Paper No.
`Filed: January 6, 2017
`
`Filed on behalf of Teva Pharmaceuticals USA, Inc.
`By: Gary J. Speier
`
`Mark D. Schuman
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`CARLSON, CASPERS, VANDENBURGH,
`
`LINDQUIST & SCHUMAN, P.A.
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`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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`
`
`TEVA PHARMACEUTICALS USA, INC.
`Petitioner,
`
`v.
`
`ALLERGAN, INC.,
`Patent Owner.
`
`
`
`Case No. IPR2017-00578
`Patent No. 8,629,111
`
`
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,629,111
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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 
`
`A. Brief Overview of the ’111 Patent ........................................................ 3 
`
`B. Brief Overview of the Prosecution History ........................................... 4 
`
`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 (200) (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 
`
`D. Brief Overview of the Level of Skill in the Art .................................. 11 
`
`III.  GROUNDS FOR STANDING ............................................................................... 13 
`
`IV.   Mandatory Notices Under 37 C.F.R. § 42.8 .................................................. 13 
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`V.  
`
`Statement of the Precise Relief Requested for Each Claim Challenged ....... 15 
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`VI.  STATEMENT OF NON-REDUDANCY ................................................................. 15 
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`VII. CLAIM CONSTRUCTION ................................................................................... 16 
`
`A.
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`B.
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`C.
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`“buffer” ................................................................................................ 16 
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`“substantially no detectable concentration” ........................................ 17 
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`“effective,” and “therapeutically effective” ........................................ 17 
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`i
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`VIII.  Background Knowledge in the Art Prior to September 15, 2003 ................. 18 
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`IX.  Detailed Explanation of Grounds for Unpatentability .................................. 24 
`
`A.
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`[Ground 1] Claims 1-27 are Anticipated under 35 U.S.C.
`§ 102(b) by Ding ’979 ......................................................................... 24 
`
`i.
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`Claims 1-10, 12-15, and 18-19 ................................................. 24 
`
`ii. Claims 17, 20-27 ....................................................................... 31 
`
`iii. Claims 11 and 16....................................................................... 32 
`
`B.
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`[Ground 2] Claims 1-27 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979 and Sall ............................................................ 40 
`
`i.
`
`Claims 1-16, and 18-19 ............................................................. 40 
`
`ii. Claims 17, 20-27 ....................................................................... 43 
`
`iii. Claims 11 and 16....................................................................... 44 
`
`C.
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`[Ground 3] Claims 11 and 16 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979, Sall, and Acheampong .................................... 49 
`
`X.   No Objective Indicia of Non-Obviousness .................................................... 50 
`
`A. No Unexpected Results ....................................................................... 51 
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`B. No Evidence of Commercial Success ................................................. 62 
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`C. No Industry Praise ............................................................................... 64 
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`D. No Long-Felt, Unmet Need ................................................................. 64 
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`E. No Failure of Others ............................................................................ 65 
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`XI.   CONCLUSION ................................................................................................... 66 
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`XII.   CERTIFICATE OF COMPLIANCE ........................................................................ 67 
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`XIII.  PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15(A) AND 42.103 ....................... 68 
`
`XIV. APPENDIX – LIST OF EXHIBITS ......................................................................... 69 
`
`
`
`ii
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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.
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`8,629,111 to Acheampong et al. (“the ’111 patent,” EX1001) that issued on
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`January 14, 2014. PTO records indicate the ’111 patent is assigned to Allergan,
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`Inc. (“Patent Owner”). This Petition demonstrates, by a preponderance of the
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`evidence, that there is a reasonable likelihood that claims 1-27 of the ’111 patent
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`are unpatentable for failure to distinguish over the asserted prior art. Additional
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`petitions are being filed to address related patents that are assigned to Patent
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`Owner. All challenged patents are continuations from the same family and are
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`terminally disclaimed over one another. The patents claim an ophthalmic emulsion
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`for the treatment of overlapping ocular disorders, or conventional methods of
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`administering the emulsion.
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`In particular, the ’111 patent claims a topical ophthalmic emulsion as in
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`related U.S. Patent No. 8,685,930, but further recites that cyclosporin A (“CsA”) is
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`the only peptide present in the emulsion. Each element of the emulsion, however,
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`including the claimed CsA and castor oil percentages, preferred ratios for
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`combining them, and CsA as the only peptide present in the emulsion, was
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`disclosed in a single prior art reference (Ding ’979) for use in topical ophthalmic
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`1
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`emulsions to treat the same dry eye disease, such as keratoconjunctivitis sicca
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`(“KCS”). In fact, during prosecution of a parent application, applicants admitted
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`that the claimed emulsion containing 0.05% CsA and 1.25% castor oil “is squarely
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`within the teaching of the Ding [’979] reference” and “would have been obvious”
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`to a person of skill in the art at the time of the invention. EX1005, 0435; EX1025,
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`¶18.
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`Four years later, in prosecuting the ’111 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. The supposed “unexpected results” are weak, at best, and fail to rebut the
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`strong evidence of obviousness. The data relied upon by applicants lack scientific
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`parameters necessary to demonstrate statistical significance and materiality and, in
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`many cases, appear to be copies of graphs from a 102(b) prior art reference, Sall.
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`Thus, Patent Owner’s cited evidence does not support non-obviousness of the
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`claims, and merely confirms that the results were expected in view of and were
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`already disclosed in the prior art.
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`2
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`II. OVERVIEW
`
`
`
`The Board has already issued its Decision Instituting Inter Partes Review
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`(“Decision”) on all challenged claims of the ’111 patent on the same grounds
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`raised herein.
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`Ground 1: Claims 1−27 under 35 U.S.C. § 102(b) as anticipated by Ding
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`’979;
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`Ground 2: Claims 1−27 under 35 U.S.C. § 103(a) as obvious over the
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`combination of Ding ’979 and Sall; and
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`Ground 3: Claims 11 and 16 under 35 U.S.C. § 103(a) as obvious over the
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`combination of Ding ’979, Sall, and Acheampong.
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`Mylan Pharmaceuticals Inc. v. Allergan Inc., IPR2016-01128 (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 ’111 Patent
`
`The ’111 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 in 1.25% castor oil,
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`polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer (“cross-polymer”)
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`and water, wherein CsA is the only peptide present in the emulsion. Claims 2-6
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`and 9-10 recite that the emulsion comprises a tonicity or demulcent agent,
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`specifically glycerine, and/or a buffer, specifically sodium hydroxide. Claim 12
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`3
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`specifies a range of pH values for the emulsion of claim 6, which comprises
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`glycerine and a buffer. Claims 7-8 are dependent claims that specify known weight
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`percentages of polysorbate 80 and cross-polymer, respectively. Claim 11 recites
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`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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`Independent claim 13 recites an emulsion incorporating the ingredients
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`and/or weight percentage limitations of claims 1 and 7-9, and the pH value recited
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`in claim 12. Dependent claims 14-17 further specify that the buffer is sodium
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`hydroxide, the tonicity component is glycerine, the blood has substantially no
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`detectable concentration of CsA, and that the emulsion is effective in treating KCS.
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`Independent claim 18 recites the same emulsion as claim 13 but specifies
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`glycerine as the tonicity/demulcent agent and sodium hydroxide as the buffer.
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`Dependent claim 19 recites the same pH range as claims 1 and 13.
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`Claims 20-22 depend from claim 1, claims 23-24 depend from claim 13, and
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`claims 25-27 depend from claim 18. Claims 20, 23, and 25, claims 21 and 26, and
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`claims 22, 24, and 27, respectively recite that the emulsion is therapeutically
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`effective in treating dry eye disease or KCS, or in increasing tear production.
`
`B.
`
`Brief Overview of the Prosecution History
`
`U.S. Patent Application No. 13/967,163 (“the ’163 application”) was filed
`
`on August 14, 2013, and issued five months later on January 14, 2014, as the ’111
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`4
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`

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`patent. The ’163 application is a continuation, via U.S. applications 13/961,828
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`and 11/897,177, of U.S. application 10/927,857 (“the ’857 application,” EX1005),
`
`which further claims the benefit of U.S. provisional application 60/503,137, filed
`
`September 15, 2003.
`
`During prosecution of the related ’857 application, Patent Owner admitted
`
`that Composition II, which is identical to the emulsion claimed in the ’111 patent
`
`(EX1025, ¶¶18-19), was “squarely within the teachings of Ding [’979]”:
`
`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.
`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).
`
`During prosecution of the ’163 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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`5
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`0170-89. Patent Owner responded to the rejection, nakedly asserting that “the
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`prima facie case of obviousness has not been properly established against the
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`pending claims,” but arguing that the claims were patentable based on objective
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`indicia. Id. at 0235. It also filed a terminal disclaimer for the applications or parent
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`applications that resulted in the ’930, ’556, ’162, ’048, and ’191 patents. Id. at
`
`0159-60.
`
`In remarks accompanying a Notice of Allowance (id. at 0428; EX1025, ¶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, 0439-41. 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 0443.
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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, ¶¶122-46. 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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`6
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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. EX1025, ¶¶97-98,
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`114. The Patent Owner’s alleged evidence of unexpected results cannot render
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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).
`
`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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`7
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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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`that would be employed by a person of ordinary skill in the art. 550 U.S. 398, 418
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`(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.
`
`
`
`§ 102(b). EX1006. Ding ’979 teaches topical ophthalmic emulsions for the
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`8
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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/KCS “as an
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`immunosuppressant and in the enhancement or restoring of lacrimal gland tearing.”
`
`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 discloses
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`CsA-containing emulsions in Example 1 using the vehicles from Example 2.
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`EX1006, 4:32-54. The emulsions in Example 1 have CsA and castor oil
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`percentages covering the ranges disclosed in claims 7 and 8 (0.05% - 0.40% CsA
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`and 0.625% - 5.00% castor oil) of Ding ’979. Id. at 4:32-43; EX1025, ¶¶66, 70.
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`One emulsion (Example 1D) specifically used the 1.25% castor oil vehicle
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`(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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`9
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`

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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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`0435; EX1025, ¶¶67, 94. Ding ’979 does not expressly discuss twice-daily
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`administration of the emulsions.
`
`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; EX1025, ¶¶73-74. Sall teaches the 0.05% CsA emulsion
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`was safe and effective, was at least as effective as the 0.10% CsA emulsion, and
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`resulted in fewer adverse side effects and in trough CsA blood concentrations
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`below 0.1 ng/mL. EX1007, 631, 634-37; EX1025, ¶¶73-77, 80. Sall does not
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`expressly disclose the exact composition of the vehicle, but compares the 0.05%
`
`and 0.10% CsA emulsions to the same vehicle. EX1007, 632; EX1025, ¶¶111-12.
`
`
`
`10
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`

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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
`
`human patients with KCS twice a day for a period of three months. EX1008 at
`
`1002; EX1025, ¶¶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; EX1025, ¶¶85-86.
`
`D. Brief Overview of the Level of Skill in the Art
`
`A person of ordinary skill in the relevant field as of September 15, 2003
`
`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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`
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`11
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`

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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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`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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`
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`12
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`

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`III. GROUNDS FOR STANDING
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`Petitioner certifies that, under 37 C.F.R. § 42.104(a), the ’111 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 ’111 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 ’111 patent was previously filed by Apotex Corp.
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`and Apotex Inc. as IPR2015-01282, as were petitions for related U.S. Patent Nos.
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`8,648,048 (IPR2015-01284), 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 ’111 patent was previously filed by Mylan as
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`IPR2016-01128 and has been instituted.
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`IPR petitions for the related patents 8,685,930 (IPR2016-1127), 8,642,556
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`(IPR2016- 01129), 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 (IPR2017-00576),
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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 ’111 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 ’111 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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`CLAIM
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`STATEMENT OF THE PPRECISE RRELIEF REQ
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`V.
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`PPetitioners rrequest revview of claaims 1-27 oof the ’1111 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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`VI. SSTATEMENT OF NON--REDUDANNCY
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`EEach of the Grounds rraised in thhis Petitionn is meaninngfully disttinct. Grouund
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`ion of claimms 1-27 baased on Diing ’979. GGround 2 aasserts
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`obvioussness of claaims 1-27 bbased on DDing ’979 aand Sall. SSall expresssly teachess
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`certain iintrinsic prroperties oof the claimmed emulsiion, includiing efficaccy, relativee
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`efficacyy, and subsstantially nno detectable blood cooncentratioon at trouggh levels, aand
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`providees additionaal reasons tto make annd use the
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`claimed emmulsion to
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`disease. Ground 3 asserts obviousness of dependent claims 11 and 16 based Ding
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`’979, Sall, and Acheampong. Acheampong expressly teaches the claimed emulsion
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`results in substantially no detectable blood concentration at trough and peak levels.
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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 13-14 of the ’111 patent.
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`Claims 5, 10, and 14 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, 12:17-18. In light of the
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`specification, the broadest reasonable interpretation of the term “buffer” includes
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`sodium hydroxide. 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 16 of the ’111 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, 5:65–6:4. 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,” and “therapeutically effective”
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`Dependent claims 17 and 20-27 state the emulsion is “effective” or
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`“therapeutically effective” in increasing tear production, treating dry eye disease or
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`treating KCS. The ’111 patent characterizes KCS as “an absolute or partial
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`deficiency in aqueous tear production.” EX1001, 3:3-6. 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); EX1025, ¶¶40-41. During prosecution, Patent Owner relied on an
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`increase in tearing to assert unexpected therapeutic efficacy of the claimed
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`emulsion for treating dry eye disease/KCS. EX1004, 0253; EX1025, ¶42. The plain
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`meaning of the word “therapeutic” includes palliative (remediating) treatments as
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`well as curative treatments. EX1025, ¶¶43-44; EX1022, 0007 (therapeutic), 0004
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`(palliative), 0005 (remedy). Thus, in the context of the ’111 patent, an emulsion
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`that is effective in increasing tear production is an example of an emulsion
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`therapeutically effective in treating dry eye disease/KCS.
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`VIII. BACKGROUND KNOWLEDGE IN THE ART PRIOR TO SEPTEMBER 15, 2003
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`The background publications below reflect knowledge skilled artisans would
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`bring to bear in reading the prior art at the time of the invention, i.e., September 15,
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`2003, and thereby assist in understanding why one would have been motivated to
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`combine or modify the references as asserted in this Petition. Ariosa Diagnostics v.
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`Verinata Health, Inc., No. 15-1215, slip op. 1, 11-12 (Fed. Cir. Nov. 16, 2015). As
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`established in KSR, 550 U.S. at 406, the knowledge of a skilled artisan is part of
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`the store of public knowledge that must be consulted when considering whether a
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`claimed invention would have been obvious. Randall Mfg. v. Rea, 733 F.3d 1355,
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`1362-63 (Fed. Cir. 2013).
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`Prior to September 15, 2003, it was known that inflammation contributed to
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`dry eye diseases such as KCS. E.g., K. Kunert et al., Analysis of Topical
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`Cyclosporine Treatment of Patients with Dry Eye Syndrome 118 ARCH.
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`OPHTHALMOL. 1489 (2000) (“Kunert,” EX1012); EX1025, ¶47. CsA, a known
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`anti-inflammatory agent, had been shown to significantly reduce inflammation
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`markers associated with dry eye upon topical ophthalmic administration. EX1012,
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`1489; EX1025, ¶48. Dry eye disease was defined in the art as, “a deficiency in
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`either the aqueous or mucin components of the precorneal tear film. The most
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`commonly encountered aqueous-deficient dry eye in the United States is
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`keratoconjunctivitis sicca [KCS].” Medications for Dry Eye (1999) In PHYSICIANS’
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`DESK REFERENCE FOR OPHTHALMOLOGY (27th ed.) Montvale, NJ: PDR Network
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`(“Ophthalmic PDR,” EX1013) at 13. The Ophthalmic PDR also notes that a topical
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`CsA therapy, Sandimmune®, was readily available, and was prescribed for ocular
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`disorders including conjunctivitis and keratitis. Id. at 18; EX