Phase
`
`ResuLts
`
`Phase
`
`Target
`
`Subpopulation
`
`Change
`
`from
`
`BaseLine
`
`in
`
`Corneal
`
`pJgat
`
`Week
`
`12
`
`Change
`
`from
`
`Baseline
`
`in
`
`Schirmer
`
`Score
`
`at
`
`Week
`
`12
`
`O.6
`
`-02
`
`Vehicle
`
`0.05%
`
`0010%
`
`0.20%
`
`0.40%
`
`OVehicle
`
`O.O5%
`
`00.10%
`
`O.2O%
`
`D0.40%
`
`FAMY CARE - EXHIBIT 1004-0231
`
`

`

`EXHBT
`
`FAMY CARE- EXHIBIT 1004-0232
`
`FAMY CARE - EXHIBIT 1004-0232
`
`

`

`CQI
`
`0.05%
`
`0.05%
`
`CSA
`
`CsA
`
`0.625%
`
`CO
`
`125%
`
`CO
`
`0.1%
`
`CsA
`
`1.25%
`
`CO
`
`0.0
`
`0.5
`
`Cornea
`
`Conjuctva
`
`FAMY CARE - EXHIBIT 1004-0233
`
`

`

`EXHIBIT
`
`FAMY CARE- EXHIBIT 1004-0234
`
`FAMY CARE - EXHIBIT 1004-0234
`
`

`

`LC1
`
`Change
`
`From
`
`Baseline
`
`in
`
`Comeal
`
`Staining
`
`Month
`
`Month
`
`Month
`
`Month
`
`Change
`
`From
`Values
`
`Baseline
`
`in
`
`Categorized
`
`Schirmer
`
`Measured
`
`With
`
`Anesthesia
`
`CsA
`
`OO5%
`
`CsA
`
`0.10%
`
`Vehice
`
`CsA
`
`005%
`
`CsA
`
`0.10%
`
`VehcIe
`
`Month
`
`Month
`
`P16.1
`
`P16.2
`
`FAMY CARE - EXHIBIT 1004-0235
`
`

`

`Change
`
`From
`
`Baseline
`
`in
`
`Blurred
`
`Vision
`
`Change
`
`From
`
`Baseline
`
`in
`
`Use
`
`of
`
`Artificial
`
`Average
`Tears
`
`Daily
`
`Month
`
`Month
`
`Month
`
`Month
`
`Manth
`
`Month
`
`Month
`
`Month
`
`-03
`
`0.1
`
`-02
`
`-01
`
`-0.3
`
`-0.5
`
`05%DCsAO.1O%jce
`
`CsA
`
`0.05%
`
`CsA
`
`0.10%
`
`Vehde
`
`F/1i3
`
`FAMY CARE - EXHIBIT 1004-0236
`
`

`

`EXHIBIT
`
`FAMY CARE- EXHIBIT 1004-0237
`
`FAMY CARE - EXHIBIT 1004-0237
`
`

`

`Phase
`
`001
`
`Phase
`
`1st
`
`study
`
`Phase
`
`2study
`
`0.05%
`
`CsA
`
`0.625%
`
`Co
`
`0.05%
`
`CsA
`
`in
`
`1.25%
`
`Co
`
`0.05%
`
`CsA
`
`in
`
`1.25%
`
`CO
`
`Compared
`
`with
`
`0.1%
`
`CsA
`
`in
`
`1.25%
`
`CO
`
`mpravement
`
`SIT
`
`Decrease
`Cornea
`Staining
`
`0.25
`
`0.25
`
`8Fod
`
`mprovement
`
`4Fod
`
`mpravement
`
`4Fod
`
`mprovement
`
`4Fod
`
`mprovement
`
`Compared
`
`to
`
`the
`
`0.05%
`
`CsA/0.625%
`
`CO
`
`Phase
`
`formuation
`
`disdosed
`
`in
`
`Ding
`
`FAMY CARE - EXHIBIT 1004-0238
`
`

`

`EXHIBIT
`
`FAMY CARE- EXHIBIT 1004-0239
`
`FAMY CARE - EXHIBIT 1004-0239
`
`

`

`fO
`
`1.5
`
`2.5
`
`Re1atve
`
`Efficacy
`
`of
`
`0.05%
`
`C5A
`
`125%
`
`CO
`
`from
`
`Phase
`
`vs
`
`0.05%
`
`CsA
`
`in
`
`0.625%
`
`Co
`
`from
`
`Phase
`
`0.05%
`
`0.05%
`
`0.05%
`
`CsA
`
`CsA
`
`CsA
`
`0.625%
`
`Co
`
`1.25%
`
`1.25%
`
`CO
`
`CO
`
`vii
`
`__LJ__
`
`__
`
`Phase
`
`Phase
`Study
`
`Phase
`Study
`
`Phase
`
`Phase
`Study
`
`Phase
`Study
`
`mprovement
`
`SIT
`
`Decrease
`
`in
`
`Comeal
`
`Staining
`
`FAMY CARE - EXHIBIT 1004-0240
`
`

`

`EXHIBT2
`
`FAMY CARE- EXHIBIT 1004-0241
`
`FAMY CARE - EXHIBIT 1004-0241
`
`

`

`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`DECLARATION UNDER 37 C.F.R 1.132
`
`of Dr Mayssa Attar Ph.D
`
`Mayssa Attar Ph.D declare as follows
`
`Research
`
`am currently
`at Allergan Inc Allergan specializing in
`Investigator
`Ph.D in
`preclinical and clinical pharmacokinetics
`have
`and pharmacodynamics
`Pharmaceutical Sciences Bachelors and Masters degrees in Biochemistry and almost
`15 years of experience in the pharmaceutical
`also serve as adjunct
`industry
`faculty at
`the the University of Southern California School of Pharmacy My curriculum vita
`which contains
`list of my publications
`to which
`contributed is attached
`declaration as Exhibit
`
`to this
`
`have been informed of the general nature of the rejections made by the Patent Office
`with respect to the previously presented claims of the above-referenced patent application
`am familiar with the references that the Patent Office has relied on in making these
`and
`am aware of the Ding reference U.S Patent No 5474979
`rejections For example
`to Ding et al
`
`that
`
`is
`
`commercial
`
`embodiment of
`
`the
`
`Restasis is an FDA approved product
`Specifically Restasis is approved as
`0.05% by weight
`invention
`cyclosporine
`ophthalmic emulsion useful
`for the treatment of ophthalmic conditions such as dry eye
`Specifically Restasis ophthalmic emulsion is indicated to increase tear production in
`patients whose tear production is presumed to be suppressed due to ocular
`associated with keratoconjunctivitis
`sicca
`
`inflammation
`
`have reviewed the pending claims in the present application and the pending claims
`cover the specific formulation of Restasis and/or
`the approved methods of treatment of
`sicca with Restasis
`
`dry eye or keratoconjunctivitis
`
`In creating and testing the claimed methods and compositions several unexpected results
`were discovered using the claimed compositions and methods
`
`It was known in the art at
`
`the time this application was filed that cyclosporin could be
`administered topically locally to the eye to target and treat dry eye by using cyciosporin
`As iinmunomodulatory properties to inhibit
`cell activation which would lead to an
`and potentially
`increase
`in tear production
`
`other
`
`therapeutic
`
`effects
`
`related to
`
`FAMY CARE - EXHIBIT 1004-0242
`
`

`

`and anti-apoptotic
`cyclosporins
`anti-inflammatory
`inflammation in the pathology of dry eye To elicit
`must be effectively delivered to multiple target
`tissues of the ocular surface such as the
`cornea conjunctiva and lacrimal gland
`The rate and extent at which cyclosporin is
`differentially delivered to the putative sites of action is critical
`
`effects
`
`and thus
`
`limit
`
`chronic
`
`its therapeutic effect cyclosporin
`
`to achieving therapeutic
`
`success
`
`in
`
`treating
`
`dry
`
`speaking
`
`it
`
`was
`
`understood
`
`that
`
`pharinacokinetic/phannacodynamic
`
`eye Generally
`relationship would indicate that as more cyclosporin
`reaches the target tissues of the ocular surface such as the cornea and conjunctiva
`more immunomodulatory and more anti-inflammatory activity that can take place and the
`more therapeutically effective
`drug can be in treating dry eye
`
`the
`
`Pharmacokinetic
`
`pharmacokinetic
`
`studies were performed on animal eyes which
`compared
`properties of several cyclosporin A-containing formulations
`As shown in Exhibit
`
`the
`
`Those
`
`the relative
`
`results are attached to this declaration in Exhibit
`
`that cyclosporin was absorbed increased in the relevant ocular
`and the conjunctiva where the amount of oil present
`the weight percentage of cyclosporin stayed the same Specifically the
`decreased but
`amount of cyclosporin
`reached
`the relevant ocular
`tissue was higher
`for the
`and 0.625% by weight castor oil
`formulation containing 0.05% by weight cyclosporin
`than the formulation containing 0.05% by weight cyclosporin
`and 1.25% by weight
`0.1% by weight cyclosporin
`and
`castor oil
`relative to the formulation containing
`1.25% by weight castor oil We also noticed that
`the amount of cyclosporin
`tissue was higher for the formulation containing 0.1% by
`reached
`the relevant ocular
`and 1.25% by weight castor oil
`than for the claimed formulation
`
`tissues here the
`
`in the formulation was
`
`that
`
`extent
`
`cornea
`
`that
`
`weight cyclosporin
`and method
`
`One of skill
`
`in the art would have understood such
`
`result to mean that since there was
`
`more cyclosporin
`present in the relevant ocular tissues with the formulation containing
`0.05% by weight cyclosporin
`and 0.625% by weight castor oil and the formulation
`containing 0.1% by weight cyclosporin
`and 1.25% by weight castor oil
`those formulations would have been more therapeutically
`claimed formulation that
`effective than the claimed formulation Specifically this data teaches one of skill
`art that the formulation containing 0.05% by weight cyclosporin
`and 0.625% by weight
`castor oil would have been more therapeutically effective than the claimed formulation
`
`than with the
`
`in the
`
`cyclosporin
`
`Surprisingly an unexpected increase in efficacy was demonstrated relative to the 0.1%
`formulation when we compared the therapeutic
`and 1.25% castor oil
`efficacy of the claimed formulation and method containing 0.05% by weight cyclosporin
`and 1.25% by weight castor oil
`in our multicenter randomized double-masked Phase
`
`FAMY CARE - EXHIBIT 1004-0243
`
`

`

`trials to the therapeutic efficacy of
`and 0.625% cyclosporin in our
`parallel-group dose-response controlled Phase
`
`cyclosporin
`
`formulation containing
`
`0.05% by weight
`
`randomized multicenter double-masked
`
`trial
`
`10 As shown in Exhibits
`
`and
`
`score
`
`for
`
`which are attached to this declaration the cornea staining
`and Schirmer scores were dramatically improved
`claimed methods
`the
`containing 0.05% by weight cyclosporin
`and 1.25% by weight castor oil compared to
`the formulations disclosed in Example 1E in Ding the formulation containing 0.05% by
`and 0.625% by weight castor oil
`weight cyclosporin
`
`11
`
`have read the Declaration of Dr Rhett
`made at paragraphs 18-19 Exhibits
`and
`
`as Exhibits
`
`and
`
`Schiffman and
`agree with his statements
`as referenced by Dr Schiffman are attached
`
`12 As seen in Exhibit
`study the 0.05% by weight cyclosporin NO.625%
`in the Phase
`by weight castor oil formulation Ding 1E only achieved 0.25 times the improvement
`Schinner Tear Test score as the 0.1
`by weight cyclosporin A/l .25% by weight castor
`oil formulation and only achieved 0.25 times the decrease in corneal staining as the 0.1
`by weight cyclosporin A/125% by weight castor oil formulation However in the Phase
`studies the claimed formulation and method achieved
`twice the improvement
`by weight cyclosporin A/I .25% by weight castor
`formulation in the first study and substantially the same improvement in Schirmer
`Tear Test score as the 01
`cyclosporin AJ1.25% by weight
`by weight
`study Also the claimed formulation achieved
`substantially the same decrease in cornea staining score compared to the 0.1
`weight cyclosporin AJ1.25% by weight castor oil formulation
`
`in
`
`in
`
`castor oil
`
`by
`
`Schirmer Tear Test score as the 0.1
`
`oil
`
`formulation in the second Phase
`
`13 As seen in Exhibit
`
`and further illustrated in Exhibit
`
`surprisingly the claimed
`
`formulation and method demonstrated an 8-fold increase
`
`score in both of
`
`in relative efficacy
`Schirmer Tear Test Score in the first study of phase
`compared to the 0.05% by weight
`cyclosporin NO.625% by weight castor oil
`formulation Ding Example 1E in the Phase
`and
`study Exhibits
`also illustrate that the claimed formulations demonstrated
`Jj improvement in the relative efficacy for the Schirmer Tear Test score for the second
`and
`study of Phase
`4-fold increase in relative efficacy for decrease in cornea staining
`the Phase
`studies compared to the 0.05% by weight
`NO.625% by weight
`formulation in the Phase
`castor oil
`disclosed in the Ding reference Ding 1E This was clearly
`
`for the
`
`4-
`
`cyclosporin
`
`study the formulation
`
`very surprising result
`
`14 Taking the results of these studies together
`the specific combination of
`0.05% by weight cyclosporin
`with 1.25% by weight castor oil
`
`it
`
`is clear that
`
`is surprisingly critical
`
`FAMY CARE - EXHIBIT 1004-0244
`
`

`

`for therapeutic effectiveness for the treatment of dry eye/keratoconjunctivitis
`sicca even
`in the art would have expected the formulation or method with the
`those persons of skill
`lower concentration of drug found in the relevant ocular
`tissue to be less therapeutically
`effective than those compositions with more drug in the ocular
`tissue e.g 0.05% by
`cyclosporin A/O.625% by weight
`formulation or 0.10% by weight
`weight
`castor oil
`cyclosporin AJ1.25% by weight castor oil formulation disclosed in Ding
`
`FAMY CARE - EXHIBIT 1004-0245
`
`

`

`hereby declare that all statements made herein of my own knowledge and belief are true and
`that all statements made on information and belief are believed to be true and further that these
`statements are made with the knowledge that willful
`false statements and the like so made are
`punishable by fine or imprisonment or both under Section 1001 of Title 18 of the United States
`Code and that such willful
`
`false statements may jeopardize the validity of the application or any
`
`patents issued thereon.
`
`___________
`Mayssa Attar Ph.D
`
`Date________________
`
`FAMY CARE - EXHIBIT 1004-0246
`
`

`

`EXHBTA
`EXHIBIT A
`
`FAMY CARE- EXHIBIT 1004-0247
`
`FAMY CARE - EXHIBIT 1004-0247
`
`

`

`MAYSSA ATTAR PHD
`
`Irvine CA 92604
`57 Shadowbrook
`714-381-1853 rnayssaattar@gmaLcom
`Linkedin Profile p//www_nkedi
`rn ub/ma yssaattar/13/7O7/b9O
`
`PROFESSIONAL SUMMARY
`
`Almost fifteen years of drug development experience Preclinical and clinical
`pharmacodynamics drug metabolism expertise Oral ophthalmic and
`pharmacokinetics
`and clinical pharmacology
`dermal drug development experience Pharmacokinetics
`representative supporting the submission of global regulatory filings Cross-functional global
`team leader functional
`line manager and matrix leader Adjunct assistant professor at the
`University of Southern California School of Pharmacy
`
`ALLERGAN
`
`Irvine CA 1/1 999
`
`present
`
`PROFESSIONAL EXPERIENCE
`
`Research Investigator Department of Pharmacokinetics and Drug Disposition
`Serve as Group Head Translational Sciences Member of PK Leadership Team
`to PhD level scientists and cross-functional
`Serve as
`team
`functional
`line manager
`launch teams with responsibility for
`leader on early development
`through market
`budgets of $15 million
`Set departmental strategy and provide oversight
`to the design conduct and data
`in vitro and in vivo studies to characterize drug pharmacokinetics
`interpretation of
`and metabolism from late stage discovery through clinical
`pharmacodynamics
`development responsible for the review of regulatory submissions
`lead representative when interacting with global regulatory agencies for
`Serve as
`both on-site compliance inspections and regulatory file review North America EU
`Asia-Pac and other Emerging Regions due diligence activities legal activities and
`key opinion leaders
`team member in the development and global registration of RESTASIS
`Serve as
`ACU VAIL ZYMAXID OZURDEX
`Received
`successive promotions
`
`UNIVERSITY OF SOUTHERN CALIFORNIA Los Angeles CA 10/2005
`
`present
`
`Adjunct Assistant Professor School of Pharmacy Department of Pharmacology and
`Pharmaceutical Sciences
`Lecture on the subjects of Pharmacogenomics
`and Drug Metabolism
`Mentor students as they consider careers in industry
`Serve as an instructor for FDA/ACCP online course Pharmacogenomics
`
`FAMY CARE - EXHIBIT 1004-0248
`
`

`

`LOEB RESEARCH INSTITUTE Ottawa ON 6/1995
`
`8/1 998
`
`Research Associate Hormones Growth and Development Unit
`EstabUshed protocols for isolation and purification of lipids
`Formulated liposomes as model plasma membrane systems
`NMR
`FTIR-Spectroscopy
`
`EDUCATION
`
`PhD Pharmaceutical Sciences University of Southern California Los Angeles CA
`Lee PhD DSc
`Advisor
`Vincent
`Cytochrome P450 3A metabolism in the rabbit
`Thesis
`
`lacrimal gland and conjunctiva
`
`MSc Biochemistry University of Ottawa Ottawa ON
`Nongnuj Tanphaichitr PhD and Morris Kates PhD
`Advisor
`Thesis
`FTIR study of the interaction between sulfoglycolipid and phosphatidylcholine
`
`BSc with honors Biochemistry University of Ottawa ON
`
`AWARDS AND HONORS
`
`pediatric
`
`Allergan Award for Excellence in recognition of team work to develop
`investigation plan to support registration of RESTASIS in EU 2011
`Allergan Award for Excellence in recognition of membership in
`team charged with
`initiative to improve efficiencies in our Scientific Writing processes
`departmental
`2010
`Allergan Award for Excellence in recognition of collaboration with Bioanalytical
`Sciences to develop more efficient processes and better laboratory use of
`LC-MS/MS equipment
`to support metabolite profiling efforts 2010
`Allergan Award for Excellence in recognition of cost savings brought about by
`introducing new gene expression technology to support Toxicology assessment
`2009
`Allergan Award for Excellence in recognition of role as Nonclinical Lead and
`contributing to the FDA approval and subsequent market
`launch of ACUVAILTM
`2009
`Allergan Award for Excellence in recognition of contribution to the development of
`an enhanced RESTASIS formulation 2006
`Rho Chi Honor Society 2005
`Allergan Award for Excellence in recognition of developing
`inhibition assay 2000
`NSERC grant to support
`term of graduate studies 1996-1998
`Travel scholarship to attend the Gordon Conference 1997
`Loeb Summer Student Scholarship 1996
`University Scholarships of Canada 1992-1996 awarded four consecutive years
`
`full
`
`high-throughput P450
`
`FAMY CARE - EXHIBIT 1004-0249
`
`

`

`PROFESSIONAL AFFRJA11ONS
`
`AAPS
`ARVO
`SSx
`Editoria Board Member Current MoIecuar Pharmacoogy
`Ad Hoc Reviewer nvestigative Ophthamoogy and Vision Science
`Ad Hoc Reviewer Journa of Pharmaceutica Sciences
`
`OTHER SKILLS
`
`Computer Watson LJMS Phoenix/WinNonLin GaHeo LJMS SMCYP Spotfire
`Languages EngUsh French Arabic
`
`PUBUCATONS
`
`Artices and Book Chapters
`
`S.H Altar
`and Wang
`Woodward
`The biodisposition and
`Tang
`in mouse skin Exp DermatoL 2013 22145148
`hypertrichotic effects of bimatoprost
`
`Ramos
`Brassard J.A Kim A.S Matsumoto
`Chapter 24
`and Vangyi
`Altar
`Comprehensive Guide to Toxicology in Preclinica Drug
`Safety Evauation of Ocular Drugs in
`Edited by Faqi A.S Elsevier Inc 2013 -_________________________________
`Development
`
`Waterbury D.L GaUndo
`Nguyen
`Viflanueva
`Altar
`Patel
`Borbridge
`Schiffman R.M Hoflander D.A Ocular Penetration and Anti-inflammatory Activity of
`Ketorolac 0.45% and Bromfenac 0.09% Against Lipopolysaccharide-lnduced
`Inflammation
`Ocul Pharmaeol Ther 2011 27 2173-8
`
`Robinson M.R Whitcup S.M Kuppermann B.D
`Chang-LinJ Altar M. Acheampong
`Pharmacokinetics and pharmacodynamics
`of the sustained-release dexamethasone
`Welty
`Invest Ophthalmol Vis Sci 2011 5280-86
`implant
`intravitreal
`
`Schiffman R.M Borbridge
`Fames Welty
`Ocular Pharrnacokinetics of
`Altar
`0.45% Ketorolac Tromethamine CUn OphthalmoL 2010 41403-1408
`
`Altar
`
`Chapter 20 The Emerging Significance of Drug Transporters and
`and Shen
`MetaboUzing Enzymes to Ophthalmic Drug Design in Ocular Transporters in Ophthalmic
`and Barnstable CJ Humana Press
`Diseases and Drug Delivery Edited by Tombran-Tink
`2008
`
`Ling KHJ Tang-Liu DDS Neamati
`and Lee V.H.L Characterization of
`Altar
`Cytochrome P450 3A in the Rabbit Lacrimal Gland Glucocorticoid Modulation and the Impact
`on Androgen Metabolism Invest Ophthalmol Vis Sci 2005 4612 4697-4706
`
`FAMY CARE - EXHIBIT 1004-0250
`
`

`

`Shen
`Ling K.H.J and Tang-Liu D.D.S Ophthalmic Drug DeDvery
`Attar
`Considerations at the Cellular Level Drug MetaboUzing Enzymes and Transporters Expert
`Opin Drug DeUv 2005 25 891-908
`
`Vu
`Vu
`Ling K.H.J and Tang-Liu D.D.S Disposition and
`Ni
`Attar
`Pharm Sci 2005 9410
`biotransformation of the acetylenic retinoid tazarotene in humans
`2246-2255
`
`Altar
`
`and Lee V.H.L Pharmacogenomic
`Pharmacogenomics 2003 44 443-461
`
`considerations in drug delivery
`
`Tanphaichitr
`Carrier
`
`Bou Khalil
`Xu
`Carmona
`Kates
`Weerachatyanukul
`Chapter 11 Physiological and biophysical properties of male germ cell
`in Lipid Metabolism and Male Fertility Edited by De Vriese
`sulfogalactosylglycerolipid
`AOCS Press 2003
`
`Altar
`
`Ling K.H.J and Tang-Liu D.D.S Cytochrome P450 2C8 and flavin
`Dong
`Altar
`containing monooxygenases are involved in the metabolism of tazarotenic acid in humans
`Drug Metab Dispos 2003 314 476-481
`
`KhaliI M.B Carrier
`and Tanphaichitr
`Kates
`Altar
`Fourier-transform infrared
`study of the interaction between germ-cell specific sulfogalactosylglyerolipid
`and
`phosphatidylcholine
`
`Chem Phys Lipids 2000 14
`
`Wong P.T.T Kates
`Altar
`Jacklis
`Carrier
`Tanphaichitr
`Interaction
`between sulfogalactosylceramide
`and dimyristoylphosphatidyftcholine
`increases the
`fluctuations of the lipid hydrocarbon chains Chem Phys Lipids 1998 942227-
`orientational
`238
`
`Tanphaichitr
`
`Taylor
`
`Altar
`
`White
`and Kates
`male germ-cell specific sulfogalactosylglycerolipid SGG and its binding protein SLIP1 in
`mammalian sperm-egg interaction in The Male Gamete From Basic Knowledge to Clinical
`Cache Press 1998
`Applications Edited by Gagnon
`
`Raltanachaiyanont
`
`Role of
`
`Gadella
`
`Suwajanakom
`White
`Kamolvarin
`and Tanphaichitr
`of sperm sulfogalactosylglycerolipid SGG on sperm-zona pellucida binding Biol Reprod
`2000 631 147-55
`
`Altar
`
`Role
`
`Abstracts and Posters
`
`Radojicic Q.C Cross-Species and Cross-Age Comparison of
`Kim
`Shen
`Altar
`Esterase Mediated Metabolism in Vitreous Human versus Rabbit Dog and Monkey
`Presented at ARVO Annual Meeting 2013
`
`Struble C.B Welty
`Sachs
`Kim
`Altar
`Scott
`Modulation of Glucocorticoid
`Receptor Gene Expression Potential Role in the Pharmacokinetic/ Pharmacodynamic
`Relationship of OZURDEX Presented at ARVO Annual Meeting 2011
`
`FAMY CARE - EXHIBIT 1004-0251
`
`

`

`Attar
`
`Schifiman R.M Borbridge
`Fames Welty
`Evaluation of the
`of Ketorolac Ophthalmic Solutions in Rabbit Presented at ARVO Annual
`Pharmacokinetics
`Meeting 2010
`
`Schiffman R.M Borbridge
`Fames
`2009 Pharmacokinetics of
`and Welty
`Attar
`Carboxymethylcellulose CMC-Based Preservative-Free Formulation of 0.45% Ketorolac
`Tromethamine Presented at ISOPT Annual Meeting 2009
`
`Robinson M.R Attar
`Whitcup S.M and Stem
`Wheeler
`Blanda
`Siemasko
`M.E 2009 Bioerodible Sustained-Release Ocular
`Impants in Mice Deliver Efficacious
`Concentrations of GsA Presented at ARVO Annual Meeting 2009
`
`Yu
`2004 Pharmacokinetic Profile of Oral
`and Tang-Liu
`Parizadeh
`Attar
`Tazarotene Presented at AAD Winter 2004 meeting
`
`Lee V.H.L Tang-Liu D.S and Ling K.H.J 2003 Characterization of Cytochrome
`Attar
`P450 1A 2D and 3A in the Rabbit Eye Presented at AOPT 2003 Kona Hawaii
`
`White
`
`Gadella
`Suwajanakorn
`Kamolvarin
`and
`1997 Role of sulfogalactosylglycerolipid SGG in sperm-egg interaction
`Tanphaichitr
`Presented at the Gordon Conference in Plymouth New Hampshire
`
`Attar
`
`Abi-Khaled
`
`Wong P.T.T Kates
`1997 An infrared
`Attar
`Carrier
`Tanphaichitr
`spectroscopic study of the interaction between sulfogalactosylceramide an analog of germ-cell
`specific sulfoglycolipid and phospholipid Presented at the Gordon Conference in Plymouth
`New Hampshire
`
`Kamolvarin
`
`Tanphaichitr
`
`Attar
`
`Lobsinger
`
`Suwajanakom
`Gadella
`Berube
`and
`1996 Role of sulfogalactosylglycerolipid SGG on sperm-egg interaction and
`the zona-induced acrosome reaction AR Presented at the Society for the Study of
`
`Reproduction meeting in London Ontario
`
`Patents
`
`Fames E.Q Attar
`Schiffman R.M Chang
`Graham R.S Welty D.F Ketorolac
`tromethamine compositions for treating or preventing ocular pain US Patent 7842714 Filed
`2009 and Issued Dec 28 2011
`Mar
`
`Blanda W.M and Attar
`Sustained action formulation of cyclosporin form
`Application 13/676551 Filed Nov 14 2012 Patent Pending
`
`US Patent
`
`Gore A.V Attar
`Cyclosporin emulsions US Patent Application
`Morgan
`Pujara
`EP2O1 10726545 Filed May 25 2011 Patent Pending
`
`Schiffman R.M Tien
`Graham R.S Morgan
`Cyclosporin compositions US
`Attar
`Filed Jul 23 2007 Patent Pending
`Patent Application PCT/US2007/074079
`
`FAMY CARE - EXHIBIT 1004-0252
`
`

`

`Schffman RM Chang
`Fames
`Graham
`VDanueva
`HoDander
`Attar
`Welty D.F Ketorolac compositions for corneal wound heafing US Patent Application
`2011 Patent Pending
`EP2O1 10715353 FUed Apr
`Graham RS lien WL Attar
`Sehiffman R.M Stem M.E Sears
`Walt J.G
`Cyclosporin compositions for ocular rosacea treatment US Patent Application
`Cassaro
`12/035698 Filed Feb 22 2008 Patent Pending
`
`FAMY CARE - EXHIBIT 1004-0253
`
`

`

`EXHBTB
`
`FAMY CARE- EXHIBIT 1004-0254
`
`FAMY CARE - EXHIBIT 1004-0254
`
`

`

`LC1
`
`4-
`
`ci
`
`1.0
`
`0.05%
`
`0.05%
`
`CSA
`
`CsA
`
`0.625%
`
`CO
`
`1.25%
`
`CO
`
`0.1%
`
`CsA
`
`1.25%
`
`CO
`
`Cornea
`
`Conjuctva
`
`FAMY CARE - EXHIBIT 1004-0255
`
`

`

`EXHBITC
`
`-FAMY CARE- EXHIBIT 1004-0256
`
`FAMY CARE - EXHIBIT 1004-0256
`
`

`

`Phase
`
`001
`
`Phase
`
`1st
`
`study
`
`Phase
`
`2nd
`
`study
`
`0.05%
`
`CsA
`
`0.625%
`
`Co
`
`0.05%
`
`CsA
`
`in
`
`1.25%
`
`Co
`
`0.05%
`
`CsA
`
`in
`
`1.25%
`
`Co
`
`Compared
`
`with
`
`0.1%
`
`CsA
`
`in
`
`1.25%
`
`CO
`
`mprovement
`nSTT
`
`Decreasen
`Cornea
`Stafflng
`
`0.25
`
`0.25
`
`8-Fod
`
`mprovement
`
`4-Fod
`
`mprovement
`
`4-Fod
`
`mprovement
`
`4-Fod
`
`mprovement
`
`Compared
`
`to
`
`the
`
`0.05%
`
`CsA/0.625%
`
`CO
`
`Phase
`
`formuation
`
`disdosed
`
`in
`
`Ding
`
`FAMY CARE - EXHIBIT 1004-0257
`
`

`

`EXHIB
`
`FAMY CARE- EXHIBIT 1004-0258
`
`FAMY CARE - EXHIBIT 1004-0258
`
`

`

`O1
`
`2.5
`
`ReLative
`
`Efficacy
`
`of
`
`0.05%
`
`CsA
`
`1.25%
`
`CO
`
`from
`
`Phase
`
`vs
`
`0.05%
`
`CsA
`
`0.625%
`
`CO
`
`from
`
`Phase
`
`0.05%
`
`0.05%
`
`0.05%
`
`CsA
`
`CsA
`
`CsA
`
`0.625%
`
`Co
`
`1.25%
`
`1.25%
`
`CO
`
`CO
`
`mprovement
`
`SIT
`
`Decrease
`
`Comeal
`
`Staining
`
`FAMY CARE - EXHIBIT 1004-0259
`
`

`

`EXHBIT3
`EXHIBIT 3
`
`FAMY CARE- EXHIBIT 1004-0260
`
`FAMY CARE - EXHIBIT 1004-0260
`
`

`

`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`DECLARATION UNDER 37 C.F.R 1.132
`
`of Aziz Mottiwala
`
`Aziz Mott.iwala declare as follows
`
`am currently Vice President of Marketing at Allergan Inc Allergan for Allergans
`have an MBA from the University of Southern California
`Dry Eye Product Franchise
`Marshall School of Business Bachelors degree in Biochemistry and over 15 years of
`industry My curricuiwn vita is
`experience in marketing and sales in the pharmaceutical
`attached to this declaration as Exhibit
`
`have reviewed the pending claims in the present application and the pending claims
`cover the specific formulation of Restasis that has been sold since 2003 To the best of
`my knowledge the Restasis formulation includes OA5% by weight cyclosporin
`1.25% by weight castor oil Pemulen polysorbate 80 sodium hydroxide and water
`Restasis was approved by the FDA on December 23 2002
`
`Over the past ten years Allergan has collected data on the world wide sales for Restasis
`and broken out by country in
`by quarter This data is illustrated generally in Exhibit
`both attached to this declaration personally supervised the compilation of the
`and Exhibit
`data presented in Exhibit
`
`Exhibit
`
`As illustrated in Exhibit
`
`the world-wide sales for Restasis have steadily increased
`since the products launch in the first quarter of 2003 Currently annual world-wide net
`sales for Restasis are over $200 million per quarter and nearing $800 million annually
`majority of the sales are in the US As there is no other
`As illustrated in Exhibit
`for dry eye available on the US market Restasis
`therapeutic treatment
`FDA-approved
`owns 100% of the market share
`
`In my expert opinion this data is strong evidence of commercial success
`
`hereby declare that all statements made herein of my own knowledge and belief ale
`true and that all statements made on information and belief are believed to be true and
`further that these statements are made with the knowledge that willful
`false statements
`and the like so made are punishable by fine or imprisonment or both under Section 1001
`the United States Code and that
`of Title 18 of
`false statements may
`jeopardize the validity of the application or any patents issued thereon
`
`such willful
`
`FAMY CARE - EXHIBIT 1004-0261
`
`

`

`Mottiwala
`
`Date
`
`FAMY CARE - EXHIBIT 1004-0262
`
`

`

`EXHIBIT
`
`FAMY CARE- EXHIBIT 1004-0263
`
`FAMY CARE - EXHIBIT 1004-0263
`
`

`

`Aziz Mottiwala
`
`EDUCATION
`
`University of Southern California Marshall School of Business Los Angeles CA
`Master of Business Administration MBA Marketing/Corporate Strategy December 2003
`Deans list Fall 2001 Spring 2002 Fall 2002 Spring 2003 Fall 2003
`Elected to Beta Gamma Sigma National Honor Society
`
`University of California San Diego Revelle College La Jolla CA
`Bachelor of Science Biochemistry and Cell Biology June 1999
`Recipient American Society of Pharmacology and Experimental Therapeutics Research Fellowship
`Howard Hughes Research Scholar UCSD School of Medicine Department of Pharmacology
`
`EXPERIENCE
`
`Allergnn Inc Irvine CA
`
`Vice Presiden4 Dry Eye Marketing
`February 2013- Current
`and professional promotions across Allergans Dry Eye product
`Leading all strategic development
`franchise Providing strategic direction
`over both Dry Eye promotions and strategic communications Also providing leadership and direction for all key brand forecasts and
`budgets Leading long term strategic planning and budgeting as well as implementation of key marketing plans to exceed corporate financial
`
`targets
`
`Marketing Director Dry Eye
`August 2010- February 2013
`and professional promotions across Allergans Dry Eye product
`Leading all strategic development
`franchise Providing strategic direction
`over both Dry Eye promotions and strategic communications Also providing leadership and direction for all key brand forecasts and
`budgets Leading long term strategic planning and budgeting as well as implementation of key marketing plans to exceed corporate financial
`targets
`
`Product Director Restasis Professional Marketing
`October 2009- August 2010
`Professional Promotions across Allergans Dry Eye product
`franchise Providing strategic direction over both Dry Eye promotions and
`strategic communications Also providing leadership and direction for all key brand forecasts and budgets
`
`Sr Manager Restasis Consumer Marketing
`October 2007- October 2009
`
`Managed Consumer Promotions across Allergans Dry Eye product
`franchise Responsible
`for RestasisDirecttoConsumer initiatives
`strategies and media planning Also directing strategies and tactics for Dry Eye Franchise CRM and
`including TV Print and Interactive
`Compliance/Persistency
`programs
`
`Product Manager Restasis/Optometric Strategies
`December 2006- October 2007
`therapeutic areas within US Eye Care
`Developed and implemented marketing plans for Optometric strategies in Dry Eye as well as other
`Worked with the entire marketing team to drive brand strategy and ensure proper execution of tactics Also managed brand forecasts and
`budgets to ensure proper alignment of resources across the brand team
`
`IMS/Cnmbridge Management Consulting El Segundo CA
`
`Sr Consultant Management Consulting
`July 2006-December 2006
`Managed project teams including both internal and external
`and delivery of client
`resources in the design development
`solutions Provided coaching and direction to Consultants across multiple projects at any given time Led teams to review and
`analyze client requirements and developed associated proposals that ensured profitability and high client satisfaction
`
`Projects across several practice areas including Pricing and Reimbursement Portfolio Development and Sales Force Effectiveness
`Assisted mid size biotech companys business development
`team in the assessment of several acquisition opportunities
`Key Projects included development of
`commercialization/launch playbook for
`and reimbursement analysis of Phase III product for major biotech finn
`
`startup biotech company as well as extensive pricing
`
`FAMY CARE - EXHIBIT 1004-0264
`
`

`

`Aziz Mottiwala
`
`EXPERIENCE continued
`
`Valeant Pharmaceuticals Costa Mesa CA
`
`Product Manager Neurosciences/Hepatology
`September 2004-July 2006
`Managing the development market analysis and implementation of marketing pians for Tasmar Zelapar and most recently Infergen
`Driving brand strategy and ensuring proper execution of tactics Also the primary marketing contact
`for field sales providing marketing
`to promote sales growth Developing brand budgets and monitoring annual expense requirements to ensure optimum utilization of
`support
`marketing resources
`Partnered with Business Development to acquire and transition marketing of Infergen for Hep-
`Produced new promotional materials and tactical programs such as sampling and speaker programs to support strategy and drive sales
`Developed Pre-Launch market research plan for Zelapar
`testing and forecast development
`Including message testing concept
`Managed key medical education initiatives including KOL Advisory boards major conference symposia publications and various
`CME programs
`
`Analyst Global Marketing/Commercial
`September 2003-September 2004
`Supported Global Marketing and Development with market analysis and forecasting
`integrated secondary data sources and
`expertise that
`primary market research Utilized IMS data to develop and execute integrated marketing analysis plans and product
`forecasts
`
`Development
`
`Led the planning and execution of multi-attribute qualitative and quantitative market research projects
`Developed KOL targeting strategy for Viramidine Phase III product for Hepatitis
`forecasts and financial valuation models for business development
`during the acquisitions of Amarmn Corp and Xcel
`Developed
`product
`Pharmaceuticals as well as the acquisition of Tasmar an in-line product for Parkinsons disease
`
`for development products
`
`Aventis Pharmaceuticals Bridgewater NJ
`
`Area Sales Manager Interim
`August 2002-September 2003
`team of 10 sales associates in the Southem Califomia area Provided guidance on selling strategies and tactics as well as
`Managed
`communicating and implementing key marketing initiatives
`District Ranking increased from to
`among
`12-month period
`districts in
`Developed nationally implemented ROl tool for sales associates to measure success of promotional programs
`
`Professional Sales Associate/Field Sales Trainer
`September 1999- August 2002
`Successfully marketing and increasing market share for therapeutic
`for various disease states Developing specialists as advocates
`products
`to ensure maximum product pull through resulting in yearly sales attainment over 100% Trained 10 new sales associates on product
`and selling skills
`knowledge
`
`in various disease states including Allergy Asthma Diabetes Arthritis and Osteoporosis
`Experience selling therapeutic products
`Nova Award 2000 National award recognizing outstanding
`new associate
`sales performance for
`
`Saier Lab U.C San Diego Department of Biology La Jolla CA
`Research Associate
`
`September 1998-June 1999
`
`Printz Lab U.C San Diego School of Medicine La Jolla CA
`Research Associate
`December 1997-February 1999
`Contributed to three separate research projects addressing genetics neurology and psychiatry Contributed work to major journal for
`Dulawa S.C Mottiwala A.A Printz M.P Pre-pulse Inhibition of the Air Puff Startle Response in Four Strains
`publication Palmer
`of Rats Behavioral Neuroscience
`2000 Ap