`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`_________________________
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`_________________________
`
`SAMSUNG BIOEPIS CO., LTD.,
`Petitioner,
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner.
`_________________________
`
`Case IPR2023-00739
`
`U.S. Patent No. 10,888,601
`_________________________
`
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 10,888,601
`
`
`
`
`
`
`
`Biocon Exhibit 1059 - Page 1
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`TABLE OF CONTENTS
`
`V.
`
`VI.
`
`IV.
`
`Page
`INTRODUCTION ........................................................................................... 1
`I.
`II. MANDATORY NOTICES PURSUANT TO 37 C.F.R. § 42.8(A)(1) ........... 6
`A.
`Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) .................................... 6
`B.
`Related Matters (37 C.F.R. § 42.8(b)(2)) .............................................. 6
`C.
`Lead and Backup Counsel (37 C.F.R. § 42.8(b)(3)-(4) ........................ 8
`D.
`Service Information (37 C.F.R. § 42.8(b)(4)) ....................................... 9
`E.
`Payment of Fees (37 C.F.R. §§ 42.103 and 42.15(a)) ........................... 9
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(A); 37 C.F.R.
`§§ 42.101(A)-(C)) ............................................................................................ 9
`IDENTIFICATION OF CHALLENGE AND RELIEF REQUESTED ......... 9
`A.
`Identification of Challenge (37 C.F.R. § 42.104(b)) ............................. 9
`Grounds of Challenge (37 C.F.R. § 42.204(b)(2)) .............................. 10
`B.
`THE ’601 PATENT ....................................................................................... 11
`A.
`Overview ............................................................................................. 11
`The Challenged Claims ....................................................................... 12
`B.
`C.
`Prosecution History ............................................................................. 13
`D.
`Level of Ordinary Skill in the Art ....................................................... 14
`PRIORITY DATE ......................................................................................... 15
`A.
`Claims 10-33 Are Not Entitled to a Priority Date Earlier Than
`July 12, 2013 ....................................................................................... 15
`VII. CONSTRUCTION OF THE CHALLENGED CLAIMS ............................. 16
`A.
`“A method for treating…” .................................................................. 16
`B.
`“Wherein the patient [loses less than/gains at least] 15 letters of
`Best Corrected Visual Acuity (BCVA) score” (Claims 13, 15, 22,
`23, 29, and 31) / “The method of [claims 15/23/32] wherein Best
`Corrected Visual Acuity (BCVA) is according to Early
`Treatment Diabetic Retinopathy Study (ETDRS) letter score”
`(Claims 14, 16, 20, 24, 30, and 32) ..................................................... 17
`Exclusion Criteria (Claims 17, 25, and 33) ......................................... 21
`
`C.
`
`i
`
`Biocon Exhibit 1059 - Page 2
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`VIII.  OVERVIEW OF THE PRIMARY PRIOR ART REFERENCES ................ 22 
`A. 
`The 2009 Press Release ....................................................................... 22 
`B. 
`Shams .................................................................................................. 23 
`C. 
`Elman 2010 .......................................................................................... 24 
`D.  Do 2011 ............................................................................................... 26 
`E. 
`2016 Eylea Label ................................................................................. 27 
`F. 
`CATT and PIER Studies ..................................................................... 28 
`G. 
`Prior Art Knowledge Regarding the Relationship Between
`DR/DME ............................................................................................. 30 
`IX.  DETAILED GROUNDS FOR INVALIDITY .............................................. 31 
`A.  Ground I: Claims 46-47 are Anticipated and/or Rendered
`Obvious by the 2009 Press Release .................................................... 31 
`Ground II: Claims 10-12, 18-19, 21, 26-28 Are Rendered
`Obvious by the 2009 Press Release Either Alone or in View of
`Shams .................................................................................................. 34 
`1. 
`Claims 11/19/27: “The method of [claims 10/18/26]
`wherein approximately every 4 weeks comprises
`approximately every 28 days or approximately monthly.” ...... 40 
`Claims 12/21/28: “The method of [claims 10/18/26]
`further comprising, after 20 weeks, administering, via
`intravitreal injection, 2 mg of aflibercept once every 4
`weeks.” ...................................................................................... 40 
`Ground III: Claims 10-12, 18-19, 21, 26-28 Are Rendered
`Obvious by the 2009 Press Release in Combination with Elman
`2010 ..................................................................................................... 41 
`1. 
`A POSA Would Have Been Motivated to Combine the
`2009 Press Release with Elman 2010’s Dosing Regimen ........ 42 
`A POSA Would Have Had a Reasonable Expectation of
`Success in Combining the 2009 Press Release with Elman
`2010’s Dosing Regimen ............................................................ 44 
`D.  Ground IV: Claims 13-16, 20, 22-24, and 29-32 Are Rendered
`Obvious by the 2009 Press Release Alone, or in Combination
`with Elman 2010, and/or Further in View of Do 2011 ....................... 46 
`
`2. 
`
`2. 
`
`B. 
`
`C. 
`
`
`
`ii
`
`Biocon Exhibit 1059 - Page 3
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`1.
`
`2.
`
`E.
`
`F.
`
`X.
`
`Alternatively, the Requirements of Claims 13-16, 20, 22-
`24, and 29-32 Are Inherent in Practicing the Method .............. 49
`Ground V: Claims 13-16, 20, 22-24, and 29-32 Are Anticipated
`by the 2016 Eylea Label ...................................................................... 50
`If the Recited Results Are Given Patentable Weight,
`1.
`Claims 13-16, 20, 22-24, and 29-32 Are Not Entitled to a
`Priority Date Earlier Than April 29, 2019 ................................ 51
`The 2016 Eylea Label Anticipates Claims 13-16, 20, 22-
`24, and 29-32 If They Are Not Entitled to a Priority Date
`Earlier Than 2019 ...................................................................... 53
`Ground VI: Claims 17, 25, and 33 Are Rendered Obvious by the
`2009 Press Release Alone or in View of Elman 2010 and Further
`in View of the CATT and PIER Studies ............................................. 54
`There Are No Secondary Considerations ............................................ 55
`G.
`DISCRETIONARY DENIAL IS UNWARRANTED .................................. 56
`A.
`The Becton Dickinson Factors Do Not Favor Denial Under 35
`U.S.C. § 325(d) .................................................................................... 56
`1.
`Becton Dickinson Factors (a), (b), and (d) ................................ 57
`2.
`Becton Dickinson Factors (c), (e), and (f) ................................. 58
`The General Plastic Factors Do Not Support Denial Under 35
`U.S.C. § 314(a) .................................................................................... 59
`General Plastic Factors 2-5 ...................................................... 61
`1.
`2.
`General Plastic Factors 6-7 ...................................................... 62
`3.
`Additional Factors ..................................................................... 62
`The Fintiv Factors Do Not Support Denial Under 35 U.S.C. §
`314(a) ................................................................................................... 63
`Fintiv Factors 1 and 2 ............................................................... 65
`1.
`2.
`Fintiv Factor 3 ........................................................................... 65
`3.
`Fintiv Factor 4 ........................................................................... 66
`4.
`Fintiv Factor 5 ........................................................................... 66
`5.
`Fintiv Factor 6 ........................................................................... 67
`XI. CONCLUSION .............................................................................................. 67
`
`B.
`
`C.
`
`iii
`
`Biocon Exhibit 1059 - Page 4
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`TABLE OF AUTHORITIES
`
`Page
`
`Cases
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Geräte GmbH,
` IPR2019-01469, Paper 6 (PTAB Feb. 13, 2020) ............................................... 56
`Amgen Inc. v. Alexion Pharms., Inc.,
` IPR2019-00739, Paper 15 (Aug. 30, 2019) ........................................................ 58
`Apple Inc. v. Fintiv, Inc.,
` IPR2022-00976, Paper 9. 11 (PTAB Nov. 15, 2022) ......................................... 67
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
` IPR2017-01586, Paper 8 (Dec. 15, 2017) .................................................... 56, 57
`Biogen Int’l GMBH v. Mylan Pharms. Inc.,
` 18 F.4th 1333 (Fed. Cir. 2021) ........................................................................... 52
`Biomarin Pharm. Inc. v. Genzyme Theraputic Prods. Ltd. P’ship,
` IPR2013-00534, Paper 81 .................................................................................. 36
`Bristol-Myers Squibb Co. v. Boehringer Ingelheim Corp.,
` 86 F. Supp. 2d 433 (D.N.J.) ................................................................................ 18
`General Plastic,
` IPR2016-01357, Paper 19 (PTAB Sept. 6, 2017) ............................................... 59
`Indivior UK Ltd. v. Dr. Reddy’s Lab’ys S.A.,
`18 F.4th 1323 (Fed. Cir. 2021) ............................................................................ 50
`In re Kao,
` 639 F.3d 1057 (Fed. Cir. 2011) .................................................................... 55, 56
`In re Kubin,
` 561 F.3d 1351 (Fed. Cir. 2009) ........................................................................... 20
`In re O’Farrell,
` 853 F.2d 894 (Fed. Cir. 1988) ............................................................................. 39
`In re Peterson,
` 315 F.3d 1325 (Fed. Cir. 2003) ........................................................................... 39
`Lockheed Martin Corp. v. Space Systems/Loral, Inc.,
` 324 F.3d 1308 (Fed. Cir. 2003) ........................................................................... 20
`
`
`
`iv
`
`Biocon Exhibit 1059 - Page 5
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`Los Angeles Biomedical Research Institute at
` Harbor-UCLA Medical Center v. Eli Lilly & Co.,
` 849 F.3d 1049 (Fed. Cir. 2017) ........................................................................... 19
`Microsoft Corp. v. Iron Oak Techs., LLC,
` IPR2019-00107, Paper 8 (May 15, 2019) ........................................................... 62
`Minton v. Nat’l Ass’n. of Sec. Dealers, Inc.,
` 336 F.3d 1373, 1381 (Fed. Cir. 2003) ................................................................. 20
`Monsanto Tech. LLC v. E.I. DuPont de Nemours & Co.,
` 878 F.3d 1336 (Fed. Cir. 2018) ........................................................................... 49
`Novartis AG v. Torrent Pharms. Ltd.,
` 853 F.3d 1316 (Fed. Cir. 2017) ........................................................................... 56
`Ormco Corp. v. Align Tech., Inc.,
` 463 F.3d 1299, 1311 (Fed. Cir. 2006) ................................................................. 55
`Persion Pharm. LLC v. Alvogen Malta Operations Ltd.,
` 945 F.3d 1184 (Fed. Cir. 2019) ........................................................................... 49
`Pfizer, Inc. v. Apotex, Inc.,
` 480 F.3d 1348 (Fed. Cir. 2007) .................................................................... 36, 39
`Praxair Distrib., Inc. v. Mallinckrodt Hosp. Prods. IP Ltd.,
` 890 F.3d 1024 (Fed. Cir. 2018) ........................................................................... 22
`Qualcomm Inc. v. Monterey Research, LLC,
`IPR2020-01493, Paper 11 (March 8, 2021) .......................................... 60, 61, 62
`Regeneron Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc.,
` NDWV-1-22-cv-00061 ......................................................................................... 8
`Samsung Elecs. Co., Ltd. v. Acorn Semi, LLC,
`No. IPR2020-01205, 2022 WL 131221 (P.T.A.B. Jan. 12, 2022) ..................... 51
`Sand Revolution II, LLC v. Continental Intermodal Group – Trucking LLC,
` IPR2019-01393, Paper 24 (June 16, 2020) .................................................. 65, 66
`Syntex (U.S.A.) LLC v. Apotex, Inc.,
` 407 F.3d 1371 (Fed. Cir. 2005) ........................................................................... 18
`The Data Company Technologies Inc, v. Bright Data Ltd.,
` IPR2022-00135, Paper 12 ................................................................................... 62
`Unified Patents, Inc. v. Certified Measurement, LLC,
` IPR2018-00548, Paper 7 (Sept. 5, 2018) ............................................................ 61
`
`
`
`v
`
`Biocon Exhibit 1059 - Page 6
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`United States v. Regeneron Pharms., Inc.,
` No. 1:20-cv-11217-FDS (D. Mass.) ..................................................................... 8
`Wyers v. Master Lock Co.,
` 616 F.3d 1231 (Fed. Cir. 2010) ........................................................................... 55
`Statutory Authorities
`35 U.S.C. § 102 ............................................................................... 10, 23, 24, 26, 29
`35 U.S.C. § 103 ................................................................................................. 10, 11
`35 U.S.C. § 112 ........................................................................................................ 31
`35 U.S.C. § 314 ................................................................................................. 59, 63
`35 U.S.C. § 325 ................................................................................................. 56, 57
`Rules and Regulations
`37 C.F.R. § 42 ............................................................................................................ 1
`37 C.F.R. § 42.6 ....................................................................................................... 70
`37 C.F.R. § 42.8 ................................................................................................ 6, 8, 9
`37 C.F.R. § 42.10 ....................................................................................................... 8
`37 C.F.R. § 42.15 ....................................................................................................... 9
`37 C.F.R. § 42.24 ..................................................................................................... 69
`37 C.F.R. §§ 42.101 ................................................................................................... 9
`37 C.F.R. § 42.103 ..................................................................................................... 9
`37 C.F.R. § 42.104 ..................................................................................................... 9
`37 C.F.R. § 42.105 ................................................................................................... 70
`MPEP § 2128 ........................................................................................................... 29
`
`
`
`
`
`vi
`
`Biocon Exhibit 1059 - Page 7
`
`

`

`TABLE OF EXHIBITS
`
`1001|U.S. Patent No. 10,888,601
`
`1002|Expert Declaration of Dr. Edward Chaum in Support ofPetition for
`Inter Partes Review of Patent No. 10,888,601, dated March 24, 2023
`(“Chaum Decl.”)
`
`1003.|Edward Chaum Curriculum Vitae
`
`U.S. Patent No. 10,888,601— Petition for Inter Partes Review
`
`Macular Degeneration Presented at 2008 Retina Society Meeting
`
`1004|Regillo CD, Brown DM,Abraham P,et al. Randomized, double-
`masked, sham-controlled trial of ranibizumab for neovascular age-
`related macular degeneration: PIER Study year 1. Am J Ophthalmol.
`2008; 145(2):239-248. (“PIER Study”).
`1005|Heier JS, et al., CLEAR-IT 2 Investigators. The 1-year results of
`CLEAR-IT 2, a phase 2 study of vascular endothelial growth factor
`trap-eye dosed as-neededafter 12-week fixed dosing. Ophthalmology.
`2011 Jun;118(6):1098-106. (“Heier 2011”)
`
`1006|Elman MJ,et al., Randomizedtrial evaluating ranibizumabplus prompt
`or deferred laser or triamcinoloneplus promptlaser for diabetic
`macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.¢35.
`(“Elman 2010”)
`
`1007|HeierJS,et al., Intravitreal aflibercept (VEGF trap-eye) in wet age-
`related macular degeneration. Ophthalmology. 2012:119(12):2537-
`2548. (“Heier 2012”)
`
`1008|Dixon JA, Oliver SC, Olson JL, Mandava N. VEGF Trap-Eyefor the
`treatment of neovascular age-related macular degeneration. Expert
`Opin Investig Drugs. 2009:;18(10):1573-1580. (“Dixon”)
`
`1009|Press Release, Enrollment Completed in Regeneron and Bayer
`Healthcare Phase 3 Studies of VEGF Trap-Eye in Neovascular Age-
`Related Macular Degeneration (Wet AMD) (September14, 2009),
`https://newsroom.regeneron.com/news-releases/news-release-
`details/enrollment-completed-regeneron-and-bayer-healthcare-phase-3
`(“2009 Press Release”)
`
`1010|WO 2006/047325 Al (“Shams”)
`
`1011|Press Release, VEGF Trap-Eye Final Phase 2 Results in Age-Related
`
`Vii
`
`Biocon Exhibit 1059 - Page 8
`
`

`

`U.S. Patent No. 10,888,601— Petition for Inter Partes Review
`
`Description
`
`AJO Website’)
`
`Exhibit
`
`1012
`
`1013
`
`1014
`
`1015
`
`1016
`
`1017
`
`1018
`
`1019
`
`
`
`(September 28, 2008), https://investor.regeneron.com/news-
`releases/news-release-details/vegf-trap-eye-final-phase-2-results-age-
`related-macular (“September 28, 2008 Press Release’)
`
`Certified Prosecution History of U.S. Patent No. 10,888,601 (“’601
`patent PH”)
`
`Adis R&D Profile, Aflibercept: AVE 0005, AVE 005, AVE0005,
`VEGFTrap - Regeneron, VEGF Trap (R1R2), VEGF Trap-Eye. Drugs
`R D. 2008;9(4):261-269. (“Adis”)
`
`Elman MJ,et al., Randomizedtrial evaluating ranibizumab plus prompt
`or deferred laser or triamcinoloneplus promptlaser for diabetic
`macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35,
`published April 28 2010, available at
`https://www.aaojournalorg/article/S0161-6420(10)00243-5/fulltext
`(“Elman AAO Website)
`
`Lucentis ® Original Approved Labeling (2006), availableat:
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125156s000
`Q Lucentis Prntlbl.pdf
`
`Eylea Label 2023 available at:
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125387s07
`SIbL.pdf
`Comparison of Age-related Macular Degeneration Treatments Trials:
`Lucentis-Avastin Trial (NCT00593450), availableat:
`https://clinicaltrials. gov/ct2/show/NCT00593450
`
`WebArchive of the CATTPatient Eligibility Criteria (July 13, 2010),
`availableat:
`https://web.archive.org/web/2010071303561 7/http://www.med.upenn.e
`du/cpob/studies/documents/CATTEligibilityCriteria_000.pdf (“CATT
`Study”)
`
`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
`
`Vill
`
`Biocon Exhibit 1059 - Page 9
`
`

`

`U.S. Patent No. 10,888,601— Petition for Inter Partes Review
`
`
`
`Exhibit
`
`1020
`
`1021
`
`1022
`
`1023
`
`1024
`
`1025
`
`1026
`
`1027
`
`1028
`
`Financ Rev. 2006;27(3):37-47. (“Halpern 2006”).
`
`Description
`
`History of Changes for Study: A Study of rhuFab V2 (Ranibizumab) in
`Subjects With Subfoveal Choroidal Neovascularization Secondary to
`Age-Related Macular Degeneration (AMD) (NCT00090623), available
`at:
`https://clinicaltrials.gov/ct2/history/NCT00090623?V_1=View#StudyP
`ageTop.
`
`ClinicalTrials.gov Background, availableat:
`https://clinicaltrials. gov/ct2/about-site/background
`ClinicalTrials.gov About the Results Database, availableat:
`https://clinicaltrials.gov/ct2/about-site/results
`
`Do DVet al., Incorporating the Latest Findings From Clinical Trials
`Into the Management of Diabetic Retinopathy for the Comprehensive
`Ophthalmologist (October 25, 2009), availableat:
`https://aao.scientificposters.com/epsView.cfm?xvTgEIiINo9X9FYIsrbB
`iIRKZIICSVGWMJbEunzn9LGZqaMHKIw4tNfe%3D%3D (“Do
`workshop 2009”)
`
`Pai A, El Shafei1 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”).
`
`Final Written Decision in Mylan Pharmaceuticals Inc. v. Regeneron
`Pharmaceuticals, Inc., {PR2021-00881 (Paper 94) (“338 FWD”)
`U.S. Dep’t Health & Human Servs., Nat’ Inst. Health, Nat’] Eye Inst.,
`Diabetic Retinopathy: What You Should Know (Sept. 2015),
`https://www.nei.nih. gov/sites/default/files/health-
`pdfs/Diabetic Retinopathy What You Should Know.pdf (“NIH
`DR”).
`
`U.S. Dep’t Health & HumanServs., Nat’! Inst. Health, Nat’] Eye Inst.,
`Age-Related Macular Degeneration: What You Should Know(Sept.
`2015),
`https://www.nei.nih. gov/sites/default/files/healthpdfs/WYSK_AMD_E
`nglish Sept2015 PRINT.pdf (“NIH AMD”)
`
`Halpern MT, Schmier JK, Covert D, Venkataraman K. Resource
`utilization and costs of age-related macular degeneration. Health Care
`
`Biocon Exhibit 1059 - Page 10
`
`

`

`U.S. Patent No. 10,888,601— Petition for Inter Partes Review
`
`Exhibit|Description
`
`1029|Holash J, Davis S, Papadopoulos N,et al. VEGF-Trap: a VEGF
`blocker with potent antitumoreffects. Proc Natl Acad Sci U S A.
`2002;99(17):11393-11398. (“Holash’”)
`
`
`
`
`
`1030|Rudge JS, Thurston G, DavisS, et al. VEGFtrap as a novel
`antiangiogenic treatmentcurrently in clinical trials for cancer and eye
`diseases, and VelociGene- based discovery of the next generation of
`angiogenesis targets. Cold Spring Harb Symp QuantBiol.
`2005;70:411-418 (“Rudge 2005”)
`1031|Gomez-ManzanoC,Holash J, Fueyo J, et al. VEGF Trap induces
`antigliomaeffect at different stages of disease. Neuro Oncol.
`2008; 10(6):940-945. (“Gomez-Manzano”)
`
`1032|US. Patent No. 7,531,173 (“’173 patent’)
`
`1033|Rudge JS, Holash J, Hylton D, et al. VEGF Trap complex formation
`measures production rates of VEGF,providing a biomarkerfor
`predicting efficacious angiogenic blockade. Proc Natl Acad Sci US A.
`2007;104(47):18363-18370. (“Rudge 2007”)
`
`1034|LiE, Donati S, Lindsley KB, Krzystolik MG, Virgili G. Treatment
`regimensfor administration of anti-vascular endothelial growth factor
`agents for neovascular age-related macular degeneration. Cochrane
`Database Syst Rev. 2020:5(5):CD012208. (“Li 2020”)
`
`1035|Brown DM,Michels M,Kaiser PK,et al. Ranibizumab versus
`verteporfin photodynamic therapy for neovascular age-related macular
`degeneration: Two-year results of the ANCHORstudy.
`Ophthalmology. 2009;116(1):57-65.e5. (“Brown 2009”)
`
`1036|Martin DF, Maguire MG,Fine SL, Ying GS,Jaffe GJ, GrunwaldJE,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-yearresults.
`Ophthalmology 2012; 119(7):1388-98 (“Martin”)
`
`1037|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
`bevacizumabto treat neovascular age-related macular degeneration:
`one-year findings from the IVAN randomizedtrial. Ophthalmology
`2012; 119(7):1399-411 (“Chakravarthy 2012”)
`
`Biocon Exhibit 1059 - Page 11
`
`

`

`U.S. Patent No. 10,888,601— Petition for Inter Partes Review
`
`
`
`Exhibit
`
`1038
`
`1039
`
`1040
`
`1041
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`1048
`
`Delivery (2006) (“Jaffe”).
`
`Description
`
`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’’)
`
`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’’)
`Jager RD, Aiello LP, Patel SC, Cunningham ETJr. Risks of
`intravitreous injection: a comprehensive review.Retina.
`2004;24(5):676-698. (“Jager”)
`
`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#StudyP
`ageTop
`(“MACTEL Study”)
`
`Ranibizumab Injections to Treat Macular Telangiectasia Without New
`Blood Vessel Growth (NCT00685854) (November 7, 2008), available
`at:
`https://web.archive.org/web/20081107014243/https://clinicaltrials.gov/
`ct2/show/NCT00685854 (“MACTEL Study Wayback Machine’”’)
`
`Using the Wayback Machine,availableat:
`https://help.archive.org/help/using-the-wayback-machine/
`
`U.S. Patent App. Pub. US 2007/0190058A1
`
`Do DVet al., The DA VINCIStudy:phase 2 primary results of VEGF
`Trap-Eyein patients with diabetic macular edema. Ophthalmology.
`2011 Sep;118(9):1819-26 (published online on May 5, 2011). (“Do
`2011”)
`
`Certified Prosecution History of U.S. Patent No. 10,130,681 B2 (“681
`patent PH”)
`
`Eylea Label 2011 available at:
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125387Ibl.
`pdf
`
`Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson, Intraocular Drug
`
`Biocon Exhibit 1059 - Page 12
`
`

`

`U.S. Patent No. 10,888,601— Petition for Inter Partes Review
`
`Exhibit|Description
`
`
`
`
`
`1049|Steps for a Safe Intravitreal Injection Technique (2009), availableat:
`https://www.retinalphysician.com/issues/2009/july-aug/steps-for-a-
`safe-intravitreal-injection-technique
`
`1050|Eylea Label May 2016, available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125387s05
`Libl.pdf (“Eylea 2016 Label”)
`
`1051|Scheduling Order (Dkt. 87) entered in Regeneron Pharmaceuticals,
`Inc. v. Mylan Pharmaceuticals Inc., NDWV-1-22-cv-00061
`
`1052|September 28, 2022 Status Conference Transcript entered in Regeneron
`Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc., NDWV-1-22-cv-
`00061
`
`1053|Institution Decision in Mylan Pharmaceuticals Inc. v. Regeneron
`Pharmaceuticals, Inc., IPR2022-01226 (Paper 22) (“’601 ID”)
`
`1054|Institution Decision in Mylan Pharmaceuticals Inc. v. Regeneron
`Pharmaceuticals, Inc., IPR2022-01225 (Paper 21) (“’681 ID”)
`
`1055|Do DV et al., The DA VINCIStudy: phase 2 primary results of VEGF
`Trap-Eyein patients with diabetic macular edema. Ophthalmology.
`2011 Sep:118(9):1819-26, availableat:
`https://www.aaojournalorg/article/S0161-6420(11)00177-1/fulltext
`(“Do 2011 AAO Website”)
`
`1056|US. Patent No. 9,254,338 (“’338 patent’)
`
`1057|WO 2012/097019A1 (“Yancopoulos PCT Application’’)
`
`Biocon Exhibit 1059 - Page 13
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`I.
`
`
`INTRODUCTION
`Samsung Bioepis Co., Ltd. (“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 10-33 and 46-47 (the “Challenged Claims”) of U.S. Patent No.
`
`10,888,601 (“’601 patent”) (Ex.1001), assigned to Patent Owner, Regeneron
`
`Pharmaceuticals, Inc.
`
`
`
`The Challenged Claims are directed to treating diabetic macular edema
`
`(“DME”), diabetic retinopathy (“DR”), or DR in a patient with DME 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 is directed to a dosing regimen with two or more monthly loading doses
`
`followed by maintenance doses administered every two months. The other subset
`
`of Challenged Claims specify a dosing schedule of five monthly loading doses
`
`followed by maintenance doses administered every two months.
`
`
`
`The concept of treating DR/DME by administering a number of monthly
`
`loading doses followed by less frequent maintenance doses was well-known in the
`
`prior art. See, e.g. Ex.1005, Heier 2011; Ex.1006, Elman 2010; Ex.1002, Chaum
`
`Declaration, ¶¶43-61. During the loading phase, an initial dose followed by
`
`sequential monthly doses were given. The purpose of the “initial intensive monthly
`
`loading dose phase” was to gain “control of neovascular leakage” by stopping the
`
`
`
`1
`
`Biocon Exhibit 1059 - Page 14
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`growth of new, leaky blood vessels that cause angiogenic eye disorders. Ex.1005,
`
`Heier 2011, 1099, 1104. Thus, for most patients, the bulk of improvement generally
`
`occurred during this phase. The purpose of the subsequent maintenance phase was
`
`to maintain the improved condition while administering fewer doses, thereby
`
`reducing “risks of cataract, intraocular inflammation, retinal detachment and
`
`endophthalmitis,” as well as the “significant time and financial burden” on patients.
`
`Ex.1008, Dixon, 1577; see generally Ex.1002, ¶¶58-61.
`
`
`
`For example, a Regeneron press release from September 14, 2009 (“2009
`
`Press Release”) explicitly teaches dividing the treatment period into a “loading”
`
`phase and “maintenance” phase. Ex.1009, 2009 Press Release. Specifically, the
`
`2009 Press Release describes administering 2 mg aflibercept to treat DR/DME using
`
`a number of different dosing regimens, including one consisting of three monthly
`
`loading doses followed by maintenance doses at 8-week intervals. Ex.1009.
`
`
`
`As shown in Ground I, the 2009 Press Release thus anticipates Challenged
`
`Claims 46 and 47, which recite the general use of loading and maintenance dosing
`
`to treat DR/DME, specifying at least two initial monthly loading doses followed by
`
`any number of maintenance doses at 8-week intervals. The 2002 Press Release
`
`explicitly teaches such a regimen to treat DR/DME.
`
`
`
`Additionally, as set out in Ground II, the 2009 Press Release alone or in
`
`combination with Shams renders obvious the Challenged Claims that require five
`
`
`
`2
`
`Biocon Exhibit 1059 - Page 15
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`specific loading doses, including independent claims 10, 18, and 26. There is no
`
`special benefit taught in the ’601 patent to using five loading doses as opposed to
`
`two, three, four, six, or more loading doses. The ’601 patent states that “[t]he
`
`methods of the invention may comprise administering to the patient any number of
`
`secondary and/or tertiary doses of a VEGF antagonist” including “e.g. 2, 3, 4, 5, 6,
`
`7, 8, or more.” Ex.1001, 4:13-22. The patent does not contain any data for the use
`
`of only five monthly loading doses for any indication, let alone DR/DME; instead,
`
`the only discussion of five doses is part of a list of twenty other loading/maintenance
`
`dosing regimens it discloses for DR/DME, none of which are supported by
`
`additional data. Id., 15:35-17:28.
`
`
`
`Five loading doses is simply the number that works for some patients, and,
`
`importantly, the claims do not require the dosing regimen to apply to all patient
`
`populations in a one-size-fits-all approach. Nor could they, as there is no data in the
`
`patent supporting such a conclusion. Thus, the claims are directed to a “method for
`
`treating diabetic macular edema in a patient in need thereof,” not an entire patient
`
`population or a percentage thereof, because that is all the specification describes.
`
`There is thus no requirement that a POSA would have been motivated to adopt five
`
`initial loading doses for all patients.
`
`
`
`As set out above, the 2009 Press Release describes using three monthly
`
`loading doses followed by 8-week maintenance doses, among other regimens.
`
`
`
`3
`
`Biocon Exhibit 1059 - Page 16
`
`

`

`U.S. Patent No. 10,888,601– Petition for Inter Partes Review
`
`Ex.1009. The only difference between this disclosure and the dosing regimen of
`
`claims 10, 18, and 26 of the ’601 patent is the number of initial monthly doses.
`
`While three might be appropriate for some patients, a POSA would have understood
`
`that other patients would benefit from additional loading doses, including five
`
`monthly loading doses. Indeed, one of the other regimens recited in the 2009 Press
`
`Release is PRN (“as needed”) dosing after three monthly doses, which requires
`
`routine monitoring and reinjection when needed.
`
`
`
`Using five monthly loading doses is thus a trivial and routine modification
`
`that amounts to the addition of a single monthly injection between the last loading
`
`dose and first maintenance dose described in the 2009 Press Release, as shown in
`
`the figure below. Ex.1002, ¶¶146-158. The black arrows correspond