UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`CELLTRION, INC.,
`Petitioner
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner.
`
` IPR2024-00260
`
`U.S. Patent No. 11,253,572
`
`DECLARATION OF DR. CHRISTINE KAY
`
`CELLTRION EXHIBIT 1002
`Page 1
`
`

`

`V.
`
`F.
`
`TABLE OF CONTENTS
`INTRODUCTION ....................................................................................... 1
`I.
`BACKGROUND AND QUALIFICATIONS .............................................. 2
`II.
`INFORMATION RELIED UPON ............................................................... 5
`III.
`IV. RELEVANT LEGAL STANDARD ............................................................ 6
`A.
`Person of Ordinary Skill in the Art..................................................... 7
`B.
`Claim Construction ............................................................................ 9
`C.
`Presumption of Validity ................................................................... 10
`D.
`Obviousness ..................................................................................... 10
`TECHNOLOGY BACKGROUND............................................................ 14
`A.
`Diabetic Retinopathy (DR) .............................................................. 14
`B.
`Diabetic Macular Edema .................................................................. 15
`C.
`Age-Related Macular Degeneration (AMD) .................................... 15
`D.
`VEGF Trap-Eye/Aflibercept ............................................................ 17
`E.
`Dosing Regimen for Intravitreal Injections of VEGF
`Antagonists ...................................................................................... 20
`Exclusion Criteria Intended to Reduce Risks Associated with
`Intravitreal Injections ....................................................................... 22
`VI. BACKGROUND OF THE ’572 PATENT ................................................. 25
`A.
`General Description ......................................................................... 25
`B.
`Prosecution History.......................................................................... 27
`VII. CHALLENGED CLAIMS ......................................................................... 28
`VIII. CLAIM CONSTRUCTION ....................................................................... 29
`A.
`“A method for treating…” ............................................................... 29
`B.
`“Exclusion Criteria” ......................................................................... 31
`PRIORITY DATE ..................................................................................... 33
`A.
`Applicable Legal Standard ............................................................... 33
`
`IX.
`
`ii
`
`CELLTRION EXHIBIT 1002
`Page 2
`
`

`

`B.
`
`X.
`
`2.
`
`Claim 25 of the ’572 Patent Has an Earliest Effective Filing
`Date of July 12, 2013 at Best ........................................................... 35
`INVALIDITY UNDER 35 U.S.C. § 103 ................................................... 37
`A.
`Overview of the Prior Art ................................................................ 37
`1.
`September 14, 2009 Press Release ......................................... 37
`2.
`November 22, 2010 Press Release ......................................... 38
`3.
`December 20, 2010 Press Release .......................................... 39
`4.
`Dixon ..................................................................................... 40
`5.
`Hecht ..................................................................................... 41
`6.
`Shams 2006 ........................................................................... 42
`7.
`Elman 2010 ............................................................................ 43
`8.
`CATT and PIER Studies ........................................................ 46
`9.
`Prior Art Regarding Efficacy of Aflibercept .......................... 50
`Analysis ........................................................................................... 52
`1.
`Claims 15 and 24 are Anticipated by Each of the 2009
`Press Release and December 2010 Press Release ................... 52
`Claims 1-5, 8-11, 16-17, and 20-21 (Generic/DME
`Results Claims) Are Anticipated by the December 2010
`Press Release ......................................................................... 55
`Claims 26-30 (AMD Results Claims) Are Anticipated by
`the November 2010 Press Release ......................................... 60
`Claims 1-5, 8-11, and 26-30 (Generic/AMD Results
`Claims) Are Rendered Obvious by Dixon Alone or In
`View of the 2006 Press Release ............................................. 64
`Claims 16-17, and 20-21 (DME Results Claims) Are
`Rendered Obvious by the 2009 Press Release Alone or in
`View of the 2007 ARVO Abstract, Dixon, and/or the
`2010 ARVO Abstract (collectively, “Section X.B.5
`References”) .......................................................................... 72
`
`B.
`
`3.
`
`4.
`
`5.
`
`iii
`
`CELLTRION EXHIBIT 1002
`Page 3
`
`

`

`6.
`
`7.
`
`Claims 6-7 and 12-13 (Aflibercept Formulation) Are
`Rendered Obvious by Each of Dixon in View of Hecht,
`Dixon in View of the 2006 Press Release and Hecht, and
`the December 2010 Press Release in View of Hecht .............. 76
`Claims 18-19 and 22-23 (Aflibercept Formulation) Are
`Rendered Obvious by Each of the December 2010 Press
`Release in View of Hecht, and the 2009 Press Release in
`View of the Section X.B.5 References and Hecht .................. 78
`Claim 14 (Exclusion Criteria) Is Rendered Obvious by
`Each of Dixon, and the December 2010 Press Release
`Alone or In View of the CATT Study and/or PIER Study ...... 78
`Claim 25 (Five Initial Doses) is Rendered Obvious by the
`2009 Press Release Alone or in View of Shams or Elman
`2010 ....................................................................................... 81
`Claims 1-5, 8-11, and 26-30 (Generic/AMD Results
`Claims) are Anticipated by Dixon Because the “Results
`Limitations” Lack Patentable Weight..................................... 98
`Claims 1-5, 8-11, 16-17, and 20-21 (Generic/DME
`Results Claims) are Anticipated by the 2009 Press
`Release Because the “Results Limitations” Lack
`Patentable Weight .................................................................. 98
`XI. NO SECONDARY CONSIDERATIONS.................................................. 99
`XII. SUPPLEMENTATION ........................................................................... 100
`
`10.
`
`8.
`
`9.
`
`11.
`
`iv
`
`CELLTRION EXHIBIT 1002
`Page 4
`
`

`

`TABLE OF EXHIBITS
`
`Description
`
`Exhibit
`1001
`1003
`1004
`
`1005
`
`1006
`
`U.S. Patent No. 11,253,572
`Christine Kay Curriculum Vitae
`Institution Decision in Apotex Inc. v. Regeneron Pharmaceuticals, Inc.,
`IPR2022-01524. (“Apotex ’572 ID”)
`Press Release, “Enrollment Completed in Regeneron and Bayer
`Healthcare Phase 3 Studies of VEGF Trap-Eye in Neovascular Age-
`Related Macular Degeneration (Wet AMD) (September 14, 2009),”
`available at: https://newsroom.regeneron.com/news-releases/news-
`release-details/enrollment-completed-regeneron-and-bayer-healthcare-
`phase-3 (“2009 Press Release”)
`Press Release, “Regeneron and Bayer Report Positive Results for VEGF
`Trap-Eye in Phase 3 Study in Central Retinal Vein Occlusion (CRVO)
`and in Phase 2 Study in Diabetic Macular Edema (DME),” Exhibit 99.1
`to Regeneron 8-K filed on December 20, 2010, available at:
`https://yahoo.brand.edgar-
`online.com/displayfilinginfo.aspx?FilingID=7617341-6436-
`23571&type=sect&TabIndex=2&companyid=5036&ppu=%252fdef%
`E2%80%A6 (“December 2010 Press Release”)
`Press Release, “Bayer and Regeneron Report Positive Top-Line Results
`of Two Phase 3 Studies with VEGF Trap-Eye in Wet Age-related
`Macular Degeneration,” Exhibit 99.1 to Regeneron 8-K filed on
`November 22, 2010, available at: https://yahoo.brand.edgar-
`online.com/displayfilinginfo.aspx?FilingID=7572010-8611-
`26486&type=sect&TabIndex=2&companyid=5036&ppu=%252fdef%
`E2%80%A6 (“November 2010 Press Release”)
`Apotex Petition for IPR filed in Apotex Inc. v. Regeneron
`Pharmaceuticals, Inc., IPR2022-01524 (Paper 1) (“Apotex Petition”)
`Dixon JA, Oliver SC, Olson JL, Mandava N. VEGF Trap-Eye for the
`treatment of neovascular age-related macular degeneration. Expert Opin
`Investig Drugs. 2009;18(10):1573-1580. (“Dixon”)
`1010 Major JC et al., “DA VINCI: DME and VEGF Trap-Eye: INvestigation
`of Clinical Impact: Phase 2 Study in Patients With Diabetic Macular
`
`1007
`
`1008
`
`1009
`
`v
`
`CELLTRION EXHIBIT 1002
`Page 5
`
`

`

`Exhibit
`
`1011
`
`1012
`
`1013
`
`1015
`
`1016
`
`1014
`
`Description
`Edema (DME), ARVO Annual Meeting Abstract (April 2010), Vol. 51,
`Issue 13, available at:
`https://iovs.arvojournals.org/article.aspx?articleid=2375028 (“2010
`ARVO Abstract”)
`Final Written Decision in Mylan Pharmaceuticals Inc. v. Regeneron
`Pharmaceuticals, Inc., IPR2021-00881 (Paper 94) (“’338 FWD”)
`Institution Decision in Mylan Pharmaceuticals Inc. v. Regeneron
`Pharmaceuticals, Inc., IPR2022-01225 (Paper 21) (“’681 ID”)
`Institution Decision in Mylan Pharmaceuticals Inc. v. Regeneron
`Pharmaceuticals, Inc., IPR2022-01226 (Paper 22) (“’601 ID”)
`Certified Prosecution History of U.S. Patent No. 11,253,572 (“’572
`patent PH”)
`Adis R&D Profile, Aflibercept: AVE 0005, AVE 005, AVE0005, VEGF
`Trap - Regeneron, VEGF Trap (R1R2), VEGF Trap-Eye. Drugs R D.
`2008;9(4):261-269. (“Adis”)
`Hecht, “Opthalmic Preparations,” Remington: The Science and Practice
`of Pharmacy, Volume II, 19th edition, Chapter 89 (1995). (“Hecht”)
`1017 WO 2006/047325 Al (“Shams”)
`1018
`Elman MJ, et al., Randomized trial evaluating ranibizumab plus prompt
`or deferred laser or triamcinolone plus prompt laser for diabetic macular
`edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. (“Elman
`2010”)
`Elman MJ, et al., Randomized trial evaluating ranibizumab plus prompt
`or deferred laser or triamcinolone plus prompt laser for diabetic macular
`edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35, published
`April 28 2010, available at https://www.aaojournal.org/article/S0161-
`6420(10)00243-5/fulltext (“Elman AAO Website”)
`Authenticating Affidavit and the July 13, 2010 Web Archive of the
`CATT Patient Eligibility Criteria, available at
`https://web.archive.org/web/20100713035617/http://www.med.upenn.e
`du/cpob/studies/documents/CATTEligibilityCriteria_000.pdf, attached
`as Exhibit B (“CATT Study”).
`
`1019
`
`1020
`
`iv
`
`CELLTRION EXHIBIT 1002
`Page 6
`
`

`

`Exhibit
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`Description
`Regillo CD, Brown DM, Abraham P, et al. Randomized, double-masked,
`sham-controlled trial of ranibizumab for neovascular age-related
`macular degeneration: PIER Study year 1. Am J Ophthalmol.
`2008;145(2):239-248. (“PIER Study”).
`Comparison of Age-related Macular Degeneration Treatments Trials:
`Lucentis-Avastin Trial (NCT00593450), available at:
`https://clinicaltrials.gov/ct2/show/NCT00593450 (“NCT-450”)
`Regillo CD, Brown DM, Abraham P, et al. Randomized, double-masked,
`sham-controlled trial of ranibizumab for neovascular age-related
`macular degeneration: PIER Study year 1. Am J Ophthalmol.
`2008;145(2):239-248, published December 3, 2007, available at
`https://www.ajo.com/article/S0002-9394(07)00881-1/fulltext (“PIER
`AJO Website”)
`History of Changes for Study: A Study of rhuFab V2 (Ranibizumab) in
`Subjects With Subfoveal Choroidal Neovascularization Secondary to
`Age-Related Macular Degeneration (AMD) (NCT00090623), available
`at:
`https://clinicaltrials.gov/ct2/history/NCT00090623?V_1=View#StudyP
`ageTop. (“NCT-623”)
`ClinicalTrials.gov Background, available at:
`https://clinicaltrials.gov/ct2/about-site/background (“ClinicalTrials.gov
`Background”)
`ClinicalTrials.gov About the Results Database, available at:
`https://clinicaltrials.gov/ct2/about-site/results (“ClinicalTrials.gov About
`the Results Database”)
`Press Release, “Regeneron Reports Positive Phase 1 Data for the VEGF
`TRAP in Age-Related Macular Degeneration,” Exhibit 99(a) to
`Regeneron 8-K filed on May 2, 2006, available at:
`https://yahoo.brand.edgar-
`online.com/displayfilinginfo.aspx?FilingID=4380124-5423-
`15279&type=sect&TabIndex=2&companyid=5036&ppu=%252fdef%
`E2%80%A6 (“May 2006 Press Release”)
`
`
`
`v
`
`CELLTRION EXHIBIT 1002
`Page 7
`
`

`

`Exhibit
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`1033
`
`1034
`
`1035
`
`1036
`
`Description
`Nguyen QD et al. A phase I study of intravitreal vascular endothelial
`growth factor trap-eye in patients with neovascular age-related macular
`degeneration. Ophthalmology. 2009 Nov;116(11):2141-8.e1. (“Nguyen
`2009”)
`Press Release, “Bayer and Regeneron Dose First Patient in Second Phase
`3 Study for VEGF Trap-Eye in Wet Age-Related Macular Degeneration”
`published on May 8, 2008, available at:
`https://investor.regeneron.com/node/10561/pdf (“May 2008 Press
`Release”)
`Do DV et al., “Results of a Phase I Study of Intravitreal VEGF Trap in
`Subjects With Diabetic Macular Edema: The CLEAR-IT DME Study,”
`ARVO Annual Meeting Abstract (May 2007), Vol. 48, Issue 3, available
`at: https://iovs.arvojournals.org/article.aspx?articleid=2384099 (“2007
`ARVO Abstract”)
`Do DV et al., The DA VINCI Study: phase 2 primary results of VEGF
`Trap-Eye in patients with diabetic macular edema. Ophthalmology. 2011
`Sep;118(9):1819-26 (published online on May 5, 2011). (“Do 2011”)
`Randolph and Jones, “Surfactant-Protein Interactions,” Rational Design
`of Stable Protein Formulations, edited by Carpenter and Manning, vol.
`13, 2002 (“Randolph”)
`Fraser et al., Journal of Clinical Endocrinology and Metabolism,
`February 2005, 90(2):1114-1122 (“Fraser”)
`Lucentis ® Original Approved Labeling (2006), available at:
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125156s000
`0_Lucentis_Prntlbl.pdf (“Lucentis Label”)
`Holash J, Davis S, Papadopoulos N, et al. VEGF-Trap: a VEGF blocker
`with potent antitumor effects. Proc Natl Acad Sci U S A.
`2002;99(17):11393-11398. (“Holash”)
`Rudge JS, Thurston G, Davis S, et al. VEGF trap as a novel
`antiangiogenic treatment currently in clinical trials for cancer and eye
`diseases, and VelociGene- based discovery of the next generation of
`angiogenesis targets. Cold Spring Harb Symp Quant Biol. 2005;70:411-
`418 (“Rudge 2005”)
`
`
`
`vi
`
`CELLTRION EXHIBIT 1002
`Page 8
`
`

`

`Exhibit
`1037
`
`1038
`
`1039
`
`1040
`
`Description
`Gomez-Manzano C, Holash J, Fueyo J, et al. VEGF Trap induces
`antiglioma effect at different stages of disease. Neuro Oncol.
`2008;10(6):940-945. (“Gomez-Manzano”)
`Heier JS, et al., Intravitreal aflibercept (VEGF trap-eye) in wet age-
`related macular degeneration. Ophthalmology. 2012;119(12):2537-
`2548. (“Heier 2012”)
`Heier JS, et al., CLEAR-IT 2 Investigators. The 1-year results of
`CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor trap-
`eye dosed as-needed after 12-week fixed dosing. Ophthalmology. 2011
`Jun;118(6):1098-106. (“Heier 2011”)
`Pai A, El Shafei MM, Mohammed OA, Al Hashimi M., Current concepts
`in intravitreal drug therapy for diabetic retinopathy. Saudi J Ophthalmol.
`2010 Oct;24(4):143-9. (“Pai 2010”)
`U.S. Patent App. Pub. US 2007/0190058A1 (“Shams US App. Pub.”)
`1041
`U.S. Patent No. 9,254,338 (“’338 patent”)
`1042
`1043 WO 2012/097019A1 (“Yancopoulos PCT Application”)
`1044
`U.S. Dep’t Health & Human Servs., Nat’l Inst. Health, Nat’l Eye Inst.,
`“Diabetic Retinopathy: What You Should Know (Sept. 2015),” available
`at:
`https://www.nei.nih.gov/sites/default/files/health-
`pdfs/Diabetic_Retinopathy_What_You_Should_Know.pdf (“NIH DR”)
`U.S. Dep’t Health & Human Servs., Nat’l Inst. Health, Nat’l Eye Inst.,
`“Age-Related Macular Degeneration: What You Should Know (Sept.
`2015),” available at:
`https://www.nei.nih.gov/sites/default/files/healthpdfs/WYSK_AMD_E
`nglish_Sept2015_PRINT.pdf (“NIH AMD”)
`Halpern MT, Schmier JK, Covert D, Venkataraman K. Resource
`utilization and costs of age-related macular degeneration. Health Care
`Financ Rev. 2006;27(3):37-47. (“Halpern 2006”)
`Rudge JS, Holash J, Hylton D, et al. VEGF Trap complex formation
`measures production rates of VEGF, providing a biomarker for
`predicting efficacious angiogenic blockade. Proc Natl Acad Sci U S A.
`2007;104(47):18363-18370. (“Rudge 2007”)
`
`1045
`
`1046
`
`1047
`
`
`
`vii
`
`CELLTRION EXHIBIT 1002
`Page 9
`
`

`

`Exhibit
`1048
`
`1049
`
`Description
`Li E, Donati S, Lindsley KB, Krzystolik MG, Virgili G. Treatment
`regimens for administration of anti-vascular endothelial growth factor
`agents for neovascular age-related macular degeneration. Cochrane
`Database Syst Rev. 2020;5(5):CD012208. (“Li 2020”)
`Brown DM, Michels M, Kaiser PK, et al. Ranibizumab versus
`verteporfin photodynamic therapy for neovascular age-related macular
`degeneration: Two-year results of the ANCHOR study. Ophthalmology.
`2009;116(1):57-65.e5. (“Brown 2009”)
`1050 Martin DF, Maguire MG, Fine SL, Ying GS, Jaffe GJ, Grunwald JE, et
`al, Comparison of Age-Related Macular Degeneration Treatments Trial
`(CATT) Research Group. Ranibizumab and bevacizumab for treatment
`of neovascular age-related macular degeneration: two-year results.
`Ophthalmology 2012; 119(7):1388-98 (“Martin”)
`Chakravarthy U, Harding SP, Rogers CA, Downes SM, Lotery AJ,
`Wordsworth S, et al, Inhibition of VEGF in Age-related choroidal
`Neovascularization (IVAN) Study Investigators. Ranibizumab versus
`bevacizumab to treat neovascular age-related macular degeneration:
`one-year findings from the IVAN randomized trial. Ophthalmology
`2012; 119(7):1399-411 (“Chakravarthy 2012”)
`Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY,
`et al. Ranibizumab for neovascular age-related macular degeneration.
`New England Journal of Medicine 2006; 355(14):1419-31 (“Rosenfeld
`2006”)
`Heimann, H. (2007). Chapter 5 Intravitreal Injections: Techniques and
`Sequelae. In: Holz, F.G., Spaide, R.F. (eds) Medical Retina. Essentials
`in Ophthalmology. Springer, Berlin, Heidelberg. (“Heimann 2007”)
`Jager RD, Aiello LP, Patel SC, Cunningham ET Jr. Risks of intravitreous
`injection: a comprehensive review. Retina. 2004;24(5):676-698. (“Jager
`2004”)
`Certified Prosecution History of U.S. Patent No. 10,130,681 B2 (“’681
`patent PH”)
`Pilot Study of Intravitreal Injection of Ranibizumab for Macular
`Telangiectasia With Neovascularization (NCT00685854) (May 24,
`2008), available at:
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`1056
`
`
`
`viii
`
`CELLTRION EXHIBIT 1002
`Page 10
`
`

`

`
`
`
`
`Exhibit
`
`1059
`
`1061
`
`Description
`https://clinicaltrials.gov/ct2/history/NCT00685854?V_1=View#StudyP
`ageTop
`(“MACTEL Study”)
`1057 Authenticating Affidavit and the November 7, 2008 Web Archive of
`Ranibizumab Injections to Treat Macular Telangiectasia Without New
`Blood Vessel Growth (NCT00685854), available at
`https://web.archive.org/web/20081107014243/https://clinicaltrials.gov/
`ct2/show/NCT00685854, attached as Exhibit A (“MACTEL Study
`Wayback Machine”)
`available
`Machine,
`Wayback
`1058 Using
`the
`https://help.archive.org/help/using-the-wayback-machine/
`Eylea Label 2011, available at:
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125387lbl.
`pdf
`1060 Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson, Intraocular Drug
`Delivery (2006) (“Jaffe”)
`Steps for a Safe Intravitreal Injection Technique (2009), available at:
`https://www.retinalphysician.com/issues/2009/july-aug/steps-for-a-
`safe-intravitreal-injection-technique
`1062 Mylan’s Emergency Motion to Modify Scheduling Order and For
`Emergency Status Conference filed in Regeneron Pharmaceuticals, Inc.
`v. Mylan Pharmaceuticals Inc., Case No. 1:22-cv-00061-TSK, Northern
`District of West Virginia. (Dkt. 415) (“Mylan April 10 Motion”)
`1063 April 19, 2023 Claim Construction Order entered in Regeneron
`Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc., Case No. 1:22-cv-
`00061-TSK, Northern District of West Virginia. (Dkt. 427) (“Mylan
`Litigation CC Order”)
`1064 U.S. Patent No. 7,531,173 (“’173 patent”)
`
`at:
`
`
`
`CELLTRION EXHIBIT 1002
`Page 11
`
`

`

`I.
`
`INTRODUCTION
`
`1.
`
`I have been retained by the law firm Gemini Law LLP on behalf of
`
`Celltrion, Inc., (hereinafter, “Petitioner”) to provide expert opinions concerning
`
`antagonists of Vascular Endothelial Growth Factor (“VEGF”) used as intravitreal
`
`injection for the treatment of angiogenic disorders such as age-related macular
`
`degeneration, diabetic retinopathy, diabetic macular edema, central retinal vein
`
`occlusion (CRVO), branch retinal vein occlusion, and corneal neovascularization.
`
`2.
`
`Specifically, I have been asked to provide my opinions related to U.S.
`
`Patent No. 11,253,572 (“the ’572 patent”) (Ex. 1001) and the scientific and technical
`
`knowledge regarding the subject matter of the ’572 patent before and for a period
`
`following the earliest priority date of the application that led to the ’572 patent. For
`
`purposes of this expert declaration, I have been asked to assume that the earliest
`
`priority date of the ’572 patent is January 13, 2011 for all claims other than claim 25.
`
`3. My opinions in this declaration are based on the documents I cite along
`
`with my professional training, experience and knowledge that I have acquired
`
`working in the field of ophthalmology during my career. I am being compensated for
`
`my services as an expert at my standard consulting rate of $800/hr. My compensation
`
`is in no way contingent on the substance of my opinions or the outcome of this case.
`
`4. My opinions and their underlying reasoning are explained in detail
`
`below.
`
`
`
`1
`
`CELLTRION EXHIBIT 1002
`Page 12
`
`

`

`II.
`
`BACKGROUND AND QUALIFICATIONS
`
`5.
`
`I am an ophthalmologist with over 15 years of experience in the
`
`research, diagnosis, treatment, and analysis of vitreoretinal eye disorders. I received
`
`a B.A. degree in Neurobiology from Harvard University in 2001. I obtained my M.D.
`
`from the University of Florida (UF) in 2005. I completed an ophthalmology residency
`
`at the University of South Florida in 2009 where I was Chief Resident. I completed
`
`a Vitreoretinal Surgery Fellowship at the University of Iowa in 2011.
`
`6.
`
`From 2009 to 2011, I was a clinical instructor for residents in both the
`
`clinic, surgery, and on-call. During this time, I also was a member of the Medical
`
`Student Lecture Series, where I lectured on Retinal Anatomy. I also served as a sub-
`
`investigator treating patients in the VIEW1 clinicals trials for exudative age-related
`
`macular degeneration during my fellowship.
`
`7.
`
`From 2011 to 2014, I was an Assistant Professor at UF, where I taught
`
`residents and fellows in both the clinic and operating room, and gave lectures on retina
`
`and fluorescein angiography. During this time, I was on a Clinician-Scientist Tract
`
`funded by a Career Development Award by the Foundation Fighting Blindness,
`
`studying inherited retinal disease and gene therapy. I served as the Retina Fellowship
`
`co-Director. I additionally was a faculty instructor for a number of residency training
`
`courses, including an ophthalmology elective and a surgery clerkship. I mentored a
`
`number of graduate students in both retina fellowships and through dissertations
`
`
`
`2
`
`CELLTRION EXHIBIT 1002
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`
`

`

`related to ophthalmology. During this time, I was also the Director of the Vitreoretinal
`
`Surgical Service and the Electrophysiology Service. From 2014 and continuing to
`
`the present day, I am an Affiliate Assistant Professor of ophthalmology at the
`
`University of South Florida, where I teach lectures to ophthalmology residents with
`
`an emphasis on inherited retinal disease.
`
`8.
`
`I received numerous awards throughout my career. I have been
`
`involved in clinical or scientific research since college, winning the Harvard Hoopes
`
`Prize for Senior Thesis, awarded the Harvard College Research Program Grant and
`
`Harvard College Scholarship, as well as a Howard Hughes research grant for
`
`undergraduate research.
`
` In 2008, I was appointed the Chief Resident at University
`
`of South Florida’s Ophthalmology Residency. In 2012, I received the Honor Award
`
`from the American Society of Retina Specialists (ASRS). In 2018, I received the
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`ASRS Senior Honor Award which is awarded for participation in oral and poster
`
`presentations at the annual ASRS meetings. During my faculty appointment at UF I
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`was awarded and partially funded by a Foundation Fighting Blindness, Career
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`Development Award (2011 – 2016) which was a five-year award amount totaling
`
`$375,000 for “Development and optimization of a viral gene delivery system for the
`
`treatment of CNGB3-associated Achromatopsia.” I also served as co-PI partially
`
`funded by the NIH sponsored study grant on “Vascular Reparative Mechanism by
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`ACE2/Ang-(1-7) in Diabetes” totaling $914,139.
`
`
`
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`9.
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`I was and/or currently am a member in several Professional and
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`Academic Societies, including the Retina Society, the Macula Society, the American
`
`Society of Retina Specialists, the American Academy of Ophthalmology, ARVO, and
`
`the American Medical Association, among others. I am a member of WINR (Women
`
`in Retina), ASRS, and was a Steering committee member and Regional direct of
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`RAFA (Retinal advocacy and federal affairs, committee of American Society of
`
`Retinal Specialists).
`
`10.
`
`I have given over twenty poster presentations, over ten courses at
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`national meetings, and at least thirty oral presentations at national meetings. I have
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`authored or co-authored over forty publications, including peer-reviewed scientific
`
`papers and book chapters. The majority of these presentations and publications
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`concerned retinal disease and other disorders of the eye.
`
`11.
`
`I am currently Director of Clinical Research and Retinal Genetics
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`Service at Vitreoretinal Associates and act as Principal Investigator on multiple (over
`
`25 either ongoing or completed) clinical trials evaluating treatments either in inherited
`
`retinal disease, age related macular degeneration (both dry and wet), diabetic eye
`
`disease or retinal vein occlusion (“RVO”). My role in these trials has been that of
`
`principal investigator, either masked or unmasked treatment physician in intravitreal
`
`trials, and I am the vitreoretinal surgeon performing subretinal injections/vitrectomies
`
`in the gene therapy trials. I have also consulted for numerous pharmaceutical
`
`
`
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`companies in the area of retinal disease, including Atsena, Kodiak, Kiora, Ascidian,
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`Astellas, Sanofi, and Novartis, among others.
`
`12. My clinical practice is focused on the diagnosis and treatment of
`
`patients suffering from all diseases of the retina, including age-related macular
`
`degeneration, diabetic retinopathy, diabetic macular edema, and related disorders. I
`
`have experience with surgical interventions as well as the prescription and
`
`administration of various intravitreally-administered anti- angiogenesis agents. I
`
`routinely administer anti-VEGF agents as part of my practice, and have for over
`
`fifteen years.
`
`13.
`
`In sum, I have over 15 years of hands-on clinical and research
`
`experience specializing in treating vitreoretinal disorders and the prescription, and
`
`intravitreal administration of VEGF antagonists. I have included a copy of my
`
`curriculum vitae in support of my opinions. Ex. 1003, Kay CV.
`
`III.
`
`INFORMATION RELIED ON
`
`14.
`
`In addition to my general knowledge gained as a result of my education
`
`and experience as an ophthalmologist, I have reviewed and considered, among other
`
`things, the ’572 patent, the prosecution history of the ’572 patent, and the prior art of
`
`record discussed herein.
`
`15.
`
`I also considered the Final Written Decision (“FWD”) issued by the
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`Patent Trial and Appeal Board (“Board”) in IPR2021-00881 (“the ’338 IPR”)
`
`
`
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`concerning U.S. Patent No. 9,254,338 (“’338 Patent”), finding all challenged claims
`
`there unpatentable. See Ex. 1011, ’338 FWD. I understand the ’338 and ’572 patents
`
`are in the same patent family and share the same specification. I have formed an
`
`opinion regarding the ’572 claims here independent of the ’338 FWD, but I found
`
`the ’338 FWD to be, in my judgment, consistent with my independent opinion
`
`expressed herein.
`
`16.
`
`I further considered the Institution Decision in IPR2022-01226 (“’601
`
`IPR”). I understand the ’601 IPR was instituted on January 11, 2023. Ex. 1013, ’601
`
`ID. I have formed an opinion regarding the ’572 claims here independent of the ’601
`
`ID, but I found the ’601 ID to be, in my judgment, consistent with my independent
`
`opinion expressed herein.
`
`17.
`
`The full list of information, in addition to my professional, academic
`
`and clinical experience, that I have relied upon in forming my opinions for this report
`
`is set forth throughout the report and in the Table of Exhibits.
`
`18.
`
`Where my conclusions are based on certain assumptions that I have
`
`adopted, I have stated such assumptions in this Declaration.
`
`IV. RELEVANT LEGAL STANDARD
`In forming my opinions and considering the patentability of the claims
`
`19.
`
`of the ’572 patent, I am relying upon certain legal principles that counsel for
`
`Petitioner have explained to me, as listed below.
`
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`20.
`
`I understand that for an invention claimed in a patent to be found
`
`patentable, it must be, among other things, new and not obvious in light of what
`
`came before it. Patents and publications which predated the invention are generally
`
`referred to as “prior art.”
`
`21.
`
`For patent invalidity under an inter partes review, I understand the
`
`burden is on the party asserting unpatentability to prove it by a preponderance of the
`
`evidence. I understand that “a preponderance of the evidence” is evidence sufficient
`
`to show that a fact is more likely than not.
`
`A.
`
`22.
`
`Person of Ordinary Skill in the Art
`I have been informed that the claims of a patent are judged from the
`
`perspective of a hypothetical construct involving “a person of ordinary skill in the
`
`art” (“POSA”). The “art” is the field of technology to which the patent is related. I
`
`understand that the purpose of using a POSA’s viewpoint is objectivity. Thus, I
`
`understand that the question of validity is viewed from the perspective of a POSA,
`
`and not from the perspective of (a) the inventor, (b) a layperson, or (c) a person of
`
`extraordinary skill in the art. I have been informed that the claims of the ’572 patent
`
`are interpreted as a POSA would have understood them at the relevant time period
`
`(i.e., when the patent application was filed or the earliest effective filing date).
`
`23.
`
`I have been informed that in the ’338 IPR, the petitioner proposed – and
`
`the Board adopted – the following definition for the relevant POSA:
`
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`A person of ordinary skill in the art at the time of the
`invention would have had (1) knowledge regarding the
`diagnosis and treatment of angiogenic eye disorders,
`including the administration of therapies to treat said
`disorders; and (2) the ability to understand results and
`findings presented or published by others in the field,
`including the publications discussed herein. Typically,
`such a person would have an advanced degree, such as an
`M.D. or Ph.D. (or equivalent, or less education but
`considerable professional experience in the medical,
`biotechnological, or pharmaceutical field), with practical
`academic or medical experience
`in (i) developing
`treatments for angiogenic eye disorders (such as AMD),
`including through the use of VEGF antagonists, or (ii)
`treating of same, including through the use of VEGF
`antagonists.
`Ex. 1011, ’338 FWD, 9-11.
`
`24.
`
`I understand that in the ’338 FWD, the Board found that petitioner’s
`
`definition was “reasonable and consistent with the ’338 Patent and the prior art or
`
`record.” Ex. 1011, ’338 FWD, 10.
`
`25.
`
`Based on my review of the patent and prior art, I agree with the Board’s
`
`definition of a POSA adopted in the ’338 FWD, and in my opinion it should be
`
`adopted here consistent with the relevant art before the earliest priority of the ’572
`
`patent.
`
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`B.
`
`26.
`
`Claim Construction
`I understand the first step in determining whether a patent claim is valid
`
`is to properly construe the claims. I understand that each claim of a patent subject
`
`to inter partes review is to be interpreted in light of the language of the claim, the
`
`written description, the figures, and the prosecution history of the patent.
`
`27.
`
`I further understand that in the absence of a specific definition within
`
`the specification or the reliance on a specific meaning in the prosecution history, the
`
`terms as used in the challenged claims of the ’572 patent are to be afforded their