactants, including tyloxapol and
`
`polysorbate 80, had been used in approved ophthalmic formulations. (EX1012,
`
`4:51-65; EX1009, 4:52-62).
`
`C. The Differences Between the Challenged Claims and the Prior Art
`
`Petitioner relies on its primary prior art references, the Ogawa patent
`
`(EX1004) and the Sallmann patent (EX1009) in combination with each other.
`
`Each discloses a prior art ophthalmic formulation of an NSAID, BAC, and a
`
`nonionic surfactant, similar to what is claimed in the ’431 patent. The challenged
`
`claims of the ’431 patent differ from prior art aqueous liquid ophthalmic
`
`formulations of an NSAID only in the replacement of bromfenac for another
`
`NSAID, or alternately, in the replacement of tyloxapol for another non-ionic
`
`surfactant (polysorbate 80), as illustrated in the following chart.
`
`
`
`6
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`Petition for Inter Partes Review of USPN 8,129,431
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`
`
`
`’431 Patent
`Claim 1
`
`Ogawa
`Example 6
`(EX1004)
`
`Sallmann
`Example 2
`(EX1009)
`
`NSAID
`
`Bromfenac
`
`Bromfenac
`
`Diclofenac
`
`Surfactant
`
`Tyloxapol
`
`Polysorbate 80
`
`Tyloxapol
`
`BAC
`
`Optional
`
`Yes
`
`Yes
`
`When viewed against the prior art, it is clear that the alleged inventors of the
`
`’431 patent did nothing more than swap one well-known component from a prior
`
`art formulation with another component known to be used for the same purpose.
`
`Thus, the alleged inventors of the aqueous preparations of the challenged claims
`
`simply switched tyloxapol for polysorbate 80—both well-known non-ionic
`
`surfactants. Alternately, the alleged inventors merely switched bromfenac for
`
`diclofenac—both well-known structurally similar NSAIDs. Swapping known
`
`alternatives from the prior art is not innovation. Sundance, Inc. v. DeMonte
`
`Fabricating Ltd., 550 F.3d 1356, 1366-67 (Fed Cir. 2008) (“a combination is more
`
`likely to be obvious where it ‘simply arranges old elements with each performing
`
`the same function it had been known to perform’ and yields no more than one
`
`would expect from such an arrangement”).
`
`All that the challenged claims accomplished was the obvious replacement of
`
`known components, according to their known functions, to achieve predictable
`
`results. (EX1003, ¶¶ 55-58). A person of ordinary skill in the art at the time
`
`
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`7
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`Petition for Inter Partes Review of USPN 8,129,431
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`(“POSA”) could have readily performed these simple component substitutions—
`
`tyloxapol for polysorbate 80 or bromfenac for diclofenac—because the functions
`
`of these components were well known in the art and the results were predictable.
`
`(EX1003, ¶¶ 55-58).
`
`Finally, the prior art disclosed only a finite number of non-ionic surfactants
`
`for ophthalmic formulations. As such, it would have been obvious to try
`
`substituting any of these known non-ionic surfactants (including tyloxapol) for
`
`polysorbate 80 in order to modify the teachings of Ogawa and arrive predictably at
`
`the claimed inventions, with a reasonable expectation of success.
`
`Further, Sallmann disclosed ophthalmic formulations containing NSAIDs,
`
`including diclofenac and ketorolac, together with ethoxylated octylphenol
`
`surfactants, including tyloxapol, as the non-ionic surfactant. (EX1003, ¶ 53).
`
`Sallmann’s ophthalmic formulation also included the preservative BAC. A POSA,
`
`therefore, would have been motivated to substitute bromfenac for diclofenac in
`
`Sallmann’s ophthalmic formulations to obtain predictable results because of the
`
`structural and functional similarities between bromfenac and diclofenac (EX1002,
`
`2:2:5; EX1003, ¶ 62), including their similar interaction with BAC, and the known
`
`preference for bromfenac over diclofenac (EX1002). The prior art also disclosed a
`
`finite number of NSAIDs for ophthalmic application, such that it would have been
`
`obvious to try substituting any of these known anti-inflammatory compounds
`
`
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`8
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`Petition for Inter Partes Review of USPN 8,129,431
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`(including bromfenac) for diclofenac in order to modify the teachings of Sallmann
`
`and arrive predictably at the claimed inventions, with a reasonable expectation of
`
`success. (EX1002, 2:2:3-3:1:1; EX1003, ¶ 62).
`
`The subject matter of many of the challenged claims of the ’431 patent is
`
`commercially embodied by Prolensa®, a product marketed by Bausch & Lomb Inc.
`
`(“B&L”). (EX1013; EX1014). The patent owner previously owned patent
`
`protection for
`
`two other bromfenac ophthalmic products—Xibrom® and
`
`Bromday®—in the United States, both of which were covered by the prior art
`
`Ogawa patent (EX1004), and over which the ’431 patent is obvious. And while
`
`some dependent claims of the ’431 patent recite more particular excipients,
`
`concentration ranges, and pH ranges, these nominal differences fall far short of
`
`imparting patentability, as discussed below.
`
`III. STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL STATEMENTS
`
`Petitioner certifies that: (1) the ’431 patent is available for IPR; and (2)
`
`Petitioner is not barred or estopped from requesting IPR of any claim of the ’431
`
`patent on the grounds identified herein. This Petition is filed in accordance with 37
`
`C.F.R. § 42.106(a). Concurrently filed herewith are a Power of Attorney and an
`
`Exhibit List pursuant to § 42.10(b) and § 42.63(e), respectively. The required fee
`
`is paid through, and the Office is authorized to charge any fee deficiencies and
`
`credit overpayments, to Deposit Acct. No. 160605 (Customer ID No. 00826).
`
`
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`9
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`Petition for Inter Partes Review of USPN 8,129,431
`
`Petitioner is aware that counsel for the patent owner has previously taken the
`
`position that there is a perceived conflict between the America Invents Act and the
`
`Hatch-Waxman Act and that the PTAB should exercise its discretion to deny IPR
`
`petitions filed by ANDA applicants. Specifically, patent owner’s counsel has
`
`asserted that the filing of a Paragraph IV Certification by an ANDA applicant is
`
`the equivalent of filing a civil action challenging the validity of a patent and, as
`
`such, prohibits the applicant from filing a petition for IPR pursuant to 35 U.S.C. §
`
`315(a)(1). The Board previously has determined that the action of filing “[a]
`
`Paragraph IV certification may represent an out-of-court challenge to patent
`
`invalidity, but it does not constitute ‘a civil action challenging the validity’ of any
`
`patent claim.” Metrics, Inc. v. Senju Pharmaceutical Co., Ltd., IPR2014-01041
`
`[Paper 19, pg. 9] (finding no conflict between the Hatch Waxman Act and the IPR
`
`provisions of the AIA) (quoting 35 U.S.C. § 315(a)).