IUNITED STATES PATENT AND TRADEMARK OFFICE
`
`_______________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_______________________________
`
`LUPIN LTD. and LUPIN PHARMACEUTICALS INC.
`Petitioners
`
`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.: Unassigned
`____________________
`
`
`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
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`TABLE OF CONTENTS
`
`Table of Contents
`
`C.
`
`INTRODUCTION ........................................................................................ 1
`I.
`II. OVERVIEW .................................................................................................. 1
`A.
`The ’431 Patent ................................................................................... 3
`B.
`The Scope and Content of the Prior Art .......................................... 5
`1.
`Aqueous Ophthalmic Preparations of Bromfenac ................ 5
`2.
`Tyloxapol and Related Surfactants in NSAID
`Aqueous Ophthalmic Preparations ........................................ 6
`The Differences Between the Challenged Claims and the
`Prior Art .............................................................................................. 7
`III. STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL
`STATEMENTS ........................................................................................... 10
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) ................................ 11
`A. Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) ............................. 11
`B.
`Related Matters (37 C.F.R. § 42.8(b)(2)) ........................................ 12
`1.
`Judicial Matters...................................................................... 12
`2.
`Administrative Matters ......................................................... 14
`C. Designation of Lead and Back-Up Counsel (37 C.F.R. §
`42.8(b)(3)): ......................................................................................... 16
`D. Notice of Service Information (37 C.F.R. § 42.8(b)(4)): ............... 16
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND
`THE REASONS THEREFORE (37 C.F.R. § 42.22(a)) .......................... 16
`VI. THE ’431 PATENT AND CLAIM CONSTRUCTION .......................... 17
`VII. PERSON OF SKILL IN THE ART (“POSA”) & STATE OF THE
`ART .............................................................................................................. 18
`VIII. IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b)) ........... 20
`A.
`Independent Claims 1 and 18 .......................................................... 22
`
`V.
`
`
`
`i
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`2.
`
`B.
`
`Ogawa in View of Sallmann .................................................. 22
`1.
`Dependent Claims 2-17 and 19-22 .................................................. 39
`1.
`Claims 2-6, 11-17, and 19-22—sodium salt of
`bromfenac ............................................................................... 39
`Claims 3, 4, 6, 12, 13, and 20—bromfenac
`concentration .......................................................................... 41
`Claims 5 and 22 ...................................................................... 43
`3.
`Claims 11, 15-17, and 21 ........................................................ 44
`4.
`Claims 3-5 and 11—tyloxapol concentration range ........... 46
`5.
`Claims 6, 15-17, and 20-22 – tyloxapol concentration ........ 48
`6.
`Claims 12-14—tyloxapol concentration ............................... 51
`7.
`Claims 7-10, 13, 14, 16 and 17—additives ........................... 53
`8.
`Claims 9 and 10—pH ............................................................. 54
`9.
`C. Objective Indicia of Nonobviousness .............................................. 55
`1.
`No Unexpected Results Over the Closest Prior Art ............ 56
`2.
`Other Objective Indicia ......................................................... 58
`IX. CONCLUSION ........................................................................................... 60
`
`
`
`
`
`
`
`
`
`
`ii
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`Petitioners’ Exhibit List
`
`Description
`
`Sawa et al., U.S. Patent No. 8,129,431 B2, “Aqueous Liquid
`Preparation Containing 2-Amino-3-(4-Bromobenzoyl) Phenylacetic
`Acid”
`
`Exhibit
`#
`
`1001
`
`1002 Certified English translation of Hara, Yoshiyuki, “Bromfenac sodium
`hydrate,” Clinics & Drug Therapy 19:1014-1015 (2002)
`
`1003 Declaration of Paul A. Laskar, Ph.D.
`
`1004 Ogawa et al., U.S. Patent No. 4,910,225 “Locally Administrable
`Therapeutic Composition for Inflammatory Disease”
`
`1005
`
`Desai et al., U.S. Patent No. 5,603,929, “Preserved Ophthalmic Drug
`Compositions Containing Polymeric Quaternary Ammonium
`Compounds”
`
`1006 Desai, et al., U.S. Patent No. 5,558,876, “Topical Ophthalmic Acidic
`Drug Formulations”
`
`1007
`
`1008
`
`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.
`
`1009
`
`Sallmann et al., U.S. Patent No. 6,107,343, “Ophthalmic And Aural
`Compositions Containing Diclofenac Potassium”
`
`1010
`
`Guttman et al., “Solubilization of Anti-inflammatory steroids by
`Aqueous Solutions of Triton-WR-1339,” Journal of Pharmaceutical
`Sciences 50: 305-307 (1961)
`
`
`
`iii
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`1011
`
`Fu et al., Australian Patent No. AU-B-22042/88, “Preservative System
`For Ophthalmic Formulations”
`
`1012
`
`1013
`
`1014
`
`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
`
`Kapin, et al., International Patent No. WO 2002/13804, “Method For
`Treating Angiogenesis-Related Disorders Using Benzoyl Phenylacetic
`Acid”
`
`1017
`
`Flach, Allan., “Topical Nonsteroidal Antiinflammatory Drugs for
`Ophthalmic Uses,” Ophthalmic NSAIDS: 77-83 (1996)
`
`1018
`
`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)
`
`1019 Bergamini et al., U.S. Patent No. 5,597,560, “Diclofenac And
`Tobramycin Formulations For Ophthalmic And Otis Topical use”
`
`1020
`
`Wong, Michelle, International Patent No. WO 94/15597, “Ophthalmic
`Compositions Comprising Benzyllauryldimethylammonium Chloride”
`(filed January 11, 1993); issued July 21, 1994)
`
`
`
`iv
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`1021 Reddy, Indra K., Ocular Therapeutics and Drug Delivery: A Multi-
`Disciplinary Approach: 42-43, 390 (1996)
`
`1022
`
`Story, M., et al., European Patent No. 0274870, “Micelles containing a
`non-steroidal antiinflammatory compound” (filed December 12, 1987;
`issued July 7, 1988)
`
`1023
`
`“Borax (Sodium tetraborate),” Biochemicals and Reagents: 175,
`Sigma-Aldrich (2000-2001)
`
`1024
`
`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)
`
`1025
`
`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)
`
`1026 Aviv, H., International Patent No. WO 94/05298, “Submicron
`Emulsions as Ocular Drug Delivery Vehicles”
`
`1027 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)
`
`v
`
`1028
`
`1029
`
`1030
`
`1031
`
`
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`1032
`
`1033
`
`1034
`
`"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
`
`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 XibromTM
`QD (once-daily), News Release, ISTA Pharmaceuticals (December 20,
`2007)
`
`1035
`
`"Acular®" and "AzoptTM," Physician’s Desk Reference 54: 486-487,
`491-492 (2000)
`
`1036 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)
`
`FDA approved "ALREXTM
`(loteprednol etabonate ophthalmic
`suspension) 0.2% Product Label," U.S. Approval: 1998, Bausch &
`Lomb Pharmaceuticals
`
`FDA approved "LOTEMAXTM (loteprednol etabonate ophthalmic
`suspension) 0.5% Product Label," U.S. Approval: 1998, Bausch &
`Lomb Pharmaceuticals
`
`"TOBRADEX®" Physician’s Desk Reference 54: 490 (2000)
`
`vi
`
`1037
`
`1038
`
`1039
`
`1040
`
`1041
`
`
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`1042
`
`"Alomide® 0.1%" Physician’s Desk Reference 50: 469 (1996)
`
`1043 Kawabata et al., Canadian Patent No. CA 2 383 971 A1, "Prophylactic
`and Therapeutic Medicaments for Ophthalmic Uses"
`
`1044
`
`1045
`
`1046
`
`Johnson, R., et al., U.S. Patent No. 2,880,130, "Anti-Inflammatory
`Steroid Solutions"
`
`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)
`
`1047 Ostrovskii, V.A., et al., "Acid-base properties of 5-substituted
`tetrazoles," Chemistry of Heterocyclic Compounds 17: 412-416 (1981)
`
`1048
`
`FDA approved "XIBROMTM (bromfenac ophthalmic solution, .09%)
`Product Label," ISTA Pharmaceuticals, Inc.
`
`1049
`
`1050
`
`1051
`
`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 "PROLENSATM (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:
`18091813, 1864-1866, The United States Pharmacopeial Convention,
`Inc. (1999)
`
`1052 Ali, et al., U.S. Patent No. 6,071,904, "Process for Manufacturing
`Ophthalmic Suspensions"
`
`
`
`vii
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`1053 Curriculum Vitae of Paul A. Laskar, Ph.D.
`
`1054 Declaration of Dr. M. Jayne Lawrence
`
`1055 Curriculum Vitae of Dr. M. Jayne Lawrence
`
`
`
`
`
`viii
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`I.
`
`INTRODUCTION
`
`Lupin Ltd. and Lupin Pharmaceuticals, Inc. (collectively, “Lupin”;
`
`“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. InnoPharma Licensing, Inc., et al. v. Senju Pharmaceutical Co., Ltd.,
`
`et al., IPR2015-00903 (Paper 15). In its Decision, the Board found that Petitioner
`
`InnoPharma Licensing, Inc. (“InnoPharma”) 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
`U.S. Patent No. 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
`U.S. Patent No. 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,”
`
`(Continued...)
`
`
`
`3
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 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
`
`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).
`
`________________________
`
`then it is benzalkonium chloride (“BAC”). (EX1001, 12:6-7) (emphasis added).
`
`Thus, BAC is an optional component of the aqueous liquid preparation of claim 1,
`
`since claim 1 also encompasses preparations “when a quaternary ammonium
`
`compound is not included.”
`
`
`
`4
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`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; EX1054,
`
`¶¶ 27-29). Each 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; EX1054, ¶¶ 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
`
`
`
`3 This Petition is accompanied by the Declaration of Paul A. Laskar, Ph.D.
`
`(Laskar Dec. (EX1003)), and the declaration of Dr. M. Jayne Lawrence (Lawrence
`
`Dec. (EX1054)).
`
`
`
`5
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`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; EX1054, ¶¶ 32, 34-37, 39). Notably, the prior art
`
`taught that tyloxapol was effective in stabilizing NSAIDs, like bromfenac.
`
`(EX1003, ¶ 37; EX1054, ¶ 37; EX1016, 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; EX1054, ¶¶ 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
`
`
`
`6
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`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.
`
`
`
`’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.
`
`
`
`7
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`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`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; EX1054, ¶¶ 55-58). A person of ordinary skill in the
`
`art at the time (“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; EX1054, ¶¶ 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
`
`
`
`8
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`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`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;
`
`EX1054, ¶ 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; EX1054, ¶ 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 (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; EX1054, ¶ 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.
`
`
`
`9
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`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`(“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 as this Petition is being filed concurrently
`
`with a Motion to Join the IPR proceeding instituted on August 7, 2015 (IPR2015-
`
`00903). 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 Office is authorized to charge the
`
`required fee, and any fee deficiencies and credit overpayments, to Deposit Acct.
`
`No. 05-1323 (Customer ID No. 23911).
`
`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
`
`
`
`10
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`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`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)). Thus, filing a Paragraph IV
`
`certification does not foreclose Petitioner’s access to an IPR under 35 U.S.C. §
`
`315(a)(1).
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))
`
`A. Real Party-In-Interest (37 C.F.R. § 42.8(b)(1))
`
`Petitioners Lupin Ltd. and Lupin Pharmaceuticals, Inc. are the real parties-
`
`in-interest.
`
`
`
`11
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`B. Related Matters (37 C.F.R. § 42.8(b)(2))
`
`1.
`
`Judicial Matters
`
`Petitioner is aware of the following district court actions which involve the
`
`’431 patent:
`
`•
`
`•
`
`•
`
`•
`
`
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. Lupin, Ltd. and Lupin Pharmaceuticals, Inc.,
`
`C.A. No. 1:14-CV-00667-MAS-LHG (D.N.J. filed Jan. 31, 2014);
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. Metrics, Inc., Pharmaceuticals, Inc., Mayne
`
`Pharma Group Limited, Mayne Pharma (USA), INC., and Coastal
`
`Pharmaceuticals, Inc., C.A. No. 1:14-cv-03962-JBS-KMW (D.N.J. filed
`
`Jun. 20, 2014, closed July 1, 2015);
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. Metrics, Inc., Mayne Pharma Group Limited and
`
`Mayne Pharma (USA), Inc., C.A. No. 1:14-cv-04964-JBS-KMW (D.N.J.
`
`filed Aug. 7, 2014, closed May 4, 2015);
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. Metrics, Inc., Coastal Pharmaceuticals, Inc.,
`
`12
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`Mayne Pharma Group Limited and Mayne Pharma (USA), Inc., C.A. No.
`
`4:14-cv-00141-BO (E.D.N.C. filed Aug. 8, 2014, closed May 6, 2015);
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. InnoPharma Licensing, Inc., InnoPharma
`
`Licensing, LLC, InnoPharma, Inc., and InnoPharma, LLC, C.A. No. 1:14-
`
`cv-06893-JBS-KMW (D.N.J. filed Nov. 3, 2014);
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. Apotex Inc. and Apotex Corp., C.A. No. 1:15-cv-
`
`00336-JBS-KMW (D.N.J. filed Jan. 16, 2015, closed May 19, 2015);
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. Paddock Laboratories, LLC L. Perrigo
`
`Company, and Perrigo Company., C.A. No. 1:15-cv-00337-JBS-KMW
`
`(D.N.J. filed Jan. 16, 2015, closed June 5, 2015);
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. Paddock Laboratories, LLC L. Perrigo
`
`Company, and Perrigo Company., C.A. No. 1:15-cv-00087-SLR (D. Del.
`
`filed Jan. 26, 2015, closed June 8, 2015);
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. InnoPharma Licensing, Inc., InnoPharma
`
`13
`
`•
`
`•
`
`•
`
`•
`
`•
`
`
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`Licensing, LLC, InnoPharma, Inc., and InnoPharma, LLC, C.A. No. 1:15-
`
`cv-03240-JBS-KMW (D.N.J. filed May 8, 2015);
`
`•
`
`Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`Pharma Holdings Corp. v. Watson Laboratories, Inc., Actavis, Inc., Actavis
`
`Pharma Inc., C.A. No. 1:15-cv-05591-JBS-KMW (D.N.J. filed July 16,
`
`2015).
`
`2.
`
`Administrative Matters
`
`The ’431 patent is presently the subject of an instituted IPR styled
`
`InnoPharma Licensing, Inc., InnoPharma Licensing LLC, InnoPharma Inc.,
`
`InnoPharma LLC, Mylan Pharmaceuticals Inc., and Mylan Inc. v. Senju
`
`Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb Pharma
`
`Holdings Corp., which is assigned Case No. IPR2015-00903. Petitioner seeks
`
`joinder with that IPR, for the reasons expressed in the concurrently filed Motion for
`
`Joinder under 35 U.S.C. § 315(c), 37 C.F.R. §§ 42.22 and 42.122(b).
`
`U.S. Patent No. 8,669,290 (“the ’290 patent”), which issued on March 6,
`
`2012 and claims priority to a parent application of the ’431 patent is the subject of
`
`an instituted IPR styled InnoPharma Licensing, Inc., InnoPharma Licensing LLC,
`
`InnoPharma Inc., InnoPharma LLC, Mylan Pharmaceuticals Inc., and Mylan Inc.
`
`v. Senju Pharmaceutical Co., Ltd., Bausch & Lomb, Inc., and Bausch & Lomb
`
`
`
`14
`
`

`

`Petition for Inter Partes Review of
`U.S. Patent No. 8,129,431
`
`
`Pharma Holdings Corp., which is assigned Case No. IPR2015-00902. The ’290
`
`patent is also the subject of pending IPR styled Lupin Ltd. and Lupin
`
`Pharmaceuticals, Inc. v. Senju Pharmaceutical Co., Ltd., which is assigned Case
`
`No. IPR2015-01099.
`
` U.S. Patent No. 8,497,304, a division of the ’431 patent, issued on July 30,
`
`2013 and claims priority to the application that issued as the ’431 patent.
`
` U.S. Patent No. 8,754,131 (“the ’131 patent”), which is a division of the
`
`’290 patent, issued on June 17, 2014 and claims priority to the application that
`
`issued as the ’431 patent is the subject of a pending IPR styled Lupin Ltd