Paper No. ____
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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`__________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`__________________________
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`ARGENTUM PHARMACEUTICALS LLC
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`Petitioner,
`
`v.
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`ALLERGAN, INC.,
`
`Patent Owner.
`
`__________________________
`
`U.S. Patent No. 8,629,111
`
`Inter Partes Review No. IPR2016-01232
`__________________________
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,629,111
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`WAS:286544.1
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`

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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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`TABLE OF CONTENTS
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`I.
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`INTRODUCTION ........................................................................................... 1
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`A. Overview of the ’111 Patent .................................................................. 2
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`B. Overview of the Prosecution History .................................................... 3
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`C. Overview of the Scope and Content of the Prior Art ............................ 7
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`Page
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`1.
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`2.
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`3.
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`U.S. Patent No. 5,474,979 to Ding et al. (“Ding ’979,”
`EX1006) ...................................................................................... 7
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`Sall et al., Two Multicenter, Randomized Studies of the
`Efficacy and Safety of Cyclosporine Ophthalmic Emulsion
`in Moderate to Severe Dry Eye Disease, 107
`Ophthamology 631 (2000) (EX1007) ......................................... 9
`
`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, in Lacrimal Gland, Tear Film, and Dry
`Eye Syndromes 2: Basic Science and Clinical Relevance
`1001 (eds. David A. Sullivan & Darlene A. Dartt 1998)
`(“Acheampong”) (EX1008) ........................................................ 9
`
`D. Overview of the Level of Skill in the Art ........................................... 10
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`II. GROUNDS FOR STANDING ...................................................................... 12
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`III. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8 ................................. 12
`
`IV. STATEMENT OF PRECISE RELIEF REQUESTED FOR EACH
`CLAIM CHALLENGED .............................................................................. 13
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`V.
`
`STATEMENT OF NON-REDUNDANCY .................................................. 14
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`VI. CLAIM CONSTRUCTION .......................................................................... 14
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`A.
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`“Buffer” ............................................................................................... 15
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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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`B.
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`C.
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`“Substantially No Detectable Concentration” ..................................... 15
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`“Effective” and “Therapeutically Effective” ...................................... 16
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`VII. BACKGROUND KNOWLEDGE IN THE ART PRIOR TO
`SEPTEMBER 15, 2003 ................................................................................. 17
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`VIII. DETAILED EXPLANATION OF GROUNDS FOR
`UNPATENTABILITY .................................................................................. 23
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`A.
`
`[Ground 1] Claims 1-27 are Anticipated under 35 U.S.C.
`§ 102(b) by Ding ’979 ......................................................................... 23
`
`1.
`
`2.
`
`3.
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`Claims 1-10, 12-15, and 18-19 ................................................. 23
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`Claims 17 and 20-27 ................................................................. 30
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`Claims 11 and 16....................................................................... 31
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`B.
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`[Ground 2] Claims 1-27 are Obvious under 35 U.S.C. § 103
`over Ding ’979 and Sall ...................................................................... 38
`
`1.
`
`2.
`
`3.
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`Claims 1-16, and 18-19 ............................................................. 38
`
`Claims 17, 20-27 ....................................................................... 41
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`Claims 11 and 16....................................................................... 42
`
`C.
`
`[Ground 3] Claims 11 and 16 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979, Sall, and Acheampong .................................... 46
`
`IX. NO OBJECTIVE INDICIA OF NON-OBVIOUSNESS .............................. 48
`
`A. No Unexpected Results ....................................................................... 48
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`B. No Evidence of Commercial Success ................................................. 60
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`C. No Industry Praise ............................................................................... 62
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`D. No Long-Felt, Unmet Need ................................................................. 62
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`E.
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`No Failure of Others ............................................................................ 63
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`X. ADDITIONAL ARGUMENTS AND/OR REASONING ............................ 63
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`A.
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`B.
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`Judicial Estoppel .................................................................................. 63
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`Later-Discovered Secondary Considerations ...................................... 64
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`C. Additional Legal Support for Anticipation ......................................... 65
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`D.
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`E.
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`Presumptive Enablement of Ding ‘979 ............................................... 66
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`Ding ‘979 Directs One to the Claimed Emulsion ............................... 66
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`XI. CONCLUSION .............................................................................................. 67
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`XII. CERTIFICATE OF COMPLIANCE ............................................................ 68
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`XIII. PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15(A) AND 42.103.......... 69
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`XIV. APPENDIX - LIST OF EXHIBITS .............................................................. 70
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`I.
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`INTRODUCTION
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`Argentum Pharmaceuticals LLC (“Petitioner”) requests review of U.S.
`
`Patent No. 8,629,111 to Acheampong et al. (“the ’111 patent,” EX1001) that
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`issued on January 14, 2014. PTO records indicate the ’111 patent is assigned to
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`Allergan, Inc. (“Patent Owner”). This Petition demonstrates a reasonable
`
`likelihood that claims 1-27 of the ’111 patent are unpatentable in view of the
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`identified prior art.
`
`The ’111 patent claims a topical ophthalmic emulsion as in related U.S.
`
`Patent No. 8,685,930 but further recites that cyclosporin A (“CsA”) is the only
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`peptide present in the emulsion. Each element of the emulsion, including the
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`claimed CsA and castor oil percentages, preferred ratios for combining them, and
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`CsA as the only peptide present in the emulsion, was disclosed in a single prior art
`
`reference (Ding ’979) for use in topical ophthalmic emulsions to treat the same dry
`
`eye disease, such as keratoconjunctivitis sicca (“KCS”). In fact, during
`
`prosecution of a parent application, applicants admitted that the claimed emulsion
`
`containing 0.05% CsA and 1.25% castor oil “is squarely within the teaching of the
`
`Ding [’979] reference” and “would have been obvious” to a person of skill in the
`
`art at the time of the invention. EX1005, 0435; EX1002, ¶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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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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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
`
`“equally or more therapeutically effective for the treatment of dry
`
`eye/keratoconjunctivitis sicca than the formulation containing 0.10% by weight
`
`cyclosporin A and 1.25% by weight castor oil.” EX1004, 0007, 0205; EX1002,
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`¶¶20-22. The supposed “unexpected results” are weak, at best, and fail to rebut the
`
`strong evidence of obviousness. The data relied upon by applicants lack scientific
`
`parameters necessary to demonstrate statistical significance and materiality and, in
`
`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
`
`claims, and merely confirms that the results were expected in view of and were
`
`already disclosed in the prior art.
`
`A. Overview of the ’111 Patent
`The ’111 patent has an earliest claimed priority date of September 15, 2003.
`
`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
`
`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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`specifies a range of pH values for the emulsion of claim 6, which comprises
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`glycerine and a buffer. Dependent claims 7-8 specify known weight percentages
`
`of polysorbate 80 and cross-polymer, respectively. Claim 11 recites that, when the
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`emulsion is administered to the eye, there is substantially no detectable
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`concentration of CsA in the blood.
`
`Independent claim 13 recites an emulsion incorporating the ingredients
`
`and/or weight percentage limitations of claims 1 and 7-9, and the pH value recited
`
`in claim 12. Dependent claims 14-17 specify that the buffer is sodium hydroxide,
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`the tonicity component is glycerine, the blood has substantially no detectable
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`concentration of CsA, and that the emulsion is effective in treating KCS.
`
`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 buffer.
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`Dependent claim 19 recites the same pH range as claims 1 and 13.
`
`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. 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
`
`patent. The ’163 application is a continuation, via U.S. applications 13/961,828
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`U.S. Patent No. 8,629,111
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`and 11/897,177, of U.S. application 10/927,857 (“the ’857 application,” EX1005),
`
`which 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,
`
`EX1002, ¶¶18-19, was “squarely within the teachings of Ding [’979]”:
`
`[A]pplicants 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, applicants acknowledged their
`
`prior admissions but claimed that newly-collected evidence supported the
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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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`patentability of the claims “[s]ince these comments have been filed.” EX1004,
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`0007. The examiner subsequently rejected the claims as obvious over Ding ’979.
`
`Id. at 0170-89. Patent Owner responded to the rejection, arguing that “the prima
`
`facie case of obviousness has not been properly established against the pending
`
`claims” and that the claims were patentable based on objective indicia. Id. at 0235.
`
`A terminal disclaimer was filed for the applications or parent 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, EX1002, ¶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. Relying on declarations submitted
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`by Drs. Schiffman and Attar, the examiner stated that “the specific combination of
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`0.05% by weight cyclosporin A with 1.25% by weight castor oil is surprisingly
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`critical for therapeutic effectiveness in the treatment of dry eye or [KCS]” and,
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`therefore, “demonstrate[s] surprising and unexpected results.” Id. at 0443.
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`The alleged “unexpected results” are addressed in the declaration of Dr.
`
`Dileep Bhagwat accompanying this Petition. EX1002, ¶¶122-46. As Dr. Bhagwat
`
`notes, applicants’ data lacks scientific parameters necessary to demonstrate
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`statistical significance and materiality. In many cases, the data appear to be
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`repackaged from graphs published in the prior art Sall reference asserted against
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`U.S. Patent No. 8,629,111
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`the claims in this Petition. Thus, applicants’ declarations do not demonstrate
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`surprising or unexpected results. Id.
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`During prosecution, the Patent Owner did not identify, and the examiner did
`
`not address, deficiencies in the Schiffman and Attar Declarations that made them
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`unreliable, which are discussed in this Petition. Considering the new information
`
`presented herein and supported by Dr. Bhagwat’s testimony, the Board ought not
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`defer to the examiner’s conclusions which relied on the one-sided information.
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`In addition to demonstrating the flaws in Patent Owner’s alleged unexpected
`
`results, Dr. Bhagwat’s declaration provides insight not previously presented to the
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`Patent Office about how a person of ordinary skill in the art would interpret
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`Ding ’979. Among other things, Dr. Bhagwat’s testimony establishes that the
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`presently claimed emulsion would have been immediately apparent to one of
`
`ordinary skill in the art based on Ding ’979. EX1002, ¶¶97-98, 114. The Patent
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`Owner’s alleged evidence of unexpected results cannot render patentable an
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`anticipated claim. In re Wiggins, 488 F.2d 538, 543 (C.C.P.A. 1973).
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`Further, this Petition presents new arguments based on expert testimony as
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`to why the claims are obvious over Ding ’979 and other references that were not
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`substantively analyzed during prosecution. Among other things, Dr. Bhagwat
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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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`U.S. Patent No. 8,629,111
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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. Overview of the Scope and Content of the Prior Art
`A prior art reference anticipates a claim if it discloses all elements of the
`
`claimed combination, or if the claimed combination would be “immediately
`
`apparent to one of ordinary skill in the art,” or “at once envisaged” from the prior
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`art reference. Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683 F.3d 1356,
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`1361 (Fed. Cir. 2012). An obviousness analysis requires an evaluation of any
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`differences between the claimed subject matter and the asserted prior art. Graham
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`v. John Deere Co. of Kansas City, 383 U.S. 1, 17-18 (1966). The obviousness
`
`inquiry may consider inferences that would be employed by a person of ordinary
`
`skill in the art. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
`
`1.
`
`U.S. Patent No. 5,474,979 to Ding et al. (“Ding ’979,”
`EX1006)
`
`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
`
`treatment of KCS or “dry eye disease/KCS.” Id. at 5:9-12; EX1002, ¶61. Claims
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`7-8 recite emulsions containing 0.05-0.40% CsA in 0.625-5.00% castor oil, 1.00%
`
`polysorbate 80, 0.05% Pemulen® (an acrylate/C10-30 alkyl acrylate cross-
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`U.S. Patent No. 8,629,111
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`polymer), 2.20% glycerine, sodium hydroxide, and water, and having a pH range
`
`of 7.2-7.6. EX1006, 4:4-5; id. at 6:27-42; EX1002, ¶64. Ding ’979 teaches that
`
`CsA is effective in treating dry eye disease/KCS “as an immunosuppressant and in
`
`the enhancement or restoring of lacrimal gland tearing.” EX1006, 1:10-16, 37-39.
`
`Ding ’979 discloses four examples of castor oil-based vehicles (Examples
`
`2A-D) for delivery of CsA. EX1006, 4:44-54; EX1002, ¶65. Example 2C is the
`
`exact same castor oil vehicle used in the challenged claims. Ding ’979 discloses
`
`CsA-containing emulsions in Example 1 using the vehicles from Example 2.
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`EX1006, 4:32-54. Example 1’s emulsions have CsA and castor oil percentages
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`covering the ranges disclosed in claims 7 and 8 (0.05%–0.40% CsA and 0.625%–
`
`5.00% castor oil) of Ding ’979. Id. at 4:32-43; EX1002, ¶¶66, 70. One emulsion
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`(Example 1D) specifically used the 1.25% castor oil vehicle (Example 2C) to
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`deliver 0.10% CsA. EX1006, 4:32-43.
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`Ding ’979 identifies a “more preferred” range for the ratio of CsA to castor
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`oil of 0.02-0.12. Id. at 3:17-20; EX1002, ¶67. Each exemplified CsA-containing
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`emulsion in Ding ’979 falls within a narrower ratio range of 0.04-0.08, which, for
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`the 1.25% castor oil vehicle (Example 2C) disclosed in Ding ’979, equates to a
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`CsA range of 0.05% to 0.10% CsA. EX1006, 4:32-43; EX1005, 0435; EX1002,
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`¶¶67, 94. Ding ’979 does not expressly discuss twice-daily administration of the
`
`emulsions.
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`U.S. Patent No. 8,629,111
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`2.
`
`Sall et al., Two Multicenter, Randomized Studies of the Efficacy
`and Safety of Cyclosporine Ophthalmic Emulsion in Moderate
`to Severe Dry Eye Disease, 107 Ophthamology 631 (2000)
`(EX1007)
`
`Sall is prior art under 35 U.S.C. § 102(b). Sall describes a multi-center,
`
`randomized, double-masked Phase 3 clinical trial that assesses the safety and
`
`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,
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`631-32 & n.1; id. at figs. 1-4; EX1002, ¶¶73-74. Sall teaches the 0.05% CsA
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`emulsion was safe and effective, was at least as effective as the 0.10% CsA
`
`emulsion, and resulted in fewer adverse side effects and in trough CsA blood
`
`concentrations below 0.1 ng/mL. EX1007, 631, 634-37; EX1002, ¶¶73-77, 80.
`
`Sall does not expressly disclose the exact composition of the vehicle, but compares
`
`the 0.05% and 0.10% CsA emulsions to the same vehicle. EX1007, 632; EX1002,
`
`¶¶111-12.
`
`3.
`
`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, in Lacrimal Gland, Tear Film, and Dry Eye
`Syndromes 2: Basic Science and Clinical Relevance 1001 (eds.
`David A. Sullivan & Darlene A. Dartt 1998) (“Acheampong”)
`(EX1008)
`
`Acheampong is prior art under 35 U.S.C. § 102(b). Acheampong describes
`
`administration of CsA formulations having from 0.05%-0.4% twice-a-day to
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`human patients with KCS for three months. EX1008, 1002; EX1002, ¶¶85-86.
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`Acheampong measured CsA blood concentration at both peak and trough levels
`
`following topical ophthalmic administration. EX1008, 1002. No detectable
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`amount of CsA was measured in patients receiving the 0.05% CsA emulsion.
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`EX1008, 1002, 1004; EX1002, ¶¶85-86.
`
`D. 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
`
`products; (b) experience designing and preparing drug emulsions intended for
`
`topical ocular administration; and (c) the ability to understand results and findings
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`presented or published by others in the field. EX1002, ¶36. Typically this person
`
`would have an advanced degree, such as a medical degree, or a Ph.D. in organic
`
`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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`Petitioner’s expert, Dr. Dileep Bhagwat, is a Senior Pharmaceutical
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`Consultant and the CEO of WPDC, LLC which focuses on consulting on
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`pharmaceutical (formulation) development, quality, clinical and global regulatory
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`filings. In this capacity, Dr. Bhagwat has consulted for U.S. and foreign
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`companies. EX1002, ¶1; EX1003. Dr. Bhagwat received an M.S. and Ph.D. in
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`Industrial Pharmacy from St. John’s University, New York. He also received an
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`MBA in International Business from Pace University, New York, and a B.S.in
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`Pharmacy from Bombay University, India.
`
`Dr. Bhagwat has worked in the pharmaceutical industry for over 35 years.
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`His work encompasses pharmaceutical research and development and
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`pharmaceutical quality, manufacturing, regulations. He has worked on many
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`dosage forms, for example solid/liquid oral (immediate released/controlled
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`release), sub-lingual, intra-nasal, topicals (patches/creams/lotions/gels/emulsions),
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`injectables, and metered dose inhalers. Dr. Bhagwat has been responsible for all
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`aspects of drug product development (Phase I – III).
`
`Dr. Bhagwat is an inventor on 16 U.S. issued patents plus numerous
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`international patents. He has lectured and presented at various pharmaceutical and
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`medical conferences including at the American Association of Pharmaceutical
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`Scientists (AAPS), American Pain Society (APS), European Hematology
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`Association, American Society of Hematology (ASH), and the Controlled Release
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`Society.
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`Dr. Bhagwat is well qualified as an expert, possessing the necessary
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`scientific, technical, and other specialized knowledge and training to assist in an
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`understanding of the evidence presented herein, as well as possessing the expertise
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`U.S. Patent No. 8,629,111
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`necessary to determine and explain the level of ordinary skill in the art as of
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`September 2003. EX1003.
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`II. GROUNDS FOR STANDING
`Petitioner certifies that, under 37 C.F.R. § 42.104(a), the ’111 patent is
`
`available for inter partes review, and Petitioner is not barred or estopped from
`
`requesting inter partes review of the ’111 patent on the grounds identified.
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`III. MANDATORY NOTICES UNDER 37 C.F.R. § 42.8
`Real Parties-in-Interest (37 C.F.R. § 42.8(b)(1)): The following real parties-
`
`in-interest are identified: KVK-TECH, Inc.; Argentum Pharmaceuticals LLC;
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`Intelligent Pharma Research LLC; APS GP LLC; and APS GP Investors LLC.
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`Related Matters (37 C.F.R. § 42.8(b)(2)): An IPR petition for the ’111
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`patent was filed by Apotex Corp. and Apotex Inc. as IPR2015-01282, as were
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`petitions for related U.S. Patent Nos. 8,648,048 (IPR2015-01284), 8,633,162
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`(IPR2015-01278), 8,642,556 (IPR2015-01286), and 8,685,930 (IPR2015-01283),
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`but all were terminated before institution decisions. U.S. Application No.
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`15/011,159, filed January 29, 2016, claims the benefit of U.S. Application No.
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`14/222,478 (the ’191 patent), which is a continuation, via U.S. Application Nos.
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`13/961,828 and 11/897,177, of the ’857 application.
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`Petitioner also identifies the following pending, consolidated actions
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`involving the ’111 patent: (i) Allergan, Inc. v. Innopharma, Inc., No. 2:15cv1504
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`WAS:286544.1
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`

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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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`(E.D. Tex. filed Sept. 8, 2015) (EX 1025); (ii) Allergan, Inc. v. Teva
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`Pharmaceuticals USA, Inc., No. 2:15-cv-01455 (E.D. Tex. filed Aug. 24, 2015)
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`(EX 1023); and (iii) Allergan, Inc. v. Famy Care Ltd., No. 16-00401 (E.D. Tex.
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`filed Apr. 12, 2016) (EX 1026).
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`Lead/Back-Up Counsel (37 C.F.R. § 42.8(b)(3)):
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`Lead Counsel: Matthew J. Dowd (Reg. No. 47,534)
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`Back-Up Counsel: John Murray (Reg. No. 61,497)
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`Service Information (37 C.F.R. § 42.8(b)(4)):
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`Petitioner consents to electronic service.
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`Email: MatthewDowd@andrewskurth.com;
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`JohnMurray@andrewskurth.com
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`Post:
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`Andrews Kurth, LLP
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`1350 I Street NW, Suite 1100
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`Washington, D.C. 20005
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`Phone: (202) 662-2701
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`Fax: (202) 974-9511
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`IV. STATEMENT OF PRECISE RELIEF REQUESTED FOR EACH
`CLAIM CHALLENGED
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`Petitioner requests review of claims 1-27 of the ’111 patent under 35 U.S.C.
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`§ 311 and AIA § 6 and that each claim be canceled as unpatentable:
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`WAS:286544.1
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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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`Description
`Ground Claims
`Anticipated under §102 by Ding ’979
`1
`1-27
`Obvious under §103 over Ding ’979 and Sall
`2
`1-27
`3
`11 and 16 Obvious under §103 over Ding ’979, Sall, and Acheampong
`
`
`V.
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`STATEMENT OF NON-REDUNDANCY
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`Each Ground raised in this Petition is meaningfully distinct. Ground 1
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`asserts anticipation of claims 1-27 based on Ding ’979. Ground 2 asserts
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`obviousness of claims 1-27 based on Ding ’979 and Sall. Sall expressly teaches
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`certain intrinsic properties of the claimed emulsion, including efficacy, relative
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`efficacy, and substantially no detectable blood concentration at trough levels, and
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`provides additional reasons to make and use the claimed emulsion to treat dry eye
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`disease. Ground 3 asserts obviousness of dependent claims 11 and 16 based on
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`Ding ’979, Sall, and Acheampong. Acheampong expressly teaches the claimed
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`emulsion results in substantially no detectable blood concentration at trough and
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`peak levels.
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`VI. CLAIM CONSTRUCTION
`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);
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`Cuozzo Speed Techs., LLC v. Lee, No. 15-446, 2016 WL 1626647 (U.S. June 20,
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`2016). Claim terms are also “generally given their ordinary and customary
`
`meaning,” which is the meaning that the term would have to a person of ordinary
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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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`skill in the art at the time of the invention in view of the specification. In re
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`Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). Under either
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`standard, there is a reasonable likelihood that Petitioner will prevail with respect to
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`the challenged claims. A few terms are discussed below.
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`“Buffer”
`
`A.
`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 recite “the buffer is sodium hydroxide.” The patent states
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`that “[t]he pH of the emulsions can be adjusted in a conventional manner using
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`sodium hydroxide ... to a physiological pH level.” EX1001, 12:17-18. In light of
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`the specification, the broadest reasonable interpretation of the term “buffer”
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`includes sodium hydroxide. EX1002, ¶38.
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`“Substantially No Detectable Concentration”
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`B.
`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, cyclosporin concentration is preferably determined
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`“using a liquid chromatography-mass spectroscopy-mass spectroscopy,” which has
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`a cyclosporin component detection limit of 0.1 ng/mL.” EX1001, 5:65–6:4.
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`Concentrations lower than “0.1 ng/ml are therefore considered substantially
`
`undetectable.” Id. A skilled artisan could measure blood concentration at either
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`peak or trough levels. EX1002, ¶39. Accordingly, the broadest reasonable
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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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`interpretation of the phrase “substantially no detectable concentration” includes a
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`blood concentration below 0.1 ng/mL measured at either peak or trough levels.
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`“Effective” and “Therapeutically Effective”
`
`C.
`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,
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`or treating KCS. The ’111 patent characterizes KCS as “an absolute or partial
`
`deficiency in aqueous tear production.” EX1001, 3:3-6. This is consistent with its
`
`plain meaning. EX1022 at 0003 (KCS is an “inflammation of the conjunctiva and
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`of the cornea” that is “associated with decreased tears” and is a species of, and is
`
`often used interchangeably with, or as a partial synonym of, dry eye disease);
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`EX1002, ¶¶40-41. During prosecution, Patent Owner relied on an increase in
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`tearing to assert unexpected therapeutic efficacy of the claimed emulsion for
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`treating dry eye disease/KCS. EX1004, 0253; EX1002, ¶42. The plain meaning of
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`the word “therapeutic” includes palliative (remediating) treatments as well as
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`curative treatments. EX1002, ¶¶43-44; EX1022 at 0007 (therapeutic), 0004
`
`(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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`WAS:286544.1
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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
`VII. BACKGROUND KNOWLEDGE IN THE ART PRIOR TO
`SEPTEMBER 15, 2003
`
`The background publications below reflect knowledge skilled artisans would
`
`bring to bear in reading the prior art at the time of the invention, i.e., September 15,
`
`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
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`v. Verinata Health, Inc., 805 F.3d 1359, 1364 (Fed. Cir. 2015). The knowledge of
`
`a skilled artisan is part of the store of public knowledge that must be consulted
`
`when considering whether a claimed invention would have been obvious. KSR,
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`550 U.S. at 406; Genzyme Therapeutic Prods. Ltd. P’ship v. Biomarin Pharm. Inc.,
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`Nos. 2015-1720, -1721, slip op. at 9-14 (Fed. Cir. June 14, 2016); Randall Mfg. v.
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`Rea, 733 F.3d 1355, 1362-63 (Fed. Cir. 2013).
`
`Prior to September 15, 2003, it was known that inflammation contributed to
`
`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 Archives of
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`Ophthalmology 1489 (2000) (“Kunert,” EX1012); EX1002, ¶47. CsA, a known
`
`anti-inflammatory agent, had been shown to significantly reduce inflammation
`
`markers associated with dry eye upon topical ophthalmic administration. EX1012,
`
`1489; EX1002, ¶48. Dry eye disease was defined in the art as, “a deficiency in
`
`either the aqueous or mucin components of the precorneal tear film. The most
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`Petition for Inter Partes Review IPR2016-01232
`U.S. Patent No. 8,629,111
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`commonly encountered aqueous-deficient dry eye in the United States is [KCS].”
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`Medications for Dry Eye (1999) in Physicians’ Desk Reference for Ophthalmology
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`(27th ed.) Montvale, NJ: PDR Network (“Ophthalmic PDR,” EX1013) at 13. The
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`Ophthalmic PDR also notes that a topical CsA therapy, Sandimmune®, was readily
`
`available and was prescribed for ocular disorders including conjunctivitis an