UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`APOTEX INC.,
`Petitioner
`v.
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner
`
`Inter Partes Review No.: IPR2022-01524
`
`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
`
`EXHIBIT LIST ........................................................................................................ iv 
`I. 
`INTRODUCTION ........................................................................................... 1 
`II.  MANDATORY NOTICES (37 C.F.R. § 42.8) ............................................... 2 
`A. 
`REAL PARTIES-IN-INTEREST (37 C.F.R. § 42.8(b)(1)) .................. 2 
`B. 
`RELATED MATTERS (37 C.F.R. § 42.8(b)(2)) ................................. 2 
`C. 
`LEAD AND BACK-UP COUNSEL AND SERVICE
`INFORMATION (37 C.F.R. § 42.8(b)(3)-(4)) ..................................... 4 
`PAYMENT UNDER 37 C.F.R. § 42.15(a) AND § 42.103 ............................ 5 
`III. 
`IV.  GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)) ................................. 5 
`V. 
`THE BOARD SHOULD NOT EXERCISE ITS DISCRETION TO DENY
`INSTITUTION ........................................................................................................... 6 
`VI.  THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW ............. 11 
`VII.  OVERVIEW OF CHALLENGE AND PRECISE RELIEF REQUESTED . 11 
`A. 
`CHALLENGED CLAIMS .................................................................. 11 
`B. 
`STATUTORY GROUNDS OF CHALLENGE ................................. 12 
`VIII.  OVERVIEW OF THE ‘572 PATENT .......................................................... 13 
`A. 
`THE ‘572 PATENT............................................................................. 13 
`IX.  CLAIM CONSTRUCTION (37 C.F.R. § 42.104(b)(3)) ............................... 15 
`A. 
`“INITIAL DOSE,” “SECONDARY DOSE,” AND “TERTIARY
`DOSE” ................................................................................................. 16 
`“4 WEEKS” AND “8 WEEKS,” AFTER THE IMMEDIATELY
`PRECEDING DOSE ........................................................................... 17 
`“WHEREIN THE PATIENT ACHIEVES/GAINS…” ...................... 17 
`
`B. 
`
`C. 
`
`i
`
`

`

` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
` 
`
`D. 
`
`“WHEREIN EXCLUSION CRITERIA FOR THE PATIENT
`INCLUDE BOTH OF…” .................................................................... 20 
`The “Exclusion Criteria” are entitled no patentable weight
`under the printed matter doctrine .............................................. 20 
`The Board should apply the printed matter doctrine as part of its
`claim construction analyses ...................................................... 22 
`PERSON OF ORDINARY SKILL IN THE ART ........................................ 23 
`X. 
`XI.  THE SCOPE AND CONTENT OF THE PRIOR ART ................................ 24 
`A. 
`TECHNOLOGY BACKGROUND .................................................... 24 
`B. 
`PETITIONER’S PRIOR ART REFERENCES .................................. 26 
`Dixon (Ex.1006)........................................................................ 27 
`Regeneron (8-May-2008) (Ex.1009) ........................................ 28 
`NCT-795 (Ex.1010) .................................................................. 29 
`NCT-377 (Ex.1011) .................................................................. 31 
`Hecht (Ex.1025) ........................................................................ 33 
`XII.  GROUNDS FOR UNPATENTABILITY ..................................................... 33 
`A.  ANTICIPATION ................................................................................. 33 
`Legal standards ......................................................................... 34 
`Ground 1: Dixon anticipates Claims 1-5, 8-11, 14, and 26-30 . 35 
`Ground 2: Regeneron (8-May-2008) anticipates Claims 1-5, 8-
`11, 14, and 26-30 ....................................................................... 48 
`Grounds 3 and 4: NCT-795 and NCT-377 each anticipate
`Claims 1-5, 8-11, 14, and 26-30 ............................................... 58 
`OBVIOUSNESS ................................................................................. 68 
`
` 
`
` 
`
` 
`
` 
`
`B. 
`
`ii
`
`

`

` 
`
` 
`
`Ground 5: Claims 6, 7, 12, and 13 are obvious over Dixon, or
`Regeneron (8-May-2008), or NCT-795, or NCT-377 in
`combination with Hecht ............................................................ 69 
`No secondary considerations .................................................... 71 
`XIII.  CONCLUSION .............................................................................................. 72 
`CERTIFICATE OF SERVICE ................................................................................ 74 
`CERTIFICATE OF COMPLIANCE ....................................................................... 75 
`
`
`
`
`
`
`iii
`
`

`

`EXHIBIT LIST
`
`Exhibit
`
`Description
`
`1001 U.S. Patent No. 11,253,572 (“’572 patent”)
`
`1002 Declaration of Angelo P. Tanna, M.D.
`
`1003 Curriculum Vitae of Angelo P. Tanna, M.D.
`
`1004
`
`1005
`
`1006
`
`1007
`
`1008
`
`1009
`
`1010
`
`Jocelyn Holash et al., VEGF-Trap: A VEGF Blocker with Potent
`Antitumor Effects, 99 PROC. NAT’L ACAD. SCI. 11393 (2002)
`(“Holash”)
`
`Quan Dong Nguyen et al., A Phase I Study of Intravitreal Vascular
`Endothelial Growth Factor Trap-Eye in Patients with Neovascular
`Age-Related Macular Degeneration, 116 OPHTHALMOLOGY 2141
`(2009) (“Nguyen-2009”)
`
`James A. Dixon et al., VEGF Trap-Eye for the Treatment of
`Neovascular Age-Related Macular Degeneration, 18 EXPERT OPINION
`ON INVESTIGATIONAL DRUGS 1573 (2009) (“Dixon”)
`
`Adis R&D Profile, Aflibercept: AVE 0005, AVE 005, AVE0005, VEGF
`Trap – Regeneron, VEGF Trap (R1R2), VEGF Trap-Eye, 9 DRUGS
`R&D 261 (2008) (“Adis”)
`
`F. Semeraro et al., Aflibercept in Wet AMD: Specific Role and Optimal
`Use, 7 DRUG DESIGN, DEV. & THERAPY 711 (2013) (“Semeraro”)
`
`Press Release, Regeneron, Bayer and Regeneron Dose First Patient in
`Second Phase 3 Study for VEGF Trap-Eye in Wet Age-Related
`Macular Degeneration (May 8, 2008),
`http://investor.regeneron.com/releasedetail.cfm?ReleaseID=394065
`(“Regeneron (8-May-2008)”)
`
`Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation
`of Efficacy and Safety in Wet Age-Related Macular Degeneration
`(AMD) (VIEW1), NCT00509795, ClinicalTrials.gov (Apr. 28, 2009),
`https://clinicaltrials.gov/ct2/show/NCT00509795 (“NCT-795”)
`
`iv
`
`

`

`1011
`
`VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD
`(VIEW 2), NCT00637377, ClinicalTrials.gov (Mar. 17, 2008),
`https://clinicaltrials.gov/ct2/show/NCT00637377 (“NCT-377”)
`1012 U.S. Patent Nos. 7,303,746 B2; 7,303,747 B2; 7,306,799 B2; and
`7,521,049 B2 (“Monthly-Dosing-Patents”)
`
`1013
`
`File History of U.S. Patent No. 9,254,338 B2 (“’338 FH”)
`
`1014
`
`Jeffrey S. Heier et al., Intravitreal Aflibercept (VEGF Trap-Eye) in
`Wet Age-Related Macular Degeneration, 119 OPHTHALMOLOGY 2537
`(2012) (“Heier-2012”)
`
`1015
`
`Jeffrey S. Heier, Intravitreal VEGF Trap for AMD: An Update,
`RETINA TODAY, Oct. 2009, 44 (“Heier-2009”)
`1016 Regeneron Pharm., Inc., Quarterly Report (Form 10-Q) (Sept. 30,
`2009) (“2009 10-Q”)
`
`1017
`
`1018
`
`Press Release, Bayer AG, Bayer and Regeneron Start Additional
`Phase 3 Study for VEGF Trap-Eye in Wet Age-Related Macular
`Degeneration (May 8, 2008) (“Bayer (8-May-2008)”)
`
`David M. Brown & Carl D. Regillo, Anti-VEGF Agents in the
`Treatment of Neovascular Age-Related Macular Degeneration:
`Applying Clinical Trial Results to the Treatment of Everyday Patients,
`144 AM. J. OPHTHALMOLOGY 627 (2007) (“Brown”)
`
`1019 LUCENTIS® Prescribing Information (2006) (“Lucentis”)
`
`1020
`
`Janice M. Reichert, Antibody-Based Therapeutics To Watch In 2011, 3
`MABS 76 (2011) (“Reichert”)
`
`1021
`
`1022
`
`ClinicalTrials.gov, 1997: Congress Passes Law (FDAMA) Requiring
`Trial Registration, U.S. NAT’L LIBRARY MED. (Oct. 2020),
`https://clinicaltrials.gov/ct2/about-site/history (“History-
`ClinicalTrials.gov”)
`
`Affidavit of Duncan Hill (Internet Archive Records Request
`Processor) Regarding Vascular Endothelial Growth Factor (VEGF)
`Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related
`Macular Degeneration (AMD) (VIEW1), NCT00509795,
`
`v
`
`

`

`ClinicalTrials.gov (Apr. 28, 2009) and VEGF Trap-Eye: Investigation
`of Efficacy and Safety in Wet AMD (VIEW 2), NCT00637377,
`ClinicalTrials.gov (Mar. 17, 2008), dated January 27, 2021
`(“Wayback-Affidavit-038”)
`
`1023
`
`Quan Dong Nguyen et al., A Phase I Trial of an IV-Administered
`Vascular Endothelial Growth Factor Trap for Treatment in Patients
`with Choroidal Neovascularization due to Age-Related Macular
`Degeneration, 113 OPHTHALMOLOGY 1522 (2006) (“Nguyen-2006”)
`1024 Expert Declaration of David M. Brown, M.D., submitted in IPR2021-
`00881 as Patent Owner Exhibit 2050 on February 11, 2022.
`1025 Hecht, “Opthalmic Preparations,” Remington: The Science and
`Practice of Pharmacy, Volume II, 19th edition, Chapter 89 (1995).
`
`1026
`
`1027
`
`1028
`
`1029
`
`1030
`
`1031
`
`1032
`
`Rosenfeld et al. Ranibizumab for neovascular age-related macular
`degeneration. N Engl J Med 2006;355:1419-31; supplemental
`appendix (“Rosenfeld”)
`
`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”)
`
`Saishin et al., “VEGF-TRAPR1R2 Suppresses Choroidal
`Neovascularization and VEGF-Induced Breakdown of the Blood-
`Retinal Barrier,” Journal of Cellular Physiology, 195:241-248 (2003)
`(“Saishin”).
`
`Appendix to Heier et al., Intravitreal Aflibercept (VEGF Trap-Eye) in
`Wet Age-Related Macular Degeneration, 119 OPHTHALMOLOGY 2537
`(2012) (“Heier-2012 Appendix”)
`
`FDA, Non-Inferiority Clinical Trials to Establish Effectiveness:
`Guidance for Industry (Nov. 2016).
`
`Heinrich Heimann, Intravitreal Injections: Techniques and Sequelae,
`in MEDICAL RETINA 67 (Frank G. Holtz & Richard F. Spaide eds.
`2007) (“Heimann-2007”)
`
`vi
`
`

`

`1033
`
`1034
`
`1035
`
`Rama D. Jager, Risks of Intravitreous Injection: A Comprehensive
`Review, 24 J. RETINAL & VITREOUS DISEASE 676 (2004) (“Jager-
`2004”)
`
`U.S. DEP’T HEALTH & HUMAN SERVS., NAT’L INST. HEALTH, NAT’L
`EYE INST., Age-Related Macular Degeneration: What You Should
`Know (Sept. 2015), https://www.nei.nih.gov/sites/default/files/health-
`pdfs/WYSK_AMD_English_Sept2015_PRINT.pdf (“NIH AMD”)
`
`U.S. DEP’T HEALTH & HUMAN SERVS., NAT’L INST. HEALTH, NAT’L
`EYE INST., Diabetic Retinopathy: What You Should Know (Sept.
`2015), https://www.nei.nih.gov/sites/default/files/2019-06/Diabetic-
`Retinopathy-What-You-Should-Know-508.pdf (“NIH DR”)
`
`1036
`
`Press Release, Regeneron, Regeneron and Bayer HealthCare
`Announce Encouraging 32-Week Follow-Up Results from a Phase 2
`Study of VEGF Trap-Eye in Age-Related Macular Degeneration (Apr.
`28, 2008),
`http://investor.regeneron.com/releasedetail.cfm?releaseid=394066
`(“Regeneron (28-April-2008)”)
`1037 Napoleone Ferrara & Robert S. Kerbel, Angiogenesis as a Therapeutic
`Target, 438 NATURE 967 (2005) (“Ferrara-2005”)
`
`1038
`
`1039
`
`J.S. Rudge 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, 70 COLD SPRING HARBOR SYMPOSIA
`QUANTITATIVE BIOLOGY 411 (2005) (“Rudge”)
`
`Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation
`of Efficacy and Safety in Central Retinal Vein Occlusion (CRVO),
`NCT01012973, ClinicalTrials.gov (Nov. 12, 2009),
`https://clinicaltrials.gov/ct2/show/NCT01012973 (“NCT-973”)
`
`1040 Reserved
`
`1041
`
`Press Release, Regeneron, Positive Interim Phase 2 Data Reported for
`VEGF Trap-Eye in Age-Related Macular Degeneration (Mar. 27,
`2007), https://newsroom.regeneron.com/news-releases/news-release-
`
`vii
`
`

`

`details/positive-interim-phase-2-data-reported-vegf-trap-eye-age-
`related?releaseid=394105 (“Regeneron (27-March-2007)”)
`
`Press Release, Regeneron, Regeneron and Bayer HealthCare Initiate
`Phase 3 Global Development Program for VEGF Trap-Eye in Wet
`Age-Related Macular Degeneration (AMD) (Aug. 2, 2007),
`https://investor.regeneron.com/news-releases/news-release-
`details/regeneron-and-bayer-healthcare-initiate-phase-3-global
`(“Regeneron (2-August-2007)”)
`
`Press Release, Regeneron, Regeneron and Bayer Healthcare Announce
`VEGF Trap-Eye Achieved Durable Improvement in Vision Over 52
`Weeks in a Phase 2 Study in Patients with Age Related Macular
`Degeneration (Aug. 19, 2008), https://investor.regeneron.com/news-
`releases/news-release-details/regeneron-and-bayer-healthcare-
`announce-vegf-trap-eye-achieved?ReleaseID=394056 (“Regeneron
`(19-August-2008)”)
`
`Press Release, Regeneron, VEGF Trap-Eye Final Phase 2 Results in
`Age-related Macular Degeneration Presented at 2008 Retina Society
`Meeting (Sept. 28, 2008), https://investor.regeneron.com/news-
`releases/news-release-details/vegf-trap-eye-final-phase-2-results-age-
`related-macular?ReleaseID=393906 (“Regeneron (28-September-
`2008)”)
`
`Press Release, Regeneron, Bayer and Regeneron Extend Development
`Program for VEGF Trap-Eye to Include Central Retinal Vein
`Occlusion (Apr. 30, 2009), https://investor.regeneron.com/news-
`releases/news-release-details/bayer-and-regeneron-extend-
`development-program-vegf-trap-eye (“Regeneron (30-April-2009)”)
`
`Press Release, Regeneron, Enrollment Completed in Regeneron and
`Bayer HealthCare Phase 3 Studies of VEGF Trap-Eye in Neovascular
`Age-Related Macular Degeneration (Wet AMD) (Sept. 14, 2009),
`https://investor.regeneron.com/news-releases/news-release-
`details/enrollment-completed-regeneron-and-bayer-healthcare-phase-
`3?ReleaseID=408872 (“Regeneron (14-September-2009)”)
`
`1042
`
`1043
`
`1044
`
`1045
`
`1046
`
`1047
`
`Press Release, Regeneron, VEGF Trap-Eye Shows Positive Results in
`a Phase 2 Study in Patients with Diabetic Macular Edema (Feb. 18,
`2010), https://investor.regeneron.com/news-releases/news-release-
`
`viii
`
`

`

`details/vegf-trap-eye-shows-positive-results-phase-2-study-
`patients?releaseid=445521 (“Regeneron (18-February-2010)”)
`
`Press Release, Bayer, Bayer HealthCare and Regeneron Announce
`VEGF Trap-Eye Achieved Durable Improvement in Vision Over 52
`Weeks in a Phase 2 Study in Patients with Age-Related Macular
`Degeneration (Aug. 19, 2008) (“Bayer (19-August-2008)”)
`
`Campochiaro et al., Antagonism of vascular endothelial growth factor
`for macular edema caused by retinal vein occlusions: two-year
`outcomes, Ophthalmology, 117 (2010), pp. 2387-2394.
`(“Campochiaro”)
`
`Adam Hayes, SEC Filings: Forms You Need To Know, INVESTOPEDIA
`(Jan. 18, 2021), https://www.investopedia.com/articles/fundamental-
`analysis/08/sec-forms.asp (“Hayes”)
`
`Owen A. Anderson et al., Delivery of Anti-Angiogenic Molecular
`Therapies for Retinal Disease, 15 DRUG DISCOVERY TODAY 272
`(2010) (“Anderson”)
`
`Thomas A. Ciulla & Philip J. Rosenfeld, Antivascular Endothelial
`Growth Factor Therapy For Neovascular Age-Related Macular
`Degeneration, 20 CURRENT OPINION OPHTHALMOLOGY 158 (2009)
`(“Ciulla”)
`
`Zhang Ni & Peng Hui, Emerging Pharmacologic Therapies for Wet
`Age-Related Macular Degeneration, 223 OPHTHALMOLOGICA 401
`(2009) (“Ni”)
`
`Marco A. Zarbin & Philip J. Rosenfeld, Pathway-Based Therapies for
`Age-Related Macular Degeneration: An Integrated Survey of
`Emerging Treatment Alternatives, 30 RETINA 1350 (2010) (“Zarbin”)
`
`1048
`
`1049
`
`1050
`
`1051
`
`1052
`
`1053
`
`1054
`
`1055
`
`Corporate Finance Institute, SEC Filings: Public Disclosures About
`Public Companies,
`https://corporatefinanceinstitute.com/resources/data/public-filings/sec-
`filings/ (last visited May 5, 2021) (“Corporate Finance Institute”)
`1056 Carl W. Schneider, Nits, Grits, and Soft Information in SEC Filings,
`121 U. PA. L. REV. 254 (1972) (“Schneider”)
`
`ix
`
`

`

`Justin Kuepper, The Best Investment Information Sources: Using SEC
`Filings, Analyst Reports, and Company Websites, BALANCE (Jan. 13,
`2021), https://www.thebalance.com/top-best-sources-of-investor-
`information-1979207 (“Kuepper”)
`
`Kristina Zucchi, EDGAR: Investors’ One-Stop-Shop For Company
`Filings, YAHOO!LIFE (Jan. 31, 2014),
`https://www.yahoo.com/lifestyle/tagged/health/edgar-investors-one-
`stop-shop-170000800.html (“Zucchi”)
`
`1057
`
`1058
`
`
`
`
`
`
`
`x
`
`

`

`Apotex 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 1-14
`
`and 26-30 (the “Challenged Claims”) of U.S. Patent No. 11,253,572 (“‘572 patent”)
`
`(Ex.1001), assigned to Regeneron Pharmaceuticals, Inc. (“Regeneron” or “Patent
`
`Owner”).
`
`I.
`
`INTRODUCTION
`The Challenged Claims are directed to a method of treating a known
`
`indication with a known dosage regimen of a known active ingredient. Long before
`
`the patent’s alleged 2011 priority date, Regeneron had disclosed that it’s age-related
`
`macular degeneration (“AMD”) clinical trials (VIEW1/VIEW2) with EYLEA®
`
`(aflibercept) were designed to use the precise dosing regimen now covered by the
`
`Challenged Claims. Regeneron publicly disclosed the exact dosing regimen as early
`
`as 2008, three years prior to filing its patent application. While Regeneron added
`
`certain efficacy endpoints that result upon administering the claimed dosage
`
`regimen, such claim elements are not given patentable weight. But even if they
`
`were, the prior art nevertheless anticipates the Challenged Claims.
`
`The caselaw is clear here. It is not patentable to merely observe the efficacy
`
`of administering a known compound using a known method to treat a known
`
`condition. See, e.g., In re Montgomery, 677 F.3d 1375, 1381 (Fed. Cir. 2013); King
`
`Pharms., Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1275 (Fed. Cir. 2010); In re
`
`1
`
`

`

`Omeprazole Patent Litig., 483 F.3d 1364, 1373 (Fed. Cir. 2007); Perricone v.
`
`Medicis Pharm. Corp., 432 F.3d 1368, 1378 (Fed. Cir. 2005); Bristol–Myers Squibb
`
`Co. v. Boehringer Ingelheim Corp., 86 F. Supp. 2d 433, 443 (D.N.J. 2000), aff'd in
`
`relevant part, 246 F.3d 1368 (Fed. Cir. 2001). Simply put, the Challenged Claims
`
`are not patentable.
`
`II. MANDATORY NOTICES (37 C.F.R. § 42.8)
`Pursuant to 37 C.F.R. §§ 42.8(a)(1) and 42.8(b), the following mandatory
`
`notices are provided as part of this Petition.
`
`A. REAL PARTIES-IN-INTEREST (37 C.F.R. § 42.8(b)(1))
`Petitioner Apotex Inc. is the real party-in-interest. Additional real parties-in-
`
`interest are Apotex Corp., Apotex Pharmaceutical Holdings Inc. and Aposherm
`
`Delaware Holdings Corp.
`
` No other parties exercised or could have exercised control over this Petition;
`
`no other parties funded, directed and controlled this Petition. See Trial Practice
`
`Guide, 77 Fed. Reg. 48759- 60 (Aug. 14, 2021).
`
`B. RELATED MATTERS (37 C.F.R. § 42.8(b)(2))
`Petitioner identifies the following IPR proceedings that are currently pending
`
`on patents related to the ’572 patent:
`
` Challenging U.S. Patent No. 9,254,338 (the ‘338 patent):
`
`2
`
`

`

`o Mylan Pharms. Inc. v. Regeneron Pharms. Inc., No. IPR2021-
`
`00881 (P.T.A.B.), filed May 5, 2021,
`
`o Celltrion Inc. v. Regeneron Pharms, Inc., No. IPR2022-00258
`
`(P.T.A.B.), filed December 9, 2021, and
`
`o Apotex Inc. v. Regeneron Pharms, Inc., No. IPR2022-00298
`
`(P.T.A.B.), filed December 9, 2021.
`
` Challenging U.S. Patent No. 9,669,069:
`
`o Mylan Pharms. Inc. v. Regeneron Pharms., Inc., No. IPR2021-
`
`00880 (P.T.A.B.), filed May 5, 2021,
`
`o Celltrion Inc. v. Regeneron Pharms, Inc., No. IPR2022-00257
`
`(P.T.A.B.), filed December 9, 2021, and
`
`o Apotex Inc. v. Regeneron Pharms, Inc., No. IPR2022-00301
`
`(P.T.A.B.), filed December 9, 2021.
`
` Challenging U.S. Patent No. 10,130,681:
`
`o Mylan Pharms. Inc. v. Regeneron Pharms., Inc., No. IPR2022-
`
`01225 (P.T.A.B.), filed July 1, 2022.
`
` Challenging U.S. Patent No. 10,888,601:
`
`3
`
`

`

`o Mylan Pharms. Inc. v. Regeneron Pharms., Inc., No. IPR2022-
`
`01226 (P.T.A.B.), filed July 1, 2022.
`
`Petitioner identifies the following district court proceeding that is currently
`
`pending and involves the ‘572 patent as well as related patents: Regeneron Pharms.,
`
`Inc. v. Mylan Pharms. Inc., No. 1:22-cv-00061-TSK (N.D. W.Va).
`
`To the best of Petitioner’s knowledge, there are no other judicial or
`
`administrative matters that would affect, or be affected by, a decision in this
`
`proceeding; nonetheless, out of an abundance of caution, Petitioner further identifies
`
`Chengdu Kanghong Biotechnology Co. v. Regeneron Pharms., Inc., No. PGR2021-
`
`00035 (P.T.A.B.).
`
`U.S. Patent Nos. 9,254,338; 9,669,069; 10,130,681; 10,857,205; 10,828,345;
`
`and 10,888,601; and U.S. Patent Application Nos. 17/072,417; 17/112,404;
`
`17/112,063; and 17/350,958 are all related to the ’572 patent.
`
`C. LEAD AND BACK-UP COUNSEL AND SERVICE
`INFORMATION (37 C.F.R. § 42.8(b)(3)-(4))
`Petitioner identifies its lead and backup counsel below. A Power of Attorney
`
`is filed concurrently herewith under 37 C.F.R. § 42.10(b).
`
`Lead
`Teresa Stanek Rea (Reg. No. 30,427)
`CROWELL & MORING LLP
`Intellectual Property Group
`
`Back-Up
`Deborah H. Yellin (Reg. No. 45,904)
`CROWELL & MORING LLP
`Intellectual Property Group
`
`4
`
`

`

`1001 Pennsylvania Avenue, N.W.
`Washington, DC 20004-2595
`Telephone No.: (202) 624-2620
`Facsimile No.: (202) 628-5116
`TRea@Crowell.com
`
`1001 Pennsylvania Avenue, N.W.
`Washington, DC 20004-2595
`Telephone No.: (202) 624-2947
`Facsimile No.: (202) 628-5116
`DYellin@Crowell.com
`
`Shannon M. Lentz (Reg. No. 65,382)
`CROWELL & MORING LLP
`Intellectual Property Group
`1001 Pennsylvania Avenue, N.W.
`Washington, DC 20004-2595
`Telephone No.: (202) 624-2897
`Facsimile No.: (202) 628-5116
`SLentz@Crowell.com
`
`
`
`Please direct all correspondence to lead and back-up counsel at the contact
`
`information above. Petitioner also consents
`
`to
`
`service by email at:
`
`TRea@Crowell.com, DYellin@Crowell.com, and SLentz@Crowell.com.
`
`III. PAYMENT UNDER 37 C.F.R. § 42.15(a) AND § 42.103
`The required fees are submitted herewith. The undersigned representative of
`
`Petitioner hereby authorizes the Patent Office to charge any additional fees or credit
`
`any overpayment to Deposit Account No. 05-1323 (Customer ID No. 23911).
`
`IV. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a))
`Petitioner certifies that the ‘572 patent—which issued on February 22, 2022—
`
`is available for IPR and that Petitioner is not barred or estopped from requesting an
`
`IPR challenging any claim thereof on the grounds identified herein. Neither
`
`Petitioner nor any other real party-in-interest has filed a civil action challenging the
`
`5
`
`

`

`validity, or been served with a complaint alleging infringement, of the ‘572 patent,
`
`more than one year prior to the filing of this Petition. See Motorola Mobility LLC v.
`
`Arnouse, No. IPR2013-00010, 2013 WL 12349001, *3 (P.T.A.B. Jan. 30, 2013).
`
`V. THE BOARD SHOULD NOT EXERCISE ITS DISCRETION TO
`DENY INSTITUTION
`The Board should not exercise its discretion to deny institution based on the
`
`mere citation by the Applicant of certain references used in this Petition in
`
`Information Disclosure Statements (“IDS”). The examiner’s failure to address any
`
`of the references used in this Petition on the merits favors institution.
`
`To apply §325(d), the Board uses the following two-part framework: “(1)
`
`whether the same or substantially the same art previously was presented to the Office
`
`or whether the same or substantially the same arguments previously were presented
`
`to the Office; and (2) if either condition of first part of the framework is satisfied,
`
`whether the petitioner has demonstrated that the Office erred in a manner material
`
`to the patentability of the challenged claims.” Advanced Bionics, LLC v. Med-El
`
`Elektromedizinische Gerate GmbH, IPR2019-01469, Paper 6 at 8 (PTAB Feb. 13,
`
`2020). “An example of material error may include misapprehending or overlooking
`
`specific teachings of the relevant prior art where those teachings impact patentability
`
`of the challenged claims.” Id. at 8 n.9. In applying this two-part framework, the
`
`Board has identified several nonexclusive factors that may be considered (“the
`
`6
`
`

`

`Becton factors”). Becton, Dickinson & Co. v. B. Braun Melsungen AG, IPR2017-
`
`01586, Paper 8 at 17-18 (PTAB Dec. 15, 2017). Factors (a), (b), and (d) correspond
`
`to the first part of the framework, and factors (c), (e), and (f) fall within part two of
`
`the framework. Advanced Bionics, at 8-10.
`
`Dixon, Regeneron (8-May-2008), NCT-795, and NCT-377, used in this
`
`Petition as anticipatory references, are merely a few of the hundreds of references
`
`submitted to the Patent Office in various Information Disclosure Statements during
`
`the very short prosecution. Although the examiner acknowledged the IDSs, there is
`
`no evidence that he substantively considered the references relied upon herein. In
`
`fact, the Examiner did not present any rejections based on prior art in the one and
`
`only Office Action, instead only presenting double patenting rejections over several
`
`patents in the same family.
`
`The Board “has consistently declined exercising its discretion under Section
`
`325(d) when the only fact a Patent Owner can point to is that a reference was
`
`disclosed to the Examiner during the prosecution.” Amgen Inc. v. Alexion Pharm.,
`
`Inc., IPR2019-00740, Paper 15 at 65 (PTAB Aug. 30, 2019); Amneal Pharms. LLC
`
`v. Alkermes Pharma Ireland Ltd., IPR2018-00943, slip op. at 40 (PTAB Nov. 7,
`
`2018) (Paper 8) (declining to deny institution based on § 325(d) where reference was
`
`listed on the face of the patent, but patent owner provided no evidence “about the
`
`extent to which the [e]xaminer evaluated” the reference during prosecution); Digital
`
`7
`
`

`

`Check Corp. d/b/a ST Imaging v. E-Imagedata Corp., IPR2017-00178, slip op. at
`
`12-13 (PTAB Apr. 25, 2017) (Paper 6) (granting institution even though a prior art
`
`reference was cited in an IDS because there was no indication that the claims were
`
`substantively discussed by the examiner during prosecution); Fox Factory, Inc. v.
`
`SRAM, LLC, IPR2016-01876, slip op. at 7-9 (PTAB Apr. 3, 2017) (Paper 8)
`
`(refusing to deny institution based on § 325(d) when a prior art reference was cited
`
`in an IDS but was not considered by the examiner at any length). This pattern is
`
`particularly consistent where, as here, a relevant reference is merely cited in an IDS
`
`but not applied by the Examiner in making a rejection. See Apotex, Inc. v. UCB
`
`Biopharma, SPRL, IPR2019-00400, Paper 17 at 24-25 (PTAB July 15, 2019).
`
`Petitioner does not contend that Dixon, Regeneron (8-May-2008), NCT-795,
`
`and NCT-377 were not presented to the Office. Thus, the relevant analysis here
`
`relates to part two of the Advanced Bionics framework. Part two of the Advanced
`
`Bionics framework considers whether the petitioner has demonstrated that the Office
`
`erred in a manner material to the patentability of the challenged claims. Advanced
`
`Bionics, at 8. As Advanced Bionics explains, considering Becton factors (c), (e), and
`
`(f) can provide guidance as to whether the Office erred. Roku, Inc. v. Universal
`
`Elecs., Inc., IPR2019-01619, Paper 11 at 12 (PTAB Apr. 2, 2020). As explained
`
`below, each of these factors demonstrate the material error by the Office.
`
`8
`
`

`

`Regarding factor (c), there is no evidence that Dixon, Regeneron (8-May-
`
`2008), NCT-795, or NCT-377 were evaluated at all during examination, and it is
`
`indisputable that they were never the basis for a rejection. There is no discussion of
`
`any of these references in the one Office Action in the ’572 patent’s prosecution
`
`history. This factor therefore weighs strongly against exercising § 325(d) discretion.
`
`See Hyperbranch Med. Tech., Inc. v. Confluent Surgical, Inc., IPR2018-01097,
`
`Paper 14 at 24 (PTAB Nov. 14, 2018) (Prior art “simply being of record, but not
`
`applied in any rejection by the Examiner during examination…, provides little
`
`impetus for [the Board] to exercise [its] discretion to deny institution under §
`
`325(d)”); Mylan Pharm. Inc. v. Merck Sharp & Dohme Corp., IPR2020-00040,
`
`Paper 21 at 18 (PTAB May 12, 2020) (finding material error where “[t]he Examiner
`
`never discussed [asserted prior art cited in IDS] or made a rejection based on it”).
`
`Regarding factors (e) and (f), as demonstrated herein, the asserted references
`
`anticipate all but four of the Challenged Claims, and these references, in combination
`
`with a reference that was not before the Office during prosecution (Hecht) renders
`
`obvious the remaining Challenged Claims. Thus, Petitioner has demonstrated that
`
`the Examiner’s failure to consider Dixon, Regeneron (8-May-2008), NCT-795, or
`
`NCT-377 and the disclosures relied on in this Petition constitutes material error. The
`
`Amgen case cited above is highly instructive in this regard. The Board held that the
`
`failure of the examiner to apply prior art that served as the primary reference in an
`
`9
`
`

`

`IPR can itself constitute material error. Amgen, IPR2019-00740, Paper 15 at 65.
`
`And, in arriving at that holding, the Board credited five other proceedings where the
`
`Board declined to exercise its discretion under § 325(d) when a reference was
`
`previously disclosed, but never substantively considered by the Examiner. Amneal
`
`Pharms., IPR2018-00943, Paper 8 at 40; Digital Check, IPR2017-00178, Paper 6 at
`
`12–13; Fox Factory, IPR2016-01876, Paper 8 at 7–9; HyperBranch Med. Tech.,
`
`IPR2018-01097, Paper 14 at 17; Praxair Distrib., Inc. v. INO Therapeutics LLC, No.
`
`IPR2015-00893, Paper 14 at 8 (PTAB Sept. 22, 2015).
`
`Furthermore, the Board has consistently held that under these circumstances,
`
`the question of whether an Examiner materially erred under Becton factor (e) cannot
`
`be answered without evaluating whether the prior art challenge presented in the
`
`Petition demonstrates a likelihood of success on the merits. These cases find material
`
`error consistent with factor (e) when such a likelihood has been demonstrated. See
`
`e.g, Skechers U.S.A., Inc. v. Nike, Inc., Paper 10 at 19-20 (PTAB May 19, 2021)
`
`(petitioner demonstrated material error by demonstrating a “reasonable likelihood of
`
`prevailing” in its anticipation argument regarding a reference cited in an IDS but not
`
`substantively considered by the Examiner); HTC Corp. v. Motiva Patents, LLC,
`
`IPR2019-01666, Paper 9 at 10 (PTAB Apr. 3, 2020) (petitioner demonstrated a
`
`material error under the second part of the Advanced Bionics framework when two
`
`references cited in an IDS but not substantively considered by the Examiner during
`
`10
`
`

`

`prosecution disclosed all the limitations of the claims). The Board has already
`
`preliminarily evaluated whether Dixon, Regeneron (8-May-2008), NCT-795, and
`
`NCT-377 teach the dosage regimen claimed in the ‘572 patent (as it’s the same
`
`dosage regimen claimed in the ‘338 patent), and found in the affirmative. See
`
`IPR2021-00881, Paper 21, Institution Decision at 28, 32 (November 10, 2021)
`
`(granting institution on claims covering the same dosage regimen based on grounds
`
`using the same prior art).
`
`Accordingly, in view of the material error by the Examiner, the Board should
`
`not exercise its discretion to deny institution.
`
`VI. THRESHOLD REQUIREMENT FOR INTER PARTES REVIEW
`This Petition meets and exceeds the threshold required under 35 U.S.C. §
`
`314(a). For each ground, there is a reasonable likelihood that Petitioner will prevail
`
`with respect to at least one of the Challenged Claims.
`
`VII. OVERVIEW OF CHALLENGE AND PRECISE RELIEF
`REQUESTED
`A. CHALLENGED CLAIMS
`Petitioner requests IPR of claims 1-14 and 26-30 of the ’572 patent, and
`
`cancellation of these claims as unpatentable.
`
`11
`
`

`

`B.
`STATUTORY GROUNDS OF CHALLENGE
`Each of the following prior art references anticipate claims 1-5, 8-11, 14, and
`
`26-30:
`
`Ground
`
`Claims
`
`Proposed Rejections Under
`35 U.S.C. § 102
`
`1
`2
`3
`4
`
`1-5, 8-11, 14, and 26-30 Dixon
`
`1-5, 8-11, 14, and 26-30
`
`Regeneron (8-May-2008)
`
`1-5, 8-11, 14, and 26-30 NCT-795
`
`1-5, 8-11, 14, and 26-30 NCT-377
`
`
`In addition, at least the following render the claims 6, 7, 12, and 13 obvious:
`
`Ground
`
`5
`
`Claims
`
`Proposed Rejections Under 35 U.S.C.
`§ 103
`6, 7, 12, and 13 Dixon or Regeneron (8-May-2008) or
`NCT-795 or NCT-377 in view of Hecht
`
`
`
`Petitioner’s full statement of reasons for the relief requested is set forth in
`
`greater detail