`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________________
`
`METRICS, INC.
`Petitioner
`
`v.
`
`SENJU PHARMACEUTICAL CO., LTD.
`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.: IPR2014-01041
`_____________________
`
`SECOND CORRECTED 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 USPN 8,129,431
`
`TABLE OF CONTENTS
`
`TABLE OF AUTHORITIES ................................................................................ iv
`
`I.
`
`INTRODUCTION ........................................................................................ 1
`
`II. OVERVIEW .................................................................................................. 1
`
`A.
`
`B.
`
`The ’431 Patent ..................................................................................... 2
`
`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 ................................................................................................. 5
`
`III. STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL
`STATEMENTS ............................................................................................. 8
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) ................................ 12
`
`A.
`
`B.
`
`Each Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) ......................... 12
`
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) ............................ 12
`
`1.
`
`2.
`
`Judicial Matters ........................................................................ 12
`
`Administrative Matters ............................................................ 12
`
`C.
`
`Designation of Lead and Back-Up Counsel (37 C.F.R. §
`42.8(b)(3)) ........................................................................................... 13
`
`D. Notice of Service Information (37 C.F.R. § 42.8(b)(4)) ..................... 13
`
`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 .......................... 14
`
`ii
`
`
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`
`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 .............................................................. 19
`
`1.
`
`Ogawa in View of Sallmann .................................................... 19
`
`B.
`
`Dependent Claims 2-17 and 19-22 ...................................................... 35
`
`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 ............................................................................ 37
`
`Claims 5 and 22 ........................................................................ 40
`
`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 ............ 43
`
`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
`
`IX. CONCLUSION ........................................................................................... 55
`
`CERTIFICATION OF SERVICE
`
`iii
`
`
`
`
`
`Cases
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`TABLE OF AUTHORITIES
`
`Amneal Pharmaceuticals, LLC v. Supernus Pharmaceuticals, Inc.,
`IPR2013-00368, Paper 8 (December, 17, 2013) .......................................... 10, 51
`
`Chapman v. Casner,
`315 F. App’x 294 (Fed. Cir. 2009) ................................................... 38, 39, 42, 50
`
`Ecolab, Inc. v. FMC Corp.,
`569 F.3d 1335 ..................................................................................................... 14
`
`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 454, (C.C.P.A. 1955) ........................................................................... 47
`
`In re De Blauwe,
`736 F.2d 699 (Fed. Cir. 1984) ............................................................................ 51
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .............................................................. 41, 47, 52
`
`In re Woodruff,
`919 F.2d 1575 (Fed. Cir. 1990) .......................................................................... 43
`
`Iron Grip Barbell Co., Inc. v. USA Sports, Inc.,
`392 F.3d 1317 (Fed. Cir. 2004) ........................................................ 38, 41, 42, 48
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) .................................................................................. 1, 16, 26
`
`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) .......................................................................... 54
`
`iv
`
`
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`
`Purdue Pharma Prods. L.P. v. Par Pharm., Inc.,
`377 F. App’x 978 (Fed. Cir. 2010) ..................................................................... 54
`
`Sinclair & Carroll Co., v. Interchemical Corp.,
`325 U.S. 327 (1945) ............................................................................................ 25
`
`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) .......................................................................... 29
`
`Tokai Corp. v. Eason Enters., Inc.,
`632 F.3d 1358 (Fed. Cir. 2011) .......................................................................... 55
`
`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) ............................................................................................passim
`
`35 U.S.C. § 112 .................................................................................................passim
`
`Regulations
`
`37 C.F.R. § 42.106(a) ................................................................................................. 8
`
`v
`
`
`
`
`
` Exhibit
`#
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Petitioner’s Exhibit List
`
`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"
`
`Hara, Yoshiyuki , "Bromfenac sodium hydrate," Clinics & Drug
`Therapy 19:1014-1015 (2002)
`
`Second Corrected Declaration of Uday B. Kompella, 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 "BROMDAY™ (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"
`
`vi
`
`
`
`
`
` Exhibit
`#
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Description
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`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?A
`ppl_No=203168&TABLE1=OB_Rx, last accessed on February 14,
`2014
`
`“ophthalmic” Webster’s Deluxe Unabridged Dictionary: 1254,
`Webster’s New Twentieth Century Dictionary, Simon and Schuster
`(1979)
`
`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)
`
`1019
`
`Bergamini et al., U.S. Patent No. 5,597,560, "Diclofenac And
`Tobramycin Formulations For Ophthalmic And Otis Topical use"
`
`vii
`
`
`
`
`
` Exhibit
`#
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Description
`
`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)
`
`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)
`
`1029
`
`Selected pages from the file history of U.S. Patent No. 8,129,431,
`March 28, 2005 Amendment.
`
`viii
`
`
`
`
`
` Exhibit
`#
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Description
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`1037
`
`1038
`
`"Duract™," 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?A
`ppl_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
`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).
`
`ix
`
`
`
`
`
` Exhibit
`#
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Description
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`1049
`
`FDA approved "ALREX™ (loteprednol etabonate ophthalmic
`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".
`
`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.
`
`x
`
`
`
`
`
` Exhibit
`#
`
`1050
`
`1051
`
`1052
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`Description
`
`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".
`
`1053
`
`Curriculum Vitae of Dr. Uday B. Kompella, Ph.D.
`
`xi
`
`
`
`
`I.
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`INTRODUCTION
`Metrics, Inc. (“Petitioner”) petitions for Inter Partes Review, 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”).
`
`II. OVERVIEW
`
`Claims 1-22 of the ’431 patent are unpatentable for failing to satisfy the
`
`nonobviousness requirement of 35 U.S.C. § 103. The alleged “inventions” involve
`
`only the (i) “simple and obvious substitution of one known element for another to
`
`obtain predictable results” over what was taught in the prior art; (ii) “choosing
`
`from a finite number of identified, predictable solutions,” with a reasonable
`
`expectation of success; and/or (iii) obvious modification of prior art teachings,
`
`with a reasonable expectation of success. Thus, these claims fall squarely, and
`
`fatally, under KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007).
`
`In essence 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). Tyloxapol was a known non-ionic surfactant in aqueous
`
`formulations of NSAIDs and bromfenac was a known NSAID previously
`
`formulated with another non-ionic surfactant, polysorbate 80. Thus, the inventors
`
`of the aqueous preparations of the challenged claims of the ’431 patent simply
`
`1
`
`
`
`
`switched tyloxapol for polysorbate 80 (both well-known non-ionic surfactants). Or
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`viewed another way, the 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.
`
`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
`2-amino-3-(4-bromobenzoyl)-
`component
`is
`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.
`
`2
`
`
`
`
`(EX1001, 11:66-12:101) (emphasis added).
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`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
`
`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
`
`
`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
`
`claim 1, since claim 1 also encompasses preparations “when a quaternary
`
`ammonium compound is not included.”
`
`3
`
`
`
`
`formulation, including a preservative, buffer, thickener, stabilizer, chelating agent,
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`and pH controlling agent, or an additional active ingredient. (EX1001, claims 7
`
`and 8 and 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 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 BAC in aqueous ophthalmic formulations in a way that
`
`weakens the preservative efficacy of BAC. 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), BROMDAY Prescribing Information (EX1008)).
`
`
`3 This Petition is accompanied by the Second Corrected Declaration of
`
`Professor Uday B. Kompella, Ph.D. (Kompella Dec. (EX1003)).
`
`4
`
`
`
`
`
`Petition for Inter Partes Review of USPN 8,129,431
`
`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,
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`8:1-15).
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`Tyloxapol, like polysorbate 80, was successfully used to stabilize aqueous
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`ophthalmic formulations as early as the 1960’s. (EX1009, 8:1-15; EX1010, 4:2:2-
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`4; EX1003, ¶¶32, 34-37, 39). Notably, the prior art taught that tyloxapol was
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`effective in stabilizing NSAIDs, like bromfenac. (EX1003,¶37; EX1016, 6:8-9,
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`7:13-22, Formulation 3, EX1011.). The prior art also disclosed examples where
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`tyloxapol is a preferred non-ionic surfactant for use in ophthalmic formulations
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`containing acidic NSAIDs, like bromfenac (EX1009, 4:62; EX1003, ¶¶34, 39, 56),
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`and where tyloxapol was superior to polysorbate 80 as a surfactant in aqueous
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`liquid formulations of an acidic compound. (EX1012, 7:20-43). In the prior art a
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`finite number of non-ionic surfactants, including tyloxapol and polysorbate 80, had
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`been used in approved ophthalmic formulations. (EX1012, 4:51-63; EX1009,
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`4:52-62).
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`C. The Differences Between the Challenged Claims and the Prior Art
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`Petitioner relies on its primary prior art references, the Ogawa patent
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`5
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`(EX1004) and the Sallmann patent (EX1009) in combination with each other.
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`Petition for Inter Partes Review of USPN 8,129,431
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`Each discloses a prior art ophthalmic formulation of an NSAID, BAC and a non-
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`ionic surfactant, similar to what is claimed in the ’431 patent. The challenged
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`claims of the ’431 patent differ from prior art aqueous liquid ophthalmic
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`formulations of an NSAID only in the replacement of bromfenac for another
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`NSAID, or alternately, in the replacement of tyloxapol for another non-ionic
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`surfactant (polysorbate 80), as illustrated in the following chart.
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`
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`’431 Patent
`Claim 1
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`Ogawa
`Example 6
`(EX1004)
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`NSAID
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`Bromfenac
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`Bromfenac
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`Sallmann
`Example 2
`(EX1009)
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`Diclofenac
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`Surfactant
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`Tyloxapol
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`Polysorbate 80
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`Tyloxapol
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`BAC
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`Optional
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`Yes
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`Yes
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`
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`
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`When viewed against the prior art, what becomes clear is that the inventors
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`of the ’431 patent did nothing more than swap one well-known component from a
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`prior art formulation with another component known to be used for the same
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`purpose. Thus, the inventors of the aqueous preparations of the challenged claims
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`of the ’431 patent simply switched tyloxapol for polysorbate 80 (both well-known
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`non-ionic surfactants). Alternately, the inventors merely switched bromfenac for
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`diclofenac (both well-known structurally similar NSAIDs). Swapping known
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`6
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`alternatives from the prior art is not innovation. All the inventors of the ’431
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`Petition for Inter Partes Review of USPN 8,129,431
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`patent accomplished was the mere obvious replacement of known components,
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`according to their known functions, to achieve predictable results. (EX1003, ¶¶55-
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`58). A person of ordinary skill in the art (“POSA”) could have readily performed
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`these simple component substitutions—tyloxapol for polysorbate 80 or bromfenac
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`for diclofenac—because the functions of these components were well known in the
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`art and the results were predictable. (EX1003, ¶¶55-58).
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`And, finally, the prior art disclosed only a finite number of non-ionic
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`surfactants for ophthalmic formulations, such that it would have been obvious to
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`try substituting any of these known non-ionic surfactants (including tyloxapol) for
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`polysorbate 80 to modify the teachings of Ogawa to arrive predictably at the
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`claimed inventions, with a reasonable expectation of success.
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`Sallmann disclosed ophthalmic formulations containing NSAIDs, including
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`diclofenac and ketorolac, together with ethoxylated octylphenol surfactants,
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`including tyloxapol, as the non-ionic surfactant. (EX1003, ¶53). Sallmann’s
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`ophthalmic formulation also included the preservative BAC. A POSA, therefore,
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`would have been motivated to substitute bromfenac for diclofenac in Sallmann’s
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`ophthalmic formulations to obtain predictable results because of the structural and
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`functional similarities between bromfenac and diclofenac (EX1002, 3:2:2;
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`EX1003, ¶62), including their similar interaction with BAC, and the known
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`preference for bromfenac over diclofenac (EX1002). The prior art also only
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`Petition for Inter Partes Review of USPN 8,129,431
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`disclosed a finite number of NSAIDs for ophthalmic application, such that it would
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`have been obvious to try substituting any of these known anti-inflammatory
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`compounds (including bromfenac) for diclofenac to modify the teachings of
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`Sallmann and to arrive predictably at the claimed inventions, with a reasonable
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`expectation of success. (EX1002, 2:2:3-3:1:1; EX1003, ¶62).
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`The subject matter of many of the challenged claims of the ‘431 patent is
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`commercially embodied by Prolensa®, a product marketed by Bausch & Lomb Inc.
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`(“B&L”). (EX1013; EX1014). The patent owner previously owned patent
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`protection for two other bromfenac ophthalmic products—Xibrom® and
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`Bromday®—in the United States, both of which were covered by the prior art
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`Ogawa patent (EX1004), and over which the ’431 patent is obvious. And while
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`some dependent claims of the ’431 patent recite more particular excipients,
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`concentration ranges, and pH ranges, these nominal differences fall far short of
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`imparting patentability as discussed below.
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`III. STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL STATEMENTS
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`Petitioner certifies that (1) the ’431 patent is available for IPR; and (2)
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`Petitioner is not barred or estopped from requesting IPR of any claim of the ’431
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`patent on the grounds identified herein. This Petition is filed in accordance with 37
`
`CFR § 42.106(a). Concurrently filed herewith are a Power of Attorney and an
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`
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`Exhibit List pursuant to § 42.10(b) and § 42.63(e), respectively. The required fee
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`Petition for Inter Partes Review of USPN 8,129,431
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`is paid through online credit card payment. The Office is authorized to charge fee
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`deficiencies and credit overpayments to Deposit Acct. No. 04-1679 (Customer ID
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`No. 39290).
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`Petitioner is aware that counsel for the patent owner has previously taken the
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`position that the PTAB should exercise its discretion and deny IPR petitions filed
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`by ANDA applicants. Specifically, patent owner’s counsel has asserted that the
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`filing of a Paragraph IV Certification by an ANDA applicant is the equivalent of
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`filing a civil action challenging the validity of a patent, and as such prohibits the
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`applicant from filing a petition for IPR pursuant to 35 U.S.C. 315(a)(1). However,
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`such a position is contrary to the express terms of the IPR provisions and contrary
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`to the stated purpose of AIA. Should the patent owner assert a similar challenge in
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`its Preliminary Patent Owner Response, Petitioner requests that the PTAB set an
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`expedited supplemental briefing schedule to afford the Petitioner due process to
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`fully respond to such assertions.
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`As a preliminary matter, the provisions of the AIA apply equally to Hatch
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`Waxman Act disputes unless otherwise exempted. For example, with respect to
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`the AIA provisions of joinder, the statute expressly exempts Hatch Waxman
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`271(e)(2) cases:
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` § 299 (a) Joinder of accused infringers. With respect
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`Petition for Inter Partes Review of USPN 8,129,431
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`to any civil action arising under any Act of Congress
`relating to patents, other than an action or trial in which
`an act of infringement under 271(e)(2) has been pled…
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`Thus, because Congress has indicated its intention to exempt some provision of the
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`AIA for Hatch Waxman disputes, Congress’ intention to allow the IPR provisions
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`to fully apply to Hatch Waxman disputes is clear. As a result, the PTAB has
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`previously granted Petitions for IPR filed by ANDA applicants. See Amneal
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`Pharmaceuticals, LLC v. Supernus Pharmaceuticals, Inc., IPR2013-00368, 00371
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`and 00372; Ranbaxy Laboratories, Ltd v. Vertex Pharms., Inc., IPR2013-0024.
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`Importantly, an invalidity determination by the PTAB that is affirmed by the
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`Federal Circuit is immediately binding on a federal district court presiding over a
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`case involving those same claims. See Fresenius USA Inc. v. Baxter Int’l Inc., 721
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`F.3d 1330 (Fed. Cir. 2013). Given the 30 month stay automatically provided upon
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`the filing of an infringement action by a patent owner, the expedited proceeding of
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`an IPR may be a particularly desirable route for ANDA applicants and may assist
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`to resolve the underlying infringement action within the 30 month stay based on
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`the binding effect of the PTAB invalidity decision.
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`Patent Owner’s anticipated argument that the filing of a Paragraph IV
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`Certification challenging the validity of a patent is somehow equivalent to filing a
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`declaratory judgment action challenging validity is without support. The filing of a
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`Paragraph IV Certification is deemed to be an act of infringement pursuant to
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`Petition for Inter Partes Review of USPN 8,129,431
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`271e(2), but it is not the equivalent of filing a lawsuit challenging validity. The
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`Hatch Waxman statute imposes stringent timelines in which the ANDA applicant
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`must provide notice of the Paragraph IV Certification to the patent owner which
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`opens the window for the patent owner to file a lawsuit asserting
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`infringement. In support of its argument, the patent owner has previously
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`identified the AIA’s “supplemental examinations” provision as evidence that
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`Paragraph IV Certification is a functional equivalent of a declaratory judgment
`
`action. However, the substantive examination provision of AIA provides that once
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`a patent owner receives notice of particularly plead facts regarding invalidity or
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`unenforceability, either in a defense to an infringement complaint, or through
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`notice of a Paragraph IV Certification, the patent owner is no longer permitted to
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`seek supplemental examination of its patent. Thus, the AIA does not treat a
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`Paragraph IV certification as the equivalent of filing a declaratory judgment action,
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`but rather considers both as providing adequate notice to a patent owner to prohibit
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`the subsequent filing of supplemental examination by the patent owner.
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`Thus, there is no