`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`
`APOTEX INC.,
`Petitioner
`v.
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner
`
`
`
`
`
`
`
`Inter Partes Review No.: IPR2022-00298
`
`
`
`
`
`
`
`U.S. Patent No. 9,254,338 B2
`Filed: July 12, 2013
`Issued: February 9, 2016
`Inventor: George D. Yancopoulos
`
`Title: USE OF A VEGF ANTAGONIST TO TREAT
`ANGIOGENIC EYE DISORDERS
`
`
`
`
`
`
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 9,254,338 B2
`
`
`
`
`
`
`
`
`APOTEX V. REGENERON IPR2022-01524
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`

`

`TABLE OF CONTENTS
`
`EXHIBIT LIST ...................................................................................................... viii 
`I. 
`INTRODUCTION. .......................................................................................... 1 
`II.  MANDATORY NOTICES (37 C.F.R. § 42.8). .............................................. 3 
`A. 
`REAL PARTIES-IN-INTEREST (37 C.F.R. § 42.8(b)(1)). ................. 3 
`B. 
`RELATED MATTERS (37 C.F.R. § 42.8(b)(2)). ................................ 3 
`C. 
`LEAD AND BACK-UP COUNSEL AND SERVICE
`INFORMATION (37 C.F.R. § 42.8(b)(3)-(4)). .................................... 4 
`PAYMENT UNDER 37 C.F.R. § 42.15(a) AND § 42.103. ........................... 5 
`III. 
`IV.  GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)). ................................ 5 
`V. 
`THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW. .............. 5 
`VI.  OVERVIEW OF CHALLENGE AND PRECISE RELIEF REQUESTED. .. 6 
`A. 
`CHALLENGED CLAIMS. ................................................................... 6 
`B. 
`STATUTORY GROUNDS OF CHALLENGE. .................................. 6 
`VII.  OVERVIEW OF THE ‘338 PATENT. ........................................................... 7 
`A. 
`THE ‘338 PATENT. ............................................................................ 7 
`B. 
`EUROPEAN EQUIVALENT, EP-325. .............................................. 10 
`VIII.  CLAIM CONSTRUCTION (37 C.F.R. § 42.104(b)(3)). .............................. 11 
`A. 
`“INITIAL DOSE,” “SECONDARY DOSE,” AND “TERTIARY
`DOSE.” ................................................................................................ 12 
`Regeneron’s contradictory construction for “tertiary dose,”
`if presented here, must be rejected. ........................................... 13 
`“4 WEEKS” AND “8 WEEKS,” AFTER THE IMMEDIATELY
`PRECEDING DOSE. .......................................................................... 16 
`
`B. 
`
`i
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`

`

`C. 
`
` 
`
` 
`
` 
`
`D. 
`
`“VEGFR1 COMPONENT,” “VEGFR2 COMPONENT” AND
`THE “MULTIMERIZATION COMPONENT.” ................................ 17 
`“TREATING.” .................................................................................... 17 
`The “method for treating” element of the preamble is not a
`limitation of the Challenged Claims, and therefore does not
`require construction. ................................................................. 17 
`Regeneron’s anticipated argument that the “method for
`treating” preamble is a positive limitation should be rejected. . 19 
`If construed to be a limitation, the preamble’s plain and
`ordinary meaning—which does not provide any specific
`efficacy requirement—must govern. ........................................ 21 
`IX.  PERSON OF ORDINARY SKILL IN THE ART. ....................................... 22 
`X. 
`THE SCOPE AND CONTENT OF THE PRIOR ART. ............................... 23 
`A.  VEGF TRAP-EYE/AFLIBERCEPT BACKGROUND. .................... 23 
`B. 
`PETITIONER’S PRIOR ART REFERENCES .................................. 26 
`Dixon (Ex.1006)........................................................................ 27 
`Adis (Ex.1007). ......................................................................... 30 
`Regeneron (8-May-2008) (Ex.1013). ....................................... 31 
`NCT-795 (Ex.1014). ................................................................. 32 
`NCT-377 (Ex.1015). ................................................................. 35 
`The ‘758 patent (Ex.1010). ....................................................... 36 
`Dix (Ex.1033). ........................................................................... 37 
`XI.  GROUNDS FOR UNPATENTABILITY—DETAILED ANALYSIS. ....... 37 
`A.  ANTICIPATION. ................................................................................ 37 
`Legal standards. ........................................................................ 38 
`Ground 1: Dixon anticipates the Challenged Claims. .............. 39 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
`ii
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`APOTEX V. REGENERON IPR2022-01524
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`

`

` 
`
` 
`
` 
`
`B. 
`
`Ground 2: Adis anticipates the Challenged Claims. ................. 44 
`Ground 3: Regeneron (8-May-2008) anticipates the
`Challenged Claims. ................................................................... 49 
`Grounds 4 and 5: NCT-795 and NCT-377 each anticipate
`the Challenged Claims. ............................................................. 54 
`Obviousness. ........................................................................................ 60 
`Legal standard. .......................................................................... 61 
`Ground 6: The Challenged Claims are obvious over Dixon
`(either alone or in combination with the ‘758 patent or
`Dix). .......................................................................................... 62 
`No secondary considerations. ................................................... 65 
`XII.  CONCLUSION. ............................................................................................. 69 
`CERTIFICATE OF SERVICE ................................................................................ 70 
`CERTIFICATE OF COMPLIANCE ....................................................................... 71 
`
` 
`
` 
`
` 
`
`
`
`
`
`
`
`iii
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`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2032 PAGE 004
`
`

`

`TABLE OF AUTHORITIES
`
`
`
`Page(s)
`
`Cases
`
`Advanced Display Sys., Inc. v. Kent State Univ.,
`212 F.3d 1272 (Fed. Cir. 2000)................................................................................................28
`
`In re Antor Media Corp.,
`689 F.3d 1282 (Fed. Cir. 2012)................................................................................................59
`
`Arctic Cat Inc. v. GEP Power Prods., Inc.,
`919 F.3d 1320 (Fed. Cir. 2019)................................................................................................17
`
`Ariosa Diagnostics v. Verinata Health, Inc.,
`805 F.3d 1359 (Fed. Cir. 2015)................................................................................................23
`
`In re Baxter Travenol Labs,
`952 F.2d 388 (Fed. Cir. 1991)..................................................................................................41
`
`Bayer Healthcare Pharm., Inc. v. Watson Pharm., Inc.,
`713 F.3d 1369 (Fed. Cir. 2013)................................................................................................64
`
`Bayer Schering Pharma AG v. Barr Lab’ys, Inc.,
`575 F.3d 1341 (Fed. Cir. 2009)................................................................................................64
`
`Bio-Rad Lab’ys, Inc. v. 10X Genomics Inc.,
`967 F.3d 1353 (Fed. Cir. 2020)..........................................................................................17, 18
`
`Bristol-Myers Squibb Co. v. Ben Venue Lab’ys, Inc.,
`246 F.3d 1368 (Fed. Cir. 2001)..............................................................................17, 20, 38, 59
`
`Chengdu Kanghong Biotechnology Co. v. Regeneron Pharms., Inc.,
`No. PGR2021-00035, 9 (P.T.A.B. Apr. 15, 2021) .......................................................... passim
`
`In Re: Copaxone Consol. Cases,
`906 F.3d 1013 (Fed. Cir. 2018)..........................................................................................18, 20
`
`In re Cruciferous Sprout Litig.,
`301 F.3d 1343 (Fed. Cir. 2002)................................................................................................38
`
`Cubist Pharms., Inc. v. Hospira, Inc.,
`75 F. Supp. 3d 641 (D. Del. 2014) ...........................................................................................59
`
`GlaxoSmithKline LLC v. Glenmark Pharms., Inc.,
`No. 14-877-LPS-CJB, 2016 WL 3186657 (D. Del. June 3, 2016) ..........................................20
`
`iv
`
`APOTEX V. REGENERON IPR2022-01524
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`
`

`

`Grünenthal GMBH v. Antecip Bioventures II LLC,
`No. PGR2019-00026, 2020 WL 4341822 (P.T.A.B. May 5, 2020) ..................................33, 35
`
`In re Huai-Hung Kao,
`639 F.3d 1057 (Fed. Cir. 2011)..........................................................................................61, 66
`
`Hulu, LLC v. Sound View Innovations,
`No. IPR2018-01039, 2019 WL 7000067 (P.T.A.B. Dec. 20, 2019)..................................32, 35
`
`King Pharms., Inc. v. Eon Labs, Inc.,
`616 F.3d 1267 (Fed. Cir. 2010)................................................................................................38
`
`KSR Int’l Co. v. Teleflex Inc.,
`550 U.S. 398 (2007) .....................................................................................................23, 61, 63
`
`Merck & Co. v. Teva Pharms. USA, Inc.,
`395 F.3d 1364 (Fed. Cir. 2005)................................................................................................15
`
`Motorola Mobility LLC v. Arnouse,
`No. IPR2013-00010, 2013 WL 12349001 (P.T.A.B. Jan. 30, 2013) .........................................5
`
`Multiform Desiccants, Inc. v. Medzam, Ltd.,
`133 F.3d 1473 (Fed. Cir. 1998)................................................................................................15
`
`Mylan Lab’ys Ltd. v. Aventis Pharma S.A.,
`No. IPR2016-00712, 2016 WL 5753968 (P.T.A.B. Sept. 22, 2016) .......................................19
`
`In re O’Farrell,
`853 F.2d 894 (Fed. Cir. 1988)..................................................................................................64
`
`In re Omeprazole Patent Litig.,
`483 F.3d 1364 (Fed. Cir. 2007)................................................................................................38
`
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006)..........................................................................................61, 66
`
`Perricone v. Medicis Pharm. Corp.,
`432 F.3d 1368 (Fed. Cir. 2005)................................................................................................38
`
`Pfizer, Inc. v. Apotex, Inc.,
`480 F.3d 1348 (Fed. Cir. 2007)................................................................................................64
`
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005)....................................................................................11, 14, 21
`
`Purdue Pharma L.P. v. Endo Pharms. Inc.,
`438 F.3d 1123 (Fed. Cir. 2006) (en banc) ................................................................................19
`
`v
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2032 PAGE 006
`
`

`

`Rasmusson v. SmithKline Beecham Corp.,
`413 F.3d 1318 (Fed. Cir. 2005)................................................................................................39
`
`Regeneron Pharms., Inc. v. Novartis Pharma AG,
`IPR2021-00816, Paper No. 1, 23 (Apr. 16, 2021) ...................................................................27
`
`Rosco, Inc. v. Mirror Lite Co.,
`304 F.3d 1373 (Fed. Cir. 2002)................................................................................................25
`
`Ruckus Wireless, Inc. v. Innovative Wireless Sols., LLC,
`824 F.3d 999 (Fed. Cir. 2016)..................................................................................................15
`
`Sandoz Inc. v. Abbvie Biotechnology Ltd.,
`No. IPR2018-00156, 2018 WL 2735468 (P.T.A.B. June 5, 2018) ....................................33, 35
`
`Sinorgchem Co., Shandong v. Int’l Trade Comm’n,
`511 F.3d 1132 (Fed. Cir. 2007)................................................................................................13
`
`TomTom, Inc. v. Adolph,
`790 F.3d 1315 (Fed. Cir. 2015)................................................................................................18
`
`Vizio, Inc. v. Int’l Trade Comm’n,
`605 F.3d 1330 (Fed. Cir. 2010)................................................................................................17
`
`Wyers v. Master Lock Co.,
`616 F.3d 1231 (Fed. Cir. 2010)................................................................................................66
`
`Statutes
`
`35 U.S.C. § 102 ...................................................................................................................... passim
`
`35 U.S.C. § 102.9 ...........................................................................................................................31
`
`35 U.S.C. § 103 ..........................................................................................................................6, 64
`
`35 U.S.C. § 103(a) .........................................................................................................................61
`
`35 U.S.C. § 282(b) .........................................................................................................................11
`
`35 U.S.C. §§ 311–319 ......................................................................................................................1
`
`35 U.S.C. § 314(a) ...........................................................................................................................5
`
`Food and Drug Modernization Act of 1997 ...................................................................................32
`
`Other Authorities
`
`37 C.F.R. §§ 42 et seq. .....................................................................................................................1
`
`vi
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2032 PAGE 007
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`

`

`37 C.F.R. § 42.8 ...............................................................................................................................3
`
`37 C.F.R. §§ 42.8(a)(1) and 42.8(b) ................................................................................................3
`
`37 C.F.R. § 42.8(b)(1) ......................................................................................................................3
`
`37 C.F.R. § 42.8(b)(2) ......................................................................................................................3
`
`37 C.F.R. § 42.8(b)(3)-(4)) ..............................................................................................................4
`
`37 C.F.R. § 42.10(b) ........................................................................................................................4
`
`37 C.F.R. § 42.15(a) AND § 42.103 ................................................................................................5
`
`37 C.F.R. § 42.100(b) ....................................................................................................................11
`
`37 C.F.R. § 42.104(a).......................................................................................................................5
`
`37 C.F.R. § 42.104(b)(3) ................................................................................................................11
`
`77 Fed. Reg. 48759- 60 (Aug. 14, 2021) .........................................................................................3
`
`83 Fed. Reg. 197, 51340-51359 (Oct. 11, 2018) ...........................................................................11
`
`MPEP § 2128 ...........................................................................................................................33, 35
`
`U.S. Patent No. 9,220,631..............................................................................................................27
`
`U.S. Patent No. 9,254,338...................................................................................................... passim
`
`U.S. Patent Nos. 9,669,069 B2, 10,130,681 B2, 10,857,205 B2, 10,828,345 B2,
`and 10,888,601 ...........................................................................................................................4
`
`
`
`
`
`vii
`
`APOTEX V. REGENERON IPR2022-01524
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`
`

`

`Exhibit
`
`EXHIBIT LIST
`
`Description
`
`1001 U.S. Patent No. 9,254,338 B2 (“’338 patent”)
`
`1002
`
`1003
`
`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”)
`
`1004
`
`Jocelyn Holash et al., VEGF-Trap: A VEGF Blocker with Potent
`Antitumor Effects, 99 PROC. NAT’L ACAD. SCI. 11393 (2002) (“Holash”)
`
`1005
`
`1006
`
`1007
`
`Quan Dong Nguyen et al., A Phase I Study of Intravitreal Vascular
`Endothelial Growth Factor Trap-Eye in Patients with Neovascular Age-
`Related Macular Degeneration, 116 OPHTHALMOLOGY 2141 (2009)
`(“Nguyen-2009”)
`
`James A Dixon et al., VEGF Trap-Eye for the Treatment of Neovascular
`Age-Related Macular Degeneration, 18 EXPERT OPINION ON
`INVESTIGATIONAL DRUGS 1573 (2009) (“Dixon”)
`
`Adis R&D Profile, Aflibercept: AVE 0005, AVE 005, AVE0005, VEGF
`Trap – Regeneron, VEGF Trap (R1R2), VEGF Trap-Eye, 9 DRUGS
`R&D 261 (2008) (“Adis”)
`
`1008 U.S. Patent No. 7,531,173 B2 (“’173 patent”)
`
`1009 U.S. Patent No. 7,396,664 B2 (“’664 patent”)
`
`1010 U.S. Patent No. 7,374,758 B2 (“’758 patent”)
`1011 F Semeraro et al., Aflibercept in Wet AMD: Specific Role and Optimal
`Use, 7 DRUG DESIGN, DEV. & THERAPY 711 (2013) (“Semeraro”)
`
`1012
`
`Press Release, Regeneron, Regeneron and Bayer Health Care Announce
`Encouraging 32-Week Follow-Up Results from a Phase 2 Study of
`VEGF Trap-Eye in Age-Related Macular Degeneration (Apr. 28, 2008),
`
`viii
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2032 PAGE 009
`
`

`

`http://investor.regeneron.com/releasedetail.cfm?releaseid=394066
`(“Regeneron (28-April-2008)”)
`
`1013
`
`1014
`
`Press Release, Regeneron, Bayer and Regeneron Dose First Patient in
`Second Phase 3 Study for VEGF Trap-Eye in Wet Age-Related Macular
`Degeneration (May 8, 2008),
`http://investor.regeneron.com/releasedetail.cfm?ReleaseID=394065
`(“Regeneron (8-May-2008)”)
`
`Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of
`Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD)
`(VIEW1), NCT00509795, ClinicalTrials.gov (Apr. 28, 2009),
`https://clinicaltrials.gov/ct2/show/NCT00509795 (“NCT-795”)
`
`1015
`
`VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD
`(VIEW 2), NCT00637377, ClinicalTrials.gov (Mar. 17, 2008),
`https://clinicaltrials.gov/ct2/show/NCT00637377 (“NCT-377”)
`1016 U.S. Patent Nos. 7,303,746 B2; 7,303,747 B2; 7,306,799 B2; and
`7,521,049 B2 (“Monthly-Dosing-Patents”)
`
`1017 File History of U.S. Patent No. 9,254,338 B2 (“’338 FH”)
`
`1018
`
`Jeffrey S. Heier et al., Intravitreal Aflibercept (VEGF Trap-Eye) in Wet
`Age-Related Macular Degeneration, 119 OPHTHALMOLOGY 2537 (2012)
`(“Heier-2012”)
`
`1019 U.S. Patent No. 9,669,069 B2 (“’069 patent”)
`
`1020
`
`Jeffrey S. Heier, Intravitreal VEGF Trap for AMD: An Update, RETINA
`TODAY, Oct. 2009, 44 (“Heier-2009”)
`1021 Regeneron Pharm., Inc., Quarterly Report (Form 10-Q) (Sept. 30, 2009)
`(“2009 10-Q”)
`
`1022 U.S. Patent No. 7,374,757 B2 (“’757 patent”)
`
`1023 U.S. Patent No. 7,070,959 B1 (“’959 patent”)
`1024 File History of U.S. Patent No. 7,374,758 B2, 12/22/2011 Patent Term
`Extension Application (“’758 FH, 12/22/2011 PTE”)
`
`ix
`
`APOTEX V. REGENERON IPR2022-01524
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`
`

`

`1025
`
`1026
`
`1027
`
`1028
`
`1029
`
`Michael Engelbert et al., Long-Term Follow-Up For Type 1 (Subretinal
`Pigment Epithelium) Neovascularization Using A Modified “Treat And
`Extend” Dosing Regimen of Intravitreal Antivascular Endothelial
`Growth Factor Therapy, 30 RETINA, J. RETINAL & VITREOUS DISEASES
`1368 (2010) (“Engelbert-2010”)
`
`Michael Engelbert et al., “Treat and Extend” Dosing of Intravitreal
`Antivascular Endothelial Growth Factor Therapy For Type 3
`Neovascularization/Retinal Angiomatous Proliferation, 29 J. RETINAL &
`VITREOUS DISEASES 1424 (2009) (“Engelbert-2009”)
`
`Richard F. Spaide et al., Prospective Study of Intravitreal Ranibizumab
`as a Treatment for Decreased Visual Acuity Secondary to Central
`Retinal Vein Occlusion, 147 AM. J. OPHTHALMOLOGY 298 (2009)
`(“Spaide”)
`
`Press Release, Regeneron, Bayer and Regeneron Extend Development
`Program for VEGF Trap-Eye to Include Central Retinal Vein Occlusion
`(Apr. 30, 2009), https://investor.regeneron.com/news-releases/news-
`release-details/bayer-and-regeneron-extend-development-program-vegf-
`trap-eye (“Regeneron (30-April-2009)”)
`
`Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of
`Efficacy and Safety in Central Retinal Vein Occlusion (CRVO),
`NCT01012973, ClinicalTrials.gov (Nov. 12, 2009),
`https://clinicaltrials.gov/ct2/show/NCT01012973 (“NCT-973”)
`
`1030
`
`P Mitchell et al., Ranibizumab (Lucentis) in Neovascular Age-Related
`Macular Degeneration: Evidence from Clinical Trials, 94 BRIT. J.
`OPHTHALMOLOGY 2 (2009) (date of online publication) (“Mitchell”)
`1031 Pascale G. Massin, Anti-VEGF Therapy for Diabetic Macular Edema:
`An Update, RETINA TODAY, SEPT./Oct. 2008, 54 (“Massin”)
`
`1032
`
`Press Release, Bayer AG, Bayer and Regeneron Start Additional Phase
`3 Study for VEGF Trap-Eye in Wet Age-Related Macular Degeneration
`(May 8, 2008) (“Bayer (8-May-2008)”)
`
`1033 U.S. Patent Application Publication No. 2006/0217311 A1 (“Dix”)
`
`x
`
`APOTEX V. REGENERON IPR2022-01524
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`
`

`

`1034
`
`1035
`
`1036
`
`1037
`
`Anne E. Fung et al., An Optical Coherence Tomography-Guided,
`Variable Dosing Regimen with Intravitreal Ranibizumab (Lucentis) for
`Neovascular Age-related Macular Degeneration, 143 AM. J.
`OPHTHALMOLOGY 566 (2007) (“Fung”)
`
`Geeta A. Lalwani et al., A Variable-dosing Regimen with Intravitreal
`Ranibizumab for Neovascular Age-Related Macular Degeneration:
`Year 2 of the PrONTO Study, 148 AM. J. OPHTHALMOLOGY 43 (2009)
`(“Lalwani”)
`
`Peter A Campochiaro et al., Ranibizumab for Macular Edema Due to
`Retinal Vein Occlusions: Implication of VEGF as a Critical Stimulator,
`16 MOLECULAR THERAPY 791 (2008) (“Campochiaro”)
`
`Robert Steinbrook, The Price of Sight — Ranibizumab, Bevacizumab,
`and the Treatment of Macular Degeneration, 355 N. ENG. J. MED. 1409
`(2006) (“Steinbrook”)
`
`1038 Curriculum Vitae of Dr. Thomas Albini (“Albini CV”)
`
`1039 U.S. Patent No. 7,378,095 B2 (“’095 patent”)
`
`1040
`
`International Nonproprietary Names for Pharmaceutical Substances
`(INN), 20 WHO DRUG INFORMATION 115 (2006) (“WHO Drug Info”)
`
`1041
`
`1042
`
`1043
`
`Press Release, Regeneron, Regeneron Reports Full Year and Fourth
`Quarter 2008 Financial and Operating Results (Feb. 26, 2009),
`https://investor.regeneron.com/news-releases/news-release-
`details/regeneron-reports-full-year-and-fourth-quarter-2008-financial
`(“Regeneron (26-February-2009)”)
`
`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), https://www.nei.nih.gov/sites/default/files/health-
`pdfs/WYSKAMDEnglishSept2015PRINT.pdf (“NIH AMD”)
`
`David M. Brown & Carl D. Regillo, Anti-VEGF Agents in the
`Treatment of Neovascular Age-Related Macular Degeneration:
`Applying Clinical Trial Results to the Treatment of Everyday Patients,
`144 AM. J. OPHTHALMOLOGY 627 (2007) (“Brown”)
`
`xi
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`APOTEX V. REGENERON IPR2022-01524
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`

`

`1044
`
`U.S. DEP’T HEALTH & HUMAN SERVS., NAT’L INST. HEALTH, NAT’L
`EYE INST., Diabetic Retinopathy: What You Should Know (Sept. 2015),
`https://www.nei.nih.gov/sites/default/files/2019-06/Diabetic-
`Retinopathy-What-You-Should-Know-508.pdf (“NIH DR”)
`
`1045
`
`Napoleone Ferrara & Kari Alitalo, Clinical Applications of Angiogenic
`Growth Factors and Their Inhibitors, 5 NATURE MED. 1359 (1999)
`(“Ferrara-1999”)
`1046 Napoleone Ferrara & Robert S. Kerbel, Angiogenesis as a Therapeutic
`Target, 438 NATURE 967 (2005) (“Ferrara-2005”)
`
`1047
`
`Ziad F. Bashshur et al., Intravitreal Bevacizumab for the Management
`of Choroidal Neovascularization in Age-Related Macular Degeneration,
`142 AM. J. OPHTHALMOLOGY 1 (2006) (“Bashshur”)
`
`1048 LUCENTIS® Prescribing Information (2006) (“Lucentis”)
`
`1049
`
`1050
`
`1051
`
`1052
`
`1053
`
`L. Spielberg & A. Leys, Intravitreal Bevacizumab for Myopic
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