`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`BIOCON BIOLOGICS INC.,
`Petitioner,
`
`v.
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner.
`
`
`Inter Partes Review No.: IPR2024-00298
`
`
`U.S. Patent No. 11,253,572
`Filed: June 21, 2021
`Issued: February 22, 2022
`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. 11,253,572
`
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`TABLE OF CONTENTS
`TABLE OF AUTHORITIES .......................................................................................... vi
`EXHIBIT LIST ............................................................................................................... ix
`I.
`INTRODUCTION ................................................................................................. 1
`II. MANDATORY NOTICES (37 C.F.R. § 42.8) ..................................................... 7
`Real Parties-In-Interest (37 C.F.R. § 42.8(b)(1)) ........................................ 7
`Related Matters (37 C.F.R. § 42.8(b)(2)) .................................................... 8
`Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3)-(4)) ......................... 12
`Service Information (37 C.F.R. § 42.8(b)(4)) ........................................... 13
`Payment of Fees (37 C.F.R. §§ 42.103 and 42.15(a)) ............................... 13
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a); 37 C.F.R. §§
`42.101(a)-(c)) ....................................................................................................... 13
`IDENTIFICATION OF CHALLENGE AND RELIEF REQUESTED ............. 14
`Identification of Challenge (37 C.F.R. § 42.104(b)) ................................. 14
`Grounds of Challenge (37 C.F.R. § 42.204(b)(2)) .................................... 14
`THE ’572 PATENT ............................................................................................. 16
` Overview ................................................................................................... 16
`Priority Date .............................................................................................. 16
`The Challenged Claims ............................................................................. 17
`Prosecution History ................................................................................... 19
`Level of Ordinary Skill in the Art ............................................................. 19
`VI. CONSTRUCTION OF THE CHALLENGED CLAIMS ................................... 20
`“A method for treating…” ........................................................................ 20
`Exclusion Criteria ...................................................................................... 21
`
`IV.
`
`V.
`
`
`
`
`
`
`
`
`
`
`
`
`
`ii
`
`

`

`
`
`
`
`
`
`
`
`
`
`
`
`
`
`VII. SCOPE AND CONTENT OF THE PRIOR ART .............................................. 22
`The 2009 Press Release ............................................................................. 23
`The November 2010 Press Release ........................................................... 24
`The December 2010 Press Release ........................................................... 24
` Dixon ......................................................................................................... 25
`Hecht ......................................................................................................... 26
`Shams ........................................................................................................ 26
`Elman 2010 ............................................................................................... 27
`CATT and PIER Studies ........................................................................... 28
`Prior Art Regarding Aflibercept Efficacy ................................................. 29
`VIII. DETAILED GROUNDS FOR INVALIDITY .................................................... 31
` Ground I: Claims 15 and 24 Are Anticipated by Each of the 2009
`Press Release and December 2010 Press Release ..................................... 31
`Ground II: Claims 1-5, 8-11, 16-17, and 20-21 (Generic/DME
`Results Claims) Are Anticipated by the December 2010 Press
`Release ...................................................................................................... 34
`1.
`Claims 1 and 16 .............................................................................. 35
`2.
`Claim 2 ............................................................................................ 36
`3.
`Claims 3, 8, 10, 17, and 21 and Claims 4, 9, and 20 ...................... 36
`4.
`Claims 5 and 11 .............................................................................. 37
`Ground III: Claims 26-30 (AMD Results Claims) Are Anticipated by
`the November 2010 Press Release ............................................................ 38
`1.
`Claims 26-28 ................................................................................... 38
`2.
`Claims 29-30 ................................................................................... 40
` Ground IV: Claims 1-5, 8-11, and 26-30 (Generic/AMD Results
`Claims) Are Rendered Obvious by Dixon Alone or In View of the
`iii
`
`
`
`
`
`
`
`

`

`
`
`
`
`2006 Press Release .................................................................................... 42
`1.
`Claim 1 ............................................................................................ 43
`2.
`Claim 2 ............................................................................................ 44
`3.
`Claims 3-4 and 8-10 ........................................................................ 45
`4.
`Claims 5 and 11 .............................................................................. 46
`5.
`Claims 26-28 ................................................................................... 46
`6.
`Claims 29-30 ................................................................................... 48
`Ground V: Claims 16-17, and 20-21 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 “Ground V
`References”) .............................................................................................. 49
`Ground VI: Claims 6-7 and 12-13 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 ...... 52
` Ground VII: Claims 18-19 and 22-23 Are Rendered Obvious by Each
`of the December 2010 Press Release in View of Hecht, and the 2009
`Press Release in View of the Ground V References and Hecht ............... 54
` Ground VIII: Claim 14 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 .......................................................................... 54
`Ground IX: Claim 25 is Rendered Obvious by the 2009 Press Release
`Alone or in View of Shams or Elman 2010 .............................................. 55
`Grounds X and XI ..................................................................................... 59
`1.
`The “Results Limitations” in the Results Claims Are Not
`Entitled to Patentable Weight ......................................................... 59
`Ground X: Claims 1-5, 8-11, and 26-30 are Anticipated by
`Dixon Because the “Results Limitations” Lack Patentable
`Weight ............................................................................................. 63
`Ground XI: Claims 1-5, 8-11, 16-17, and 20-21 are
`Anticipated by the 2009 Press Release Because the “Results
`iv
`
`3.
`
`
`
`
`
`2.
`
`

`

`
`
`
`
`Limitations” Lack Patentable Weight ............................................. 64
`There Are No Secondary Considerations.................................................. 64
`IX. DISCRETIONARY DENIAL IS UNWARRANTED ........................................ 65
`The Advanced Bionics and Becton Dickinson Factors Do Not Favor
`Denial Under 35 U.S.C. § 325(d) ............................................................. 65
`The General Plastic Factors Do Not Support Denial Under 35
`U.S.C. § 314(a) .......................................................................................... 67
`The Fintiv Factors Do Not Support Denial Under 35 U.S.C. § 314(a). ...... 68
`CONCLUSION ................................................................................................... 70
`
`
`
`
`
`X.
`
`
`
`
`
`v
`
`

`

`TABLE OF AUTHORITIES
`Cases
`
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Geräte GmbH,
`IPR2019-01469 (P.T.A.B. Feb. 13, 2020) ................................................................. 66
`
`Amgen Inc. v. Alexion Pharms., Inc.,
`IPR2019-00739 (Aug. 30, 2019) ................................................................................ 66
`
`Apple Inc. v. Fintiv, Inc.,
`IPR2020-00019 (P.T.A.B. Mar. 20, 2020) ................................................................. 68
`
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586 (P.T.A.B. Dec. 15, 2017) ................................................................. 66
`
`Biocon Biologics Inc. v. Regeneron Pharmaceuticals, Inc.,
`IPR2024-00201 .......................................................................................................... 10
`
`Bristol-Myers Squibb Co. v. Boehringer Ingelheim Corp.,
`86 F. Supp. 2d 433 (D.N.J. Mar. 2, 2000) .................................................................. 61
`
`Bristol-Myers Squibb Co. v. Boehringer Ingelheim Corp.,
`246 F.3d 1368, 1376 (Fed. Cir. 2001) ........................................................................ 61
`
`General Plastic Indus. Co. v. Canon Kabushiki Kaisha,
`IPR2016-01357, 2017 WL 3917706 (P.T.A.B. Sept. 6, 2017) .................................. 67
`
`In re Kao,
`639 F.3d 1057 (Fed. Cir. 2011) ............................................................................ 64, 65
`
`In re Kubin,
`561 F.3d 1351 (Fed. Cir. 2009) ................................................................ 59, 60, 62, 63
`
`In re O’Farrell,
`853 F.2d 894 (Fed. Cir. 1988) .................................................................................... 59
`
`In Re: Copaxone Consol. Cases,
`906 F.3d 1013 (Fed. Cir. 2018) .................................................................................. 61
`
`Lockheed Martin Corp. v. Space Systems/Loral, Inc.,
`324 F.3d 1308 (Fed. Cir. 2003) .................................................................................. 62
`
`vi
`
`

`

`Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center v.
`Eli Lilly & Co.,
`849 F.3d 1049 (Fed. Cir. 2017) ...................................................................... 61, 62, 63
`
`Minton v. Nat’l Ass'n. of Sec. Dealers, Inc.,
`336 F.3d 1373 (Fed. Cir. 2003) .................................................................................. 62
`
`Mylan Pharms. Inc. v. Regeneron Pharms., Inc.,
`No. IPR2021-00880 (P.T.A.B.) .................................................................................... 9
`
`Mylan Pharms. Inc. v. Regeneron Pharms., Inc.,
`No. IPR2021-00881 (P.T.A.B.) .................................................................................... 9
`
`Novartis AG v. Torrent Pharms. Ltd.,
`853 F.3d 1316 (Fed. Cir. 2017) .................................................................................. 65
`
`Ormco Corp. v. Align Tech., Inc.,
`463 F.3d 1299 (Fed. Cir. 2006) .................................................................................. 64
`
`Praxair Distrib., Inc. v. Mallinckrodt Hosp. Prods. IP Ltd.,
`890 F.3d 1024 (Fed. Cir. 2018) .................................................................................. 21
`
`Qualcomm Inc. v. Monterey Rsch., LLC,
`IPR202-01493 (P.T.A.B. Mar. 8, 2021) ..................................................................... 67
`
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc.,
`IPR2023-00566 (P.T.A.B. Feb. 10, 2023) ................................................................. 10
`
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc.,
`IPR2023-00739 .......................................................................................................... 10
`
`Sotera Wireless, Inc. v. Masimo Corp.,
`IPR2020-01019 (P.T.A.B. Dec. 1, 2020) ................................................................... 69
`
`Syntex (U.S.A.) LLC v. Apotex, Inc.,
`407 F.3d 1371 (Fed. Cir. 2005) .................................................................................. 61
`
`Wyers v. Master Lock Co.,
`616 F.3d 1231 (Fed. Cir. 2010) .................................................................................. 64
`
`Statutes
`
`35 U.S.C. § 102 ....................................................................................................... passim
`vii
`
`

`

`35 U.S.C. § 103 .............................................................................................................. 17
`
`35 U.S.C. § 315(b) ..................................................................................................... 1, 14
`
`35 U.S.C. § 315(c) ........................................................................................................... 1
`
`35 U.S.C. § 325(d) ................................................................................................... 65, 66
`
`35 U.S.C. §§ 311–319 ...................................................................................................... 1
`
`Other Authorities
`
`Katherine K. Vidal,
`Interim Procedure for Discretionary Denials (June 21, 2022) ................................... 69
`
`Manual of Patent Examining Procedure
`§ 2159 ......................................................................................................................... 17
`
`Trial Practice Guide (November 2019) ........................................................................... 7
`
`Regulations
`
`37 C.F.R. § 42.10(b) ...................................................................................................... 12
`
`37 C.F.R. §§ 42 et seq. ..................................................................................................... 1
`
`
`
`
`
`
`
`viii
`
`

`

`EXHIBIT LIST
`
`
`1005
`
`Exhibit Description
`1001 U.S. Patent No. 11,253,572
`1002 Expert Declaration of Dr. Edward Chaum in Support of Petition for
`Inter Partes Review of Patent No. 11,253,572, dated April 27, 2023
`(“Chaum Decl.”)
`1003 Edward Chaum Curriculum Vitae
`1004
`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 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.edgaronline.com/displayfilinginfo.aspx?FilingI
`D=7572010-8611-
`26486&type=sect&TabIndex=2&companyid=5036&ppu=%252fde
`f% E2%80%A6 (“November 2010 Press Release”)
`1008 Apotex Petition for IPR filed in Apotex Inc. v. Regeneron
`Pharmaceuticals, Inc., IPR2022-01524 (Paper 1) (“Apotex Petition”)
`1009 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
`ix
`
`1006
`
`1007
`
`

`

`1012
`
`1013
`
`1011
`
`of Clinical Impact: Phase 2 Study in Patients With Diabetic Macular
`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”)
`1014 Certified Prosecution History of U.S. Patent No. 11,253,572 (“’572
`patent PH)
`1015 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”)
`1016 Hecht, “Ophthalmic 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”)
`1019 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)
`1020 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.upen
`n.edu/cpob/studies/documents/CATTEligibilityCriteria_000.pdf,
`attached as Exhibit B (“CATT Study”).
`1021 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.
`x
`
`

`

`2008;145(2):239-248. (“PIER Study”).
`1022 Comparison of Age-related Macular Degeneration Treatments Trials:
`Lucentis-Avastin Trial (NCT00593450), available at:
`https://clinicaltrials.gov/ct2/show/NCT00593450 (“NCT-450”)
`1023 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”)
`1024 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#Stud
`yPageTop (“NCT-623”)
`1025 ClinicalTrials.gov Background, available at:
`https://clinicaltrials.gov/ct2/about-site/background
`(“ClinicalTrials.gov Background”)
`1026 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.edgaronline.com/displayfilinginfo.aspx?FilingID
`=4380124-5423-
`15279&type=sect&TabIndex=2&companyid=5036&ppu=%252fdef
`% E2%80%A6 (“May 2006 Press Release”)
`1028 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”)
`1030 Do DV et al., “Results of a Phase I Study of Intravitreal VEGF Trap
`xi
`
`1027
`
`1029
`
`

`

`1033
`
`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”)
`1031 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”)
`1032 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”)
`1034 Lucentis ® Original Approved Labeling (2006), available at:
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125156s0
`00 0_Lucentis_Prntlbl.pdf
`1035 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”)
`1036 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”)
`1037 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”)
`1038 Heier JS, et al., Intravitreal aflibercept (VEGF trap-eye) in wet
`agerelated macular degeneration. Ophthalmology.
`2012;119(12):2537- 2548. (“Heier 2012”)
`1039 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
`trapeye 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”)
`1041 U.S. Patent App. Pub. US 2007/0190058A1 (“Shams US App.
`xii
`
`1040
`
`

`

`Pub.”)
`1042 U.S. Patent No. 9,254,338 (“’338 patent”)
`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”)
`1045 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_
`English_Sept2015_PRINT.pdf (“NIH AMD”)
`1046 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”)
`1047 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”)
`1048 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”)
`1049 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”)
`1051 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”)
`xiii
`
`

`

`1054
`
`1052 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”)
`1053 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”)
`1055 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:
`https://clinicaltrials.gov/ct2/history/NCT00685854?V_1=View#Stud
`yP 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.go
`v/ ct2/show/NCT00685854, attached as Exhibit A (“MACTEL Study
`Wayback Machine”)
`1058 Using the Wayback Machine, available at:
`https://help.archive.org/help/using-the-wayback-machine/
`1059 Eylea Label 2011 available at:
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125387l
`bl. 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-
`asafe-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”)
`
`1056
`
`1061
`
`xiv
`
`

`

`1067
`
`1063 April 19, 2023 Claim Construction Order entered in Regeneron
`Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc., Case No.
`1:22-cv00061-TSK, Northern District of West Virginia. (Dkt. 427)
`(“Mylan Litigation CC Order”)
`1064 U.S. Patent No. 7,531,173 (“’173 patent”)
`1065 Docket Navigator, Time to Trial
`1066
`Institution Decision in Samsung Bioepis Co., Ltd. v. Regeneron
`Pharmaceuticals, Inc., IPR2023-00884 (Paper 13).
`Patent Owner Preliminary Response in Samsung Bioepis Co., Ltd. v.
`Regeneron Pharmaceuticals, Inc., IPR2023-00884 (Paper 6).
`1068 April 27, 2023 Stipulation Regarding Summary Judgment and Case
`Narrowing entered in Regeneron Pharmaceuticals, Inc. v. Mylan
`Pharmaceuticals Inc., Case No. 1:22-cv00061-TSK, Northern
`District of West Virginia. (Dkt. 433)
`1069 Exhibit A to May 19, 2023 Surreply to Address New Arguments
`Raised in Mylan’s Reply in Support of its Motion for Summary
`Judgment entered in Regeneron Pharmaceuticals, Inc. v. Mylan
`Pharmaceuticals Inc., Case No. 1:22-cv00061-TSK, Northern
`District of West Virginia. (Dkt. 484-2)
`Petition in Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals,
`Inc., IPR2023-00884 (Paper 2).
`
`1070
`
`xv
`
`

`

`Biocon Biologics Inc. (“Petitioner”) petitions for inter partes review (“IPR”)
`
`under 35 U.S.C. §§ 311–319 and 37 C.F.R. §§ 42 et seq., seeking cancellation of
`
`claims 1-30 (“Challenged Claims”) of U.S. Patent No. 11,253,572 (“’572 patent”)
`
`(Ex.1001), assigned
`
`to Patent Owner, Regeneron Pharmaceuticals,
`
`Inc.
`
`(“Regeneron” or “PO”). This petition replicates Samsung Bioepis Co., Ltd.’s
`
`(“Samsung”) petition filed in IPR2023-00884 (“Samsung IPR”), with the exception
`
`of the petitioner-specific mandatory notices and certain sections relating to
`
`discretionary denial, and asserts the same grounds of unpatentability upon which the
`
`Patent Trial and Appeal Board (the “Board”) has already instituted review in the
`
`Samsung IPR. Accordingly, there exists a reasonable likelihood that Petitioner will
`
`prevail in demonstrating unpatentability of at least one of the Challenged Claims,
`
`and Petitioner respectfully seeks to join the Samsung IPR as set forth in the
`
`accompanying motion for joinder filed concurrently. Samsung indicated it does not
`
`oppose Petitioner’s motion for joinder.
`
`This Petition is timely and proper under 35 U.S.C. § 315(b) (the 1-year time
`
`bar “shall not apply to a request for joinder under subsection (c)”) and 35 U.S.C.
`
`§ 315(c).
`
`I.
`
`INTRODUCTION
`The Challenged Claims are directed to treating angiogenic eye disorders,
`
`including diabetic macular edema (“DME”) and age-related macular degeneration
`
`1
`
`

`

`(“AMD”), by administering aflibercept via a number of initial monthly loading doses,
`
`followed by maintenance doses administered every two months.
`
`One subset of the Challenged Claims—claims 15-25—is directed to a DME
`
`dosing regimen with two or more monthly loading doses followed by maintenance
`
`doses administered every-two-months (the “DME Claims”). Those claims were not
`
`challenged in Apotex’s prior ’572 IPR Petition (IPR2002-01524 (“Apotex
`
`Petition”)), which addressed other claims of the ’572 patent. Ex.1008.
`
`Unlike the other ’572 claims previously addressed by the Board, independent
`
`claim 15 and dependent claim 24 recite only DME dosing regimens. They do not
`
`contain what the Board previously referred to as a “results limitation”—i.e.,
`
`maintaining or gaining visual acuity. Ex.1004, 15. Instead, claim 15 recites treating
`
`DME by administering a single initial dose of aflibercept, followed by “one or more”
`
`monthly secondary doses (the “loading” phase), and then maintenance doses every
`
`two months. Claim 24 depends from claim 15 and recites that “only two secondary
`
`doses” are administered, meaning only three monthly doses are given before 8-week
`
`dosing.
`
`Thus, claims 15 and 24 are anticipated by any aflibercept DME prior art
`
`disclosing three monthly loading doses followed by 8-week maintenance dosing.
`
`Regeneron’s 2009 Press Release discloses exactly that: administering 2 mg
`
`aflibercept to treat DME using a dosing regimen of three monthly loading doses that
`
`2
`
`

`

`include an initial and two “secondary” doses, followed by maintenance doses at 8-
`
`week intervals. Ex.1005. Regeneron’s December 2010 Press Release discloses the
`
`same DME regimen. Ex.1006. Thus, as shown in Ground I, each of the 2009 Press
`
`Release and December 2010 Press Release anticipates claims 15 and 24.
`
`A second subset of Challenged Claims—1-5, 8-11, 16-17, 20-21, and 26-30—
`
`recite a loading/maintenance regimen for generic angiogenic eye disorders, DME,
`
`or AMD, and also include certain “results limitations” reciting either a general result
`
`within a specific time frame (e.g., “wherein the patient achieves a gain in visual
`
`acuity within 52 [or 24] weeks”) or a specific visual acuity gain (e.g., “wherein the
`
`patient gains at least 7 [or 8 or 9] letters” in the standard ETDRS letter score for
`
`visual acuity, or wherein the regimen is “as effective” as ranibizumab). These claims
`
`are collectively referred to as the “Results Claims” herein.
`
`Results Claims 1-5, 8-11, 16-17, and 20-21 recite treating either a generic
`
`angiogenic eye disorder or DME specifically (“Generic Results Claims”/“DME
`
`Results Claims”). As shown in Ground II, the December 2010 Press Release
`
`anticipates the Generic/DME Results Claims. The December 2010 Press Release
`
`discloses the same dosing regimens for DME as the 2009 Press Release, but further
`
`reports the visual acuity results fr