`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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`
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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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`
`
`TEVA PHARMACEUTICALS USA, INC.
`Petitioner,
`
`v.
`
`ALLERGAN, INC.,
`Patent Owner.
`
`
`
`Case No. IPR2017-00585
`Patent No. 8,648,048
`
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,648,048
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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 ’048 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.
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`U.S. Patent No. 5,474,979 to Ding et al.
`(“Ding ’979,” EX1006) ............................................................... 8
`
`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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`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,” “substantially therapeutically effective as,” and
`“as much therapeutic effectiveness as” ............................................... 18
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`“adverse events” and “side effects” .................................................... 19
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`“breaks down” ..................................................................................... 19
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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] Glaims 1-10, 12-14, 16-20, and 22-23 are Obvious
`under 35 U.S.C. § 103 over Ding ’979 and Sall ................................. 26
`
`i.
`
`Claims 1-10, 12, 18-20, and 22-23 ........................................... 26
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`ii. Claims 13 and 14....................................................................... 42
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`iii. Claims 16 and 17....................................................................... 44
`
`B.
`
`C.
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`[Ground 2] Claims 11 and 21 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979, Sall, and Acheampong .................................... 46
`
`[Ground 3] Claim 15 is Obvious under 35 U.S.C. § 103
`over Ding ’979, Sall, and Glonek ........................................................ 48
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`X. NO OBJECTIVE INDICIA OF NON-OBVIOUSNESS .............................................. 50
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`A. No Unexpected Results ....................................................................... 51
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`B. No Evidence of Commercial Success ................................................. 62
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`C. No Industry Praise ............................................................................... 63
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`D. No Long-Felt, Unmet Need ................................................................. 64
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`E. No Failure of Others ............................................................................ 64
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`XI. CONCLUSION ................................................................................................... 65
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`XII. CERTIFICATE OF COMPLIANCE ........................................................................ 66
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`XIII. PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15(A) AND 42.103 ....................... 67
`
`
`
`ii
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`XIV. APPENDIX – LIST OF EXHIBITS ........................................................................ 68
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`iii
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`I.
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`INTRODUCTION
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`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.
`
`8,648,048 to Acheampong et al. (“the ’048 patent,” EX1001) that issued on
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`February 11, 2014. PTO records indicate the ʼ048 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 1-23 of the ’048 patent are unpatentable for failure to
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`distinguish over prior art. Additional petitions are being filed to address related
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`patents that are assigned to Patent Owner. All challenged patents are continuations
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`from the patent family and are terminally disclaimed over one another. The patents
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`claim an ophthalmic emulsion for the treatment of overlapping ocular disorders, or
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`conventional methods of administering the emulsion.
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`In particular, the ’048 patent claims concern conventional methods of
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`treating the dry eye disease keratoconjunctivitis sicca (hereinafter “dry eye
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`disease/KCS”) by the “twice a day” topical ophthalmic administration of an
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`emulsion containing cyclosporin A (“CsA”), castor oil, and other standard
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`ingredients, as generally claimed in related U.S. Patent No. 8,685,930. Each
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`element of the emulsion, including the claimed CsA and castor oil percentages and
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`methods for administering them to treat drye eye disease/KCS, were disclosed in a
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`1
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`
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`single prior art reference (Ding ’979). During prosecution of a parent application,
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`applicants admitted that the claimed emulsion containing 0.05% CsA and 1.25%
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`castor oil “is squarely within the teaching of the Ding [’979] reference” and
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`“would have been obvious” to a person of skill in the art at the time of the
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`invention. EX1005, 0435; EX1026, ¶18. A second 102(b) prior art reference, Sall,
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`discloses twice-daily administration of a 0.05% CsA-in-castor oil emulsion for the
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`same purpose.
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`In prosecuting the ’048 patent as a continuation application, applicants
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`changed course and attempted to withdraw the admissions regarding Ding ’979.
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`EX1004, 0007. They argued that data collected after their earlier admissions
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`established patentability because of an alleged unexpected result that the emulsion
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`was “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, 0253; EX1026,
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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 the 102(b) prior art reference, Sall. Thus, Patent Owner’s cited evidence does
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`2
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`not support non-obviousness of the claims, and merely confirms that the results
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`were expected in view of and were already disclosed in the prior art.
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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 ’048 patent on the same grounds
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`raised herein.
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`Ground 1: Claims 1–10, 12–14, 16–20, 22, and 23 as obvious over Ding
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`’979 and Sall;
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`Ground 1: Claims 11 and 21 as obvious over Ding ’979, Sall, and
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`Acheampong; and
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`Ground 1: Claim 15 as obvious over Ding ’979, Sall, Acheampong, and
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`Glonek.
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`Mylan Pharmaceuticals Inc. v. Allergan Inc., IPR2016-01131 (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.
`
`A. Brief Overview of the ’048 Patent
`
`The ’048 patent has an earliest claimed priority date of September 15, 2003.
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`Independent claim 1 recites a method of increasing tear production in the eye,
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`comprising administering twice-daily an emulsion of 0.05% CsA in 1.25% castor
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`oil, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer
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`
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`3
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`(“crosspolymer”), and water. Claims 2-6 and 9-10 recite that the emulsion
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`comprises a tonicity or demulcent agent, specifically glycerine, and/or a buffer,
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`specifically sodium hydroxide. Claim 12 specifies a range of pH values for the
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`emulsion of claim 6, which comprises glycerine and a buffer. Claims 7-8 are
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`dependent claims that specify known weight percentages of polysorbate 80 and
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`cross-polymer, respectively. Claim 11 recites that when the emulsion is
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`administered to the eye there is substantially no detectable concentration of CsA in
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`the blood.
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`Claims 13-16 compare the therapeutic effect of the claimed emulsion with
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`emulsions with different percentages of CsA or castor oil. Claims 13-14 and 16-17
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`respectively compare the therapeutic efficacy or adverse events of the claimed
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`emulsion verses one with 0.10% CsA. Claim 15 compares the breakdown rate of
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`the claimed with a second emulsion containing half as much castor oil.
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`Claim 18 recites a method of treating keratoconjunctivitis sicca (KCS) using
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`an emulsion incorporating the ingredients and/or weight percentage limitations of
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`claims 1 and 7-9, and the pH value recited in claim 12. Dependent claims 19-21
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`further specify sodium hydroxide as the buffer and glycerine as the
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`tonicity/demulcent agent, and that the blood of the human has substantially no
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`detectable concentration of CsA.
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`4
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`Independent claim 22 recites the same method as claim 18 but specifies
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`glycerine as the tonicity/demulcent agent and sodium hydroxide as the buffer and
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`that the method increases tear production in a person having KCS. Dependent
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`claim 23 simply recites a pH range for the emulsion of claim 22.
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`B.
`
`Brief Overview of the Prosecution History
`
`U.S. Patent Application No. 13/967,168 (“the ’168 application”) was filed
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`on August 14, 2013, and issued six months later on February 11, 2014, as the ’048
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`patent. The ’168 application is a continuation, via U.S. applications 13/961,835
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`and 11/897,177, of U.S. application 10/927,857 (“the ’857 application,” EX1005),
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`which claims the benefit of U.S. provisional application 60/503,137, filed
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`September 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 ’048 patent
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`(EX1026, ¶¶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[.]
`
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`EX1005, 0435 (emphases added).
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`During prosecution of the ’168 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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`0178-92. 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 0247. 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, ’556, and ’191 patents. Id. at 0164-65.
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`In remarks accompanying a Notice of Allowance (id. at 0461; EX1026, ¶23)
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`the examiner concluded that applicants had failed to demonstrate commercial
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`success or long-felt need. EX1004, 0469-71. However, relying on declarations
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`submitted by Drs. Schiffman and Attar, the examiner stated 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 0473.
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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. EX1026, ¶¶128-52. 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 that made them
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`unreliable, which are discussed in this Petition. As such, and because of the new
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`information presented herein and supported by Dr. Chambliss’s testimony, the
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`examiner’s conclusions based on one-sided information should not receive any
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`deference by 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. EX1026, ¶¶97-98,
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`114.
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`7
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`
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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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`In obviousness cases, Graham v. John Deere Co. of Kansas City, requires an
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`evaluation of any differences between the claimed subject matter and the asserted
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`prior art. 383 U.S. 1, 17-18 (1966). As noted in KSR Int’l Co. v. Teleflex Inc., the
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`obviousness inquiry may account for inferences that would be employed by a
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`person of ordinary skill in the art. 550 U.S. 398, 418 (2007).
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`i.
`
`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. §
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`
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`102(b). EX1006. Ding ’979 teaches topical ophthalmic emulsions for the treatment
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`of keratoconjunctivitis sicca (“KCS” or “dry eye disease/KCS”). Id. at 5:9-12;
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`EX1026, ¶62. Claims 7-8 recite emulsions containing 0.05-0.40% CsA in 0.625-
`8
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`
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`5.00% castor oil, 1.00% polysorbate 80, 0.05% Pemulen® (an acrylate/C10- 30
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`alkyl acrylate cross-polymer), 2.20% glycerine, sodium hydroxide, and water, and
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`having a pH range of 7.2-7.6. EX1006, 4:4-5; id. at 6:27-42; EX1026, ¶65. Ding
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`’979 teaches that CsA is effective in treating dry eye disease/KCS “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; EX1026, ¶66. 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; EX1026,
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`¶¶67-68. 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; EX1026, ¶68. 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,
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`
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`9
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`
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`0435; EX1026, ¶¶68, 99. Ding ’979 does not expressly discuss twice-daily
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`administration of the emulsions.
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`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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`
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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-
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`32 & n.1; id. at figs. 1-4; EX1026, ¶¶74-75. Sall states 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; EX1026, ¶¶74-78, 81. Sall
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`does not expressly disclose the exact composition of the castor oil vehicle, but
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`compares the 0.05% and 0.10% CsA emulsions to the same vehicle. EX1007, 632;
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`EX1026, ¶74.
`
`
`
`10
`
`
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`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
`
`
`
`study in which CsA percentages ranging from 0.05%-0.4% were administered to
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`human patients with KCS twice a day for a period of three months. EX1008 at
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`1002; EX1026, ¶¶85-86. Acheampong measured CsA blood concentration at both
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`peak and trough levels following topical ophthalmic administration. EX1008 at
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`1002. No detectable amount of CsA was measured in patients receiving the 0.05%
`
`CsA emulsion. EX1008 at 1002, 1004; EX1026, ¶¶85-86.
`
`iv. U.S. Patent No. 5,578,586 to Glonek et al. (“Glonek,” EX1009)
`
`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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`EX1026, ¶¶88-89. Glonek discloses topical emulsions for the treatment of dry eye
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`disease, “whereby blurred vision is reduced.” EX1009, 3:5-6; EX1026, ¶88. In
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`comparing the relative amounts of surfactant and oil and their effects on visual
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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; EX1026, ¶89.
`
`
`
`11
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`
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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. EX1026, ¶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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`Teva’s expert, Dr. Walter Chambliss, is a Professor of Pharmaceutics at the
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`University of Mississippi. EX1025, ¶3; EX1026 (CV). Dr. Chambliss is also a
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`Research Professor in the Research Institute of Pharmaceutical Sciences at the
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`University of Mississippi. EX1025, ¶3; EX1026. Dr. Chambliss has authored over
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`twenty publications in the field of pharmaceutical development, including a book
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`chapter concerning delivery of pharmaceutical products to the eye. EX1025, ¶¶5;
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`EX1026. He worked for seventeen years in research and development in the
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`pharmaceutical industry at G.D. Searle, Bristol-Myers and Schering-Plough, where
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`he was involved in formulation development and/or process development of over
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`300 products. EX1025, ¶2; EX1026.
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`
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`12
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`
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`Dr. Chambliss received a B.S. in Pharmacy in 1977 and a Ph.D. in
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`Pharmaceutics in 1982 from the University of Mississippi, and he has experience
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`with ophthalmic pharmaceutical emulsions, including numerous oil-based and
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`water-based formulations. EX1025, ¶¶ 1,7; EX1026. Dr. Chambliss is well
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`qualified as an expert, possessing the necessary scientific, technical, and other
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`specialized knowledge and training to assist in an understanding of the evidence
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`presented herein, as well as possessing the expertise necessary to determine and
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`explain the level of ordinary skill in the art as of September 2003. EX1026.
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`III. GROUNDS FOR STANDING
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`Petitioner certifies that, under 37 C.F.R. § 42.104(a), the ’048 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 ’048 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 ’048 patent was previously filed by Apotex Corp.
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`and Apotex Inc. as IPR2015-01284, as were petitions for related U.S. Patent Nos.
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`8,629,111 (IPR2015-01282), 8,633,162 (IPR2015-01278), 8,642,556 (IPR2015-
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`01286 ), and 8,685,930 (IPR2015-01283), but all were terminated prior to
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`institution decisions.
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`An IPR petition for the ’048 patent was previously filed by Mylan as
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`IPR2016-01130 and has been instituted.
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`IPR petitions for related 8,685,930 (IPR2016-01127), 8,629,111 (IPR2016-
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`01128), 8,642,556 (IPR2016-01129), 8,633,162 (IPR2016-01130) and 9,248,191
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`(IPR2016-01132) have been filed by Mylan and have been instituted. U.S.
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`Application No. 15/011,159, filed January 29, 2016, claims the benefit of U.S.
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`Application No. 14/222,478 (now the ’191 patent), which is a continuation, via
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`U.S. 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 (IPR2017-00576),
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`8,629,111 (IPR2017-00578), 8,642,556 (IPR2017-00579), 8,633,162 (IPR2017-
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`00583) 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 ’048 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 Texaas (EX10233). Petitionner also ideentifies thee followingg pending aactions
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`involvinng the ’0488 patent: Allergan, Innc., v. Innopopharma, InInc. and Pfifizer, Inc., NNo.
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`2:15cv11504, in thee Eastern DDistrict of Texas.
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`Lead annd Back-Upp Counsel (37 C.F.RR. § 42.8(b)) (3)):
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`Lead Counssel: Gary JJ. Speier (RReg. No. 455,458)
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`Back-Up Counsel: Maark D. Schhuman (Regg. No. 31,1197)
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`Service Informatioon (37 C.FF.R. § 42.8((b) (4)):
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`Petitioner hhereby conssents to eleectronic seervice.
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`Email: gspeeier@carlsoncaspers..com, mschhuman@caarlsoncasp
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`ers.com annd
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`IPRCycclosporine@@carlsoncaaspers.comm.
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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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`Minneapoolis, MN 555402
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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
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`Petitioners rrequest revview of claaims 1-23 oof the ’0488 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 Grounds raised in this Petition is meaningfully distinct. Ground
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`1 asserts obviousness of claims 1-10, 12-14, 16-20, and 22-23 based on Ding ’979
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`and Sall. Ground 2 challenges dependent claims 11 and 21, based Ding ’979, Sall,
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`and Acheampong. Acheampong expressly teaches the claimed emulsion results in
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`substantially no detectable blood concentration at trough and peak levels. Ground 3
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`challenges dependent claim 15 based on Ding ’979, Sall, and Glonek. Glonek
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`expressly teaches the reduction in blurring from more rapid emulsion break down,
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`and the relationship between break down rate and oil concentration.
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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, and 18-19 of the ’048 patent.
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`Claims 5, 10, and 19 state “the buffer is sodium hydroxide.” The patent states,
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`“[t]he pH of the emulsions can be adjusted in a conventional manner using sodium
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`hydroxide ... to a physiological pH level.” EX1001, 12:15-17. In light of the
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`specification, the broadest reasonable interpretation of the term “buffer” includes
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`sodium hydroxide. EX1026, ¶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 21 of the ’048 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, 5:64—6:3. A
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`skilled artisan could measure blood concentration at either peak or trough levels.
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`EX1026, ¶39. In light of the specification, broadest reasonable interpretation of the
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`phrase “substantially no detectable concentration” includes a blood concentration
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`below 0.1 ng/mL measured at either peak or trough levels.
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`C.
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`“effective,” “substantially therapeutically effective as,” and “as
`much therapeutic effectiveness as”
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`Independent claims 1 and 22 state the emulsion is “effective in increasing
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`tear production,” and independent claim 18 states the emulsion is “effective in
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`treating [KCS].” The ’048 patent characterizes KCS as “an absolute or partial
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`deficiency in aqueous tear production.” EX1001, 3:2-5. This is consistent with its
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`plain meaning. EX1022, 0003 (keratoconjunctivitis sicca is an “inflammation of
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`the conjunctiva and of the cornea” that is “associated with decreased tears” and is a
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`species of, and is often used interchangeably with, or as a partial synonym of, dry
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`eye disease); EX1026, ¶40. During prosecution, Patent Owner relied on an increase
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`in tearing to assert unexpected therapeutic efficacy of the claimed emulsion for
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`treating dry eye disease/KCS. EX1004, 0253; EX1026, ¶40. Thus, in the context of
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`the ’048 patent, an emulsion that is effective in increasing tear production is an
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`example of an emulsion therapeutically effective in treating dry eye disease/KCS.
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`Claims 13 and 14 respectively describe the emulsion of claim 1 as being “as
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`substantially therapeutically effective as” and having “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. EX1026, ¶¶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 treatment as well as
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`curative treatments.
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`D.
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`“adverse events” and “side effects”
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`Claims 16 recites that the emulsion of the claimed method has fewer
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`“adverse events” relative to a second emulsion, and claim 17 further recites that the
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`“adverse events” are “side effects.” The specification also defines adverse events to
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`include undesirable side effects. EX1001, 15:1-8. The plain meaning of “side
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`effects” is “A result of a drug or other therapy in addition to or in extension of the
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`desired therapeutic effect; usually but not necessarily, denoting an undesired
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`effect.” EX1022, 0006 (side effect). The broadest reasonable interpretation of the
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`term “adverse events” thus includes undesirable side effects, including burning
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`eye, stinging eye, and general eye pain. EX1026, ¶43.
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`E.
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`“breaks down”
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`Claim 15 recites that the first emulsion “breaks down” more quickly in the
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`eye of a human as compared to a second emulsion containing only 50% as much
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`castor oil.