`Filed: January 6, 2017
`
`Filed on behalf of Teva Pharmaceuticals USA, Inc.
`By: Gary J. Speier
`
`Mark D. Schuman
`
`CARLSON, CASPERS, VANDENBURGH,
`
`LINDQUIST & SCHUMAN, P.A.
`
`225 South Sixth Street, Suite 4200
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`Minneapolis, MN 55402
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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`
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`TEVA PHARMACEUTICALS USA, INC.
`Petitioner,
`
`v.
`
`ALLERGAN, INC.,
`Patent Owner.
`
`
`
`Case No. IPR2017-00579
`Patent No. 8,642,556
`
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,642,556
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`I.
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`II.
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`TABLE OF CONTENTS
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`INTRODUCTION ................................................................................................. 1
`
`OVERVIEW ........................................................................................................ 3
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`A. Brief Overview of the ’556 Patent ........................................................ 3
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`B. Brief Overview of the Prosecution History ........................................... 5
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`C. Brief Overview of the Scope and Content of the Prior Art ................... 8
`
`i.
`
`ii.
`
`U.S. Patent No. 5,474,979 to Ding et al.
`(“Ding ’979,” EX1006) ............................................................... 9
`
`Sall et al., Two Multicenter, Randomized Studies of
`the Efficacy and Safety of Cyclosporine Ophthalmic
`Emulsion in Moderate to Severe Dry Eye Disease,
`107 OPHTH. 631 (2000) (EX1007) ............................................ 10
`
`iii. A. Acheampong et al., Cyclosporine Distribution into
`the Conjunctiva, Cornea, Lacrimal Gland, and Systemic
`Blood following Topical Dosing of Cyclosporine to
`Rabbit, Dog, and Human Eyes, 2 LACRIMAL GLAND,
`TEAR FILM, AND DRY EYE SYNDROMES 1001 (1998)
`(“Acheampong,” EX1008) ........................................................ 11
`
`iv. U.S. Patent No. 5,578,586 to Glonek et al.
`(“Glonek,” EX1009) ................................................................. 11
`
`D. Brief Overview of the Level of Skill in the Art .................................. 12
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`III. GROUNDS FOR STANDING ............................................................................... 13
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`IV. Mandatory Notices under 37 C.F.R. § 42.8 ................................................... 13
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`V.
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`Statement of the Precise Relief Requested .................................................... 15
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`VI. STATEMENT OF NON-REDUNDANCY ............................................................... 16
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`VII. CLAIM CONSTRUCTION ................................................................................... 16
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`A.
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`“buffer” ................................................................................................ 17
`
`
`
`i
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`
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`B.
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`C.
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`D.
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`E.
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`“substantially no detectable concentration” ........................................ 17
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`“effective amount,” “therapeutically effective,” “overall efficacy,”
`and “therapeutic effectiveness” ........................................................... 18
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`“adverse events” and “side effects” .................................................... 19
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`“break down” ....................................................................................... 20
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`VIII. BACKGROUND KNOWLEDGE IN THE ART PRIOR TO SEPTEMBER 15, 2003 ...... 20
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`IX. DETAILED EXPLANATION OF GROUNDS FOR UNPATENTABILITY .................... 26
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`A.
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`[Ground 1] Claims 1-20 are Anticipated under 35 U.S.C.
`§ 102(b) by Ding ’979 ......................................................................... 26
`
`i.
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`Claims 1-10 and 12-13 .............................................................. 26
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`ii. Claim 14 .................................................................................... 34
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`iii. Claims 15-17 ............................................................................. 35
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`iv. Claims 11 and 18-20 ................................................................. 36
`
`B.
`
`[Ground 2] Claims 1-20 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979 and Sall ............................................................ 40
`
`i.
`
`Claims 1-10, 12-13 .................................................................... 40
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`ii. Claim 14 .................................................................................... 43
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`iii. Claims 15-17 ............................................................................. 43
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`iv. Claims 11 and 18-20 ................................................................. 45
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`[Ground 3] Claims 14 and 19 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979, Sall, and Glonek .............................................. 48
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`[Ground 4] Claims 11, 18, and 20 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979, Sall, and Acheampong .................................... 50
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`[Ground 5] Claim 19 is Obvious under 35 U.S.C. § 103
`over Ding ’979, Sall, Glonek, and Acheampong ................................ 52
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`C.
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`D.
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`E.
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`X. No Objective Indicia of Non-Obviousness .................................................... 53
`ii
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`A. No Unexpected Results ....................................................................... 53
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`B. No Evidence of Commercial Success ................................................. 64
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`C. No Industry Praise ............................................................................... 66
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`D. No Long-Felt, Unmet Need ................................................................. 66
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`E. No Failure of Others ............................................................................ 67
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`XI. CONCLUSION ................................................................................................... 67
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`XII. CERTIFICATE OF COMPLIANCE ........................................................................ 69
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`XIII. PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15 (A) AND 42.103 ...................... 70
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`XIV. APPENDIX – LIST OF EXHIBITS ........................................................................ 71
`
`
`
`
`
`iii
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`
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`I.
`
`INTRODUCTION
`
`Pursuant to the provisions of 35 U.S.C. § 311 and § 6 of the Leahy-Smith
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`America Invents Act (“AIA”), and to 37 C.F.R. Part 42, Teva Pharmaceuticals
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`USA, Inc. (“Petitioner” or “Teva”) hereby requests review of U.S. Patent No.
`
`8,642,556 to Acheampong et al. (“the ’556 patent,” EX1001) that issued on
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`February 4, 2014. PTO records indicate the ’556 patent is assigned to Allergan,
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`Inc. (“Patent Owner”). This Petition demonstrates that there is a reasonable
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`likelihood that claims 1-20 of the ’556 patent are unpatentable for failure to
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`distinguish over the asserted prior art. Additional petitions are being filed to
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`address related patents that are assigned to Patent Owner. All challenged patents
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`are continuations from the same family and are terminally disclaimed over one
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`another. The patents claim an ophthalmic emulsion for the treatment of
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`overlapping ocular disorders, or conventional methods of administering the
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`emulsion.
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`The ’556 patent claims a topical ophthalmic emulsion as in related U.S.
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`Patent No. 8,685,930, but further recites a comparative clause, where an effect of
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`the emulsion is compared to a prior art emulsion. Yet each element of the claimed
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`emulsion, including the claimed cyclosporin A (“CsA”) and castor oil percentages
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`and other standard emulsion ingredients, was disclosed in a single prior art
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`reference (Ding ’979) for the same therapeutic uses, i.e., treating dry eye disease.
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`
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`1
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`
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`During prosecution of a parent application, applicants even admitted that the
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`claimed emulsion containing 0.05% CsA and 1.25% castor oil “is squarely within
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`the teaching of the Ding [’979] reference” and “would have been obvious” to a
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`person of skill in the art at the time of the invention. EX1005, 0435; EX1025, ¶18.
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`Four years later, in prosecuting the ’556 patent as a continuation application,
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`applicants changed course and attempted to withdraw these admissions. EX1004,
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`0007. They argued that data collected after their earlier admissions established
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`patentability because of an alleged unexpected result that the emulsion was
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`“equally or more therapeutically effective for the treatment of dry
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`eye/keratoconjunctivitis sicca than the formulation containing 0.10% by weight
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`cyclosporin A and 1.25% by weight castor oil.” EX1004, 0007, 0205; EX1025,
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`¶¶20-22. But the supposed “unexpected results” are weak, at best, and fail to rebut
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`the strong evidence of obviousness. The data relied upon by applicants lack
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`scientific parameters necessary to demonstrate statistical significance and
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`materiality and, in many cases, appear to be copies of previously published graphs
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`from a 102(b) prior art reference, Sall. Thus, Patent Owner’s cited evidence does
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`not support non-obviousness of the claims, and merely confirms that the results
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`were already disclosed in the prior art.
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`
`
`2
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`II. OVERVIEW
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`
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`The Board has already issued its Decision Instituting Inter Partes Review
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`(“Decision”) on all challenged claims of the ’556 patent on the same grounds
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`raised herein.
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`Ground 1: Claims 1–20 under 35 U.S.C. § 102(b) as anticipated by Ding
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`’979,
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`Ground 2: Claims 1–20 under 35 U.S.C. § 103(a) as obvious over Ding ’979
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`and Sall,
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`Ground 3: Claims 14 and 19 under 35 U.S.C. § 103(a) as obvious over Ding
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`’979, Sall, and Glonek,
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`Ground 4: Claims 11, 18, and 20 under 35 U.S.C. § 103(a) as obvious over
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`Ding ’979, Sall, and Acheampong,
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`Ground 5: Claim 19 under 35 U.S.C. § 103(a) as obvious over Ding ’979,
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`Sall, Glonek, and Acheampong.
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`Mylan Pharmaceuticals Inc. v. Allergan Inc., IPR2016-01129 (Paper No. 8).
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`Petitioner Teva hereby files its own petition on the same grounds and concurrently
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`seeks to join the instituted IPR proceedings on these challenged claims.
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`A. Brief Overview of the ’556 Patent
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`The ’556 patent has an earliest claimed priority date of September 15, 2003.
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`Independent claim 1 recites an emulsion of 0.05% CsA, 1.25% castor oil,
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`3
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`polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer (“cross-polymer”)
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`and water that is therapeutically effective in treating dry eye disease and “provides
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`overall efficacy substantially equal to a second topical ophthalmic emulsion
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`comprising cyclosporin A in an amount of about 0.1% by weight and castor oil in
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`an amount of about 1.25% by weight.” Claims 2-6 and 9-10 recite that the
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`emulsion comprises a tonicity or demulcent agent, specifically glycerine, and/or a
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`buffer, specifically sodium hydroxide. Claim 12 specifies a range of pH values for
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`the emulsion of claim 6. Claims 7-8 are dependent claims that specify known
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`weight percentages of polysorbate 80 and cross-polymer, respectively. Claim 11
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`recites that when the emulsion is administered to the eye there is substantially no
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`detectable concentration of CsA in the blood.
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`Claims 13-15 are independent claims reciting the same emulsion ingredients
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`as in claim 1. Claim 13 additionally recites that the emulsion is therapeutically
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`effective in treating dry eye disease, and “achieves at least as much therapeutic
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`effectiveness” as a second emulsion comprising 0.1% CsA and 1.25% castor oil.
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`Claim 14 further recites that the emulsion “breaks down more quickly,” thereby
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`reducing vision distortion, as compared to a second emulsion that contains only
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`about 50% as much castor oil. Claims 15 further recites that the emulsion
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`“demonstrates a reduction in adverse events” relative to a 0.1% CsA / 1.25% castor
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`oil emulsion. Dependent claims 16 and 17 respectively specify that the adverse
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`4
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`
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`events are side effects and that the side effects are visual distortion or eye irritation.
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`Claims 18, 19, and 20 respectively depend from claims 12, 14, and 15, and further
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`specify that when the emulsion is administered there is “substantially no detectable
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`concentration of cyclosporin A” in the human’s blood.
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`B.
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`Brief Overview of the Prosecution History
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`U.S. Patent Application No. 13/967,189 (“the ’189 application”) was filed
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`on August 14, 2013, and issued six months later on February 4, 2014, as the ’556
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`patent. The ’189 application is a continuation, via U.S. applications 13/961,808
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`and 11/897,177, of U.S. application 10/927,857 (“the ’857 application,” EX1005),
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`and claims the benefit of U.S. provisional application 60/503,137, filed September
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`15, 2003.
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`During prosecution of the related ’857 application, Patent Owner admitted
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`that Composition II, which is identical to the emulsion claimed in the ’556 patent
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`(EX1025, ¶¶18-19), was “squarely within the teachings of Ding [’979]”:
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`The applicants concede that it would have been obvious to modify
`examples 1A-1E of the Ding reference to arrive at Composition II of
`the present application. The differences are insignificant.... As the
`examiner correctly observes, one of ordinary skill in the art “would
`readily envisage” such a composition, especially in view of Example
`1B: having selected 0.05% as the concentration of cyclosporin,
`Example 1B (wherein the ratio of cyclosporin to castor oil is 0.04)
`teaches that the concentration of castor oil should be 1.250% (0.05% /
`1.250% = 0.04). The applicants concede that in making this selection
`(0.05% cyclosporin and 1.250% castor oil) there would have been a
`reasonable expectation of success; the differences between Examples
`1A-1E and Composition II are too small to believe otherwise.
`5
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`
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`The formulation of Composition II is squarely within the teachings
`of the Ding reference, and the Office should disregard any
`statements by the applicants suggesting otherwise[.]
`
`EX1005, 0435 (emphases added).
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`During prosecution of the ’189 application, the applicants acknowledged
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`their prior admissions, but claimed that they had collected evidence to support the
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`patentability of the claims “[s]ince these comments have been filed.” EX1004,
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`0007. The examiner then rejected the claims as obvious over Ding ’979. Id. at
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`0136-40. Patent Owner responded to the rejection, nakedly asserting that “the
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`prima facie case of obviousness has not been properly established,” but arguing
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`that the claims were patentable based on objective indicia. Id. at 0200. It also filed
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`a terminal disclaimer for the applications or parent applications that resulted in the
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`’930, ’111, ’162, ’048, and ’191 patents. Id. at 0122-23.
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`In remarks accompanying a Notice of Allowance (id. at 0408; EX1025, ¶23)
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`the examiner stated that applicants had failed to demonstrate commercial success
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`or long-felt need. EX1004, 0417-19. However, relying on declarations submitted
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`by Drs. Schiffman and Attar, the examiner concluded that, “the specific
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`combination of 0.05% by weight cyclosporin A with 1.25% by weight castor oil is
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`surprisingly critical for therapeutic effectiveness in the treatment of dry eye or
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`keratoconjunctivitis sicca,” and therefore, “demonstrate[s] surprising and
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`unexpected results.” Id. at 0421.
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`
`
`6
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`
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`The alleged “unexpected results” are addressed in the declaration of Dr.
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`Walter Chambliss that accompanies this Petition. EX1025, ¶¶145-69. As noted by
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`Dr. Chambliss, the data presented by applicants lacked scientific parameters
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`necessary to demonstrate statistical significance and materiality. In many cases, the
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`data appear to be repackaged from graphs published in the prior art Sall reference
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`that is presently asserted against the claims. Thus, the declarations do not support a
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`finding of surprising or unexpected results. Id.
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`During prosecution, the Patent Owner did not identify, and the examiner did
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`not address, deficiencies in the Schiffman and Attar Declarations discussed in this
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`Petition that made them unreliable. As such, and because of the new information
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`presented herein and supported by Dr. Chambliss’s testimony, the examiner’s
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`conclusions based on one-sided information should not receive any deference by
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`the Board.
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`In addition to demonstrating the flaws in Patent Owner’s alleged unexpected
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`results, Dr. Chambliss’s declaration also provides insight not previously presented
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`to the Patent Office about how a person of ordinary skill in the art would interpret
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`the disclosure of Ding ’979. Among other things, Dr. Chambliss’s testimony
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`establishes that the presently claimed emulsion would have been immediately
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`apparent to one of ordinary skill in the art based on Ding ’979. EX1025, ¶¶97-98,
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`114. The Patent Owner’s alleged evidence of unexpected results cannot render
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`
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`7
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`
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`patentable an anticipated claim. In re Wiggins, 488 F.2d 538, 543, (C.C.P.A.
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`1973).
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`Further, this Petition presents new arguments based on expert testimony as
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`to why the claims are obvious over Ding ’979 and other references that were not
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`substantively analyzed during prosecution. Among other things, Dr. Chambliss
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`explains that the 1.25% castor oil emulsion vehicle of Example 2C in Ding ’979
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`was the only vehicle that was most preferred for both the 0.05% and 0.10% CsA
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`emulsions, and that Sall’s 0.05% and 0.10% CsA emulsions used the same castor
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`oil vehicle. Petitioner provides an even stronger prima facie obviousness case than
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`the examiner considered during prosecution. Accordingly, the Board should
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`institute review without deference to the limited analysis during prosecution.
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`C. Brief Overview of the Scope and Content of the Prior Art
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`A prior art reference anticipates a claim if it discloses all of the elements of
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`the claim in the claimed combination, or if the claimed combination would be
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`“immediately apparent to one of ordinary skill in the art,” or “at once envisaged”
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`from the prior art reference. Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683
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`F.3d 1356, 1361 (Fed. Cir. 2012). In obviousness cases, Graham v. John Deere Co.
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`of Kansas City, requires an evaluation of any differences between the claimed
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`subject matter and the asserted prior art. 383 U.S. 1, 17-18 (1966). As noted in
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`KSR Int’l Co. v. Teleflex Inc., the obviousness inquiry may account for inferences
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`
`
`8
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`
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`that would be employed by a person of ordinary skill in the art. 550 U.S. 398, 418
`
`(2007).
`
`i.
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`U.S. Patent No. 5,474,979 to Ding et al. (“Ding ’979,”
`EX1006)
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`Ding ’979 issued on December 12, 1995, and is prior art under 35 U.S.C.
`
`
`
`§ 102(b). EX1006. Ding ’979 teaches topical ophthalmic emulsions for the
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`treatment of keratoconjunctivitis sicca (“KCS” or “dry eye disease/KCS”). Id. at
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`5:9-12; EX1025, ¶61. Claims 7-8 recite emulsions containing 0.05-0.40% CsA in
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`0.625-5.00% castor oil, 1.00% polysorbate 80, 0.05% Pemulen® (an acrylate/C10-
`
`30 alkyl acrylate cross-polymer), 2.20% glycerine, sodium hydroxide, and water,
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`and having a pH range of 7.2-7.6. EX1006, 4:4-5; id. at 6:27-42; EX1025, ¶64.
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`Ding ’979 teaches that CsA is effective in treating dry eye disease “as an
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`immunosuppressant and in the enhancement or restoring of lacrimal gland tearing.”
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`EX1006, 1:10-16, 37-39.
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`Ding ’979 discloses four examples of castor oil-based vehicles (Examples
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`2A-D) for delivery of CsA. EX1006, 4:44-54; EX1025, ¶65. Example 2C is the
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`exact same castor oil vehicle used in the challenged claims. Ding ’979 also
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`discloses CsA-containing emulsions in Example 1 using the vehicles from
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`Example 2. EX1006, 4:32-54. The emulsions in Example 1 have CsA percentages
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`and castor oil percentages covering the ranges disclosed in claims 7 and 8 (0.05% -
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`0.40% CsA and 0.625% - 5.00% castor oil) of Ding ’979. Id. at 4:32-43; EX1025,
`9
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`
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`¶¶66-67. One emulsion (Example 1D) specifically used the 1.25% castor oil
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`vehicle (Example 2C) to deliver 0.10% CsA. EX1006, 4:32-43.
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`Ding ’979 explicitly sets forth a “more preferred” range for the ratio of CsA
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`to castor oil of 0.02-0.12. Id. at 3:17-20; EX1025, ¶67. Each of the exemplified
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`CsA-containing emulsions in Ding ’979 fall within an even narrower ratio range of
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`0.04-0.08, which, for the 1.25% castor oil vehicle (Example 2C) disclosed in Ding
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`’979, equates to a CsA range of 0.05% to 0.10% CsA. EX1006, 4:32-43; EX1005,
`
`0435; EX1025, ¶¶67, 97.
`
`ii.
`
`Sall et al., Two Multicenter, Randomized Studies of the Efficacy
`and Safety of Cyclosporine Ophthalmic Emulsion in Moderate
`to Severe Dry Eye Disease, 107 OPHTH. 631 (2000) (EX1007)
`
`Sall is prior art under 35 U.S.C. § 102(b). Sall describes a multi-center,
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`
`
`randomized, double-masked Phase 3 clinical trial that assesses the safety and
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`efficacy of increasing tear production and treating dry eye disease/KCS by twice-
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`daily ophthalmic administration of 0.05% or 0.10% CsA in a castor oil emulsion,
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`compared to the emulsion vehicle without CsA in the same regimen. EX1007, 631-
`
`32 & n.1; id. at figs. 1-4; EX1025, ¶¶73-74. Sall teaches that the 0.05% CsA
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`emulsion was safe and effective, was at least as effective as the 0.10% CsA
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`emulsion, and resulted in fewer adverse side effects and in trough CsA blood
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`concentrations below 0.1 ng/mL. EX1007, 631, 634-37; EX1025, ¶¶73-80. Sall
`
`does not expressly disclose the exact composition of the castor oil vehicle, but
`
`
`
`10
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`
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`compares the 0.05% and 0.10% CsA emulsions to the same vehicle. EX1007, 632;
`
`EX1025, ¶73, 120.
`
`iii. A. Acheampong et al., Cyclosporine Distribution into the
`Conjunctiva, Cornea, Lacrimal Gland, and Systemic Blood
`following Topical Dosing of Cyclosporine to Rabbit, Dog, and
`Human Eyes, 2 LACRIMAL GLAND, TEAR FILM, AND DRY EYE
`SYNDROMES 1001 (1998) (“Acheampong,” EX1008)
`
`Acheampong is prior art under 35 U.S.C. § 102(b). Acheampong describes a
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`
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`study in which CsA percentages ranging from 0.05%-0.4% were administered to
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`human patients with dry eye disease. EX1008 at 1002; EX1025, ¶¶85-86.
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`Acheampong measured CsA blood concentration at both peak and trough levels
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`following topical ophthalmic administration. EX1008 at 1002. No detectable
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`amount of CsA was measured in patients receiving the 0.05% CsA emulsion.
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`EX1008 at 1002, 1004; EX1025, ¶¶85-86.
`
`iv. U.S. Patent No. 5,578,586 to Glonek et al. (“Glonek,” EX1009)
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`Glonek issued Nov. 6, 1996 and is prior art under 35 U.S.C. § 102(b).
`
`EX1009. Glonek teaches that “an emulsion over the surface of the eye is expected
`
`to cause blurring. The duration of the blurring is dependent upon the time required
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`for the emulsion to differentiate and form separate layers.” EX1009, 6:37-40;
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`EX1025, ¶88. Glonek discloses topical emulsions for the treatment of dry eye
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`disease, “whereby blurred vision is reduced.” EX1009, 3:5-6; EX1025, ¶88. In
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`comparing the relative amounts of surfactant and oil and their effects on visual
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`
`
`11
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`
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`blurring, Glonek teaches that higher concentrations of oil lead to faster
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`differentiation and decreased blurring. EX1009, 20:24-30; EX1025, ¶89.
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`D. Brief Overview of the Level of Skill in the Art
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`A person of ordinary skill in the relevant field as of September 15, 2003
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`would likely have some combination of: (a) experience formulating pharmaceutical
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`products; (b) experience designing and preparing drug emulsions intended for
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`topical ocular administration; and (c) the ability to understand results and findings
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`presented or published by others in the field. EX1025, ¶36. Typically this person
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`would have an advanced degree, such as a medical degree, or a Ph.D. in organic
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`chemistry, pharmaceutical chemistry, medicinal chemistry, pharmaceutics,
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`physical pharmacy, or a related field, or less education but considerable
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`professional experience in these fields. Id. at ¶35.
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`Dr. Chambliss received a Ph.D. in Pharmaceutical Science/Biomaterials
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`Science from Purdue University in 1992, and he has extensive experience with
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`ophthalmic pharmaceutical emulsions, including castor oil emulsions. EX1025,
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`¶¶2-4; EX1026. Dr. Chambliss is well qualified as an expert, possessing the
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`necessary scientific, technical, and other specialized knowledge and training to
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`assist in an understanding of the evidence presented herein, as well as possessing
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`the expertise necessary to determine and explain the level of ordinary skill in the
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`art as of September 2003. EX1026.
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`
`
`12
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`
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`III. GROUNDS FOR STANDING
`
`Petitioner certifies that, under 37 C.F.R. § 42.104(a), the ’556 patent is
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`available for inter partes review, and Petitioner is not barred or estopped from
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`requesting inter partes review of the ’556 patent on the grounds identified.
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`IV. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
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`Real Parties-in-Interest (37 C.F.R. § 42.8(b) (1)): Teva Pharmaceuticals
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`USA, Inc. is a real party-in-interest. Teva Pharmaceuticals USA, Inc. is a
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`subsidiary of Teva Pharmaceuticals Industries, Inc.
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`Related Matters (37 C.F.R. § 42.8(b) (2)): Petitioner indicates that the
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`following judicial matters may affect or be affected by a decision in this
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`proceeding:
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`An IPR petition for the ’556 patent was previously filed by Apotex Corp.
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`and Apotex Inc. as IPR2015-01286, as were petitions for the related patents U.S.
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`Patent Nos. 8,648,048 (IPR2015- 01284), 8,629,111 (IPR2015-01282), 8,633,162
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`(IPR2015-01278), and 8,685,930 (IPR2015-01283), but all were terminated prior
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`to an institution decision.
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`An IPR petition for the ’556 patent was previously filed by Mylan as
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`IPR2016-01129 and has been instituted.
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`IPR petitions for the related patents 8,685,930 (IPR2016-01127), 8,629,111
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`(IPR2016- 01128), 8,633,162 (IPR2016-01130), 8,648,048 (IPR2016-01131), and
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`9,248,191 (IPR2016-01132) have been filed by Mylan and have been instituted.
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`U.S. Application No. 15/011,159, filed January 29, 2016, claims the benefit of U.S.
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`Application No. 14/222,478 (the ’191 patent), which is a continuation, via U.S.
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`Application Nos. 13/961,828 and 11/897,177, of the ’857 application.
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`Teva filed IPR petitions for the related patents 8,685,930 (IPR2017-00),
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`8,642,556 (IPR2017-00579), 8,633,162 (IPR2017-00583), 8,648,048 (IPR2017-
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`00585), and 9,248,191 (IPR2017-00586) on the same grounds and concurrently
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`seeks to join these instituted IPR proceedings on the same challenged claims.
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`Petitioner and other entities are involved in litigation over the ’556 patent
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`and related patents in the action styled Allergan, Inc. v. Teva Pharmaceuticals
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`USA, Inc., et al., No. 2:15-cv-01455, filed by Allergan, Inc. in the Eastern District
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`of Texas (EX1023). Petitioner also identifies the following pending actions
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`involving the ’556 patent: Allergan, Inc., v. Innopharma, Inc. and Pfizer, Inc., No.
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`2:15cv1504, in the Eastern District of Texas.
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`Lead and Back-Up Counsel (37 C.F.R. § 42.8(b) (3)):
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`Lead Counsel: Gary J. Speier (Reg. No. 45,458)
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`Back-Up Counsel: Mark D. Schuman (Reg. No. 31,197)
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`Service Information (37 C.F.R. § 42.8(b) (4)):
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`Petitioner hereby consents to electronic service.
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`EEmail: gspeeier@carlsoncaspers..com, mschhuman@caarlsoncasp
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`PPost: CARRLSON, CAASPERS, VVANDEN
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`BURGH, LLINDQUIIST &
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`SCHUUMAN, P
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`225 SSouth Sixthh Street, Suuite 4200,
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`Tel.: (612) 436
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`-9600 Fax: (612) 4366-9605
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`V.
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`STATEMENT OF THE PPRECISE RRELIEF REQ
`QUESTED
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`Petitioners rrequest revview of claaims 1-20 oof the ’5566 patent unnder 35 U.SS.C.
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`§ 311 annd AIA § 66 and that each of thee claims bee canceled
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`as unpatenntable:
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`VI. STATEMENT OF NON-REDUNDANCY
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`Each of the five Grounds raised in this Petition is meaningfully distinct.
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`Ground 1 asserts anticipation of claims 1-20 by Ding ’979. Ground 2 asserts
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`obviousness of claims 1-20 based on Ding ’979 and Sall. Sall expressly teaches
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`certain properties intrinsic to the claimed emulsion, including efficacy, relative
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`efficacy, relative adverse events, and substantially no detectable blood
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`concentration at trough levels, and provides additional reasons to make and use the
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`claimed emulsion to treat dry eye disease. Ground 3 challenges claims 14 and 19
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`based on Ding ’979, Sall, and Glonek. Glonek expressly teaches the reduction in
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`blurring from more rapid emulsion break down, and the relationship between break
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`down rate and oil concentration. Ground 4 asserts the obviousness of dependent
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`claims 11, 18, and 20, based Ding ’979, Sall, and Acheampong. Acheampong
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`expressly teaches the claimed emulsion results in substantially no detectable blood
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`concentration at trough and peak levels. Ground 5 challenges dependent claim 19
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`based on Ding ’979, Sall, Glonek, and Acheampong based on the properties taught
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`therein.
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`VII. CLAIM CONSTRUCTION
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`In an inter partes review, a claim in an unexpired patent is given its broadest
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`reasonable construction in light of the specification. 37 C.F.R. § 42.100(b); In re
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`Cuozzo Speed Techs., LLC, 793 F.3d 1268, 1275-1280 (Fed. Cir. 2015), cert.
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`granted sub nom. Cuozzo Speed Techs., LLC v. Lee, 2016 U.S. LEXIS 632 (U.S.
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`Jan. 15, 2016) (No. 15-446). Claims terms are also “generally given their ordinary
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`and customary meaning,” which is the meaning that the term would have to a
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`person of ordinary skill in the art at the time of the invention in view of the
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`specification. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007).
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`Under either standard, there is a reasonable likelihood that Petitioner will prevail
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`with respect to the challenged claims. A few terms are discussed below.
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`A.
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`“buffer”
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`The term “buffer” appears in claims 4-6, 9-10 of the ’556 patent. Claims 5
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`and 10 state “the buffer is sodium hydroxide.” The patent states, “[t]he pH of the
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`emulsions can be adjusted in a conventional manner using sodium hydroxide ... to
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`a physiological pH level.” EX1001, 13:4-6. In light of the specification, the
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`broadest reasonable interpretation of the term “buffer” includes sodium hydroxide.
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`EX1025, ¶38.
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`B.
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`“substantially no detectable concentration”
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`The term “substantially no detectable concentration” appears in claims 11
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`and 18-20 of the ’556 patent with regard to measuring CsA in human blood.
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`According to the specification, “[c]yclosporin component concentration in blood
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`preferably is determined using a liquid chromatography-mass spectroscopy-mass
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`spectroscopy (LC-MS/MS), which test has a cyclosporin component detection
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`limit of 0.1 ng/ml. Cyclosporin component concentrations below or less than 0.1
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`ng/ml are therefore considered substantially undetectable.” EX1001, 5:36 – 6:5. A
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`skilled artisan could measure blood concentration at either peak or trough levels.
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`EX1025, ¶39. In light of the specification, the broadest reasonable interpretation of
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`the phrase “substantially no detectable concentration” includes a blood
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`concentration below 0.1 ng/mL measured at either peak or trough levels.
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`C.
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`“effective amount,” “therapeutically effective,” “overall efficacy,”
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`Independent claims 1 and 13 state that the emulsion is “therapeutically
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`effective in treating dry eye disease.” Claim 11 further recites administering “an
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`effective amount in treating dry eye disease.” Keratoconjunctivitis sicca (“KCS”),
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`an “inflammation of the conjunctiva and of the cornea” that is “associated with
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`decreased tears,” is a species of, and is often used interchangeably with, or as a
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`partial synonym of, dry eye disease. EX1022, 0003 (keratoconjunctivitis sicca);
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`EX1025, ¶40, 47. The ’556 patent teaches that CsA “acts to enhance or restore
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`lacrimal gland tearing in providing the desired therapeutic effect.” EX1001, 9:39-
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`40. During prosecution, Patent Owner relied on an increase in tearing to assert
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`unexpected therapeutic efficacy of the claimed emulsion for treating dry eye
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`disease/KCS. EX1004, 0200-02; EX1025, ¶40. Thus, in the context of the ’556
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`patent, an emulsion effective in increasing tear production is an example of an
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`emulsion therapeutically effective in treating dry eye disease.
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`Claims 1 and 13 respectively state that the emulsion “provides overall
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`efficacy substantially equal to” and “achieves at least as much therapeutic
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`effectiveness” as a second emulsion with 0.10% CsA and 1.25% castor oil. The
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`plain meaning of the word “therapeutic” includes palliative (remediating)
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`treatments as well as curative treatments. EX1025, ¶¶41-42; EX1022, 0007
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`(therapeutic), 0004 (palliative), 0005 (remedy). Accordingly, the broadest
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`reasonable interpretation of these terms include palliative treatments as well as
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`curative treatments.
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`D.
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`“adverse events” and “s