`________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________________
`
`FAMY CARE LIMITED
`Petitioner
`
`v.
`
`ALLERGAN, INC.
`Patent Owner
`________________________________
`
`Patent No. 8,642,556 B2
`________________________________
`
`Declaration of Michael A. Lemp, M.D.
`
`FAMY CARE - EXHIBIT 1003-0001
`
`
`
`TABLE OF CONTENTS
`
`I.
`
`INTRODUCTION. .......................................................................................... 1
`
`II.
`
`QUALIFICATIONS. ....................................................................................... 1
`
`III.
`
`SCOPE OF ENGAGEMENT. ......................................................................... 3
`
`IV. SUMMARY OF OPINIONS. .......................................................................... 4
`
`V.
`
`THE ’556 PATENT OVERVIEW. ................................................................. 6
`
`A.
`
`The ’556 Patent Specification. .............................................................. 6
`
`B.
`
`The ’556 Patent Claims. ........................................................................ 8
`
`1.
`
`2.
`
`3.
`
`4.
`
`Independent Claims. ................................................................... 8
`
`Formulation Dependent Claims. ...............................................10
`
`“Reduction in Adverse Events” Dependent Claims. ................11
`
`“Substantially No Detectable Concentration of CsA”
`Dependent Claims. ....................................................................11
`
`C.
`
`’556 Patent File History. .....................................................................11
`
`VI. LEGAL STANDARDS. ................................................................................15
`
`A. Anticipation – 35 U.S.C. § 102. ..........................................................15
`
`B.
`
`Obviousness – 35 U.S.C. § 103. ..........................................................15
`
`VII. STATE OF THE ART AS OF SEPTEMBER 15, 2003. ..............................19
`
`A.
`
`CsA Was a Known Treatment for Dry Eye Disease. ..........................19
`
`B.
`
`CsA-in-Castor Oil Emulsions Were Known In The Art. ....................25
`
`VIII. DETAILED BASES FOR OPINIONS. ........................................................29
`
`A.
`
`Person Of Ordinary Skill In The Art. ..................................................29
`
`B.
`
`Claim Construction..............................................................................30
`
`
`
`ii
`
`
`FAMY CARE - EXHIBIT 1003-0002
`
`
`
`1.
`
`2.
`
`3.
`
`4.
`
`“Therapeutically Effective,” “Effective Amount,”
`“Overall Efficacy” and “Therapeutic Effectiveness.” ..............31
`
`“Substantially No Detectable Concentration Of
`Cyclosporin A.” ........................................................................33
`
`“Adverse Events” And “Side Effects.” .....................................34
`
`“Breaks down.” .........................................................................35
`
`C.
`
`Comparison of the Claims of the ’556 Patent to the Prior Art. ...........36
`
`1.
`
`Ground 1: Anticipation By Ding ’979. ....................................36
`
`a.
`
`b.
`
`Efficacy claim elements (claims 1, 13). .........................41
`
`Breaks Down (Claim 14) and Adverse Event claim
`elements (claims 15-17). .................................................44
`
`c.
`
`Blood level claim elements (claims 11, 18-20). .............48
`
`2.
`
`Ground 2: Obviousness In View Of Sall And Ding ’979. .......52
`
`a.
`
`b.
`
`c.
`
`d.
`
`e.
`
`f.
`
`0.05% CsA. .....................................................................56
`
`1.25% Castor Oil. ...........................................................59
`
`Efficacy & Comparative Efficacy claim elements
`(claims 1, 13). .................................................................63
`
`Breaks Down (Claim 14) and Adverse Event claim
`elements (Claims 15-17) .................................................65
`
`Blood Level claim elements (claims 11, 18-20). ............67
`
`All performance-related elements: inherency. ...............69
`
`Ground 3: Obviousness Of The’556 Patent Claims 14
`And 19 In View Of Sall, Ding ’979, And Glonek. ...................69
`
`Ground 4: Obviousness of The ’556 Patent Claims 11
`and 18-20 In View Of Sall, Ding ’979, And
`Acheampong. ............................................................................72
`
`3.
`
`4.
`
`
`
`iii
`
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`FAMY CARE - EXHIBIT 1003-0003
`
`
`
`5.
`
`Ground 5: Obviousness Of ’556 Patent Claim 19 In
`View Of Sall, Ding ’979, Glonek And Acheampong. ..............75
`
`D.
`
`Secondary Considerations of Nonobviousness. ..................................76
`
`1.
`
`No Unexpected Results. ............................................................81
`
`a.
`
`b.
`
`c.
`
`d.
`
`Schiffman Exhibit B. ......................................................83
`
`Schiffman Exhibit C/Attar Exhibit B. ............................88
`
`Schiffman Exhibit D. ......................................................90
`
`Schiffman Exhibits E and F/Attar Exhibits D and
`E. .....................................................................................95
`
`IX. CONCLUDING STATEMENTS. .................................................................99
`
`
`
`iv
`
`
`FAMY CARE - EXHIBIT 1003-0004
`
`
`
`TABLE OF EXHIBITS
`
`Exhibit
`
`Description
`
`1001 U.S. Patent No. 8,642,556 B2 to Acheampong et al., filed August 14,
`2013 (“the ’556 patent”)
`
`1002 Declaration of Peter Kador, Ph.D.
`
`1003
`
`Intentionally Blank
`
`1004
`
`1005
`
`File history of U.S. Patent No. 8,642,556 to Acheampong et al., filed
`August 14, 2013 (“’556 patent FH”)
`
`File history of U.S. Patent Application No. 10/927,857 to Acheampong
`et al., filed August 27, 2004 (“’857 application FH”)
`
`1006 U.S. Patent No. 5,474,979 to Ding et al., filed May 17, 1994 (“Ding
`’979”)
`
`1007 K. Sall et al., Two Multicenter, Randomized Studies of the Efficacy and
`Safety of Cyclosporine Ophthalmic Emulsion in Moderate to Severe
`Dry Eye Disease, 107 OPHTHALMOLOGY 631 (2000) (“Sall”)
`
`1008 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 2
`LACRIMAL GLAND, TEAR FILM, & DRY EYE SYNDROMES 1001 (David A.
`Sullivan et al. eds., 1998) (“Acheampong”)
`
`1009 U.S. Patent No. 5,578,586 to Glonek et al., filed February 4, 1994
`(“Glonek”)
`
`1010 U.S. Patent No. 5,981,607 to Ding et al., filed January 20, 1998 (“Ding
`’607”)
`
`1011
`
`R. Kaswan, Intraocular Penetration of Topically Applied Cyclosporine,
`20 TRANSPL. PROC. 650 (1988) (“Kaswan”)
`
`
`
`v
`
`
`FAMY CARE - EXHIBIT 1003-0005
`
`
`
`1012 K. Kunert et al., Analysis of Topical Cyclosporine Treatment of
`Patients with Dry Eye Syndrome, 118 ARCH OPHTHALMOL 1489 (2000)
`(“Kunert”)
`
`1013
`
`PHYSICIANS’ DESK REFERENCE FOR OPHTHALMOLOGY 13-18 (Medical
`Economics Co., 27th ed. 1999) (“Ophthalmic PDR”)
`
`1014 K. Turner et al., Interleukin-6 Levels in the Conjunctival Epithelium of
`Patients with Dry Eye Disease Treated with Cyclosporine Ophthalmic
`Emulsion, 19 CORNEA 492 (2000) (“Turner”)
`
`1015 D. Stevenson et al., Efficacy and Safety of Cyclosporin A Ophthalmic
`Emulsion in the Treatment of Moderate-to-Severe Dry Eye Disease,
`107 OPHTHALMOLOGY 967 (2000) (“Stevenson”)
`
`1016 G. Hecht, Ophthalmic Preparations, in Remington: The Science and
`Practice of Pharmacy 821 (20th ed. 2000) (“Remington”)
`
`1017
`
`E. Goto et al., Low-Concentration Homogenized Castor Oil Eye Drops
`for Noninflamed Obstructive Meibomian Gland Dysfunction, 109
`OPHTHALMOLOGY 2030 (2002) (“Goto”)
`
`1018 A. Kanpolat et al., Penetration of Cyclosporin A into the Rabbit Cornea
`and Aqueous Humor After Topical Drop and Collagen Shield
`Administration, 20 CLAO J. 119 (1994) (“Kanpolat”)
`
`1019
`
`C. Vieira et al., Effect of Ricinoleic Acid in Acute and Subchronic
`Experimental Models of Inflammation, 9 MEDIATORS INFLAMMATION
`223 (2000) (“Vieira”)
`
`1020
`
`R. Murphy, The Once and Future Treatment of Dry Eye, REVIEW OF
`OPTOMETRY ONLINE (Feb. 15, 2000) (“Murphy”)
`
`1021 D. Small et al., Blood Concentrations of Cyclosporin A During Long-
`Term Treatment with Cyclosporin A Ophthalmic Emulsions in Patients
`with Moderate
`to Severe Dry Eye Disease, 18 J. OCULAR
`PHARMACOLOGY & THERAPEUTICS 411 (2002) (“Small”)
`
`1022
`
`STEDMAN’S MEDICAL DICTIONARY 585, 944, 958, 1300, 1548, 1634,
`1788, 1821 (27th ed. 2000) (“Stedman’s”)
`
`
`
`vi
`
`
`FAMY CARE - EXHIBIT 1003-0006
`
`
`
`1023 Allergan, Inc.’s Complaint for Patent Infringement, Allergan, Inc. v.
`Famy Care Ltd., No. 2:16-cv-401 (E.D. Tex. Apr. 12, 2016)
`
`1024 APPROVED DRUG PRODUCTS WITH THERAPEUTIC EQUIVALENCE
`EVALUATIONS (34th ed. 2014) (Excerpts)
`
`1025
`
`Intentionally Blank
`
`1026
`
`7/30/2003 Allergan Correspondence to FDA regarding RESTASIS™
`
`1027
`
`RESTASIS Orange Book Listing (dated Jan. 12, 2015)
`
`1028 U.S. Patent No. 6,635,654 B1 to Chang et al., filed January 9, 2003
`(“the ’654 patent”)
`
`1029 U.S. Patent No. 6,984,628 B2 to Bakhit et al., filed July 15, 2003 (“the
`’628 patent”)
`
`1030
`
`Stephen C. Pflugfelder et al., The Diagnosis and Management of Dry
`Eye, 19 CORNEA 644 (2000) (“Pflugfelder”)
`
`1031 Mylan Pharm., Inc. v. Allergan, Inc., IPR2016-01132, Paper No. 8
`(P.T.A.B. Dec. 8, 2016)
`
`1032
`
`Curriculum Vitae of Dr. Peter Kador
`
`1033
`
`Curriculum Vitae of Dr. Michael A. Lemp
`
`
`
`vii
`
`
`
`
`FAMY CARE - EXHIBIT 1003-0007
`
`
`
`I, Michael A. Lemp, M.D., hereby declare as follows.
`
`I.
`
`
`1.
`
`INTRODUCTION.
`
`I, Michael A. Lemp, M.D., submit this Declaration on behalf of Famy
`
`Care Limited (“Petitioner”). I understand that Petitioner is filing a petition with
`
`the Patent Trial and Appeal Board (“PTAB”) of the United States Patent and
`
`Trademark Office (“USPTO”) for inter partes review of U.S. Patent No. 8,642,556
`
`B2 (“the ’556 patent”) (EX1001).
`
`
`2.
`
`This Declaration contains my qualifications; my opinions based on
`
`my expertise and my review of the ’556 patent; the factual basis for those opinions;
`
`and data or other information I considered in forming my opinions. The opinions
`
`and facts set forth in this Declaration are based upon information and my analysis
`
`of the ’556 patent, as well as my knowledge and experience in the area of
`
`ophthalmology and treating patients experiencing ophthalmic or ocular conditions
`
`such as dry eye.
`
`II. QUALIFICATIONS.
`
`
`3.
`
`Prior to my retirement from clinical practice, I held positions as
`
`Professor and Chairman of the Department of Ophthalmology. I am currently
`
`clinical professor of ophthalmology at Georgetown University School of Medicine
`
`and George Washington University Schools of Medicine. I have served on the
`
`board of directors for the International Society of Refractive Surgery and the
`
`
`
`1
`
`FAMY CARE - EXHIBIT 1003-0008
`
`
`
`International Eye Foundation, the FDA Ophthalmic Devices advisory panel and
`
`currently as Chief Medical Officer of TearLab Corporation, a manufacturer of
`
`diagnostic devices for dry eye disease. I am the author of more than 234 scientific
`
`papers and six books, including The Dry Eye (1992) and Clinical Anatomy of the
`
`Eye (second edition 1997). I was the Founding Editor –in-Chief of “The Ocular
`
`Surface,” and currently serve as a scientific reviewer for seven ophthalmic
`
`journals. I also organized and chaired the workshops which led to the publication
`
`of The National Eye Institute’s global guidelines for classification and diagnosis of
`
`dry eye in 1995. I have received a number of national and international awards,
`
`including the 1998 Castroviejo Medal, the highest honor in the field of corneal
`
`research for lifetime achievement.
`
`
`4.
`
`I am a 1962 graduate of the Georgetown University School of
`
`Medicine. I completed residency training in ophthalmology at Georgetown
`
`University and a fellowship in corneal and external disease at the Massachusetts
`
`Eye and Ear Infirmary and the Schepens Eye Research Institute—Harvard
`
`University clinical and research facilities ophthalmic. I returned to Washington in
`
`1970 to found the Cornea Service at Georgetown, which I directed for 13 years. In
`
`1983, I was selected to become the professor, chairman, and director of the Center
`
`for Sight at Georgetown University, a post I held until 1992, when I founded
`
`University Ophthalmic Consultants of Washington with my partners.
`
`
`
`2
`
`FAMY CARE - EXHIBIT 1003-0009
`
`
`
` My major areas of research interest have included dry eye, the ocular
`5.
`
`surface, corneal and cataract surgery, contact lenses, and laser and other forms of
`
`refractive correction of vision. I have been a visiting professor and lecturer at over
`
`60 universities and organizations in the U.S. and abroad, and have delivered eight
`
`named lectureships.
`
`
`6.
`
`In my clinical practice I have been a consultant managing referred
`
`cases with dry eye disease and other conditions of the ocular surface with both
`
`medication and surgical treatment.
`
`
`7.
`
`Accordingly, I am an expert in the field of ophthalmology and treating
`
`patients experiencing ophthalmic or ocular conditions such as dry eye. Additional
`
`information concerning my education and experience can be found in my
`
`curriculum vitae, a copy of which is attached. (See EX1033).
`
`III. SCOPE OF ENGAGEMENT.
`
`
`8.
`
`I have been retained by Petitioner as a technical expert to consider the
`
`claims of the ’556 patent in relation to the state of the art as of September 15, 2003.
`
`I have also considered the prosecution history of the ’556 patent, including the
`
`purported objective evidence of non-obviousness alleged in the Declarations of
`
`Drs. Rhett M. Schiffman and Mayssa Attar. (’556 patent FH (EX1004 -216-40
`
`(Schiffman Declaration I), 0242-59 (Attar Declaration), 0271-384 (Schiffman
`
`Declaration II)).
`
`
`
`3
`
`FAMY CARE - EXHIBIT 1003-0010
`
`
`
` My opinions and views set forth in this Declaration are based on my
`9.
`
`education and training; my experience as a clinician, educator, researcher, and
`
`consultant to government and industry in the field of ophthalmology and treating
`
`patients experiencing ophthalmic or ocular conditions for over 50 years; and on the
`
`materials I have reviewed for this case.
`
` My time spent on this project is compensated at $500 per hour. My
`10.
`
`compensation does not depend in any way on the outcome of Petitioner’s petition
`
`for inter partes review of the ’556 patent. Furthermore, I have no financial interest
`
`in this matter.
`
`IV. SUMMARY OF OPINIONS.
`
`
`
` First, it is my opinion that claims 1-20 of the ’556 patent are 11.
`
`anticipated and obvious. More specifically, Ding ’979 discloses and teaches each
`
`and every element of the claims of the ’556 patent, and the claims of the ’556
`
`patent are anticipated because they would have been immediately apparent to one
`
`of ordinary skill in the art in view of Ding ’979 at the time of the invention. It is
`
`also my opinion that claims 1-20 of the ’556 patent would have been obvious to a
`
`person of ordinary skill in the art at the time of the invention in view of Ding ’979
`
`in combination with Sall.
`
`
`12.
`
`In addition, the obviousness of the inherent properties of the
`
`emulsions claimed by the ’556 patent are further demonstrated by Acheampong
`
`
`
`4
`
`FAMY CARE - EXHIBIT 1003-0011
`
`
`
`and Glonek. Acheampong (like Sall) shows that the cyclosporine A (“CsA”) blood
`
`level limitations of the claims are obvious because it was known in the art at the
`
`time of the invention that 0.05% CsA emulsions will produce no detectable
`
`concentrations of CsA in the blood after administration. Glonek shows that the
`
`limitations requiring the claimed emulsion to break down faster and reduce
`
`blurring in comparison to a second emulsion with half as much castor oil are
`
`obvious because it was known at the time of the invention that a less stable oil-in-
`
`water emulsion will break down faster and reduce vision distortion in comparison
`
`to a more stable emulsion.
`
`
`
` Second, in my opinion, the data presented in Schiffman Declaration I 13.
`
`and the Attar Declaration do not support the conclusion that the ophthalmic
`
`emulsions claimed by the ’556 patent provided unexpectedly superior results over
`
`the closest prior art. Among other reasons, the data relied upon by Drs. Schiffman
`
`and Attar lack the necessary parameters (e.g., raw data values and error rates) to
`
`support a scientific conclusion that the claimed emulsions achieved any superior
`
`results in comparison to the closest prior art that would have been unexpected at
`
`the time of the invention.
`
`
`
` Third, in my opinion the validity of the ’556 patent is not supported 14.
`
`by commercial success and industry praise for RESTASIS™. Ding ’979 taught
`
`and claimed the 0.05% CsA/1.25% castor oil emulsion that is the subject of the
`
`
`
`5
`
`FAMY CARE - EXHIBIT 1003-0012
`
`
`
`’556 patent years before the ’556 patent’s priority application was ever filed. The
`
`prior art Ding ’979 patent was listed in the FDA’s Orange Book by Allergan as
`
`covering RESTASIS™. (EX1026; EX1027). Any evidence of commercial
`
`success or industry praise for RESTASIS™ should be attributed to the prior art
`
`Ding ’979 patent, because this evidence lacks a nexus to any novel feature of the
`
`’556 patent claims.
`
`
`
` Fourth, in my opinion, the validity of the ’556 patent is not supported 15.
`
`by long-felt need or failure of others. Ding ’979 satisfied any purported long-felt
`
`need for an emulsion comprising 0.05% CsA, 1.25% castor oil, 1.00% polysorbate,
`
`0.05% Pemulen®, 2.20% glycerine, sodium hydroxide, and water with a pH
`
`between 7.2-7.6 long before the ’556 patent was filed. Moreover, the ’556 patent
`
`concedes that the “compositions may be produced using conventional and well
`
`known methods useful in producing ophthalmic products including oil-in-water
`
`emulsions.” (EX1001, 14:8-10). In my opinion, this admission shows that
`
`Allergan’s purported evidence of other failures is irrelevant and not credible.
`
`V. THE ’556 PATENT OVERVIEW.
`
`A. THE ’556 PATENT SPECIFICATION.
`
`
`
` The ’556 patent cover page states that the ’556 patent issued February 16.
`
`4, 2014 to Applicant and Assignee Allergan, Inc., and is entitled “Methods of
`
`Providing Therapeutic Effects Using Cyclosporin Components.” (EX1001-0001).
`
`
`
`6
`
`FAMY CARE - EXHIBIT 1003-0013
`
`
`
`The named inventors are Andrew Acheampong, Diane D. Tang-Liu, James N.
`
`Chang, and David F. Power. (Id.)
`
`
`
` The ’556 patent cover page further states that the application for the 17.
`
`’556 patent—U.S. Patent Application No. 13/967,189 (“the ’189 application”)—
`
`was filed on August 14, 2013, and asserts priority through a series of continuations
`
`to U.S. Patent Application No. 10/927,857 (“the ’857 application”) (see EX1005),
`
`and to U.S. Provisional Patent Application No. 60/503,137, filed on September 15,
`
`2003. (EX1001-0001).
`
`
`18.
`
`I understand that the earliest claimed priority date—September 15,
`
`2003—is a key date relevant to my analysis.
`
`
`
` The ’556 patent is generally directed to pharmaceutical compositions 19.
`
`of CsA for the treatment of ophthalmic conditions in humans and animals.
`
`(EX1001, Abstract). The ’556 patent is also directed to methods of providing
`
`desired therapeutic effects to humans or animals using compositions containing
`
`CsA. (Id. at 1:18-25).
`
`
`
` The ’556 patent specification acknowledges that the use of CsA and 20.
`
`CsA derivatives to treat ophthalmic conditions was previously known in the art.
`
`(EX1001, 1:26-57). The ’556 patent specification further acknowledges that CsA
`
`oil-in-water emulsions had previously been clinically tested, including emulsions
`
`with castor oil. (Id. at 1:53-57).
`
`
`
`7
`
`FAMY CARE - EXHIBIT 1003-0014
`
`
`
`B.
`
`1.
`
`THE ’556 PATENT CLAIMS.
`
`Independent Claims.
`
`
`
` The ’556 patent recites 20 claims, including independent claims 1, 13, 21.
`
`14 and 15:
`
`1.
`
`A first topical ophthalmic emulsion for treating an eye of
`
`a human, wherein the first topical ophthalmic emulsion
`
`comprises cyclosporin A in an amount of about 0.05% by
`
`weight, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-
`
`polymer, water, and castor oil in an amount of about 1.25% by
`
`weight; and
`
`wherein
`
`the first
`
`topical ophthalmic emulsion
`
`is
`
`therapeutically effective in treating dry eye disease; and
`
`wherein the first topical ophthalmic emulsion 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.
`
`. . .
`
`13. A first topical ophthalmic emulsion for treating an eye of
`
`a human, wherein the first topical ophthalmic emulsion
`
`comprises cyclosporin A in an amount of about 0.05% by
`
`weight, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-
`
`polymer, water, and castor oil in an amount of about 1.25% by
`
`weight; and
`
`wherein
`
`the first
`
`topical ophthalmic emulsion
`
`is
`
`therapeutically effective in treating dry eye disease and
`
`
`
`8
`
`FAMY CARE - EXHIBIT 1003-0015
`
`
`
`wherein the first topical ophthalmic emulsion achieves at
`
`least as much therapeutic effectiveness as 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.
`
`. . .
`
`14. A first topical ophthalmic emulsion for treating an eye of
`
`a human, wherein the first topical ophthalmic emulsion
`
`comprises cyclosporin A in an amount of about 0.05% by
`
`weight, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-
`
`polymer, water, and castor oil in an amount of about 1.25% by
`
`weight; and
`
`wherein the first topical ophthalmic emulsion breaks
`
`down more quickly in the eye of a human, once administered to
`
`the eye of a human, thereby reducing vision distortion in the
`
`eye of a human as compared to a second emulsion that contains
`
`only about 50% as much castor oil as the first topical
`
`ophthalmic emulsion.
`
`. . .
`
`15.
`
` A first topical ophthalmic emulsion for treating an eye of
`
`a human, wherein the first topical ophthalmic emulsion
`
`comprises cyclosporin A in an amount of about 0.05% by
`
`weight, polysorbate 80, acrylate/C10-30 alkyl acrylate cross-
`
`polymer, water, and castor oil in an amount of about 1.25% by
`
`weight; and
`
`wherein the first topical ophthalmic emulsion, when
`
`administered to the eye of a human, demonstrates a reduction in
`
`
`
`9
`
`FAMY CARE - EXHIBIT 1003-0016
`
`
`
`the adverse events in the human, relative 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.
`
`
`2.
`
`Formulation Dependent Claims.
`
`
`
` Claims 2-3, depending directly or indirectly from claim 1, recite that 22.
`
`the first topical ophthalmic emulsion further comprises a tonicity agent or
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`demulcent component (claim 2), and that the tonicity agent or demulcent
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`component is glycerine (claim 3).
`
`
`
` Claims 4-5, depending directly or indirectly from claim 1, recite that 23.
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`the first topical ophthalmic emulsion further comprises a buffer (claim 4), and that
`
`the buffer is sodium hydroxide (claim 5).
`
`
`
` Claims 6-9, depending from claim 1, recite that: (A) the first topical 24.
`
`ophthalmic emulsion further comprises glycerine and a buffer (claim 6); (B) the
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`first topical ophthalmic emulsion comprises polysorbate 80 in an amount of about
`
`1.0% by weight (claim 7); (C) the first topical ophthalmic emulsion comprises
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`acrylate/C10-30 alkyl acrylate cross-polymer in an amount of about 0.05% by
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`weight (claim 8); and (D) the first topical ophthalmic emulsion comprises
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`glycerine in an amount of about 2.2% by weight and a buffer (claim 9). Percent
`
`values refer to % by weight throughout this Declaration unless otherwise indicated.
`
`
`
` Claim 10 depends directly from claim 9 (and indirectly from 25.
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`
`
`10
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`FAMY CARE - EXHIBIT 1003-0017
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`
`
`independent claim 1) and recites that the buffer is sodium hydroxide.
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`
`
` Claim 12 depends directly from claim 6 (and indirectly from 26.
`
`independent claim 1) and recites that the emulsion has a pH in the range of about
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`7.2 to about 7.6.
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`3.
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`“Reduction in Adverse Events” Dependent Claims.
`
`
`
` Claims 16-17 depend from independent claim 15, and specify that the 27.
`
`claimed emulsion reduces “side effects” (claim 16), and that the side effects are
`
`selected from the group consisting of visual distortion and eye irritation (claim 17).
`
`4.
`
`“Substantially No Detectable Concentration of CsA”
`Dependent Claims.
`
`
`
` Claims 11 (depending from claim 1), 18 (depending from claim 13), 28.
`
`19 (depending from claim 14), and 20 (depending from claim 15) recite that when
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`the first topical ophthalmic emulsion is administered to an eye of a human, “the
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`blood of the human has substantially no detectable concentration of cyclosporin
`
`A.”
`
`C.
`
`’556 PATENT FILE HISTORY.
`
`
`
` As noted above, the ‘556 patent asserts to be a continuation of the 29.
`
`’857 application. (See EX1001-0001). During prosecution of the ’857 application,
`
`the Applicants expressly admitted that the emulsion—referred to as Composition II
`
`and which remains the emulsion recited in the claims of the ’556 patent—was
`
`squarely within the teachings of U.S. Patent No. 5,474,979 (filed May 17, 1994) to
`
`
`
`11
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`FAMY CARE - EXHIBIT 1003-0018
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`
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`Ding et al. (“Ding ’979”) (EX1006). The Applicants stated:
`
`The applicants concede that it would have been obvious to modify
`
`examples 1A-1E of the Ding [’979] reference to arrive at
`
`Composition II of the present application. The differences are
`
`insignificant. One need only use the cyclosporin concentration of
`
`Example 1E (0.05%), the castor oil concentration of Example 1D
`
`(1.250%), and the remaining ingredients of those examples. 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 teaching of the Ding [’979] reference, and the
`
`Office should disregard any statements by the applicants suggesting
`
`otherwise[.]
`
`(’857 application FH (EX1005-0435) (emphasis added)). As discussed below, I
`
`agree with these statements.
`
`
`30.
`
`I have reviewed the ’857 application concurrently with the ’556
`
`patent, and find that the ’857 application Composition II is indistinguishable from
`
`the emulsion claimed in the ’556 patent. In fact, the Applicants submitted a table
`
`
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`12
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`FAMY CARE - EXHIBIT 1003-0019
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`
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`(below) during prosecution of the ’857 application comparing the ’857 application
`
`Composition II with Ding ’979. The chart below from the Declaration of Dr.
`
`Kador includes the emulsion claimed in the ’556 patent for comparison.
`
`
`
`
`
`‘556 patent
`Composition
`
`0.05%
`
`1.25%
`
`1.00%
`
`0.05%
`
`2.20%
`
`qs
`
`qs
`
`7.2-7.6
`
`0.04
`
`
`
`
`
`
`(EX1002, ¶47). The ’857 application was ultimately abandoned. (See EX1001-
`
`0001).
`
`
`
` The Applicants acknowledged 31.
`
`their prior admissions during
`
`prosecution of the ’556 patent, and alleged that evidence supporting the
`
`patentability of the claims had been collected “[s]ince these comments have been
`
`filed.” (EX1004-0007). The pending claims were rejected by the Examiner under
`
`35 U.S.C. § 103 in view of Ding ’979. (Id. at 0136-40).
`
`
`
` The Applicants’ written summary of an October 3, 2013 examiner 32.
`
`interview states that the “Applicants presented data demonstrating unexpected
`
`results, commercial success, and satisfaction of a long felt need of the claimed
`
`
`
`13
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`FAMY CARE - EXHIBIT 1003-0020
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`
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`formulation.” (EX1004-0199). The Applicants argued that “the evidence of non-
`
`obviousness presented at the interview overcomes the prima facie obviousness
`
`rejection.” (Id.)
`
`
`
` Four declarations were submitted to the USPTO in support of these 33.
`
`arguments: declarations from Dr. Rhett Schiffman (“Schiffman Declaration I”) and
`
`Dr. Mayssa Attar (the “Attar Declaration”) concerning surprising and unexpected
`
`results; and declarations from Aziz Mottiwala (the “Mottiwala Declaration”) and
`
`Dr. Rhett Schiffman (“Schiffman Declaration II”) concerning commercial success
`
`and satisfaction of a long-felt need. (EX1004-0216-40, 0242-59, 0261-69, 0271-
`
`384). Schiffman Declaration I and the Attar Declaration assert that “the claimed
`
`formulations, including 0.05% by weight cyclosporin A and 1.25% by weight
`
`castor oil, demonstrate surprising and unexpected results, including improved
`
`Schirmer Tear Test scores and corneal staining scores (key objective measures of
`
`efficacy for dry eye or keraconjunctivitis sicca) and improved visual blurring and
`
`reduced artificial tear use as compared to the prior art . . . .” (Id. at 0205).
`
`
`
` As discussed in Section VIII.D below, I disagree with the opinions of 34.
`
`Dr. Schiffman and Dr. Attar that the results in the submitted declarations were
`
`unexpected or surprising.
`
`
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`14
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`FAMY CARE - EXHIBIT 1003-0021
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`
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`VI. LEGAL STANDARDS.
`
`A. ANTICIPATION – 35 U.S.C. § 102.
`
`
`35.
`
`I understand that a patent claim is anticipated if each and every
`
`element of the claimed invention is found, expressly or inherently, in a single prior
`
`art reference. I further understand that a combination of elements disclosed in a
`
`single prior art reference anticipate a patent claim if the combination of elements in
`
`the patent claim would be “immediately apparent to one of ordinary skill in the
`
`art,” or “at once envisaged” from the prior art reference.
`
`B. OBVIOUSNESS – 35 U.S.C. § 103.
`
`
`36.
`
`I have been informed and understand that a person cannot obtain a
`
`patent if his or her invention would have been obvious to a person of ordinary skill
`
`in the field of the invention at the time of the invention.
`
`
`37.
`
`I have been informed that a patent is invalid as obvious “if the
`
`differences between the subject matter sought to be patented and the prior art are
`
`such that the subject matter as a whole would have been obvious at the time the
`
`invention was made to a person having ordinary skill in the art.”
`
`
`38.
`
`In evaluating obviousness, I have been asked to consider: (1) the
`
`scope and content of the prior art; (2) what the level of ordinary skill in the art was
`
`at the time the invention was made; (3) if there are any perceived differences
`
`between the prior art and the asserted claims and whether the differences involve a
`
`modification that would have been beyond the existing knowledge, or ordinary
`
`
`
`15
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`FAMY CARE - EXHIBIT 1003-0022
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`
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`creativity, to the person of ordinary skill in the art (in other words, were not
`
`obvious to the person of ordinary skill), and to provide my opinions on the reasons
`
`why the person of ordinary skill would have had a reason or motivation or other
`
`suggestion to make these modifications; and (4) any secondary considerations of
`
`non-obviousness (also known as objective indicia of non-obviousness).
`
`
`39.
`
`I have been informed and understand that in analyzing the question of
`
`obviousness, it is improper to use hindsight reconstruction, and that one cannot use
`
`the patent as a road map for selecting and combining items of prior art. I have
`
`been informed and understand that the relevant question is what a person of
`
`ordinary skill in the art would have understood at the time the invention was made.
`
`
`40.
`
`I have been informed and understand that the combination of familiar
`
`elements according to known methods is likely to be obvious when it does no more
`
`than yield predictable results. I have been informed that it is not necessary for a
`
`person having ordinary skill in the art to know with certainty that such results will
`
`occur; a reasonable expectation of success is enough.
`
`
`41.
`
`I have been informed and understand that in an obviousness analysis,
`
`it is not necessary that the prior art contain an explicit teaching, suggestion, or
`
`motivation to combine the references in order to make the claimed invention.
`
`Instead, when a patent merely arranges known elements from the prior art, with
`
`each performing the same kn