`
`
`
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_____________
`
`SAMSUNG BIOEPIS CO., LTD., CELLTRION INC,
`and BIOCON BIOLOGICS INC.
`Petitioners,
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.
`Patent Owner.
`
`
`Patent No. 11,253,572
`
`_______________
`
`Inter Partes Review No. IPR2023-008841
`____________________________________________________________
`
`PATENT OWNER’S UPDATED EXHIBIT LIST
`
`
`1 IPR2024-00260 and IPR2024-00298 are joined with IPR2023-00884.
`
`

`

`IPR2023-00884
`
`
`
`
`
`Updated Exhibit List for Inter Partes Review of U.S. Patent No. 11,253,572
`
`Exhibit Description
`
`Exhibit No.
`
`2001
`
`2002
`2003
`
`2004
`
`2005
`
`2006
`
`2007
`
`2008
`
`2009
`
`2010
`
`2011
`
`2012
`
`2013
`
`2014
`
`
`
`Expert Declaration of Richard Manning, Ph.D., Mylan Pharms.
`Inc. v. Regeneron Pharms., Inc., IPR2021-00881, Ex. No. 2052
`(Feb. 11, 2022)
`EYLEA® Label (rev. Oct. 2014)
`Trial Transcript (unsealed portions), Regeneron Pharms., Inc. v.
`Mylan Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.)
`Press Release, Positive Interim Phase 2 Data Reported for VEGF
`Trap-Eye in Age-Related Macular Degeneration, Regeneron
`Pharmaceuticals, Inc. (Mar. 27, 2007)
`Email from George Yancopoulos to Murray Goldberg re Top Line
`sum for PR (Mar. 22, 2007)
`Interim Analysis of Phase 2 Study of VEGF Trap in AMD patients
`(Mar. 22, 2007) (Attachment to Ex.2005)
`George D. Yancopoulos, VEGF Trap : Scientific Background,
`BSP / REGN Kick-Off (Feb. 16, 2007)
`Email from Kathleen Lawrence re Decisions & Actions: AMD
`Ph3 Program Mtg – 4/2/07 (Apr. 2, 2007)
`Email from George Yancopoulos to Darlene Jody re Summary of
`issues for call: AMD P3 Planning with enclosed outline attached
`(Apr. 4, 2007)
`Email from Robert Terifay to George Yancopoulos re VGTeye
`VIEW 430 presentation (Nov. 19, 2010)
`Vascular Endothelial Growth Factor (VEGF) Trap-Eye:
`Investigation of Efficacy and Safety in Wet Age-Related Macular
`Degeneration (AMD) - VIEW 1 and VIEW 2 – 1-Year Results
`(Attachment to Ex.2010)
`Regeneron Pharmaceuticals, Phase 1 Study of VEFT Trap in
`Patients With Diabetic Macular Edema,
`https://clinicaltrials.gov/study/NCT00320814 (last updated Jun.
`10, 2011)
`Regeneron, Clinical Study Concept - Ophthalmology-Diabetic
`Macular Edema-Phase 2-IVT-VGFT-OD-0706 (updated May 19,
`2008)
`Diana V. Do et al., One-Year Outcomes of the DA VINCI Study of
`VEGF Trap-Eye in Eyes with Diabetic Macular Edema, 119
`OPHTHALMOLOGY 1658-1665 (Aug. 2012).
`i
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2015
`
`2016
`
`2017
`2018
`
`2019
`
`2020
`
`2021
`
`2022
`
`2023
`
`2024
`
`2025
`
`2026
`
`2027
`
`2028
`
`DA VINCI – DME And VEGF Trap-Eye: Investigation of Clinical
`Impact: One Year Data (Dec. 8, 2010) (attachment to Ex.2024)
`Regeneron Pharmaceuticals, DME And VEGF Trap-Eye
`[Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)]
`Investigation of Clinical Impact (DA VINCI),
`https://clinicaltrials.gov/study/NCT00789477 (last updated Sep. 9,
`2014)
`Email from Caroline Saxton re Data Review (Feb. 1, 2010)
`Regeneron Pharmaceuticals, Inc., VGFT-OD-0706 Week 24
`Topline Results (Feb. 1, 2010) (attachment to Ex.2017)
`DRAFT – DA VINCI – 6-Month Primary Endpoint (Feb. 1, 2010)
`(attachment to Ex.2017)
`Regeneron Pharmaceuticals, Inc., VEGF Trap-Eye Shows Positive
`Results in a Phase 2 Study in Patients With Diabetic Macular
`Edema (Feb. 18, 2010)
`Email from Alyson Berliner to Dave Brown re ARVO late
`breakers (Mar. 1, 2010)
`DA VINCI: DME And VEGF Trap-Eye: Investigation of Clinical
`Impact: Phase 2 study in patients with Diabetic Macular Edema
`(DME) (Mar. 1, 2010) (Attachment to Ex.2021)
`Email from Dave Brown to Alyson Berliner and James Major re
`ARVO abstract (Mar. 3, 2010)
`Email from Caroline Saxton re Slides and tables – DaVinci (Dec.
`8, 2010)
`U.S. Provisional Patent Application No. 61/434,836 (Jan. 21,
`2011)
`Mylan Pharmaceuticals Inc.’s Answer, Defenses, and
`Counterclaims to Plaintiff's Complaint, Regeneron Pharms., Inc. v.
`Mylan Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.),
`ECF No. 47 (filed Aug. 25, 2022)
`Stipulation and Order Joining Biocon Biologics Inc. as Defendant,
`Regeneron Pharms., Inc. v. Mylan Pharms. Inc., No. 1:22-cv-
`00061-TSK-JPM (N.D.W. Va.), ECF No. 523 (filed Jun. 5, 2023)
`Complaint for Patent Infringement, Regeneron Pharms., Inc. v.
`Mylan Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.),
`ECF No. 1 (filed Aug. 2, 2022)
`
`
`
`ii
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2029
`
`2030
`
`2031
`
`2032
`
`2033
`
`2034
`
`2035
`
`2036
`2037
`
`2038
`
`2039
`
`2040
`
`2041
`
`2042
`
`
`
`Order on Claim Construction, Regeneron Pharms., Inc. v. Mylan
`Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.), ECF
`No. 427 (filed Apr. 19, 2023)
`Scheduling Order, Regeneron Pharms., Inc. v. Mylan Pharms.
`Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.), ECF No. 87
`(filed Oct. 25, 2022)
`Regeneron's Stipulation Regarding Summary Judgment and Case
`Narrowing, Regeneron Pharms., Inc. v. Mylan Pharms. Inc., No.
`1:22-cv-00061-TSK-JPM (N.D.W. Va.), ECF No. 433 (filed Apr.
`27, 2023)
`Defendant's Opening Post Trial Brief - Issues Where Defendants
`Bear the Burden of Proof, Regeneron Pharms., Inc. v. Mylan
`Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.), ECF
`No. 576 (filed July 7, 2023)
`Order Setting Briefing Schedule, Regeneron Pharms., Inc. v.
`Mylan Pharms. Inc., No. 1:22-cv-00061-TSK-JPM (N.D.W. Va.),
`ECF No. 514 (filed May 30, 2023)
`Transcript of the Status Conference held on Sept. 28, 2022,
`Regeneron Pharms., Inc. v. Mylan Pharms. Inc., No. 1:22-cv-
`00061-TSK-JPM (N.D.W. Va.), ECF No. 90 (filed Nov. 2, 2022)
`Email from George Yancopoulos re DME Phase 2 – ALL
`TABLES (Feb. 2, 2010)
`DME Target Product Profile - VEGF Trap-Eye (Sept. 26, 2007)
`Clinical Development & Regulatory Affairs Weekly Update (Oct.
`29, 2010)
`Clinical Development & Regulatory Affairs Weekly Update (Dec.
`3, 2010)
`Email from George Yancopoulos re DME PLANS & FDA
`meeting pre-discussion (Jan. 9, 2008)
`MEMO re Guidance From Bayer/ REGN Sr. Management
`Regarding Additional Indications in Ophthalmology from George
`Yancopoulos to Bayer/REGN Joint Development Group (Mar. 28,
`2008)
`Action Items by GD Yancopoulos - Bayer/REGN JSC (Feb. 15,
`2008)
`Email from Yuhwen Soo to George Yancopoulos re Can you send
`me that slide you made combining the VA curves for View1 &
`View2 (Nov. 20, 2010)
`
`iii
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2043
`
`2044
`
`2045
`
`2046
`
`2047
`
`2048
`
`2049
`
`2050
`
`2051
`
`2052
`
`2053
`2054
`
`
`
`Vascular Endothelial Growth Factor (VEGF): Investigation of
`Efficacy and Safety in Wet Age-Related Macular Degeneration
`(AMD)—VIEW1 + VIEW 2: 1-Year Results (Nov. 20, 2010)
`(Attachment to Ex.2042)
`Email from Michael Aberman to George Yancopoulos and
`Leonard Schleifer re Press Release (Nov. 19, 2010)
`Regeneron, Bayer and Regeneron Report Positive Top-Line
`Results of Two Phase 3 Studies with VEGF Trap-Eye in Wet Age-
`related Macular Degeneration (Nov. 19, 2010) (Attachment to
`Ex.2044)
`U.S. Food & Drug Administration, 22 Case Studies Where Phase
`2 and Phase 3 Trials Had Divergent Results (Jan. 2017)
`VEGF Trap-Eye in Wet AMD - CLEAR-IT 2: Summary of One-
`Year Key Results, Presented at 2008 Retina Society Meeting,
`Scottsdale, Arizona (Sep. 28, 2008)
`Regeneron Pharmaceuticals, Inc., A Double-Masked, Randomized,
`Controlled Study of the Safety, Tolerability and Biological Effect
`of Repeated Intravitreal Administration of VEGF Trap-Eye in
`Patients with Diabetic Macular Edema (DME) (Issued Jan. 28,
`2009)
`Appendix to Heier et al., Intravitreal Aflibercept (VEGF Trap-
`Eye) in Wet Age-Related Macular Degeneration, 119
`OPHTHALMOLOGY 2537 (2012)
`Retinal Physician Symposium Covers Broad Range of Topics,
`Retinal Physician (Sept. 1, 2006),
`https://www.retinalphysician.com/issues/2006/september2006/reti
`nal-physician-symposium-covers-broad-range-of
`Prema Abraham et al., Randomized, Double-Masked,
`ShamControlled Trial of Ranibizumab for Neovascular Age-
`Related Macular Degeneration: PIER Study Year 2, 150 AM. J.
`OPHTHALMOLOGY 315 (2010)
`FDA, Step 3: Clinical Research,
`https://www.fda.gov/patients/drug-development-process/step-3-
`clinical-research (last accessed Aug. 23, 2023)
`Prosecution History of U.S. Patent App. No. 16/159,282 B2
`Anant Pai et al., Current concepts in intravitreal drug therapy for
`diabetic retinopathy, 24 SAUDI J. OPHTHALMOLOGY 143 (June 30,
`2010)
`
`iv
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2055
`
`2056
`
`2057
`
`2058
`
`2059
`2060
`
`2061
`
`2062
`
`2063
`
`
`2064
`
`
`2065
`2066
`2067
`
`
`2068
`
`
`2069
`
`
`2070
`
`
`
`
`David M. Brown et al., Long-term Outcomes of Ranibizumab
`Therapy for Diabetic Macular Edema: The 36-Month Results from
`Two phase Ill Trials, 120 OPHTHALMOLOGY 2013 (2013)
`Jean-Francois Korobelnik et al., Intravitreal Aflibercept for
`Diabetic Macular Edema, 121 OPHTHALMOLOGY 2247 (2014)
`Quan Dong Nguyen et al., Ranibizumab for Diabetic Macular
`Edema, Results from 2 Phase Ill Randomized Trials: RISE and
`RIDE, 119 OPHTHALMOLOGY 789 (2012)
`Ursula Schmidt-Erfurth et al., Three-Year Outcomes of
`Individualized Ranibizumab Treatment in Patients with Diabetic
`Macular Edema. 121 OPHTHALMOLOGY 1045 (2014)
`Default Protective Order
`Declaration of Kira A. Davis in Support of Motion for Admission
`Pro Hac Vice (“Davis Decl.”)
`Declaration of Daralyn J. Durie in Support of Motion for
`Admission Pro Hac Vice (“Durie Decl.”)
`Deposition Transcript of Edward Chaum, M.D., Ph.D. (January 5,
`2024)
`Declaration of George Yancopoulos, M.D., PH.D. (February 19,
`2024) – CONFIDENTIAL MATERIAL - SUBJECT TO
`PROTECTIVE ORDER
`Declaration of Karen Chu (February 19, 2024) –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Declaration of Michael W. Stewart, M.D. (February 21, 2024)
`Declaration of David M. Brown, M.D. (February 21, 2024)
`Declaration of Richard Manning, Ph.D. (February 22, 2024) –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Press Release, Regeneron, Bayer HealthCare and Regeneron to
`Collaborate on VEGF Trap for the Treatment of Eye Diseases
`(October 18, 2006)
`Regeneron/Bayer Alliance, Internal Kick-Off Meeting (November
`8, 2006) – CONFIDENTIAL MATERIAL - SUBJECT TO
`PROTECTIVE ORDER
`Email from Robert Terifay to Leonard Schleifer and George
`Yancopoulos (March 22, 2007) – CONFIDENTIAL MATERIAL
`- SUBJECT TO PROTECTIVE ORDER
`v
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2071
`
`2072
`
`
`2073
`
`
`2074
`
`2075
`
`
`2076
`
`2077
`2078
`
`2079
`
`
`2080
`
`
`2081
`2082
`
`
`2083
`
`
`2084
`
`
`2085
`
`
`Email from Peter Powchik to George Yancopoulos (March 22,
`2007)
`PowerPoint Presentation (Attachment to Ex.2071) –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`PowerPoint Presentation (Attachment to Ex. 2074) –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Email from George Yancopoulos to Leonard Schleifer (March 22,
`2007)
`Email from George Yancopoulos to Darlene Jody (April 10, 2007)
`– CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`CLEAR-IT 3 Clinical Trial Protocol – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`Email from Alyson Berliner to Dave Brown (March 1, 2020)
`Email from Dave Brown to Alyson Berliner; Robert Vitti; James
`Major (March 2, 2010)
`Draft of document titled DA VINCI: DME and VEGF Trap-Eye:
`Investigation of Clinical Impact: Phase 2 study in patients with
`Diabetic Macular Edema (DME)
`Document titled DA VINCI: DME and VEGF Trap-Eye:
`Investigation of Clinical Impact: Phase 2 study in patients with
`Diabetic Macular Edema (DME)
`Curriculum Vitae of David Mark Brown MD FACS
`David M. Brown et al., Ranibizumab versus verteporfin for
`neovascular age-related macular degeneration, New England
`Journal of Medicine, 355(14), 1432-1444 (2006)
`Philip J. Rosenfeld et al., Ranibizumab for neovascular age-
`related macular degeneration, New England Journal of
`Medicine, 355(14), 1419-1431 (2006)
`Press Release, Genentech, Inc. Submits Biologics License
`Application for FDA Review of Lucentis(TM) In Wet Age-Related
`Macular Degeneration (Dec. 30, 2005)
`Jonathan P. Levine et al., Macular Hemorrhage in Neovascular
`Age-Related Macular Degeneration After Stabilization with
`Antiangiogenic Therapy, 29 Retina, 1074-79 (2009)
`
`
`
`vi
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2086
`
`
`2087
`
`2088
`
`
`2089
`
`
`2090
`
`2091
`2092
`
`
`2093
`
`2094
`
`
`2095
`
`
`2096
`2097
`
`
`2098
`
`
`2099
`
`
`
`Irene Barbazetto et al., Dosing Regimen and The Frequency of
`Macular Hemorrhages in Neovascular Age-Related Macular
`Degeneration Treated with Ranibizumab, 30 RETINA 1376-85
`(2010)
`Daniele Cruz, PIER Data Suggest a Need for Tailored Injection
`Schedule, Ocular Surgery News, (Sept. 1, 2006)
`Press Release, Genentech, FDA Approves Lucentis for the
`Treatment of Wet Age-Related Macular Degeneration (June 30,
`2006)
`Drugs@FDA, Lucentis Label, c. 2006, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/12515
`6lbl.pdf.
`Deposition Transcript of Edward Chaum, M.D., Ph.D. Volume 2
`(February 2, 2024)
`Declaration of Jeffrey Spada (February 20, 2024)
`Document Containing Screenshots of Database –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron Pharms., Inc. v. Mylan Pharms. Inc. et al, No. 22-cv-
`00061, Dkt. No. 692 (N.D.V.A. Jan. 31, 2024)
`Carl D. Regillo et al., Randomized, Double-Masked, Sham-
`Controlled Trial of Ranibizumab for Neovascular Age-Related
`Macular Degeneration: PIER Study Year 2, 150 AM. J.
`OPHTHALMOLOGY 315 (2010)
`Candelaria Gomez-Manzano et al., VEGF Trap induces
`antiglioma effect at different stages of disease, Neuro-oncology,
`10(6), 940-945 (2008)
`Curriculum Vitae of Michael W. Stewart, MD
`Geeta A. Lalwani et al., A variable-dosing regimen with
`intravitreal ranibizumab for neovascular age-related macular
`degeneration: year 2 of the PrONTO Study, American journal of
`ophthalmology, 148(1), 43-58 (2009)
`F.G. Holz et al., SUSTAIN Study Group, Safety and Efficacy of
`RanibizumabTreatment in Patients with Neovascular Age-Related
`Macular Degeneration: 12-MonthResults of the SUSTAIN
`Study, Investigative Ophthalmology & Visual Science, 50(13),
`3095-3095 (2009)
`RESERVED
`
`vii
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2100
`2101
`
`2102
`2103
`
`
`2104
`
`2105
`
`
`2106
`
`
`2107
`2108
`2109
`
`
`2110
`
`
`2111
`2112
`
`2113
`
`2114
`
`
`Eylea® Label (2016)
`Jean-Francois Korobelnik et al., Intravitreal Aflibercept for
`Diabetic Macular Edema, 121 OPHTHALMOLOGY 2247 (2014)
`LUCENTIS® Label (rev. Aug. 2012)
`Prema Abraham et al., Randomized, Double-Masked, Sham-
`Controlled Trial of Ranibizumab for Neovascular Age-Related
`Macular Degeneration: PIER Study Year 2, 150 AM. J.
`OPHTHALMOLOGY 315-324 (2010)
`Retinal Physician Symposium Covers Broad Range of Topics,
`Retinal Physician (Sept. 1, 2006)
`Regeneron Pharmaceuticals, DME and VEGF Trap-Eye
`[Intravitreal Aflibercept Injection (IAI;EYLEA®;BAY86-5321)]
`Investigation of Clinical Impact (DA VINCI),
`https://classic.clinicaltrials.gov/ct2/show/study/NCT00789477
`Regeneron Press Release, Regeneron Announces FDA Acceptance
`of EYLEA® (aflibercept) Injection Supplemental Biologics License
`Application for Review for Diabetic Macular Edema Indication
`(Dec. 18, 2013)
`AVASTIN™ Label (2004)
`AVASTIN Approval Letter (February 26, 2004)
`Genentech, Inc., A Study of Ranibizumab Injection in Subjects
`With Clinically Significant Macular Edema (ME) With Center
`Involvement Secondary to Diabetes Mellitus (RISE),
`NCT00473330, ClinicalTrials.gov (December 14, 2023),
`https://www.clinicaltrials.gov/ct2/show/NCT00473330
`Genentech Press Release, FDA Approves Genentech’s Lucentis
`(Ranibizumab Injection) for Diabetic Retinopathy, the Leading
`Cause of Blindness Among Working Age Adults in the United
`States, (April 17, 2017)
`LUCENTIS® Label (2017)
`Sarah Whelan, What is Angiogenesis?, Technology Networks
`(July 6, 2022)
`Matthew Dombrow et al., Ocular Angiogenesis: The Science
`Behind the Symptoms, Retinal Physician (2011)
`Joan W. Miller, VEGF: From Discovery to Therapy: The
`Champalimaud Award Lecture, Translational Vision Science &
`Technology, 5(2), 9-9 (2016)
`
`
`
`viii
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2115
`2116
`
`2117
`2118
`
`
`2119
`
`
`2120
`
`2121
`
`
`2122
`
`
`2123
`
`2124
`
`
`2125
`
`2126
`
`
`2127
`
`
`2128
`
`
`
`
`Macugen Approval Letter (December 14, 2004)
`Press Release, Genentech, FDA Approves Genentech’s Lucentis
`(Ranibizumab Injection) Prefilled Syringe (October 14, 2016)
`RESERVED
`Press Release, Genentech, Genentech, Inc. Submits Biologics
`License Application For FDA Review Of Lucentis(TM) In Wet
`Age-Related Macular Degeneration (December 30, 2005)
`P Mitchell et al., Ranibizumab (Lucentis) in Neovascular Age-
`Related Macular Degeneration: Evidence from Clinical Trials, 94
`BRIT. J. OPHTHALMOLOGY 2-13 (2009)
`Donald S. Fong et al., Diabetic Retinopathy, Diabetes Care, 27
`(10), 2540-2553 (2004).
`Early Treatment Diabetic Retinopathy Study Research Group,
`Early photocoagulation for diabetic retinopathy: ETDRS Report
`Number 9, Ophthalmology, 98(5), 766-785 (1991)
`Diabetic Retinopathy Study Research Group, Photocoagulation
`treatment of proliferative diabetic retinopathy: clinical application
`of Diabetic Retinopathy Study (DRS) findings, DRS Report
`Number 8, Ophthalmology, 88(7), 583-600 (1981)
`Ovidiu Musat et al., Diabetic macular edema, Romanian Journal
`of Ophthalmology, 59(3), 133 (2015)
`Early Treatment Diabetic Retinopathy Study Research Group,
`Photocoagulation for Diabetic Macular Edema, ETDRS report
`Number 1, Arch Ophthalmol, 103(12), 1796-1806 (1985)
`Anita Prasad, The DRCR Network Aids DR Treatment, Review of
`Ophthalmology (2006)
`Pedro Romero-Aroca et al., Laser treatment for diabetic macular
`edema in the 21st century, Current Diabetes Reviews, 10(2), 100-
`112 (2014)
`Treatment of Age-Related Macular Degeneration with
`Photodynamic Therapy (TAP) Study Group, Photodynamic
`therapy of subfoveal choroidal neovascularization in age-related
`macular degeneration with verteporfin: one-year results of 2
`randomized clinical trials—TAP report 1, Archives of
`Ophthalmology, 117(10), 1329-1345 (1999)
`FDA, Step 3: Clinical Research,
`https://www.fda.gov/patients/drug-development-process/step-3-
`clinical-research (last accessed Aug. 23, 2023)
`ix
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2129
`
`
`2130
`
`2131
`
`
`2132
`
`
`2133
`
`
`2134
`2135
`
`2136
`
`2137
`
`
`2138
`
`
`2139
`
`
`2140
`
`
`2141
`
`
`Press Release, BioSpace, Opko Health, Inc. Announces Update on
`Phase III Clinical Trial of Bevasiranib; Company Decided to
`Terminate Clinical Study (March 6, 2009)
`Press Release, Opko Health, Opko Health Initiates Phase 3 Trial
`of Bevasiranib for the Treatment of AMD (July 11, 2007)
`Press Release, Opko Health, OPKO's Bevasiranib Named One of
`Most Promising Drugs Recently Entering Phase III Trials
`(December 6, 2007)
`Dhyana Sharma et al., Mechanisms of Acquired Resistance to
`Anti-VEGF Therapy for Neovascular Eye Diseases, Investigative
`Ophthalmology & Visual Science, 64(5), 28-28 (2023)
`How to Read a Study Record, ClinicalTrials.gov, available at
`https://clinicaltrials.gov/study-basics/how-to-read-study-
`record#record-history-tab (last updated Jan. 9, 2024).
`Archived Webpage Re: Clinical Trial No. NCT00473330
`Sarah Whelan, What is Angiogenesis?, Technology Networks
`(July 6, 2022)
`Thomas H. Adair & Jean-Pierre Montani, Angiogenesis, Morgan
`& Claypool Life Sciences (2011)
`Michael J. Tolentino et al., Intravitreous Injections of Vascular
`Endothelial Growth Factor Produce Retinal Ischemia and
`Microangiopathy in an Adult Primate, Ophthalmology, 103(11),
`1820-1828 (1996)
`David M. Brown et al., Evaluation of intravitreal aflibercept for
`the treatment of severe nonproliferative diabetic retinopathy:
`results from the PANORAMA randomized clinical trial, JAMA
`Ophthalmology, 139(9), 946-955 (2021)
`Jeffrey S. Heier et al., Intravitreal aflibercept for diabetic macular
`edema: 148-week results from the VISTA and VIVID
`studies, Ophthalmology, 123(11), 2376-2385 (2016)
`Drugs@FDA, Eylea label, 2/2023, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/12538
`7s075lbl.pdf
`American Society of Retina Specialists, “2015 Preferences and
`Trends (PAT) Survey,” c. 2015 - CONFIDENTIAL MATERIAL -
`SUBJECT TO PROTECTIVE ORDER
`
`
`
`x
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2142
`
`
`2143
`
`
`2144
`
`
`2145
`2146
`2147
`
`
`2148
`
`
`2149
`
`
`2150
`
`
`2151
`
`
`2152
`
`2153
`
`
`2154
`
`
`American Society of Retina Specialists, “2016 Preferences and
`Trends (PAT) Survey,” c. 2016 - CONFIDENTIAL MATERIAL -
`SUBJECT TO PROTECTIVE ORDER
`Regeneron, “DME Market Assessment,” 8/2014 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Q2 2020 Performance Update,” 7/2020 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`U.S. Patent Provisional Application No. 61/432,245
`U.S. Patent No. 11,730,794 B2
`American Society of Retina Specialists, "2009 Preferences and
`Trends Membership Survey," c. 2009 – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`Beovu label, 10/2019, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/76112
`5s000lbl.pdf
`Beovu label, 12/2022, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/76112
`5s017lbl.pdf
`Centers for Disease Control and Prevention, Vision Loss: A Public
`Health Problem, 12/19/2022,
`https://www.cdc.gov/visionhealth/basic_information/vision_loss.h
`tm
`Centers for Medicare & Medicaid Services Website, Medicare
`Physician & Other Practitioners - by Provider and Service,
`https://data.cms.gov/provider-summary-by-type-of-
`service/medicare-physician-other-practitioners/medicare-
`physician-other-practitioners-by-provider-and-service
`Drugs.com Website, Eylea FDA Approval History,
`https://www.drugs.com/history/eylea.html (accessed 1/16/2024)
`Eylea label, 5/2019, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/12538
`7s061lbl.pdf
`Eylea label, 9/2012, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/12538
`7s004lbl.pdf
`
`
`
`xi
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2155
`
`
`2156
`
`
`2157
`
`
`2158
`
`
`2159
`
`
`2160
`
`
`2161
`
`2162
`
`
`2163
`
`
`2164
`
`
`2165
`
`
`2166
`
`
`Guha, Rahul, Jian Li, and Andrea L. Scott (2009), The Economics
`of Commercial Success in Pharmaceutical Patent Litigation,
`Landslide 1(5) (2009)
`Lucentis label, 3/2018, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/12515
`6s117lbl.pdf
`Lucentis label, 6/2010, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/12515
`6s053lbl.pdf
`Manning, Richard, et al. (2015), Similar Products at Different
`Prices: Can Biopharmaceutical Companies Segment Markets?,
`International Journal of the Economics of Business 22(2): 231–
`243 (2015)
`NCI, Second-Line Therapy,
`https://www.cancer.gov/publications/dictionaries/cancer-
`terms/def/second-line-therapy (accessed 1/16/2024)
`Regeneron Press Release, Eylea (Aflibercept) Injection Receives
`FDA Approval for the Treatment of Diabetic Macular Edema
`(DME), 7/29/2014
`Regeneron Website, History,
`https://www.regeneron.com/about/history (accessed 1/15/2024).
`Regeneron, “DME Market Assessment Q1 2015,” 4/2015 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q1 2016,” 4/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q1 2017,” 5/2017 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q1 2018,” 5/2018 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q2 2015,” 8/2015 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`
`
`
`xii
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2167
`
`
`2168
`
`
`2169
`
`
`2170
`
`
`2171
`
`
`2172
`
`
`2173
`
`
`2174
`
`
`2175
`
`
`2176
`
`
`2177
`
`
`2178
`
`
`Regeneron, “DME Market Assessment Q2 2016,” 8/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q2 2017,” 7/2017 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q2 2018,” 7/2018 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q3 2015,” 11/2015 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q3 2016,” 10/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q3 2017,” 10/2017 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q4 2014,” 1/2015 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q4 2015,” 2/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q4 2016,” 1/2017 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Q4 2017,” 2/2018 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “DME Market Assessment Wave 3, Q3 2014,”
`11/2014 – CONFIDENTIAL MATERIAL - SUBJECT TO
`PROTECTIVE ORDER
`Regeneron, “DME Market Assessment, Benchmark Wave,”
`11/8/2013 – CONFIDENTIAL MATERIAL - SUBJECT TO
`PROTECTIVE ORDER
`
`
`
`xiii
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2179
`
`
`2180
`
`
`2181
`
`
`2182
`
`
`2183
`
`
`2184
`
`
`2185
`
`
`2186
`
`
`2187
`
`
`2188
`
`
`2189
`
`
`2190
`
`
`Regeneron, “Physician ATU: Q1 2015,” 4/2015 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Q2 2015,” 7/2015 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Q3 2014,” 11/2014 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Q3 2015,” 11/2015 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Q4 2014,” 1/2015 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Q4 2015,” 1/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Wave 2,” 2/2013 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Wave 4,” 8/6/2013 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Wave 5,” 11/2013 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Wave 6,” 1/2014 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Wave 7,” 4/2014 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Physician ATU: Wave 8,” 8/2014 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`
`
`
`xiv
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2191
`
`
`2192
`
`
`2193
`
`
`2194
`
`
`2195
`
`
`2196
`
`
`2197
`
`
`2198
`
`
`2199
`
`
`2200
`2201
`2202
`2203
`2204
`2205
`2206
`2207
`2208
`2209
`
`Regeneron, “Q1 2019 Performance Update Wet AMD, DME, &
`MEfRVO,” 5/2019 – CONFIDENTIAL MATERIAL - SUBJECT
`TO PROTECTIVE ORDER
`Regeneron, “Q1 2020 Performance Update Wet AMD, DME,
`MEfRVO & DR w/out DME,” 4/2020 – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`Regeneron, “Q2 2019 Performance Update Wet AMD, DME,
`MEfRVO & DR w/out DME,” 8/2019 – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`Regeneron, “Q3 2018 Performance Update Wet AMD, DME, &
`MEfRVO,” 11/2018 – CONFIDENTIAL MATERIAL -
`SUBJECT TO PROTECTIVE ORDER
`Regeneron, “Q3 2019 Performance Update Wet AMD, DME,
`MEfRVO & DR w/out DME,” 11/2019 – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`Regeneron, “Q3 2020 Performance Update Wet AMD, DME,
`MEfRVO & DR w/out DME,” 11/2020 – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`Regeneron, “Q4 2018 Performance Update Wet AMD, DME, &
`MEfRVO,” 2/2019 – CONFIDENTIAL MATERIAL - SUBJECT
`TO PROTECTIVE ORDER
`Regeneron, “Q4 2019 Performance Update Wet AMD, DME, &
`MEfRVO,” 1/2020 – CONFIDENTIAL MATERIAL - SUBJECT
`TO PROTECTIVE ORDER
`Regeneron, “Q4 2020 Performance Update Wet AMD, DME,
`MEfRVO & DR w/out DME,” 1/29/2021 – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`RESERVED
`RESERVED
`RESERVED
`RESERVED
`RESERVED
`RESERVED
`RESERVED
`RESERVED
`RESERVED
`RESERVED
`
`
`
`xv
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2210
`2211
`2212
`2213
`2214
`
`2215
`
`
`2216
`
`
`2217
`
`
`2218
`
`
`2219
`
`
`2220
`
`
`2221
`
`
`2222
`
`
`2223
`
`
`2224
`
`
`RESERVED
`RESERVED
`RESERVED
`RESERVED
`Regeneron, “US Eylea P&L LTD,” c. 2021 – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`Regeneron, “Wet AMD Physician ATU: Q1 2016,” 4/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q1 2017,” 4/2017 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q1 2018,” 5/2018 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q2 2016,” 8/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q2 2017,” 7/2017 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q2 2018,” 7/2018 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q3 2016,” 10/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q3 2017,” 10/2017 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q4 2016,” 1/2016 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, “Wet AMD Physician ATU: Q4 2017,” 1/2018 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`
`
`
`xvi
`
`

`

`IPR2023-00884
`
`Exhibit No.
`
`
`
`Exhibit Description
`
`
`
`2225
`
`
`2226
`2227
`2228
`2229
`2230
`2231
`2232
`
`
`2233
`2234
`
`
`2235
`
`
`2236
`
`
`2237
`
`
`2238
`
`
`2239
`
`
`2240
`2241
`[NEW]
`2242
`[NEW]
`
`
`
`
`
`Regeneron, “Wave 1 2021 Performance Update Wet AMD, DME,
`MEfRVO, and DR w/out DME,” 9/2021 – CONFIDENTIAL
`MATERIAL - SUBJECT TO PROTECTIVE ORDER
`Regeneron, ATU Sales Share Data: All Indications, c. 2021
`Regeneron, ATU Sales Share Data: BRVO, c. 2021
`Regeneron, ATU Sales Share Data: CRVO, c. 2021
`Regeneron, ATU Sales Share Data: DME, c. 2021
`Regeneron, ATU Sales Share Data: DR w/o DME, c. 2021
`Regeneron, ATU Sales Share Data: Wet AMD, c. 2021
`Regeneron, Eylea Gross & Net Sales P&L YTD, c.2021 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`Regeneron, Form 10-K, 2020
`Susvimo Label, 10/2021, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/76119
`7s000lbl.pdf
`Susvimo Label, 4/2022, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/76119
`7s002lbl.pdf
`Vabysmo Label, 1/2022, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/76123
`5s000lbl.pdf
`Vabysmo Label, 1/2023, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/76123
`5s001lbl.pdf
`Vestrum, Anti-VEGF Category Sales Shares, c. 2/2022 –
`CONFIDENTIAL MATERIAL - SUBJECT TO PROTECTIVE
`ORDER
`World Health Organization, "Blindness and Vision Impairment
`Fact Sheet," 8/10/2023, https://www.who.int/news-room/fact-
`sheets/detail/blindness-and-visual-impairment
`Declaration of Nathaniel E Frank-White (February 15, 2024)
`Declaration of Matthew M. Wilk in Support of this Motion for
`Admission Pro Hac Vice (“Wilk Decl.”).
`Declaration of Jeremy Cobb in Support of this Motion for
`Admission Pro Hac Vice (“Cobb Decl.”).
`
`
`xvii
`
`

`

`IPR2023-00884
`
`Date: March 15, 2024
`
`Respectfully Submitted,
`
`By: /Adam R. Brausa/
`Adam R. Brausa, Reg. No. 60,287
`MORRISON & FOERSTER LLP
`425 Market Street
`San Francisco, California 94105
`Tel: (415) 268-6053
`ABrausa@mofo.com
`
`Counsel for Patent Owner
`
`1
`
`

`

`IPR2023-00884
`
`Certificate of Service (37 C.F.R. § 42.6(e)(4))
`
`I hereby certify that the attached PATENT OWNER’S UPDATED
`
`EXHIBIT LIST was served on the date listed below via email (by agreement) upon
`
`the following counsel of record for Petitioners:
`
`Raymond N. Nimrod (Reg. No. 31,987)
`Matthew A. Traupman (Reg. No. 50,832)
`Elliot Choi (pro hac vice granted)
`Zachariah Summers (pro hac vice granted)
`Sarah Cork (pro hac vice to be applied for)
`Landon Andrew Smith (Reg. No. 79,248)
`QUINN EMANUEL URQUHART
`& SULLIVAN, LLP
`51 Madison Ave., 22nd Floor
`New York, NY 10010
`General Tel: (212) 849-7000
`Direct Tel: (212) 849-7322
`Fax: (212) 849-7100
`Email: raynimrod@quinnemanuel.com
`Email: matthewtraupman@quinnemanuel.com
`Email: elliotchoi@quinnemanuel.com
`Email: zachsummers@quinnemanuel.com
`Email: la