`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`__________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_____________________________
`
`MYLAN PHARMACEUTICALS, INC., CELLTRION, INC., and
`APOTEX, INC.,
`Petitioners,
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner.
`
`_____________________________
`
`IPR2021-008811
`Patent No. 9,254,338
`
`_____________________________
`
`PETITIONER UPDATED EXHIBIT LIST
`
`1 IPR2022-00258 has been joined with this proceeding.
`
`
`
`Exhibit
`No.
`1001
`
`1002
`
`1003
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`1009
`1010
`1011
`
`Description
`
`U.S. Patent No. 9,254,338 B2 (“’338 patent”)
`
`Expert Declaration of Dr. Thomas A. Albini in Support of Petition for
`Inter Partes Review of Patent No. 9,254,338 B2, dated May 4, 2021
`(“Albini”)
`
`Expert Declaration of Mary Gerritsen, Ph.D. in Support of Petition
`for Inter Partes Review of U.S. Patent No. 9,254,338 B2, dated Apr.
`26, 2021(“Gerritsen”)
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`
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`
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`
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`Ex. 3, Klibanov Amgen Decl.”)
`
`Klibanov Dep. Ex. 18, J. Hanhart & I. Chowers, Correspondence
`regarding Fellow Eye Effect of Unilateral Intravitreal Anti-VEGF
`Injections in Eyes with Diabetic Macular Edema, 29 EYE 292 (2015)
`(“Klibanov Dep. Ex. 18, Hanhart”)
`
`Klibanov Dep. Ex. 19, Marianne O. Stefanini et al., Increase of
`Plasma VEGF after Intravenous Administration of Bevacizumab Is
`Predicted by a Pharmacokinetic Model, 70 CANCER RESEARCH 9886
`(2010) (“Klibanov Dep. Ex. 19, Stefanini”)
`
`Klibanov Dep. Ex. 20, Jihong Yang, Comparison of Binding
`Characteristics and In Vitro Activities of Three Inhibitors of Vascular
`Endothelial Growth Factor A, 11 Molecular Pharmaceutics 3421
`(2014) (“Klibanov Dep. Ex. 20, Yang”)
`
`Klibanov Dep. Ex. 22, International Nonproprietary Names for
`Pharmaceutical Substances (INN), 20 WHO DRUG INFORMATION 118
`(2006) (“Klibanov Dep. Ex. 22, WHO Drug Info”)
`
`Alexander Klibanov Deposition Transcript (March 24, 2022)
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER (“Klibanov Dep. Tr.”)
`
`Diana V. Do Deposition Transcript (April 21, 2022) (“Do Dep. Tr.”)
`
`David M. Brown Deposition Transcript (April 26, 2022) (“Brown
`Dep. Tr.”)
`
`Lucian V. Del Priore Deposition Transcript (April 29, 2022)
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER (“Del Priore Dep. Tr.”)
`
`Klibanov Dep. Ex. 14, W. Colin Duncan et al., Inhibition of
`Vascular Endothelial Growth Factor in the Primate Ovary Up-
`Regulates Hypoxia-Inducible Factor-1α in the Follicle and Corpus
`-13-
`
`
`
`1113
`
`1114
`
`1115
`
`1116
`
`1117
`
`1118
`
`1119
`
`1120
`
`1121
`
`1122
`
`Luteum, 149 ENDOCRINOLOGY 3313 (2008) (“Klibanov Dep. Ex. 14,
`Duncan”)
`Del Priore Dep. Ex. 10, John S. Rudge et al., CLINCAL
`DEVELOPMENT OF VEGF TRAP, in ANGIOGENESIS (William D. Figg
`& Judah Folkman eds. 2008) (“Del Priore Dep. Ex. 10, Rudge
`2008”)
`Expert Declaration of Dr. Thomas A. Albini in Support of Petitioner’s
`Reply, dated May 27, 2022 (“Albini Reply Decl.”)
`
`Expert Declaration of Mary Gerritsen, Ph.D. in Support of Petitioner’s
`Reply, dated May 26, 2022 (“Gerritsen Reply Decl.”)
`
`Transcript of the Teleconference before the United States Patent
`Trial and Appeal Board on May 19, 2022 (“Transcript (19-May-
`2022)”)
`
`Klibanov Dep. Ex. 6, amino acid sequence alignment of SEQ ID
`NO:2 of the ’338 patent, aflibercept amino acid sequence from WHO
`2006, and SEQ ID NO:2 of the ’173 patent (“Klibanov Dep. Ex. 6,
`’173 patent SEQ. ID No:2”)
`
`Klibanov Dep. Ex. 9, CAS registry for No. 862111-32-8 (“Klibanov
`Dep. Ex. 9, CAS”)
`
`Klibanov Dep. Ex. 12, John S. Rudge et al., VEGF Trap Complex
`Formation Measures Production Rates of VEGF, Providing a
`Biomarker for Predicting Efficacious Angiogenic Blockade, 104
`PNAS 18363 (2007) (“Klibanov Dep. Ex. 12, Rudge 2007”)
`
`Klibanov Dep. Ex. 13, Candelaria Gomez-Manzano et al., VEGF
`Trap Induces Antiglioma Effect at Different Stages of Disease, 10
`NEURO-ONCOLOGY 940 (2008) (“Klibanov Dep. Ex. 13, Gomez-
`Manzano”)
`
`Klibanov Dep. Ex. 21, Lily Liu et al., A Novel Engineered VEGF
`Blocker with an Excellent Pharmacokinetic Profile and Robust Anti-
`Tumor Activity, 15 BMC CANCER 1 (2015) (“Klibanov Dep. Ex. 21,
`Liu”)
`
`Amino acid sequence alignment of SEQ ID NO:2 of the ’338 and
`’069 patents with aflibercept amino acid sequence from WHO 2006,
`-14-
`
`
`
`1123
`
`1124
`
`1125
`
`1126
`
`1127
`
`1128
`
`1129
`
`1130
`
`1131
`
`SEQ ID NO:16 of the ’758 patent, and SEQ ID NO:16 of the ’959
`patent (“AA Alignment”)
`
`Polly A. Quiram & Yahui Song, Exudative Age-Related Macular
`Degeneration: Current Therapies and Potential Treatments, 1
`CLINICAL MEDICINE: THERAPEUTICS 1003 (2009) (“Quiram”)
`
`Nucleic acid sequence alignment of SEQ ID NO:1 of the ’338 and
`’069 patents with SEQ ID NO:15 of the ’758 patent and SEQ ID
`NO:15 of the ’959 patent (“NA Alignment”)
`
`HANDBOOK OF PHARMACEUTICAL EXCIPIENTS (5th ed. 2006) (“HPE
`2006”)
`
`D.B. Volkin & A.M. Klibanov, Alterations in the Structure of
`Proteins that Cause Their Irreversible Inactivation, 74
`DEVELOPMENTS BIOLOGICAL STANDARDIZATION 73 (1992) (“Volkin
`& Klibanov 1992”)
`
`File History for U.S. Patent No. 7,070,959, 4/5/2016 Election for
`Patent Term Extension (“959 FH, Election re PTE”)
`
`File History for U.S. Patent No. 7,070,959, 5/25/2016 Patent Term
`Extension Certificate (“959 FH, PTE Certificate”)
`
`Christine Wulff et al., Prevention of Thecal Angiogenesis, Antral
`Follicular Growth, and Ovulation in the Primate by Treatment with
`Vascular Endothelial Growth Factor Trap R1R2, 143
`ENDOCRINOLOGY 2797 (2002) (“Wulff”)
`
`Do Dep. Ex. 2, Regeneron’s Yancopoulos Receives Columbia
`College’s Alexander Hamilton Award (Nov. 22, 2019)
`(https://www.prnewswire.com/news-releases/regenerons-
`yancopoulos-receives-columbia-colleges-alexander-hamilton-award-
`300963506.html) (“Do Dep. Ex. 2, Regeneron (22-Nov-2019)”)
`
`Do Dep. Ex. 3, Laura Vanderkam, George Yancopoulos: Doing Well
`by Trying to Do Good, SCIENTIFIC AMERICAN (Oct. 6, 2008)
`(https://www.scientificamerican.com/article/george-yancopoulos-
`westinghouse/) (“Do Dep. Ex. 3, Vanderkam”)
`
`1132
`
`Exhibit Number Unused
`
`-15-
`
`
`
`1133
`
`1134
`
`1135
`
`1136
`
`1137
`
`1138
`
`1139
`
`1140
`
`1141
`
`1142
`
`1143
`
`1144
`
`1145
`
`1146
`
`U.S. Patent No.: 10,828,345 B2 (“’345 patent”)
`
`U.S. Patent No.: 10,888,601 B2 (“’601 patent”)
`
`U.S. Patent Application Publication No. 2007 /0190058 A1 (“’058
`publication”)
`
`Ivan T. Hofmann CV and Testimony (“Hofmann CV”)
`
`Expert Declaration of Ivan T. Hofmann Support of Petitioner’s Reply,
`dated May 27, 2022 (“Hofmann Reply Decl.”)
`
`Do Dep. Ex. 4, annotated version of ’338 patent claim 1 (“Do Dep.
`Ex. 4, ’338 patent claim 1”)
`
`Brown Dep. Ex. 10, ASRS Clinical Updates, ASRS Fights Novitas
`Decision to Interpret Eylea Usage More Frequently than q8 as “Off
`Label” (May 24, 2016) (“Brown Dep. Ex. 10, ASRS Clinical
`Update”)
`
`Brown Dep. Ex. 11, L36962: Medicare Part A/B Local Coverage
`Determination (LCD) Comment Summary (May 2, 2014) (“Brown
`Dep. Ex. 11, Medicare Comment Summary”)
`
`Chengdu Kanghong Biotechnology Co. v. Regeneron
`Pharmaceuticals, Inc., PGR20221-00035, Paper 6 (April 15, 2021)
`(“PGR20221-00035, Paper 6”)
`
`Sascha Fauser et al., Suppression of Intraocular Vascular
`Endothelial Growth Factor During Aflibercept Treatment of Age-
`Related Macular Degeneration, 158 AM. J. OPHTHALMOLOGY 532
`(2014) (“Fauser”)
`
`Diana V. Do, Pharmacokinetic Study of Intravitreal Aflibercept In
`Humans with Neovascular Age-Related Macular Degeneration, 00
`RETINA 1 (2019) (“Do”)
`
`U.S. Patent No.: 7,300,563 B2 (“’563 patent”)
`
`U.S. Patent No.: 7,300,653 B2 (“’653 patent”)
`
`DRUGS@FDA: FDA-APPROVED DRUGS, EYELA, BIOLOGIC LICENSE
`
`-16-
`
`
`
`APPLICATION (BLA) NO.: 125387
`(https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=o
`verview.process&ApplNo=125387), accessed May 18, 2022
`(“Drugs@FDA_ Eylea”)
`
`Regeneron Form 10-K for the year ended December 31, 2005
`(“Regeneron 2005 10-K”)
`
`U.S. Patent No.: 7,303,748 B2 (“’748 patent”)
`
`Regeneron Form 10-K for the year ended December 31, 2011
`(“Regeneron 2011 10-K”)
`
`Deposition Transcript of Doris Weber (May 13, 2022) (“Weber Dep.
`Tr.”)
`
`Richard Manning Deposition Transcript (May 4, 2022) (“Manning
`Dep. Tr.”) CONFIDENTIAL MATERIAL - SUBJECT TO
`PROTECTIVE ORDER
`
`1147
`
`1148
`
`1149
`
`1150
`
`1151
`
`1152 Manning Dep. Ex. 6, Highlights of Prescribing Information for Eylea
`(Revised: 6/2021) (“Manning Dep. Ex. 6, Eylea Label 06.2021”)
`
`1153 Manning Dep. Ex. 7, Regeneron, Representative Regeneron U.S.
`Product Related Patents, EYLEA® (aflibercept) Injection,
`(https://www.regeneron.com/downloads/us-patent-products.pdf)
`(updated January 2022) (“Manning Dep. Ex. 7, Eylea Patent List”)
`
`1154
`
`1155
`
`1156
`
`1157
`
`1158
`
`Complaint, United States v. Regeneron Pharms., Inc., No. 1:20-cv-
`11217-FDS (D. Mass. June 24, 2020), ECF Nos. 1 – 1-39 (“2020-06-
`24 Complaint”)
`
`Angelika Batta et al., Trends in FDA Drug Approvals Over Last 2
`Decades: An Observational Study, 9 J. FAMILY MEDICINE &
`PRIMARY CARE 105 (2020) (“Batta”)
`Eylea® Label, Highlights of Prescribing Information for Eylea
`(Revised: 5/2016) (“Eylea Label 05.2016”))
`U.S. Patent No. 7,608,261 (“’261 patent”)
`
`U.S. Patent No. 7,972,598 (“’598 patent”)
`
`-17-
`
`
`
`1159
`
`1160
`
`1161
`
`1162
`
`1163
`
`1164
`
`1165
`
`1166
`
`1167
`
`1168
`
`1169
`
`1170
`
`1171
`
`1172
`
`U.S. Patent No. 8,029,791 (“’791 patent”)
`
`U.S. Patent No. 8,092,803 (“’803 patent”)
`
`U.S. Patent No. 8,343,737 (“’737patent”)
`
`U.S. Patent No. 8,647,842 (“’842 patent”)
`
`U.S. Patent No. 10,464,992 (“’992 patent”)
`
`U.S. Patent No. 11,066,458 (“’458 patent”)
`
`U.S. Patent No. 11,084,865 (“’865 patent”)
`
`FDA, PURPLE BOOK DATABASE OF LICENSED BIOLOGICAL PRODUCTS,
`https://purplebooksearch.fda.gov/patent-list (last visited May 13,
`2022) (“Purple Book List”)
`
`United Healthcare, Ophthalmologic Policy: VEGF Inhibitors,
`effective January 1, 2022 (“United Healthcare Ophthalmologic
`Policy, VEGF”)
`
`BCBS Florida, Vascular Endothelial Growth Factor Inhibitors for
`Ocular Neovascularization, revised April 1, 2022 (“BCBS Florida
`VEGF”)
`EYLEA® FDA SUMMARY REVIEW
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/125387O
`rig1s000SumR.pdf (last visited May 20, 2022) (“Eylea Summary
`Review”)
`
`GOOD DAYS, https://www.mygooddays.org/ (last visited May 18,
`2022) (“mygoodays.org CDF”)
`
`REGENERON PHARMACEUTICALS, INC., EYLEA, https://eylea.us/ (last
`visited May 18, 2022) (“Official EYLEA (aflibercept) Injection
`Website”)
`
`BIOSPACE, Bayer HealthCare AG and Regeneron Pharmaceuticals,
`Inc. to Collaborate on VEGF Trap for the Treatment Of Eye
`Diseases; Regeneron Retains U.S. Commercialization Rights,
`Receives $75 Million Upfront, and Eligible for up to $245 Million of
`
`-18-
`
`
`
`Milestone Payments (Oct. 19, 2006),
`https://www.biospace.com/article/releases/bayer-healthcare-ag-and-
`regeneron-pharmaceuticals-inc-to-collaborate-on-vegf-trap-for-the-
`treatment-of-eye-diseases-b-regeneron-b-retains-u-s-c/ (“Bayer and
`Regeneron to Collaborate on VEGF Trap”)
`
`Complaint, Horizon Healthcare Servs., Inc. v. Regeneron Pharms.,
`Inc., No. 1:22-cv-10493-FDS (D. Mass. April 4, 2022), ECF Nos. 1 –
`1-18 (“Complaint, Horizon v Regeneron, 2022-04”)
`
`Publication of OIG Special Fraud Alerts, 59 Fed. Reg. 242 (Dec. 19,
`1994), available at https://oig.hhs.gov/documents/physicians-
`resources/980/121994.pdf (“oig.hhs.gov Publication of OIG Special
`Fraud Alerts”)
`
`Zachary D. Miller, Taking Advantage of the New Purple Book Patent
`Requirements for Biologics (Apr. 26, 2021),
`https://www.morganlewis.com/pubs/2021/04/taking-advantage-of-
`the-new-purple-book-patent-requirements-for-biologics
`(“MorganLewis - New Purple Book Patent Requirements”)
`Hajir Dadgostar et al., Evaluation of Injection Frequency and Visual
`Acuity Outcomes for Ranibizumab Monotherapy in Exudative Age-
`related Macular Degeneration, 116 OPHTHALMOLOGY 1740 (2009)
`(“Dadgostar”)
`Declaration of Robert V. Cerwinski in Support of Motion for Pro
`Hac Vice Admission
`
`Declaration of Aviv A. Zalcenstein in Support of Motion for Pro Hac
`Vice Admission
`
`Declaration of Brigid M. Morris in Support of Motion for Pro Hac
`Vice Admission
`
`1173
`
`1174
`
`1175
`
`1176
`
`1177
`
`1178
`
`1179
`
`Dated: May 31, 2022
`
`
`
`Respectfully submitted,
`
`/Lora M. Green/
`
` Lora M. Green, Lead Counsel
` Reg. No. 43,541
`
`-19-
`
`
`
`CERTIFICATE OF SERVICE
`This is to certify that I caused to be served true and correct copy of the
`
`foregoing Updated Exhibit List and EX1177-EX1079 on this 31st day of May 2022,
`
`on the Patent Owner at the correspondence address of the Patent Owner as follows:
`
`Deborah Fishman
`
`Deborah.fishman@arnoldporter.com
`
`David Cain
`
`David.Caine@arnoldporter.com
`
`Alice Sin Yu Ho
`
`Alice.ho@arnoldporter.com
`
`Victoria Reines
`
`Victoria.Reines@arnoldporter.com
`
`Jeremy Cobb
`
`Jeremy.Cobb@arnoldporter.com
`
`Daniel Reisner
`
`Daniel.Reisner@arnoldporter.com
`
`Matthew Wilk
`
`Matthew.Wilk@arnoldporter.com
`
`RegeneronEyleaIPRs@arnoldporter.com
`
`And to Counsel for Petitioner Mylan Pharmaceuticals in IPR2021-00880, as follows:
`
`Paul Molino
`
`paul@rmmslegal.com
`
`William A. Rakoczy
`
`wrakoczy@rmmslegal.com
`
`Heinz Salmen
`
`hsalmen@rmmslegal.com
`
`-20-
`
`
`
`Neil McLaughlin
`
`nmclaughlin@rmmslegal.com
`
`Teresa Rea
`
`Deborah Yellin
`
`Shannon Lentz
`
`Eric R. Hunt
`
`trea@crowell.com
`
`dyellin@crowell.com
`
`slentz@crowell.com
`
`ehunt@rmmslegal.com
`
`MYL_REG_IPR@rmmslegal.com
`
`Dated: May 31, 2022
`
`
`
`Respectfully submitted,
`
`/Lora M. Green/
`
` Lora M. Green, Lead Counsel
` Reg. No. 43,541
`
`-21-
`
`