`
`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 IPR2023-00884
`
`U.S. Patent No. 11,253,572
`_________________________
`
`
`PETITION FOR INTER PARTES REVIEW
`OF U.S. PATENT NO. 11,253,572
`
`
`
`
`
`
`
`

`

`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`TABLE OF CONTENTS
`
`IV. 
`
`V. 
`
`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) ........................ 9 
`D. 
`Service Information (37 C.F.R. § 42.8(b)(4)) ..................................... 10 
`E. 
`Payment of Fees (37 C.F.R. §§ 42.103 and 42.15(a)) ......................... 10 
`III.  GROUNDS FOR STANDING (37 C.F.R. § 42.104(A); 37 C.F.R.
`§§ 42.101(A)-(C)) .......................................................................................... 11 
`IDENTIFICATION OF CHALLENGE AND RELIEF REQUESTED ....... 11 
`A. 
`Identification of Challenge (37 C.F.R. § 42.104(b)) ........................... 11 
`B. 
`Grounds of Challenge (37 C.F.R. § 42.204(b)(2)) .............................. 11 
`THE ’572 PATENT ....................................................................................... 13 
`A.  Overview ............................................................................................. 13 
`B. 
`Priority Date ........................................................................................ 14 
`C. 
`The Challenged Claims ....................................................................... 15 
`D. 
`Prosecution History ............................................................................. 16 
`E. 
`Level of Ordinary Skill in the Art ....................................................... 16 
`VI.  CONSTRUCTION OF THE CHALLENGED CLAIMS ............................. 17 
`A. 
`“A method of treating…” .................................................................... 17 
`B. 
`Exclusion Criteria ................................................................................ 18 
`VII.  SCOPE AND CONTENT OF THE PRIOR ART ......................................... 20 
`A. 
`The 2009 Press Release ....................................................................... 20 
`B. 
`The November 2010 Press Release ..................................................... 21 
`C. 
`The December 2010 Press Release ..................................................... 21 
`D.  Dixon ................................................................................................... 22 
`E. 
`Hecht .................................................................................................... 23 
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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`B. 
`
`C. 
`
`Shams .................................................................................................. 23 
`F. 
`Elman 2010 .......................................................................................... 24 
`G. 
`CATT and PIER Studies ..................................................................... 25 
`H. 
`Prior Art Regarding Aflibercept Efficacy ........................................... 26 
`I. 
`VIII.  DETAILED GROUNDS FOR INVALIDITY .............................................. 28 
`A.  Ground I: Claims 15 and 24 Are Anticipated by Each of the 2009
`Press Release and December 2010 Press Release ............................... 28 
`Ground II: Claims 1-5, 8-11, 16-17, and 20-21 (Generic/DME
`Results Claims) Are Anticipated by the December 2010 Press
`Release ................................................................................................. 31 
`1. 
`Claims 1 and 16 ......................................................................... 32 
`2. 
`Claim 2 ...................................................................................... 33 
`3. 
`Claims 3, 8, 10, 17, and 21 and Claims 4, 9, and 20 ................ 33 
`4. 
`Claims 5 and 11 ......................................................................... 34 
`Ground III: Claims 26-30 (AMD Results Claims) Are
`Anticipated by the November 2010 Press Release ............................. 35 
`1. 
`Claims 26-28 ............................................................................. 35 
`2. 
`Claims 29-30 ............................................................................. 37 
`D.  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 2006 Press Release ........................................................................ 39 
`1. 
`Claim 1 ...................................................................................... 40 
`2. 
`Claim 2 ...................................................................................... 41 
`3. 
`Claims 3-4 and 8-10 .................................................................. 42 
`4. 
`Claims 5 and 11 ......................................................................... 43 
`5. 
`Claims 26-28 ............................................................................. 43 
`6. 
`Claims 29-30 ............................................................................. 45 
`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”) ..................................................................... 46 
`
`E. 
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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`F. 
`
`I. 
`
`J. 
`
`2. 
`
`3. 
`
`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 ................................................................................. 49 
`G.  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 .................................................................................................... 51 
`H.  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 ......................................................... 51 
`Ground IX: Claim 25 is Rendered Obvious by the 2009 Press
`Release Alone or in View of Shams or Elman 2010 ........................... 52 
`Grounds X and XI ............................................................................... 56 
`1. 
`The “Results Limitations” in the Results Claims Are Not
`Entitled to Patentable Weight ................................................... 56 
`Ground X: Claims 1-5, 8-11, and 26-30 are Anticipated by
`Dixon Because the “Results Limitations” Lack Patentable
`Weight ....................................................................................... 60 
`Ground XI: Claims 1-5, 8-11, 16-17, and 20-21 are
`Anticipated by the 2009 Press Release Because the
`“Results Limitations” Lack Patentable Weight ........................ 61 
`There Are No Secondary Considerations ............................................ 61 
`K. 
`IX.  DISCRETIONARY DENIAL IS UNWARRANTED .................................. 63 
`A. 
`The Becton Dickinson Factors Do Not Favor Denial Under 35
`U.S.C. § 325(d) .................................................................................... 63 
`1. 
`Becton Dickinson Factors (a), (b), and (d) ................................ 63 
`2. 
`Becton Dickinson Factors (c), (e), and (f) ................................. 64 
`The General Plastic Factors Do Not Support Denial Under 35
`U.S.C. § 314(a) .................................................................................... 65 
`The Fintiv Factors Do Not Support Denial Under 35 U.S.C. §
`314(a) ................................................................................................... 67 
`CONCLUSION .............................................................................................. 68 
`
`
`B. 
`
`C. 
`
`X. 
`
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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`TABLE OF AUTHORITIES
`
`Page
`
`Cases
`Amgen Inc. v. Alexion Pharms., Inc., IPR2019-00739, Paper,
` 15, 62 (Aug. 30, 2019) ........................................................................................ 64
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
` IPR2017-01586, Paper 8, 17-18 (Dec. 15, 2017) ........................................ 63, 64
` Bristol-Myers Squibb Co. v. Boehringer Ingelheim Corp.,
` 86 F. Supp. 2d 443 (D.N.J.) aff’d in relevant part, 246 F.3d 1368
` (Fed. Cir. 2001) ................................................................................................... 58
`In Re: Copaxone Consol. Cases,
` 906 F.3d 1013 (Fed. Cir. 2018) ........................................................................... 58
`In re Kao,
` 639 F.3d 1057, 1068-69 (Fed. Cir. 2011) ........................................................... 62
`In re Kubin,
` 561 F.3d 1351, 1353 (Fed. Cir. 2009) .......................................................... 57, 60
`Lockheed Martin Corp. v. Space Systems/Loral, Inc.,
` 324 F.3d 1308, 1319 (Fed. Cir. 2003) ................................................................. 60
`Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center v. Eli
`Lilly & Co.,
` 849 F.3d 1049 (Fed. Cir. 2017) .............................................................. 58, 59, 60
`Minton v. Nat’l Ass’n. of Sec. Dealers, Inc.,
` 336 F.3d 1373, 1381, (Fed. Cir. 2003) ................................................................ 60
`Novartis AG v. Torrent Pharms. Ltd.,
` 853 F.3d 1316, 1330–31 (Fed. Cir. 2017) ........................................................... 62
`In re O’Farrell,
` 853 F.2d 894, 903 (Fed. Cir. 1988) ..................................................................... 56
`Ormco Corp. v. Align Tech., Inc.,
` 463 F.3d 1299, 1311-12 (Fed. Cir. 2006) ........................................................... 62
`Praxair Distrib., Inc. v. Mallinckrodt Hosp. Prods. IP Ltd.,
` 890 F.3d 1024, 1032 (Fed. Cir. 2018) .......................................................... 18, 19
`Qualcomm Inc. v. Monterey Research, LLC, IPR2020-01493, Paper,
` 11, 15 (March 8, 2021) ................................................................................. 65, 67
`
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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`Sanofi-Aventis U.S. LLC v. Immunex Corp., IPR2017-01884, Paper,
`, No. 14 (PTAB Feb. 15, 2018) ............................................................................ 66
`Syntex (U.S.A.) LLC v. Apotex, Inc.,
` 407 F.3d 1371 (Fed. Cir. 2005) ........................................................................... 58
`Unified Patents, Inc. v. Certified Measurement, LLC,
` IPR2018-00548, Paper 7, 7-8 (Sept. 5, 2018) ..................................................... 67
`Wyers v. Master Lock Co.,
` 616 F.3d 1231, 1246 (Fed. Cir. 2010) ................................................................. 61
`Statutory Authorities
`35 U.S.C. §102 .......................................................................... 20, 21, 22, 23, 24, 26
`35 U.S.C. §§ 311-319 ................................................................................................ 1
`35 U.S.C. § 314(a) ............................................................................................ 65, 67
`35 U.S.C. § 325(d) ............................................................................................ 63, 64
`Rules and Regulations
`37 C.F.R. § 42 ............................................................................................................ 1
`37 C.F.R. § 42.8(b)(1) ................................................................................................ 6
`37 C.F.R. § 42.8(b)(2) ................................................................................................ 6
`37 C.F.R. § 42.8(b)(3) ................................................................................................ 9
`37 C.F.R. § 42.8(b)(4) ......................................................................................... 9, 10
`37 C.F.R. § 42.10(b) ................................................................................................ 10
`37 C.F.R. § 42.15(a) ................................................................................................. 10
`37 C.F.R. §§ 42.101(a)-(c) ....................................................................................... 11
`37 C.F.R. § 42.103 ................................................................................................... 10
`37 C.F.R. § 42.104(a) ............................................................................................... 11
`37 C.F.R. § 42.104(b) .............................................................................................. 11
`37 C.F.R. § 42.204(b)(2) .......................................................................................... 11
`MPEP §2159 ............................................................................................................ 14
`
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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`TABLE OF EXHIBITS
`
`
`
`
`
`
`1003
`1004
`
`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.”)
`Edward Chaum Curriculum Vitae
`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 Study in 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.edgar-
`online.com/displayfilinginfo.aspx?FilingID=7572010-8611-
`26486&type=sect&TabIndex=2&companyid=5036&ppu=%252fdef%
`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”)
`
`1006
`
`1007
`
`vi
`
`

`

`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`1011
`
`1012
`
`
`
`Exhibit Description
`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
`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, “Opthalmic 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”)
`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
`
`1013
`
`1019
`
`
`
`vii
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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`Exhibit Description
`https://web.archive.org/web/20100713035617/http://www.med.upenn.e
`du/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.
`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#StudyP
`ageTop. (“NCT-623”)
`at:
`available
`Background,
`1025 ClinicalTrials.gov
`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.edgar-
`online.com/displayfilinginfo.aspx?FilingID=4380124-5423-
`15279&type=sect&TabIndex=2&companyid=5036&ppu=%252fdef%
`E2%80%A6
`
`1027
`
`
`
`viii
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`

`

`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`1029
`
`Exhibit Description
`(“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 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”)
`Lucentis ® Original Approved Labeling (2006), available at:
`https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/125156s000
`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”)
`
`1033
`
`1034
`
`
`
`ix
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`

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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`1040
`
`Exhibit Description
`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 age-
`related 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 trap-
`eye 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.
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`1042 U.S. Patent No. 9,254,338 (“’338 patent”)
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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),” available
`at:
`https://www.nei.nih.gov/sites/default/files/health-
`pdfs/Diabetic_Retinopathy_What_You_Should_Know.pdf
`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_E
`nglish_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”)
`
`(“NIH
`
`
`
`x
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`

`

`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`Exhibit Description
`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”)
`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:
`
`1056
`
`1054
`
`
`
`xi
`
`

`

`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`at:
`
`Exhibit Description
`https://clinicaltrials.gov/ct2/history/NCT00685854?V_1=View#StudyP
`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.gov/
`ct2/show/NCT00685854, attached as Exhibit A (“MACTEL Study
`Wayback Machine”)
`available
`Machine,
`Wayback
`1058 Using
`the
`https://help.archive.org/help/using-the-wayback-machine/
`Eylea Label 2011 available at:
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/125387lbl.
`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-a-
`safe-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”)
`1063 April 19, 2023 Claim Construction Order entered in Regeneron
`Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc., Case No. 1:22-cv-
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`1064 U.S. Patent No. 7,531,173 (“’173 patent”)
`
`1059
`
`1061
`
`
`
`xii
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`

`U.S. Patent No. 11,253,572 – 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 1-30 (the “Challenged Claims”) of U.S. Patent No. 11,253,572
`
`(“’572 patent”) (Ex.1001), assigned to Patent Owner, Regeneron Pharmaceuticals,
`
`Inc.
`
`
`
`The Challenged Claims are directed to treating angiogenic eye disorders,
`
`including diabetic macular edema (“DME”) and age-related macular degeneration
`
`(“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 dosing
`
`regimen for DME 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 the non-DME claims of the ’572 patent. Ex.1008.
`
`Unlike the other ’572 claims previously addressed by the Patent Trial and
`
`Appeal Board (“Board”), independent claim 15 and dependent claim 24 recite only
`
`DME dosing regimens and nothing more. 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
`
`
`
`1
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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
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`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. A
`
`Regeneron press release from September 14, 2009 (“2009 Press Release”) discloses
`
`exactly that. It describes administering 2 mg aflibercept to treat DME using a dosing
`
`regimen of three monthly loading doses that include an initial and two “secondary”
`
`doses, followed by maintenance doses at 8-week intervals. Ex.1005. Another press
`
`release from December 20, 2010 (“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
`
`
`
`2
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`

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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
`
`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 (the “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 from DME clinical trials in which these regimens
`
`were applied. The December 2010 Press Release explicitly discloses that DME
`
`patients both achieved the results recited within the recited 24 or 52 week time
`
`frames, and that they achieved the specific visual acuity gains recited (e.g., a gain of
`
`at least 7, 8, or 9 letters).
`
`
`
`Similarly, Results Claims 26-30 recite a method for treating AMD via a
`
`loading/maintenance regimen (the “AMD Results Claims”), and further recite that
`
`the method is “as effective” as monthly ranibizumab at week 52. As shown in
`
`Ground III, the AMD Results Claims are anticipated by a November 22, 2010 Press
`
`Release (“November 2010 Press Release”), which discloses the same dosing
`
`regimen as the other press releases, but for treatment of AMD. Ex.1007. That Press
`
`Release further explicitly discloses the ranibizumab comparison results recited by
`
`the claim. Id.
`
`
`
`3
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`

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`U.S. Patent No. 11,253,572 – Petition for Inter Partes Review
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`The Results Claims are also rendered obvious by the 2009 Press Release or
`
`separately by Dixon’s disclosure of the claimed dosing regimen for AMD. Notably,
`
`in the Apotex Petition, Apotex argued that the “results limitations” only were
`
`inherent or not entitled to patentable weight based on Dixon—an argument the Board
`
`rejected; Apotex did not argue that they were obvious. Ex.1008, 12. It would have
`
`been obvious to a POSA, however, that at least some patients, when treat