Paper No. ____
`Filed: June 3, 2016
`
`Filed on behalf of: Mylan Pharmaceuticals Inc.
`By: Steven W. Parmelee
`
`Michael T. Rosato
`Jad A. Mills
`WILSON SONSINI GOODRICH & ROSATI
`701 Fifth Avenue, Suite 5100
`Seattle, WA 98104-7036
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________________
`
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner,
`
`v.
`
`ALLERGAN, INC.,
`Patent Owner.
`
`_____________________________
`
`
`Case No. IPR2016-01129
`Patent No. 8,642,556
`
`_____________________________
`
`PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 8,624,556
`
`

`

`
`
`TABLE OF CONTENTS
`
`Page
`
`I. 
`
`INTRODUCTION ................................................................................................. 1 
`
`A. 
`
`B. 
`
`C. 
`
`D. 
`
`Brief Overview of the ’556 Patent ........................................................ 2 
`
`Brief Overview of the Prosecution History ........................................... 3 
`
`Brief Overview of the Scope and Content of the Prior Art ................... 6 
`
`Brief Overview of the Level of Skill in the Art .................................. 10 
`
`II. 
`
`GROUNDS FOR STANDING ............................................................................... 11 
`
`III.  MANDATORY NOTICES UNDER 37 C.F.R. § 42.8 ............................................ 11 
`
`IV.  STATEMENT OF THE PRECISE RELIEF REQUESTED ........................................... 12 
`
`V. 
`
`STATEMENT OF NON-REDUNDANCY ............................................................... 13 
`
`VI.  CLAIM CONSTRUCTION ................................................................................... 14 
`
`A. 
`
`B. 
`
`C. 
`
`D. 
`
`E. 
`
`“buffer” ................................................................................................ 14 
`
`“substantially no detectable concentration” ........................................ 14 
`
`“effective amount,” “therapeutically effective, “overall
`efficacy,” and “therapeutic effectiveness” .......................................... 15 
`
`“adverse events” and “side effects” .................................................... 16 
`
`“breaks down” ..................................................................................... 16 
`
`VII.  BACKGROUND KNOWLEDGE IN THE ART PRIOR TO SEPTEMBER 15, 2003 ...... 17 
`
`VIII.  DETAILED EXPLANATION OF GROUNDS FOR UNPATENTABILITY ................... 22 
`
`A. 
`
`[Ground 1] Claims 1-20 are Anticipated under 35 U.S.C.
`§ 102(b) by Ding ’979 ......................................................................... 22 
`
`i. 
`
`ii. 
`
`Claims 1-10 and 12-13 .............................................................. 22 
`
`Claim 14 .................................................................................... 29 
`
`-i-
`
`

`

`
`iii.  Claims 15-17 ............................................................................. 29 
`
`iv. 
`
`Claims 11 and 18-20 ................................................................. 30 
`
`B. 
`
`[Ground 2] Claims 1-20 are Obvious under 35 U.S.C. § 103
`over Ding ’979 and Sall ...................................................................... 34 
`
`i. 
`
`ii. 
`
`Claims 1-10, 12-13 .................................................................... 34 
`
`Claim 14 .................................................................................... 36 
`
`iii.  Claims 15-17 ............................................................................. 37 
`
`iv. 
`
`Claims 11 and 18-20 ................................................................. 38 
`
`C. 
`
`D. 
`
`E. 
`
`[Ground 3] Claims 14 and 19 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979, Sall, and Glonek .............................................. 41 
`
`[Ground 4] Claims 11, 18, and 20 are Obvious under 35 U.S.C.
`§ 103 over Ding ’979, Sall, and Acheampong .................................... 43 
`
`[Ground 5] Claim 19 is Obvious under 35 U.S.C. § 103 over
`Ding ’979, Sall, Glonek, and Acheampong ........................................ 45 
`
`IX.  NO OBJECTIVE INDICIA OF NON-OBVIOUSNESS .............................................. 45 
`
`A.  No Unexpected Results ....................................................................... 46 
`
`B. 
`
`C. 
`
`No Evidence of Commercial Success ................................................. 56 
`
`No Industry Praise. .............................................................................. 57 
`
`D.  No Long-Felt, Unmet Need ................................................................. 58 
`
`E. 
`
`No Failure of Others ............................................................................ 58 
`
`X. 
`
`CONCLUSION ................................................................................................... 59 
`
`XI.  CERTIFICATE OF COMPLIANCE ........................................................................ 60 
`
`XII.  PAYMENT OF FEES UNDER 37 C.F.R. §§ 42.15(A) AND 42.103 ....................... 61 
`
`XIII.  APPENDIX – LIST OF EXHIBITS ........................................................................ 62 
`
`-ii-
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`

`

`
`
`I.
`
`INTRODUCTION
`
`Mylan Pharmaceuticals Inc. (“Petitioner”) requests review of U.S. Patent
`
`No. 8,642,556 to Acheampong et al. (“the ’556 patent,” EX1001) that issued on
`
`February 4, 2014. PTO records indicate the ’556 patent is assigned to Allergan,
`
`Inc. (“Patent Owner”). This Petition demonstrates that there is a reasonable
`
`likelihood that claims 1-20 of the ’556 patent are unpatentable for failure to
`
`distinguish over the asserted prior art. Additional petitions are being filed to
`
`address related patents that are assigned to Patent Owner. All challenged patents
`
`are continuations from the same family and are terminally disclaimed over one
`
`another. The patents claim an ophthalmic emulsion for the treatment of
`
`overlapping ocular disorders, or conventional methods of administering the
`
`emulsion.
`
`The ’556 patent claims a topical ophthalmic emulsion as in related U.S.
`
`Patent No. 8,685,930, but further recites a comparative clause, where an effect of
`
`the emulsion is compared to a prior art emulsion. Yet each element of the claimed
`
`emulsion, including the claimed cyclosporin A (“CsA”) and castor oil percentages
`
`and other standard emulsion ingredients, was disclosed in a single prior art
`
`reference (Ding ’979) for the same therapeutic uses, i.e., treating dry eye disease.
`
`During prosecution of a parent application, applicants even 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.
`
`1
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`

`

`
`
`Four years later, in prosecuting the ’556 patent as a continuation application,
`
`applicants changed course and attempted to withdraw these admissions. EX1004,
`0007. They argued that data collected after their earlier admissions established
`
`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,
`
`¶¶20-22. But 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 previously published graphs
`
`from a 102(b) prior art reference, Sall. Thus, Patent Owner’s cited evidence does
`
`not support non-obviousness of the claims, and merely confirms that the results
`
`were already disclosed in the prior art.
`A. Brief Overview of the ’556 Patent
`The ’556 patent has an earliest claimed priority date of September 15, 2003.
`
`Independent claim 1 recites an emulsion of 0.05% CsA, 1.25% castor oil,
`
`polysorbate 80, acrylate/C10-30 alkyl acrylate cross-polymer (“cross-polymer”)
`
`and water that is therapeutically effective in treating dry eye disease and “provides
`
`overall efficacy substantially equal to a second topical ophthalmic emulsion
`
`comprising cyclosporin A in an amount of about 0.1% by weight and castor oil in
`
`an amount of about 1.25% by weight.” Claims 2-6 and 9-10 recite that the
`
`emulsion comprises a tonicity or demulcent agent, specifically glycerine, and/or a
`
`-2-
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`

`

`
`
`buffer, specifically sodium hydroxide. Claim 12 specifies a range of pH values for
`
`the emulsion of claim 6. Claims 7-8 are dependent claims that specify known
`
`weight percentages of polysorbate 80 and cross-polymer, respectively. Claim 11
`
`recites that when the emulsion is administered to the eye there is substantially no
`
`detectable concentration of CsA in the blood.
`
`Claims 13-15 are independent claims reciting the same emulsion ingredients
`
`as in claim 1. Claim 13 additionally recites that the emulsion is therapeutically
`
`effective in treating dry eye disease, and “achieves at least as much therapeutic
`
`effectiveness” as a second emulsion comprising 0.1% CsA and 1.25% castor oil.
`
`Claim 14 further recites that the emulsion “breaks down more quickly,” thereby
`
`reducing vision distortion, as compared to a second emulsion that contains only
`
`about 50% as much castor oil. Claims 15 further recites that the emulsion
`
`“demonstrates a reduction in adverse events” relative to a 0.1% CsA / 1.25% castor
`
`oil emulsion. Dependent claims 16 and 17 respectively specify that the adverse
`
`events are side effects and that the side effects are visual distortion or eye irritation.
`
`Claims 18, 19, and 20 respectively depend from claims 12, 14, and 15, and further
`
`specify that when the emulsion is administered there is “substantially no detectable
`
`concentration of cyclosporin A” in the human’s blood.
`B.
`U.S. Patent Application No. 13/967,189 (“the ’189 application”) was filed
`
`Brief Overview of the Prosecution History
`
`
`
`on August 14, 2013, and issued six months later on February 4, 2014, as the ’556
`
`patent. The ’189 application is a continuation, via U.S. applications 13/961,808
`
`and 11/897,177, of U.S. application 10/927,857 (“the ’857 application,” EX1005),
`
`-3-
`
`

`

`
`
`and 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 ’556 patent
`
`(EX1002, ¶¶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 ’189 application, the applicants acknowledged
`
`their prior admissions, but claimed that they had collected evidence to support the
`
`patentability of the claims “[s]ince these comments have been filed.” EX1004,
`
`0007. The examiner then rejected the claims as obvious over Ding ’979. Id. at
`
`0136-40. Patent Owner responded to the rejection, nakedly asserting that “the
`
`-4-
`
`

`

`
`
`prima facie case of obviousness has not been properly established,” but arguing
`
`that the claims were patentable based on objective indicia. Id. at 0200. It also filed
`
`a terminal disclaimer for the applications or parent applications that resulted in the
`
`’930, ’111, ’162, ’048, and ’191 patents. Id. at 0122-23.
`
`In remarks accompanying a Notice of Allowance (id. at 0408; EX1002, ¶23)
`
`the examiner stated that applicants had failed to demonstrate commercial success
`
`or long-felt need. EX1004, 0417-19. However, relying on declarations submitted
`
`by Drs. Schiffman and Attar, the examiner concluded that, “the specific
`
`combination of 0.05% by weight cyclosporin A with 1.25% by weight castor oil is
`
`surprisingly critical for therapeutic effectiveness in the treatment of dry eye or
`
`keratoconjunctivitis sicca,” and therefore, “demonstrate[s] surprising and
`
`unexpected results.” Id. at 0421.
`
`The alleged “unexpected results” are addressed in the declaration of Dr.
`
`Mansoor Amiji that accompanies this Petition. EX1002, ¶¶145-69. As noted by Dr.
`
`Amiji, the data presented by applicants lacked scientific parameters necessary to
`
`demonstrate statistical significance and materiality. In many cases, the data appear
`
`to be repackaged from graphs published in the prior art Sall reference that is
`
`presently asserted against the claims. Thus, the declarations do not support a
`
`finding of surprising or unexpected results. Id.
`
`During prosecution, the Patent Owner did not identify, and the examiner did
`
`not address, deficiencies in the Schiffman and Attar Declarations discussed in this
`
`Petition that made them unreliable. As such, and because of the new information
`
`presented herein and supported by Dr. Amiji’s testimony, the examiner’s
`
`-5-
`
`

`

`
`
`conclusions based on one-sided information should not receive any deference by
`
`the Board.
`
`In addition to demonstrating the flaws in Patent Owner’s alleged unexpected
`
`results, Dr. Amiji’s declaration also provides insight not previously presented to
`
`the Patent Office about how a person of ordinary skill in the art would interpret the
`
`disclosure of Ding ’979. Among other things, Dr. Amiji’s testimony establishes
`
`that the 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
`
`Owner’s alleged evidence of unexpected results cannot render patentable an
`
`anticipated claim. In re Wiggins, 488 F.2d 538, 543, (C.C.P.A. 1973).
`
`Further, this Petition presents new arguments based on expert testimony as
`
`to why the claims are obvious over Ding ’979 and other references that were not
`
`substantively analyzed during prosecution. Among other things, Dr. Amiji
`
`explains that the 1.25% castor oil emulsion vehicle of Example 2C in Ding ’979
`
`was the only vehicle that was most preferred for both the 0.05% and 0.10% CsA
`
`emulsions, and that Sall’s 0.05% and 0.10% CsA emulsions used the same castor
`
`oil vehicle. Petitioner provides an even stronger prima facie obviousness case than
`
`the examiner considered during prosecution. Accordingly, the Board should
`
`institute review without deference to the limited analysis during prosecution.
`C. Brief Overview of the Scope and Content of the Prior Art
`A prior art reference anticipates a claim if it discloses all of the elements of
`
`the claim in the claimed combination, or if the claimed combination would be
`
`“immediately apparent to one of ordinary skill in the art,” or “at once envisaged”
`
`-6-
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`

`

`
`
`from the prior art reference. Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC,
`
`683 F.3d 1356, 1361 (Fed. Cir. 2012). In obviousness cases, Graham v. John
`
`Deere Co. of Kansas City, requires an evaluation of any differences between the
`
`claimed subject matter and the asserted prior art. 383 U.S. 1, 17-18 (1966). As
`
`noted in KSR Int’l Co. v. Teleflex Inc., the obviousness inquiry may account for
`
`inferences that would be employed by a person of ordinary skill in the art. 550 U.S.
`
`398, 418 (2007).
`
`i. 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 keratoconjunctivitis sicca (“KCS” or “dry eye disease/KCS”). Id. at
`
`5:9-12; EX1002, ¶61. Claims 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-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 “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 also
`
`discloses CsA-containing emulsions in Example 1 using the vehicles from
`
`Example 2. EX1006, 4:32-54. The emulsions in Example 1 have CsA percentages
`
`-7-
`
`

`

`
`
`and castor oil percentages 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,
`
`¶¶66-67. One emulsion (Example 1D) specifically used the 1.25% castor oil
`
`vehicle (Example 2C) to deliver 0.10% CsA. EX1006, 4:32-43.
`
`Ding ’979 explicitly sets forth a “more preferred” range for the ratio of CsA
`
`to castor oil of 0.02-0.12. Id. at 3:17-20; EX1002, ¶67. Each of the exemplified
`
`CsA-containing emulsions in Ding ’979 fall within an even narrower ratio range of
`
`0.04-0.08, which, for the 1.25% castor oil vehicle (Example 2C) disclosed in Ding
`
`’979, equates to a CsA range of 0.05% to 0.10% CsA. EX1006, 4:32-43; EX1005,
`
`0435; EX1002, ¶¶67, 97.
`
`ii. Sall et al., Two Multicenter, Randomized Studies of the Efficacy
`and Safety of Cyclosporine Ophthalmic Emulsion in Moderate to
`Severe Dry Eye Disease, 107 OPHTH. 631 (2000) (EX1007)
`
`Sall is prior art under 35 U.S.C. § 102(b). Sall describes a multi-center,
`
`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-
`
`daily ophthalmic administration of 0.05% or 0.10% CsA in a castor oil emulsion,
`
`compared to the emulsion vehicle without CsA in the same regimen. EX1007,
`
`631-32 & n.1; id. at figs. 1-4; EX1002, ¶¶73-74. Sall teaches that the 0.05% CsA
`
`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, ¶¶73-80. Sall
`
`does not expressly disclose the exact composition of the castor oil vehicle, but
`
`-8-
`
`

`

`
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`compares the 0.05% and 0.10% CsA emulsions to the same vehicle. EX1007, 632;
`
`EX1002, ¶73, 120.
`
`iii. A. Acheampong et al., Cyclosporine Distribution into the
`Conjunctiva, Cornea, Lacrimal Gland, and Systemic Blood
`following Topical Dosing of Cyclosporine to Rabbit, Dog, and
`Human Eyes, 2 LACRIMAL GLAND, TEAR FILM, AND DRY EYE
`SYNDROMES 1001 (1998) (“Acheampong,” EX1008)
`
`Acheampong is prior art under 35 U.S.C. § 102(b). Acheampong describes
`
`a study in which CsA percentages ranging from 0.05%-0.4% were administered to
`
`human patients with dry eye disease. EX1008 at 1002; EX1002, ¶¶85-86.
`
`Acheampong measured CsA blood concentration at both peak and trough levels
`
`following topical ophthalmic administration. EX1008 at 1002. No detectable
`
`amount of CsA was measured in patients receiving the 0.05% CsA emulsion.
`
`EX1008 at 1002, 1004; EX1002, ¶¶85-86.
`
`iv. U.S. Patent No. 5,578,586 to Glonek et al. (“Glonek,” EX1009)
`
`Glonek issued Nov. 6, 1996 and is prior art under 35 U.S.C. § 102(b).
`
`EX1009. Glonek teaches that “an emulsion over the surface of the eye is expected
`
`to cause blurring. The duration of the blurring is dependent upon the time required
`
`for the emulsion to differentiate and form separate layers.” EX1009, 6:37-40;
`
`EX1002, ¶88. Glonek discloses topical emulsions for the treatment of dry eye
`
`disease, “whereby blurred vision is reduced.” EX1009, 3:5-6; EX1002, ¶88. In
`
`comparing the relative amounts of surfactant and oil and their effects on visual
`
`blurring, Glonek teaches that higher concentrations of oil lead to faster
`
`differentiation and decreased blurring. EX1009, 20:24-30; EX1002, ¶89.
`
`-9-
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`

`

`
`
`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
`
`products; (b) experience designing and preparing drug emulsions intended for
`
`topical ocular administration; and (c) the ability to understand results and findings
`
`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,
`
`physical pharmacy, or a related field, or less education but considerable
`
`professional experience in these fields. Id. at ¶35.
`
`Petitioner’s expert, Dr. Mansoor Amiji, is the Bouvé College Distinguished
`
`Professor in the Department of Pharmaceutical Sciences at Northeastern University
`
`in Boston, Massachusetts. EX1002, ¶1; EX1003 (CV). Dr. Amiji is also an affiliate
`
`faculty member in the Departments of Chemical Engineering and Biomedical
`
`Engineering at Northeastern, as well as a Distinguished Adjunct Professor of
`
`Pharmacy at King Abdulaziz University. EX1002, ¶1; EX1003. Dr. Amiji has
`
`authored or co-authored more than 200 peer-reviewed journal articles and 43 book
`
`chapters. EX1002, ¶6; EX1003. He has served on the editorial board of 13 peer-
`
`reviewed journals, including Drug Design: Development and Therapy, Expert
`
`Opinion on Drug Delivery, Pharmaceutical Formulations and Quality, and Tissue
`
`Barriers. EX1002, ¶5; EX1003.
`
`Dr. Amiji received a Ph.D. in Pharmaceutical Science/Biomaterials Science
`
`from Purdue University in 1992, and he has extensive experience with ophthalmic
`
`-10-
`
`

`

`
`
`pharmaceutical emulsions, including castor oil emulsions. EX1002, ¶¶2-4;
`
`EX1003. Dr. Amiji is well qualified as an expert, possessing the necessary
`
`scientific, technical, and other specialized knowledge and training to assist in an
`
`understanding of the evidence presented herein, as well as possessing the expertise
`
`necessary to determine and explain the level of ordinary skill in the art as of
`
`September 2003. EX1003.
`II. GROUNDS FOR STANDING
`Petitioner certifies that, under 37 C.F.R. § 42.104(a), the ’556 patent is
`
`available for inter partes review, and Petitioner is not barred or estopped from
`
`requesting inter partes review of the ’556 patent on the grounds identified.
`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: Mylan Pharmaceuticals Inc., the Petitioner in this matter
`
`and a wholly owned subsidiary of Mylan Inc.; Mylan Inc., which is an indirectly
`
`wholly owned subsidiary of Mylan N.V.; and Mylan N.V.
`
`Related Matters (37 C.F.R. § 42.8(b) (2)): An IPR petition for the ’556
`
`patent was previously filed by Apotex Corp. and Apotex Inc. as IPR2015-01286,
`
`as were petitions for the related patents U.S. Patent Nos. 8,648,048 (IPR2015-
`
`01284), 8,629,111 (IPR2015-01282), 8,633,162 (IPR2015-01278), and 8,685,930
`
`(IPR2015-01283), but all were terminated prior to an institution decision. IPR
`
`petitions for the related patents 8,685,930, 8,629,111, 8,633,162, 8,648,048, and
`
`9,248,191 are being filed by the present Petitioner as IPR2016-01127, IPR2016-
`
`01128, , IPR2016-01130, IPR2016-01131, and IPR2016-01132, respectively. U.S.
`
`-11-
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`
`
`Application No. 15/011,159, filed January 29, 2016, claims the benefit of U.S.
`
`Application No. 14/222,478 (the ’191 patent), which is a continuation, via U.S.
`
`Application Nos. 13/961,828 and 11/897,177, of the ’857 application.
`
`Petitioner and other entities are involved in litigation over the ’556 patent
`
`and related patents in the action styled Allergan, Inc. v. Teva Pharmaceuticals
`
`USA, Inc., et al., No. 2:15-cv-01455, filed by Allergan, Inc. in the Eastern District
`
`of Texas (EX1023). A complaint asserting the ’556 patent against Petitioner was
`
`served no earlier than August 24, 2015. Petitioner also identifies the following
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`pending actions involving the ’556 patent: Allergan, Inc., v. Innopharma, Inc. and
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`Pfizer, Inc., No. 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: Steven W. Parmelee (Reg. No. 31,990)
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`Back-Up Counsel: Michael T. Rosato (Reg. No. 52,182)
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`Back-Up Counsel: Jad A. Mills (Reg. No. 63,344)
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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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`Email: sparmelee@wsgr.com; mrosato@wsgr.com; jmills@wsgr.com
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`Post: WILSON SONSINI GOODRICH & ROSATI
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`701 Fifth Avenue, Suite 5100, Seattle, WA 98104-7036
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`Tel.: 206-883-2542 Fax: 206-883-2699
`IV. STATEMENT OF THE PRECISE RELIEF REQUESTED
`Petitioners request review of claims 1-20 of the ’556 patent under 35 U.S.C.
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`§ 311 and AIA § 6 and that each of the claims be canceled as unpatentable:
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`Ground
`1
`2
`3
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`Claims
`1-20
`1-20
`14 and 19
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`4
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`5
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`11, 18, and 20
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`19
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`Description
`Anticipated under §102 by Ding ’979
`Obvious under §103 over Ding ’979 and Sall
`Obvious under §103 over Ding ’979, Sall, and Glonek
`Obvious under §103 over Ding ’979, Sall, and
`Acheampong
`Obvious under §103 over Ding ’979, Sall, Glonek, and
`Acheampong
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`V.
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`STATEMENT OF NON-REDUNDANCY
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`Each of the five Grounds raised in this Petition is meaningfully distinct.
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`Ground 1 asserts anticipation of claims 1-20 by Ding ’979. Ground 2 asserts
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`obviousness of claims 1-20 based on Ding ’979 and Sall. Sall expressly teaches
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`certain properties intrinsic to the claimed emulsion, including efficacy, relative
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`efficacy, relative adverse events, and substantially no detectable blood
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`concentration at trough levels, and provides additional reasons to make and use the
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`claimed emulsion to treat dry eye disease. Ground 3 challenges claims 14 and 19
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`based on Ding ’979, Sall, and Glonek. Glonek expressly teaches the reduction in
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`blurring from more rapid emulsion break down, and the relationship between break
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`down rate and oil concentration. Ground 4 asserts the obviousness of dependent
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`claims 11, 18, and 20, based Ding ’979, Sall, and Acheampong. Acheampong
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`expressly teaches the claimed emulsion results in substantially no detectable blood
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`concentration at trough and peak levels. Ground 5 challenges dependent claim 19
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`based on Ding ’979, Sall, Glonek, and Acheampong based on the properties taught
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`therein.
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`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); 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.
`A.
`The term “buffer” appears in claims 4-6, 9-10 of the ’556 patent. Claims 5
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`“buffer”
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`and 10 state “the buffer is sodium hydroxide.” The patent states, “[t]he pH of the
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`emulsions can be adjusted in a conventional manner using sodium hydroxide ... to
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`a physiological pH level.” EX1001, 13:4-6. In light of the specification, the
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`broadest reasonable interpretation of the term “buffer” includes sodium hydroxide.
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`EX1002, ¶38.
`B.
`The term “substantially no detectable concentration” appears in claims 11
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`“substantially no detectable concentration”
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`and 18-20 of the ’556 patent with regard to measuring CsA in human blood.
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`According to the specification, “[c]yclosporin component concentration in blood
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`preferably is determined using a liquid chromatography-mass spectroscopy-mass
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`spectroscopy (LC-MS/MS), which test has a cyclosporin component detection
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`limit of 0.1 ng/ml. Cyclosporin component concentrations below or less than 0.1
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`ng/ml are therefore considered substantially undetectable.” EX1001, 5:36 – 6:5. A
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`skilled artisan could measure blood concentration at either peak or trough levels.
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`EX1002, ¶39. In light of the specification, the broadest reasonable interpretation
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`of the phrase “substantially no detectable concentration” includes a blood
`concentration below 0.1 ng/mL measured at either peak or trough levels.
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`C.
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` “effective amount,” “therapeutically effective, “overall efficacy,”
`and “therapeutic effectiveness”
`Independent claims 1 and 13 state that the emulsion is “therapeutically
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`effective in treating dry eye disease.” Claim 11 further recites administering “an
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`effective amount in treating dry eye disease.” Keratoconjunctivitis sicca (“KCS”),
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`an “inflammation of the conjunctiva and of the cornea” that is “associated with
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`decreased tears,” is a species of, and is often used interchangeably with, or as a
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`partial synonym of, dry eye disease. EX1022, 0003 (keratoconjunctivitis sicca);
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`EX1002, ¶40, 47. The ’556 patent teaches that CsA “acts to enhance or restore
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`lacrimal gland tearing in providing the desired therapeutic effect.” EX1001, 9:39-
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`40. During prosecution, Patent Owner relied on an increase in tearing to assert
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`unexpected therapeutic efficacy of the claimed emulsion for treating dry eye
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`disease/KCS. EX1004, 0200-02; EX1002, ¶40. Thus, in the context of the ’556
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`patent, an emulsion effective in increasing tear production is an example of an
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`emulsion therapeutically effective in treating dry eye disease.
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`Claims 1 and 13 respectively state that the emulsion “provides overall
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`efficacy substantially equal to” and “achieves at least as much therapeutic
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`effectiveness” as a second emulsion with 0.10% CsA and 1.25% castor oil. The
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`plain meaning of the word “therapeutic” includes palliative (remediating)
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`treatments as well as curative treatments. EX1002, ¶¶41-42; EX1022, 0007
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`(therapeutic), 0004 (palliative), 0005 (remedy). Accordingly, the broadest
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`reasonable interpretation of these terms include palliative treatments as well as
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`curative treatments.
`D.
`Claim 15 recites that the emulsion has fewer “adverse events” relative to a
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`“adverse events” and “side effects”
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`second emulsion, and claims 16-17 further recites that the “adverse events” are
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`“side effects” and that the side effects may be “visual distortion” or “eye
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`irritation.” The specification also defines adverse events to include “undesirable
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`side effects.” EX1001, 15:51-58. The plain meaning of “side effects” is “A result
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`of a drug or other therapy in addition to or in extension of the desired therapeutic
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`effect; usually but not necessarily, denoting an undesired effect.” EX1022, 0006
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`(side effect). The broadest reasonable interpretation of the term “adverse events”
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`thus includes undesirable side effects, including burning eye, stinging eye, and
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`general eye pain. EX1002, ¶43.
`E.
`Claim 14 recites that the first emulsion “breaks down” more quickly in the
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`“breaks down”
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`eye of a human as compared to a second emulsion containing only 50% as much
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`castor oil. The ’556 patent states that “a relatively high concentration of
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`hydrophobic component is believed to provide for a more quick or rapid breaking
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`-16-
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`down or resolving of the emulsion in the eye, which reduces vision distortion
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`which may be caused by the presence of the emulsion in the eye and/or facilitates
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`the therapeutic effectiveness of the composition.