UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner
`
`____________
`
`Case IPR2021-00881
`Patent No. 9,254,338 B2
`____________
`
`PRELIMINARY RESPONSE OF PATENT OWNER
`REGENERON PHARMACEUTICALS, INC.
`
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`TABLE OF CONTENTS
`
`Page No.
`
`I.
`II.
`
`III.
`
`IV.
`
`B.
`
`INTRODUCTION ........................................................................................... 1
`THE PETITION SHOULD BE REJECTED FOR
`CIRCUMVENTING THE WORD LIMIT AND OBFUSCATING
`ITS GROUNDS ............................................................................................... 4
`A.
`The Petition Violates the Word Limit ................................................... 4
`B.
`The Petition Fails the Particularity Requirement .................................. 5
`C.
`Janssen Pharmaceuticals, Inc. Is a Real Party-in-Interest ..................... 8
`THE BOARD SHOULD DENY INSTITUTION UNDER
`35 U.S.C. § 325(d) .......................................................................................... 9
`A.
`Petitioner Mischaracterizes the Prosecution History of the ’338
`Patent and its Foreign Counterpart ........................................................ 9
`Because the Examiner Considered Substantially the Same Art and
`Petitioner Does Not Allege Any Error, Institution Should Be
`Denied.................................................................................................. 11
`1.
`The Examiner Considered Substantially the Same Art
`(Becton, Dickinson Factors (a), (b), and (d)) ............................ 11
`a.
`Grounds 1-5 .................................................................... 12
`b.
`Ground 6 ......................................................................... 14
`Petitioner Fails to Argue that the Examiner Erred in a
`Manner Material to Patentability (Becton, Dickinson
`Factors (c), (e), and (f)) ............................................................. 16
`THE BOARD SHOULD DENY INSTITUTION BECAUSE
`PETITIONER FAILS TO MAKE ITS THRESHOLD SHOWING
`THAT AT LEAST ONE CHALLENGED CLAIM IS
`UNPATENTABLE ........................................................................................ 17
`
`2.
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`A.
`
`B.
`
`C.
`
`D.
`
`b.
`
`2.
`
`Grounds 1, 3-5: Petitioner Fails to Demonstrate that “VEGF
`Trap-Eye” Was Known in the Art to Correspond to SEQ ID NO:
`2 or SEQ ID NO:1 ............................................................................... 18
`1.
`Petitioner Fails to Establish that “VEGF Trap-Eye” Was
`Known in the Art to Comprise SEQ ID NO: 2 (Claims 1, 3-
`11, and 13) ................................................................................. 18
`a.
`Petitioner and Its Expert Repeatedly Equate
`“Aflibercept” with All Variations of “VEGF Trap” ...... 21
`Petitioner Fails to Address Uncertainty in the Art as
`to the Amino Acid Sequence of “VEGF Trap-Eye” ..... 24
`Petitioner Fails to Establish that “VEGF Trap-Eye” Was
`Known in the Art to Be Encoded by SEQ ID NO:1 ................. 26
`Ground 2: Petitioner Fails to Demonstrate that There Is a
`Reasonable Likelihood that at Least One of the Challenged Clams
`Is Anticipated by Adis ......................................................................... 28
`Grounds 1-5: Petitioner Fails to Establish Any of Its References
`Disclose a “Method of Treating” and “Tertiary Dose” ....................... 30
`1.
`Claim Construction ................................................................... 31
`a.
`The Preamble of the Independent Claims Is a
`Limitation of the Claim .................................................. 32
`The Preamble Reflects the Efficacy Required by the
`Body of the Claim ........................................................... 36
`The “Tertiary Dose” Must Maintain the Efficacy
`Gain Achieved After the Initial and Secondary Doses... 38
`Petitioner’s References Fail To Disclose A “Method Of
`Treating” Or A “Tertiary Dose” ............................................... 46
`Ground 6: Petitioner Fails to Make a Threshold Showing that
`Any Challenged Claim Is Obvious Based on Dixon ........................... 49
`
`b.
`
`c.
`
`2.
`
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`1.
`
`Petitioner Fails to Show that the POSA Would Have Had a
`Reasonable Expectation of Success .......................................... 50
`Petitioner’s Argument Against Objective Evidence Should
`Be Rejected ............................................................................... 57
`CONCLUSION .............................................................................................. 62
`
`2.
`
`V.
`
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`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Abraxis Bioscience, Inc. v. Mayne Pharma (USA) Inc.,
`467 F.3d 1370 (Fed. Cir. 2006) ............................................................................39
`ABS Global, Inc. v. Cytonome/ST, LLC,
`IPR2021-00306, Paper 13 (Jun. 7, 2021) .............................................................16
`Adaptics Ltd. v. Perfect Co.,
`IPR2018-01596, Paper 20 (Mar. 6, 2019) ..........................................................5, 6
`Advanced Bionics, LLC v. MED-EL Elektromedizinische Gerate GmbH,
`IPR2019-01469, 2020 WL 740292 (Feb. 13, 2020) ..................................... 11, 16
`Amgen, Inc. v. Alexion Pharms., Inc.,
`IPR2019-00739, Paper 15 (Aug. 30, 2019) ..........................................................28
`Apple, Inc. v. ITC,
`725 F.3d 1356 (Fed. Cir. 2013) ............................................................................57
`Arthrex, Inc. v. Smith & Nephew, Inc.,
`935 F.3d 1319 (Fed. Cir. 2019), cert. denied, 141 S. Ct. 236 (2020) ..................47
`Baldwin Graphic Sys., Inc. v. Siebert, Inc.,
`512 F.3d 1338 (Fed. Cir. 2008) ............................................................................35
`Baxalta Inc. v. Genentech, Inc.,
`972 F.3d 1341 (Fed. Cir. 2020) ............................................................................42
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper 8 (Dec. 15, 2017) ............................................................11
`Bettcher Indus., Inc. v. Bunzl USA, Inc.,
`661 F.3d 629 (Fed. Cir. 2011) ..............................................................................47
`Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp.,
`320 F.3d 1339 (Fed. Cir. 2003) ............................................................................34
`Boragen, Inc. v. Syngenta Participations AG,
`IPR2020-00124, 2020 WL 2206972 (May 5, 2020) ............................................15
`Bristol-Myers Squibb Co. v. Ben Venue Lab’ys, Inc.,
`246 F.3d 1368 (Fed. Cir. 2001) ..................................................................... 43, 44
`
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`

`C.R. Bard, Inc. v. U.S. Surgical Corp.,
`388 F.3d 858 (Fed. Cir. 2004) ..............................................................................33
`Continental Can Co. USA v. Monsanto Co.,
`948 F.2d 1264 (Fed. Cir. 1991) ............................................................................21
`Dynatemp Int’l, Inc. v. R 421A LLC d/b/a Choice Refrigerants,
`IPR2020-01660, Paper 15 (Apr. 20, 2021) ..........................................................17
`E.I. Du Pont de Nemours & Co. v. Monsanto Tech. LLC,
`IPR2014-00333, 2014 WL 3507803 (July 11, 2014) ...........................................34
`Eon-Net LP v. Flagstar Bancorp,
`653 F.3d 1314 (Fed. Cir. 2011) ............................................................................33
`Forest Lab’ys, LLC v. Sigmapharm Lab’ys, LLC,
`918 F.3d 928 (Fed. Cir. 2019) ..............................................................................33
`Gardner Denver, Inc. v. Utex Indus., Inc.,
`IPR2020-00333, 2020 WL 4529832 (Aug. 5, 2020) ............................................13
`Gilead Scis, Inc. v. United States,
`IPR2019-01455, Paper 16 (Feb. 5, 2020) .......................................... 35, 37, 44, 48
`Griffin v. Bertina,
`285 F.3d 1029 (Fed. Cir. 2002) ............................................................................32
`Hill-Rom Co. v. Kinetic Concepts, Inc.,
`209 F.3d 1337 (Fed. Cir. 2000) ............................................................................34
`In Re: Copaxone Consol. Cases,
`906 F.3d 1013 (Fed. Cir. 2018) ............................................................................44
`Insite Vision Inc. v. Sandoz, Inc.,
`783 F.3d 853 (Fed. Cir. 2015) ..............................................................................51
`Irdeto Access, Inc. v. Echostar Satellite Corp.,
`383 F.3d 1295 (Fed. Cir. 2004) ............................................................................38
`Janssen Pharms., Inc. v. Watson Lab’ys, Inc.,
`C.A. No. 08-5103(SRC), 2012 WL 3990221 (D.N.J. Sept. 11, 2012) ................29
`King Pharms. Inc. v. Eon Labs, Inc.,
`616 F.3d 1267 (Fed. Cir. 2010) ............................................................................18
`Medicines Company v. Mylan, Inc.,
`853 F.3d 1296 (Fed. Cir. 2017) ..................................................................... 41, 42
`
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`Mylan Lab’ys Ltd. v. Aventis Pharma S.A.,
`No. IPR2016-00712, Paper 112 (P.T.A.B. Sept. 22, 2016) .................................44
`MyMail, Ltd. v. Am. Online, Inc.,
`476 F.3d 1372 (Fed. Cir. 2007) ............................................................................38
`Net MoneyIN, Inc. v. VeriSign, Inc.,
`545 F.3d 1359 (Fed. Cir. 2008) ............................................................................28
`Nidec Motor Corp. v. Zhongshan Broad Ocean Motor Co.,
`868 F.3d 1013 (Fed. Cir. 2017) ............................................................................32
`NXP USA, Inc. v. Impinj, Inc.,
`IPR2020-00519, 2020 WL 4805424 (Aug. 17, 2020) ............................. 13, 14, 15
`OSI Pharms. LLC v. Apotex Inc.,
`939 F.3d 1375 (Fed. Cir. 2019) ............................................................................52
`Otsuka Pharm. Co. v. Sandoz, Inc.,
`678 F.3d 1280 (Fed. Cir. 2012) ............................................................................51
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) ............................................................................38
`Pi-Net Int’l, Inc. v. JPMorgan Chase & Co.,
`600 F. App’x 774 (Fed. Cir. 2015) ......................................................................... 5
`Pitney Bowes, Inc. v. Hewlett-Packard Co.,
`182 F.3d 1298 (Fed. Cir. 1999) ............................................................................37
`Rapoport v. Dement,
`254 F.3d 1053 (Fed. Cir. 2001) ............................................................................35
`Regents of Univ. of Minn. v. AGA Med. Corp.,
`717 F. 3d 929 (Fed. Cir. 2013) .............................................................................33
`Sanofi Mature IP v. Mylan Lab’ys Ltd.,
`757 F. App’x 988 (Fed. Cir. 2019) .......................................................................35
`Schering Corp. v. Amgen Inc.,
`222 F.3d 1347 (Fed. Cir. 2000) ............................................................................24
`Sensonics, Inc. v. Aerosonic Corp.,
`81 F.3d 1566 (Fed. Cir. 1996) ..............................................................................51
`Sony Interactive Ent. LLC v. Terminal Reality, Inc.,
`IPR2020-00711, 2020 WL 6065188 (Oct. 13, 2020) ...........................................17
`
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`Transclean Corp. v. Bridgewood Servs., Inc.,
`290 F.3d 1364 (Fed.Cir.2002) ..............................................................................48
`UltimatePointer, L.L.C. v. Nintendo Co.,
`816 F.3d 816 (Fed. Cir. 2016) ..............................................................................34
`Statutes
`35 U.S.C. § 312(A)(3) ....................................................................................... 2, 5, 6
`35 U.S.C. § 314(a) .......................................................................................... 3, 8, 17
`35 U.S.C. §§ 325(d) .................................................................................. 3, 9, 11, 17
`Other Authorities
`77 Fed. Reg. 48756 (August 14, 2012) ...................................................................... 6
`77 Fed. Reg. 48763 (August 14, 2012) ..................................................................6, 7
`MPEP § 2173.05(e) ..................................................................................................39
`Regulations
`37 C.F.R. § 42.24(a)(1)(i)) ......................................................................................... 4
`
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`TABLE OF EXHIBITS
`
`2008
`
`Description
`Ex. No.
`Expert Declaration of Dr. Diana V. Do, M.D.
`2001
`Curriculum Vitae of Dr. Diana Do
`2002
`Lucentis (ranibzumab injection) label, revised June 2010
`2003
`2004 Ex. (a)(1)(a) to Tender Offer Statement to Momenta, filed with SEC on
`September 2, 2020
`2005 Press Release, Johnson & Johnson, Johnson & Johnson to Acquire
`Momenta Pharmaceuticals, Inc., Expanding Janssen’s Leadership in
`Novel Treatments for Autoimmune Diseases, dated August 19, 2020
`2006 Press Release, Johnson & Johnson, Johnson & Johnson Completes
`Acquisition of Momenta Pharmaceuticals, Inc, dated October 1, 2020
`2007 Press Release, THOMAS REUTERS INTEGRITY “VEGF Trap-Eye
`final phase II results in age-related macular degeneration presented at
`2008 Retina Society Meeting” (September 2008)
`Information from ClinicalTrials.gov archive on the VIEW 2 study
`(NCT00637377) “VEGF Trap-Eye: Investigation of Efficacy and Safety
`in Wet AMD (VIEW 2)” versions available and updated on 17 March
`2008.
`2009 U.S. Patent App. No. 2006/0058234
`2010
`Excerpts from J.M. Berg et al., Biochemistry (5th Ed. 2002)
`2011 M.W. Stewart & P.J. Rosenfeld, Predicted Biological Activity of
`Intravitreal VEGF Trap¸ Br. J. Opthamol 92:667-68 (2008)
`2012 P. Iacono et al., Antivascular Endothelial Growth Factor in Diabetic
`Retinopathy, Dev. Opthamol. 46:39-53 (2010)
`2013 D.V. Do et al., An Exploratory Study of the Safety, Tolerability and
`Bioactivity of a Single Intravitreal Injection of Vascular Endothelial
`Growth Factor Trap-Eye in Patients With Diabetic Macular Oedema,
`Br. J. Opthamol 93:144-49 (2009)
`J.W. Moroney et al., Aflibercept in Epithelial Ovarian Carcinoma,
`Future Oncol 5(5):591-600 (2009)
`2015 U.S. Patent Publication 2010/0160233 A1 to Bissery et al., published
`June 24, 2010
`2016 T. Hachiya et al., Increase in respiratory cost at high growth
`temperature is attributed to high protein turnover cost in Petunia x
`hybrida petals, Plant, Cell, and Environment, 30:1269-1283 (2007)
`
`2014
`
`v
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`

`2018
`
`2017 M. Piques et al., Ribosome and transcript copy numbers, polysome
`occupancy and enzyme dynamics in Arabidoposis, Molecular Systems
`Biology 5: Article number 314 (2009)
`Jaffe et al., Differential Response to Anti-VEGF Regimens in Age-
`Related Macular Degeneration Patients with Early Persistent Retinal
`Fluid, Ophthalmology 2016;123:1856-1864 (2016)
`Eylea (aflibercept) Injection label, revised May 2016
`2019
`2020 A Study Investigating the Safety and Efficacy of Lampalizumab
`Intravitreal Injections in Participants With Geographic Atrophy
`Secondary to Age-Related Macular Degeneration (SPECTRI),
`NCT02247531, ClinicalTrials.gov (August 2, 2021),
`https://clinicaltrials.gov/ct2/show/NCT02247531?term=lampalizumab&
`phase=2&draw=2&rank=2
`2021 A Study Investigating the Efficacy and Safety of Lampalizumab
`Intravitreal Injections in Participants With Geographic Atrophy
`Secondary to Age-Related Macular Degeneration (CHROMA),
`NCT02247479, ClinicalTrials.gov (August 2, 2021),
`https://clinicaltrials.gov/ct2/show/NCT02247479?term=lampalizumab&
`phase=2&draw=2&rank=3
`2022 Efficacy and Safety Trial of Conbercept Intravitreal Injection for
`Neovascular AMD(PANDA-2), NCT03630952, ClinicalTrials.gov
`(August 2, 2021),
`https://clinicaltrials.gov/ct2/show/NCT03630952?term=NCT03630952
`&draw=2&rank=1
`2023 Efficacy and Safety Trial of Conbercept Intravitreal Injection for
`Neovascular AMD(PANDA-1), NCT03577899, ClinicalTrials.gov
`(August 2, 2021),
`https://clinicaltrials.gov/ct2/show/NCT03577899?term=NCT03577899
`&draw=2&rank=1
`2024 A Phase 3 Safety and Efficacy Study of Fovista® (E10030)
`Intravitreous Administration in Combination With Lucentis® Compared
`to Lucentis® Monotherapy, NCT01944839, ClinicalTrials.gov (August
`2, 2021),
`https://clinicaltrials.gov/ct2/show/NCT01944839?term=fovista&phase=
`2&draw=2&rank=1
`
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`2025 A Phase 3 Safety and Efficacy Study of Fovista® (E10030)
`Intravitreous Administration in Combination With Lucentis® Compared
`to Lucentis® Monotherapy, ClinicalTrials.gov (August 2, 2021),
`https://clinicaltrials.gov/ct2/show/NCT01940900?term=fovista&phase=
`2&draw=2&rank=2
`2026 S. Elvidge, Opthotech’s Fovista crashes out in wet AMD,
`BIOPHARMADIVE (Aug. 14, 2017), available at,
`https://www.biopharmadive.com/news/opthotech-fovista-phase-3-
`failure-setback-novartis/449248/
`2027 X. Li et al., Safety and Efficacy of Conbercept in Neovascular Age-
`Related Macular Degeneration: Results from a 12-Month Randomized
`Phase 2 Study: AURORA Study, Ophthalmology 2014:121:1740-1747
`(2014)
`2028 Regeneron Pharmaceuticals Inc., “VEGF Trap-Eye CLEAR-IT 2 Final
`Primary Endpoint Results” presented at the 2007 Retina Society
`Conference in Boston, Massachusetts (September 30, 2007)
`2029 Bhisitkul, Robert B. and Stewart, Jay M., Alternative anti-VEGF
`treatment regimens in exudative age-related macular degeneration,
`Expert Rev. Ophthalmol., Vol. 5, No. 6 (2010).
`2030 Park, Young Gun et al., New Approach to Anti-VEGF Agents for Age-
`Related Macular Degeneration, Journal of Ophthalmology (2012).
`2031 Spaide, Richard, Ranibizumab According to Need: A Treatment for Age-
`related Macular Degeneration, American Journal of Ophthalmology
`(April 2007)
`2032 Boyer, David S., A Phase IIIb Study to Evaluate the Safety of
`Ranibizumab in Subjects with Neovascular Age-related Macular
`Degeneration, Ophthalmology, Vol. 116, No. 9 (Sept. 2009)
`Lucentis (ranibzumab injection) label, revised March 2018
`2033
`2034 U.S. Patent No. 7,303,746
`2035 U.S. Patent No. 7,521,049
`2036 U.S. Patent No. 7,303,747
`2037 U.S. Patent No. 7,306,799
`2038 Macugen (pegaptanib sodium injection) label submitted with NDA 21-
`756
`2039 Press Release, Regeneron, Regeneron Reports Fourth Quarter and Full
`Year 2012 Financial and Operating Results, dated February 14, 2013
`2040 Press Release, Regeneron, Regeneron Reports Fourth Quarter and Full
`Year 2019 Financial and Operating Results, dated February 6, 2030
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`2041 Press Release, Regeneron, 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),
`dated December 20, 2010
`J.P. Levine et al., Macular Hemorrhage in Neovascular Age-related
`Macular Degeneration After Stabilization With Antiangiogenic Therapy,
`Retina 29(8):1074-79 (2009)
`
`2042
`
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`Regeneron Pharmaceuticals, Inc. (“Patent Owner” or “Regeneron”) submits
`
`this preliminary response pursuant to 35 U.S.C. § 313 and 37 C.F.R. § 42.107 to
`
`Mylan Pharmaceuticals Inc.’s (“Petitioner’s” or “MPI’s”) request for inter partes
`
`review (“IPR”) of claims 1, 3-11, 13-14, 16-24 and 26 (“the Challenged Claims”)
`
`of U.S. Patent No. 9,254,338 (“the ’338 Patent,” Ex. 1001).
`
`I.
`
`INTRODUCTION
`Petitioner is developing a biosimilar of EYLEA® and files this challenge to
`
`invalidate Regeneron’s ’338 Patent, which covers the FDA-recommended dosing
`
`regimen for EYLEA®. Petitioner’s challenge relies entirely on references
`
`disclosing the design of Regeneron’s Phase 3 trials. But Petitioner fundamentally
`
`ignores that there existed great uncertainty as to whether an extended, fixed dosing
`
`regimen (Q8) would work until Regeneron’s Phase 3 clinical trial results showed
`
`that it could. Petitioner also ignores that this same prospective dosing regimen
`
`was before the Examiner during prosecution of the ’338 Patent.
`
`Before EYLEA®, the standard of care for treating angiogenic eye disorders
`
`was monthly intravitreal injections of ranibizumab (Lucentis®), an antibody
`
`fragment that binds Vascular Endothelial Growth Factor (“VEGF”), or monthly
`
`off-label use of bevacizumab (Avastin®), an anti-VEGF antibody. The great
`
`burden of monthly intravitreal injections led to several attempts to decrease the
`
`frequency of injections and physician monitoring. Ex. 1018, 1, and 9-10.
`
`However, existing VEGF inhibitors were ineffective at maintaining vision when
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`dosed on a fixed quarterly basis or on an “as-needed” (pro re nata) basis without
`
`monthly monitoring visits. Ex. 1018, 10; Ex. 1001, 1:55-59; Ex. 2003, 5. Indeed,
`
`before the results of Regeneron’s pivotal Phase 3 trials, no one had demonstrated
`
`that a longer-than-monthly fixed dosing regimen (e.g., eight weeks or longer)
`
`could maintain, let alone improve, vision.
`
`Regeneron’s Phase 3 clinical trial results surprisingly demonstrated that
`
`“remarkably similar improvement in vision and anatomic measures can be
`
`achieved” with less frequent EYLEA® dosing as compared to monthly
`
`ranibizumab injections. Ex. 1018, 10. Having secured the data necessary to
`
`support the eight-week extended dosing regimen of the instant claims, Regeneron
`
`obtained FDA approval for EYLEA® and was awarded the ’338 Patent covering
`
`its recommended dosing regimen. EYLEA®’s duration and ability to extend the
`
`time between injections has made it a life-changing drug and revolutionized the
`
`treatment of angiogenic eye disorders. Given the long-felt need and repeated
`
`failures of others to reduce treatment burden and injection frequency, EYLEA®
`
`has enjoyed great commercial success.
`
`The Petition should be denied for at least the following reasons:
`
`First, Petitioner flouts the Board’s rules by circumventing word count limits
`
`and also by disregarding the particularity requirement of 35 U.S.C. § 312(A)(3),
`
`presenting “catch-all” obviousness arguments that do not differentiate between
`
`seven references and fifteen obviousness theories.
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`Second, Petitioner’s challenges rely on substantially the same art that was
`
`previously before the U.S. Patent & Trademark Office (“Office”) and considered
`
`by the Examiner, yet Petitioner does not allege that the Examiner erred in a
`
`manner material to the patentability of the Challenged Claims, warranting
`
`discretionary denial under 35 U.S.C. §§ 325(d) and 314(a).
`
`Third, Petitioner fails to demonstrate that its cited references expressly or
`
`inherently disclose the amino acid or nucleic acid sequence limitations of the
`
`Challenged Claims. Petitioner argues that its cited art inherently discloses
`
`aflibercept and its amino acid and nucleic acid sequences through reference to
`
`“VEGF Trap-Eye.” But Petitioner relies on inference to connect “VEGF Trap-
`
`Eye” and “aflibercept” that the prior art does not support, and the Federal Circuit
`
`has repeatedly held that probabilities are insufficient for anticipation.
`
`Fourth, Petitioner’s anticipation challenges also rely on an erroneous claim
`
`construction that seeks to eliminate the efficacy requirements of the Challenged
`
`Claims and Petitioner never shows that the “method of treating” and “tertiary
`
`dose” limitations, which require efficacy, are disclosed either expressly or
`
`inherently in its cited references.
`
`Fifth, Petitioner relies on Regeneron’s Phase 2 clinical trial results for its
`
`obviousness challenge. But that trial tested a different dosing regimen from that
`
`claimed in the ‘338 Patent and failed to provide the skilled artisan with any
`
`expectation of success — let alone a reasonable one — in practicing the claimed
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`

`inventions. In fact, those clinical trial results showed just the opposite —that it
`
`was not expected that VEGF Trap-Eye would be effective if dosed at eight-week
`
`intervals. Petitioner also ignores that before the priority date, no one, including
`
`Regeneron, had ever shown that a fixed eight-week (or longer) dosing regimen
`
`could maintain, let alone improve, vision.
`
`II.
`
`THE PETITION SHOULD BE REJECTED FOR
`CIRCUMVENTING THE WORD LIMIT AND OBFUSCATING
`ITS GROUNDS
`A.
`The Petition Violates the Word Limit
`The Petition exceeds the 14,000-word limit (37 C.F.R. § 42.24(a)(1)(i)).
`
`Despite certifying that the word count for its petition is 13,904 words (Pet., Cert.
`
`of Compliance), the Petition’s word count includes only the typed words of the
`
`Petition. The word count ignores words in images of text from the ’338 Patent
`
`specification, including a lengthy passage of text on which Petitioner
`
`substantively relies for its arguments. See e.g., Pet., 12; see also Pet., 9, 29. In
`
`total, Petitioner fails to account for 224 words in text images in the Petition which,
`
`when included, results in a word count of 14,128 words. Petitioner, thus,
`
`disregards the Board’s rules, as evidenced by Petitioner’s use of the same tactic in
`
`its Petition filed in IPR2021-00880. Paper 1. This is a reason to deny institution.
`
`Trial Practice Guide (November 2019) at 40 (“Excessive words in figures,
`
`drawings, or images, deleting spacing between words, or using excessive
`
`acronyms or abbreviations for word phrases, in order to circumvent the rules on
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`4
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`word count, may lead to a party’s brief not being considered.”); see Pi-Net Int’l,
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`Inc. v. JPMorgan Chase & Co., 600 F. App’x 774 (Fed. Cir. 2015) (denying
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`request to file a corrected brief and dismissing appeal because appellant violated
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`word count).
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`The proper remedy here is to deny institution, thereby allowing Petitioner to
`
`refile a petition that properly conforms with the Board’s word count rules. No
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`time bar precludes Petitioner from refiling a petition challenging the ’338 Patent.
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`The Petition Fails the Particularity Requirement
`B.
`Despite exceeding the allowed word count, Petitioner still has not managed
`
`to state, with particularity, the grounds on which the challenge to each claim is
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`based. Accordingly, the Petition presents an inefficient use of the Board’s time
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`and resources, as well as procedural unfairness to Regeneron.
`
`A petition “may be considered only if . . . the petition identifies, in writing
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`and with particularity, each claim challenged, the grounds on which the challenge
`
`to each claim is based, and the evidence that supports the grounds for the
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`challenge to each claim.” 35 U.S.C. § 312(a)(3); see also Adaptics Ltd. v. Perfect
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`Co., IPR2018-01596, Paper 20 at 15-24 (Mar. 6, 2019) (informative). “[T]he
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`Board may consider whether a lack of particularity as to one or more of the
`
`asserted grounds justifies denial of an entire petition.” Id. at 17. Furthermore, the
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`Office Patent Trial Practice Guide advises practitioners to “focus on concise, well-
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`organized, easy-to-follow arguments supported by readily identifiable evidence of
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`US 169985497v27
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`5
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`record.” 77 Fed. Reg. 48756, 48763 (August 14, 2012).
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`Here, Petitioner does not satisfy the particularity requirements under
`
`§ 312(a)(3) for at least Ground 6 because the Petition suffers from the same
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`deficiencies identified by the Board in Adaptics. Specifically, Ground 6 is a
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`“catch-all” ground that alleges that the Challenged Claims are obvious over seven
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`references under fifteen different theories:
`
`1. Dixon;
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`2. Dixon + the ’758 Patent;
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`3. Dixon + Dix;
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`4. Adis;
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`5. Adis + the ’758 Patent;
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`6. Adis + Dix;
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`7. Regeneron (8-May-2008);
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`8. Regeneron (8-May-2008) + the ’758 Patent;
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`9. Regeneron (8-May-2008) + Dix;
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`10.NCT-795;
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`11.NCT-795 + the ’758 Patent;
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`12.NCT-795 + Dix;
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`13.NCT-377;
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`14.NCT-377 + the ’758 Patent;
`
`6
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`

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`15.NCT-377 + Dix.
`See Pet., 62.
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`Petitioner asserts that five references (Dixon, Adis, Regeneron (8-May-
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`2008), NCT-795, and NCT-377) are interchangeable. Id. at 62 n.12. Petitioner
`
`does not explain why all five are necessary for this obviousness ground, nor how
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`each combination differs from the others. Rather, these five references are cited
`
`for the disclosure of the same alleged feature. This is at odds with the Office’s
`
`direction to “avoid submitting a repository of all the information that a judge
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`could possibly consider,” and inundates the Board with excessive references for
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`its consideration. 77 Fed. Reg. at 48763.
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`Furthermore, Petitioner only addresses Dixon in Ground 6 and relegates the
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`other four primary references and fifteen different obviousness theories to a
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`footnote. Pet., 62 n.12. This leaves the Board and Regeneron to fill in the gaps of
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`the Petition. Regeneron is at an unfair disadvantage of having to guess which
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`theories Petitioner will pursue, what evidence allegedly supports those theories,
`
`and what purported motivations and reasonable expectation of success Petitioner
`
`might advance were trial instituted.
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`As each theory constitutes a distinct ground, Petitioner impermissibly shifts
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`the burden to the Board and Regeneron to understand the multiplicity of
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`obviousness grounds presented. For at least the reasons above, Regeneron
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`respectfully requests denial of the petition under 35 U.S.C. § 314(a).
`
`US 169985497v27
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`7
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`

`Janssen Pharmaceuticals, Inc. Is a Real Party-in-Interest
`C.
`Petitioner also fails to identify the correct RPIs in its Petition. Petitioner
`
`identifies Viatris Inc., Mylan Inc., Mylan Pharmaceuticals Inc., Momenta
`
`Pharmaceuticals, Inc., and Johnson & Johnson as real parties-in-interest to the
`
`instant Petition. Pet., 4. Petitioner states “[n]o other parties exercised or could
`
`have exercised control over this Petition; no other parties funded, directed and
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`controlled this Petition.” Id. However, Regeneron understands from publicly
`
`available documents that Janssen Pharmaceuticals, Inc. (“Janssen”) is a real party-
`
`in-interest for the same reasons Mylan disclosed these other entities. Multiple
`
`Johnson & Johnson press releases and Securities Exchange Commission filings
`
`indicate that Janssen, a pharmaceutical company headquartered in Beerse,
`
`Belgium, and owned by Johnson & Johnson, is managing the business and
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`operations of Momenta, generally, and the acquired Momenta pipeline of clinical
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`and pre-clinical assets, including a biosimilar to EYLEA®. Ex. 2004, 46 (“the
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`business and operations of Momenta will be managed as one of the Janssen
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`Pharmaceuticals Companies of Johnson & Johnson.”); see also Ex. 2005; Ex.
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`2006.
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`While denial of institution is warranted here, if the Board grants institution,
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`it should require Petitioner to file updated mandatory disclosures identifying
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`Janssen as a real party-in-interest.
`
`US 169985497v27
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`8
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`

`III. THE BOARD SHOULD DENY INSTITUTION UNDER
`35 U.S.C. § 325(D)
`The Board should exercise its discretion and deny institution under 35
`
`U.S.C. § 325(d) because Petitioner relies on substantially the same art that was
`
`already considered by the Examiner during prosecution of the ’338 Patent, and
`
`fails to argue that the Examiner made any error material to the patentability of the
`
`Challenged Claims in considering that art.
`
`A.
`
`Petitioner Mischaracterizes the Prosecution History of the ’338
`Patent and its Foreign Counterpart
`Petitioner repeatedly and baselessly attempts to cast doubt on Regeneron’s
`
`candor with the Office. Specifically, Petitioner incorrectly asserts that “none of
`
`the numerous pre-2011 publications disclosing the VIEW1/VIEW2 dosing
`
`regimens . . . were submitted to or cited by the Examiner during prosecution.”
`
`Pet., 27. This is incorrect. To the contrary, Regeneron’s VIEW1/2 dosing
`
`regimens were before the Examiner and considered during prosecution of the ’338
`
`Patent. On October 18, 2013, Regeneron presented a September 28, 2008,
`
`Regeneron Press Release (“9/28/2008 Press Release”) to the Office in an IDS,
`
`which was marked considered by the Examiner. Ex. 1017, 60 and 277. The
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`9/28/2008 Press Release discloses the same VIEW1/2 prospective dosing regimen
`
`that Petitioner relies on in Grounds 1-5 of its Petition. Ex. 2007, 1; see Section
`
`III.B, infra.
`
`In addition, Petitioner asserts that Regeneron never cited art from EP-325
`
`(the European counterpart to the ’338 Patent) to the Examiner of the ’338 Patent
`
`US 1