Filed on behalf of Petitioner Metrics, Inc. Paper No. 6
`Filed: July 29, 2014
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`METRICS, INC., MAYNE PHARMA, and
`JOHNSON MATTHEY, INC.
`Petitioners
`
`v.
`
`SENJU PHARMACEUTICAL CO., LTD., BAUSCH & LOMB, INC., and
`BAUSCH & LOMB PHARMA HOLDINGS CORP.
`Patent Owners
`
`
`Case IPR2014-01041
`Patent 8,129,431 Case
`
`
`Before PATRICK E. BAKER, Trial Paralegal
`
`CORRECTED Petition for Inter Partes Review of U.S. Patent No. 8,129,431
`Pursuant to the Patent Trial and Appeal Board’s July 22, 2014 Notice of
`Filing Date Accorded to Petition and Time for Filing Patent Owner
`Preliminary Response
`
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`C. 
`
`C. 
`
`TABLE OF CONTENTS
`TABLE OF AUTHORITIES ................................................................................... iii 
`I. 
`INTRODUCTION .......................................................................................... 1 
`II. 
`OVERVIEW ................................................................................................... 1 
`A. 
`The ’431 Patent ..................................................................................... 2 
`B. 
`The Scope and Content of the Prior Art ................................................ 4 
`1. 
`Aqueous Ophthalmic Preparations of Bromfenac ..................... 4 
`2. 
`Tyloxapol and Related Surfactants in NSAID
`Aqueous Ophthalmic Preparations ............................................ 5 
`The Differences Between the Challenged Claims and the
`Prior Art ................................................................................................. 6 
`STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL STATEMENTS ..... 9 
`III. 
`IV.  MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)) ................................... 12 
`A. 
`Each Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) ......................... 12 
`B. 
`Notice of Related Matters (37 C.F.R. § 42.8(b)(2)) ............................ 12 
`1. 
`Judicial Matters ........................................................................ 12 
`2. 
`Administrative Matters ............................................................ 12 
`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 
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`REASONS THEREFOR (37 C.F.R. § 42.22(a)) ......................................... 13 
`VI.  THE ’431 PATENT AND CLAIM CONSTRUCTION .............................. 14 
`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 
`Dependent Claims 2-17 and 19-22 ...................................................... 36 
`1. 
`Claims 2-6, 11-17, and 19-22 – sodium salt of
`bromfenac ................................................................................. 36 
`
`V. 
`
`B. 
`
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`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`2. 
`
`Claims 3, 4, 6, 12, 13, and 20 – bromfenac
`concentration ............................................................................ 38 
`Claims 5 and 22 ........................................................................ 40 
`3. 
`Claims 11, 15-17, and 21 ......................................................... 41 
`4. 
`Claims 3-5 and 11 – tyloxapol concentration range ................ 43 
`5. 
`Claims 6, 15-17, and 20-22 – tyloxapol concentration ............ 45 
`6. 
`Claims 12-14 – tyloxapol concentration .................................. 48 
`7. 
`Claims 7-10, 13, 14, 16 and 17- additives ............................... 50 
`8. 
`Claims 9 and 10 - pH ............................................................... 51 
`9. 
`Objective Indicia of Nonobviousness ................................................. 52 
`1. 
`No Unexpected Results Over the Closest Prior Art. ................ 52 
`2. 
`Other Objective Indicia ............................................................ 54 
`IX.  CONCLUSION ............................................................................................. 57 
`X.  Appendix: Dependent Claims Would Have Been Obvious Over the Prior
`Art ................................................................................................................... 1 
`CERTIFICATION OF SERVICE
`
`C. 
`
`ii
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`TABLE OF AUTHORITIES
`
`Cases
`
`Amneal Pharmaceuticals, LLC v. Supernus Pharmaceuticals, Inc.,
`IPR2013-00368, Paper 8 (December, 17, 2013) ................................................ 50
`
`Asyst Techs., Inc. v. Emtrak, Inc.,
`544 F.3d 1310 (Fed. Cir. 2008) .......................................................................... 27
`
`Chapman v. Casner,
`315 F. App’x 294 (Fed. Cir. 2009) ................................................... 36, 37, 41, 49
`
`Ecolab, Inc. v. FMC Corp.,
`569 F.3d 1335 ..................................................................................................... 11
`
`Friskit, Inc. v. Real Networks, Inc.,
`306 F. App’x 610 (Fed. Cir. 2009) ..................................................................... 52
`
`Galderma Labs., L.P. v. Tolmar, Inc.,
`737 F.3d 731 (Fed. Cir. 2013) .......................................................... 37, 39, 41, 47
`
`In re Aller,
`220 F.2d 454, (C.C.P.A. 1955) ........................................................................... 46
`
`In re De Blauwe,
`736 F.2d 699 (Fed. Cir. 1984) ............................................................................ 50
`
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .............................................................. 40, 46, 51
`
`In re Woodruff,
`919 F.2d 1575 (Fed. Cir. 1990) .......................................................................... 41
`
`Iron Grip Barbell Co., Inc. v. USA Sports, Inc.,
`392 F.3d 1317 (Fed. Cir. 2004) ........................................................ 37, 39, 41, 47
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) .................................................................................. 1, 14, 23
`
`Newell Cos., Inc. v. Kenney Mfg. Co.,
`864 F.2d 757 (Fed. Cir. 1988) ............................................................................ 49
`
`iii
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006) .......................................................................... 53
`
`
`
`
`
`Purdue Pharma Prods. L.P. v. Par Pharm., Inc.,
`377 F. App’x 978 (Fed. Cir. 2010) ..................................................................... 53
`
`Sinclair & Carroll Co., v. Interchemical Corp.,
`325 U.S. 327 (1945) ............................................................................................ 22
`
`Stratoflex, Inc. v. Aeroquip Corp.,
`713 F.2d 1530 (Fed. Cir. 1983) .................................................................... 52, 53
`
`Sundance, Inc. v. DeMonte Fabricating Ltd.,
`550 F.3d 1356 (Fed. Cir. 2008) .......................................................................... 27
`
`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) .............................................................. 23, 27, 31
`
`Statutes
`
`35 U.S.C. § 102(b) ............................................................................................passim
`
`35 U.S.C. § 112 .................................................................................................passim
`
`Regulations
`
`37 C.F.R. § 42.106(a) ................................................................................................. 9
`
`iv
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Corrected Petitioner’s Exhibit List
`
`Metrics
`Exhibit #
`
`Description
`
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`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)
`
`Declaration of Professor Uday B. Kompella, Ph.D., replaced with
`revised Exhibit 1087, noting citations to the revised Exhibits.
`
`Ogawa et al., U.S. Patent No. 4,910,225, "Locally Administrable
`Therapeutic Composition for Inflammatory Disease". This exhibit
`was replaced with revised Exhibit 1054, adding sequential numbering
`to each page of the exhibit.
`
`Desai et al., U.S. Patent No. 5,603,929, "Preserved Ophthalmic Drug
`Compositions Containing Polymeric Quaternary Ammonium
`Compounds". This exhibit was replaced with revised Exhibit 1055,
`adding sequential numbering to each page of the exhibit.
`
`Desai, et al., U.S. Patent No. 5,558,876, "Topical Ophthalmic Acidic
`Drug Formulations". This exhibit was replaced with revised Exhibit
`1056, adding sequential numbering to each page of the exhibit.
`
`Certified English translation of "Bromfenac sodium hydrate" in the
`Japanese Pharmacopoeia 2001 Edition: 27-29, Yakuji Nippo Limited
`(2001). This exhibit was replaced with revised Exhibit 1057, adding
`sequential numbering to each page of the exhibit.
`
`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"
`
`v
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`1010
`
`1011
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`Description
`
`Guttman et al., "Solubilization of Anti-inflammatory steroids by
`Aqueous Solutions of Triton-WR-1339," Journal of Pharmaceutical
`Sciences 50: 305-307 (1961). This exhibit was replaced with revised
`Exhibit 1058, adding sequential numbering to each page of the
`exhibit.
`
`Fu et al., Australian Patent No. AU-B-22042/88, "Preservative
`System For Ophthalmic Formulations". This exhibit was replaced
`with revised Exhibit 1059, adding sequential numbering to each page
`of the exhibit.
`
`Yasueda et al., U.S. Patent No. 6,274,609, "Aqueous Liquid
`Pharmaceutical Composition Containing as Main Component
`Benzopyran Derivative". This exhibit was replaced with revised
`Exhibit 1060, adding sequential numbering to each page of the
`exhibit.
`
`"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
`
`“ophthalmic,” Webster’s Deluxe Unabridged Dictionary: 1254,
`Webster’s New Twentieth Century Dictionary, Simon and Schuster
`(1979). This exhibit was replaced with revised Exhibit 1061, adding
`sequential numbering to each page of the exhibit.
`
`Kapin, et al., International Patent No. WO 2002/13804, "Method For
`Treating Angiogenesis-Related Disorders Using Benzoyl Phenylacetic
`Acid"
`
`vi
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`Description
`
`1017
`
`1018
`
`1019
`
`1020
`
`1021
`
`1022
`
`1023
`
`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".
`This exhibit was replaced with revised Exhibit 1062, adding
`sequential numbering to each page of the exhibit.
`
`Wong, Michelle, International Patent No. WO 94/15597, “Ophthalmic
`Compositions Comprising Benzyllauryldimethylammonium
`Chloride” (filed January 11, 1993); issued July 21, 1994). This exhibit
`was replaced with revised Exhibit 1063, adding sequential numbering
`to each page of the exhibit.
`
`Reddy, Indra K., Ocular Therapeutics and Drug Delivery: A Multi-
`Disciplinary Approach: 42-43, 390 (1996). This exhibit was replaced
`with revised Exhibit 1064, adding sequential numbering to each page
`of the exhibit.
`
`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). This exhibit was replaced with revised
`Exhibit 1065, adding sequential numbering to each page of the
`exhibit.
`
`vii
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`Description
`
`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". This exhibit was
`replaced with revised Exhibit 1066, adding sequential numbering to
`each page of the exhibit.
`
`Gennaro, A., “Boric Acid,” Remington: The Science and Practice of
`Pharmacy 20: 1041, University of Sciences, United States (2000).
`This exhibit was replaced with revised Exhibit 1067, adding
`sequential numbering to each page of the exhibit.
`
`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). This
`exhibit was replaced with revised Exhibit 1068, adding sequential
`numbering to each page of the exhibit.
`
`1029*1
`
`Selected pages from the file history of U.S. Patent No. 8,129,431,
`March 28, 2005 Amendment.
`
`
`1 All exhibits listed with an asterisk are exhibits cited only in the Declaration
`
`of Professor Uday B. Kompella, Ph.D. (EX1003, replaced with EX1087).
`
`viii
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`1030*
`
`1031*
`
`1032*
`
`1033*
`
`1034*
`
`1035*
`
`1036*
`
`Description
`
`"Duract™," Physician’s Desk Reference 52:3035-3037 (1998). This
`exhibit was replaced with revised Exhibit 1069, adding sequential
`numbering to each page of the exhibit.
`
`"monohydrate," Webster’s New World Dictionary of the American
`Language: 920, New World Dictionaries / Simon and Schuster
`(1980). This exhibit was replaced with revised Exhibit 1070, adding
`sequential numbering to each page of the exhibit.
`
`"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?App
`l_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". This exhibit was
`replaced with revised Exhibit 1071, adding sequential numbering to
`each page of the exhibit.
`
`"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). This exhibit was replaced with revised Exhibit 1072,
`adding sequential numbering to each page of the exhibit.
`
`Doughty, M., "Medicines Update for optical practitioners- Part 11.,"
`Optician 5853 (223), (2002). This exhibit was replaced with revised
`Exhibit 1073, adding sequential numbering to each page of the
`exhibit.
`
`ix
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`1037*
`
`1038*
`
`1039*
`
`1040*
`
`1041*
`
`1042*
`
`1043*
`
`Description
`
`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). This exhibit was
`replaced with revised Exhibit 1074, adding sequential numbering to
`each page of the exhibit.
`
`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). This exhibit was replaced with revised Exhibit
`1075, adding sequential numbering to each page of the exhibit.
`
`FDA approved "ALREX™ (loteprednol etabonate ophthalmic
`suspension) 0.2% Product Label," U.S. Approval: 1998, Bausch &
`Lomb Pharmaceuticals. This exhibit was replaced with revised
`Exhibit 1076, adding sequential numbering to each page of the
`exhibit.
`
`FDA approved "LOTEMAX™ (loteprednol etabonate ophthalmic
`suspension) 0.5% Product Label," U.S. Approval: 1998, Bausch &
`Lomb Pharmaceuticals. This exhibit was replaced with revised
`Exhibit 1077, adding sequential numbering to each page of the
`exhibit.
`
`"TOBRADEX®" Physician’s Desk Reference 54: 490 (2000). This
`exhibit was replaced with revised Exhibit 1078, adding sequential
`numbering to each page of the exhibit.
`"Alomide® 0.1%" Physician’s Desk Reference 50: 469 (1996). This
`exhibit was replaced with revised Exhibit 1079, adding sequential
`numbering to each page of the exhibit.
`
`Kawabata et al., Canadian Patent No. CA 2 383 971 A1,
`"Prophylactic and Therapeutic Medicaments for Ophthalmic Uses".
`This exhibit was replaced with revised Exhibit 1080, adding
`sequential numbering to each page of the exhibit.
`
`x
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`1044*
`
`1045*
`
`1046*
`
`1047*
`
`1048*
`
`1049*
`
`1050*
`
`1051*
`
`Description
`
`Johnson, R., et al., U.S. Patent No. 2,880,130, "Anti-Inflammatory
`Steroid Solutions". This exhibit was replaced with revised Exhibit
`1081, adding sequential numbering to each page of the exhibit.
`
`Johnson, R., et al., U.S. Patent No. 2,880,138, "Anti-Inflammatory
`Steroid Solutions". This exhibit was replaced with revised Exhibit
`1082, adding sequential numbering to each page of the exhibit.
`
`Patani, G., et al., "Bioisoterism: A Rational Approach in Drug
`Design," Chem. Rev. 96: 3147-3176 (1996). This exhibit was replaced
`with revised Exhibit 1083, adding sequential numbering to each page
`of the exhibit.
`
`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/2009/11/18/
`2009111814br.pdf, published November 17, 2009, 1 page. This
`exhibit was replaced with revised Exhibit 1084, adding sequential
`numbering to each page of the exhibit.
`
`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). This exhibit was replaced with revised Exhibit 1085,
`adding sequential numbering to each page of the exhibit.
`
`xi
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`1052*
`
`1053*
`
`1054
`
`1055
`
`1056
`
`1057
`
`1058
`
`1059
`
`1060
`
`1061
`
`1062
`
`Description
`
`Ali, et al., U.S. Patent No. 6,071,904, "Process for Manufacturing
`Ophthalmic Suspensions". This exhibit was replaced with revised
`Exhibit 1086, adding sequential numbering to each page of the
`exhibit.
`
`Curriculum Vitae of Dr. 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).
`
`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".
`
`Yasueda et al., U.S. Patent No. 6,274,609, "Aqueous Liquid
`Pharmaceutical Composition Containing as Main Component
`Benzopyran Derivative".
`
`“ophthalmic, Webster’s Deluxe Unabridged Dictionary: 1254,
`Webster’s New Twentieth Century Dictionary, Simon and Schuster
`(1979).
`
`Bergamini et al., U.S. Patent No. 5,597,560, "Diclofenac And
`Tobramycin Formulations For Ophthalmic And Otis Topical use".
`
`xii
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`Description
`
`1063
`
`1064
`
`1065
`
`1066
`
`1067
`
`1068
`
`1069*
`
`1070*
`
`1071*
`
`1072*
`
`1073*
`
`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).
`
`"Borax (Sodium tetraborate)," Biochemicals and Reagents: 175,
`Sigma-Aldrich (2000-2001).
`
`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).
`
`"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).
`
`Yanni et al., U.S. Patent No. 5,475,034, "Topically Administrable
`Compositions Containing 3-Benzoylphenylacetic Acid Derivatives for
`Treatment of Ophthalmic Inflammatory Disorders".
`
`"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).
`
`xiii
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`1074*
`
`1075*
`
`1076*
`
`1077*
`
`1078*
`
`1079*
`
`1080*
`
`
`1081*
`
`1082*
`
`1083*
`
`Description
`
`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 "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).
`
`xiv
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`
`
`
`
`
`Metrics
`Exhibit #
`
`1084*
`
`1085*
`
`1086*
`
`1087
`
`
`Description
`
`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/2009/11/18/
`2009111814br.pdf, published November 17, 2009, 1 page.
`
`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".
`
`Declaration of Professor Uday B. Kompella, Ph.D.
`
`xv
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`I.
`
`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
`
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`switched tyloxapol for polysorbate 80 (both well-known non-ionic surfactants). Or
`
`
`
`
`
`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.
`(EX1001, 11:66-12:102) (emphasis added).
`
`
`2 Citations are as follows: X:YY-ZZ (col:lines; patent); X:Y:Z
`
`
`
`
`
`2
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`

`

` Corrected 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.3
`
`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
`
`
`(page:col:para; journal article); X:Y (page:para; journal article).
`
`3 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
`
`

`

` Corrected Petition for Inter Partes Review of USPN 8,129,431
`
`8 and 6:42-44).
`
`
`
`
`
`B.
`
`The Scope and Content of the Prior Art
`1.
`Bromfenac, like diclofenac and ketorolac, was a well-known NSAID useful
`
`Aqueous Ophthalmic Preparations of Bromfenac
`
`for treating inflammation in the eye. (EX1002, 1014:1:2; EX10034, replaced with
`
`Exhibit 1087, ¶¶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, replaced with EX1054) described an aqueous
`
`ophthalmic formulation containing (1) bromfenac, (2) polysorbate 80, and (3)
`
`BAC. (EX1004, replaced with EX1054, 9:5-10:19; see also Hara (EX1002), the
`
`Desai patents (EX1005, replaced with EX1055, and EX1006, replaced with
`
`EX1056), BRONUCK Japanese Pharmacopeia (EX1007, replaced with EX1057),
`
`BROMDAY Prescribing Information (EX1008)).
`
`
`4 This Petition is accompanied by the Declaration of Professor Uday B.
`
`Kompella, Ph.D. (Kompella Dec. (EX1003, replaced with EX1087)).
`
`
`
`4
`
`

`

`