`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner
`
`____________
`
`Case IPR2022-01225
`Patent No. 10,130,681 B2
`____________
`
`
`
`
`PRELIMINARY RESPONSE OF PATENT OWNER
`REGENERON PHARMACEUTICALS, INC.
`
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`APOTEX V. REGENERON IPR2022-01524
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`TABLE OF CONTENTS
`
`Page No.
`
`I. 
`II. 
`
`2. 
`
`3. 
`
`4. 
`
`B. 
`
`INTRODUCTION ........................................................................................... 1 
`THE BOARD SHOULD DENY INSTITUTION UNDER
`35 U.S.C. §314(A) .......................................................................................... 4 
`A. 
`Institution Should Be Denied under General Plastic ............................ 4 
`1. 
`Petitioner Previously Challenged Substantially Similar
`Claims of a Related Patent Using the Same References
`(General Plastic Factors One and Two) ..................................... 6 
`Petitioner Uses the Prior Proceeding to Roadmap Its
`Arguments (General Plastic Factor Three) ................................ 8 
`Petitioner Fails to Explain Its Delay in Filing (General
`Plastic Factors Four and Five) .................................................. 10 
`Petitioner’s Strategically Delayed Filing Taxes the Finite
`Resources of the Board (General Plastic Factors Six and
`Seven) ........................................................................................ 11 
`Institution Should Be Denied under Fintiv ......................................... 12 
`1. 
`The Court Has Not Granted a Stay, Nor Has One Been
`Requested (Fintiv Factor One) .................................................. 13 
`The Parties Have Invested in Extensive Pre-Litigation
`Activity (Fintiv Factor Three) ................................................... 15 
`The Validity of the ’681 Patent Is Central to Both
`Proceedings (Fintiv Factor Four) .............................................. 16 
`PO and Petitioner Are Parties in Both Proceedings (Fintiv
`Factor Five) ............................................................................... 17 
`Other Circumstances Warrant Discretionary Denial of
`Institution (Fintiv Factor Six) ................................................... 17 
`
`3. 
`
`4. 
`
`5. 
`
`6. 
`
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`C. 
`
`B. 
`C. 
`
`Petitioner’s Attempt to Pass Off a Suspect Exhibit, with No
`Evidence of Public Accessibility, Requires Rejection of at Least
`Ground 5 .............................................................................................. 18 
`III.  CLAIM CONSTRUCTION .......................................................................... 20 
`A. 
`The Challenged Claims Require Efficacy ........................................... 20 
`1. 
`The Preamble Is Limiting and Requires “[T]reating” .............. 21 
`2. 
`“[M]ethod for [T]reating” Requires a High Level of
`Efficacy ..................................................................................... 24 
`a. 
`Treatments for Angiogenic Eye Disorders Were
`Expected to Achieve a High Level of Efficacy by
`2011 ................................................................................ 24 
`The Intrinsic Record Supports a High Level of
`Efficacy ........................................................................... 25 
`The “Initial,” “Secondary,” and “Tertiary Dose” Limitations
`Require Achieving and Maintaining a High Level of
`Efficacy ..................................................................................... 30 
`Petitioner’s Arguments That the Claims Do Not Require
`Efficacy Are Unavailing ........................................................... 33 
`a. 
`“High Level of Efficacy” Does Not Generate §112
`Problems ......................................................................... 33 
`PO’s Construction Does Not Eliminate the Notice
`Function .......................................................................... 36 
`The Challenged Claims Require an Intent to Treat ............................. 36 
`The Recited Exclusion Criteria Are Entitled to Patentable Weight .... 38 
`1. 
`The Printed Matter Doctrine Does Not Apply to the
`Exclusion Criteria ..................................................................... 39 
`a. 
`The Exclusion Criteria Do Not “Claim the Content of
`Information” ................................................................... 41 
`
`3. 
`
`4. 
`
`b. 
`
`b. 
`
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`–ii–
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`b. 
`
`b. 
`
`c. 
`
`b. 
`
`c. 
`
`The Exclusion Criteria Are Functionally Related to
`the Rest of the Claim ...................................................... 43 
`IV.  PETITIONER FAILS TO MAKE ITS THRESHOLD SHOWING THAT
`AT LEAST ONE CHALLENGED CLAIM IS UNPATENTABLE ............ 44 
`A.  Grounds 1-3 (§102 Anticipation): Petitioner Fails to Establish That
`Dixon, Adis, or Regeneron (8-May-2008) Disclose the Recited
`Exclusion Criteria ................................................................................ 44 
`1. 
`None of Petitioner’s References Expressly Discloses the
`Exclusion Criteria ..................................................................... 44 
`None of Petitioner’s References Inherently Discloses the
`Exclusion Criteria ..................................................................... 45 
`a. 
`Neither the VIEW Studies Nor the VIEW Clinical
`Trial Protocol Is Prior Art ............................................... 45 
`The Exclusion Criteria Are Not Necessarily Present
`in the Disclosures of Dixon, Adis, or Regeneron
`(8-May-2008) .................................................................. 47 
`The Exclusion Criteria Are Not Inherent in the
`Practice of the ’681 Claimed Method ............................. 51 
`Grounds 4–6 (§103 Obviousness): Petitioner Fails to Demonstrate
`That Any Challenged Claim Is Obvious ............................................. 52 
`1. 
`Petitioner Fails to Demonstrate Obviousness of All of the
`Recited Exclusion Criteria ........................................................ 53 
`Petitioner Fails to Demonstrate Obviousness of the
`Claimed Dosing Regimen ......................................................... 56 
`a. 
`Dixon’s Disclosure of CLEAR-IT-2 Would Not Have
`Provided a Reasonable Expectation of Success ............. 58 
`Petitioner Fails to Show Reasonable Expectation of
`Success with Respect to the Intent to Treat Limitation
`of the Challenged Claims ............................................... 62 
`Objective Evidence Confirms Non-Obviousness ........... 64 
`
`2. 
`
`2. 
`
`B. 
`
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`–iii–
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`V. 
`V.
`
`CONCLUSION .............................................................................................. 67 
`CONCLUSION 1... eee cece eseeseeeseeeeaeeeaeeeaeeesaeseaeeeaeeesaecsaessaeeeaeseseeeeaeeeeees 67
`
`
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`–iv–
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`
`
`TABLE OF AUTHORITIES
`
` Page(s)
`
`Cases
`Abiomed, Inc. v. Maquet Cardiovascular, LLC,
`IPR2017-02134, 2018 WL 1840065 (P.T.A.B. Apr. 16, 2018) ........................... 5
`Am. Honda Motor Co. v. Intellectual Ventures II LLC,
`IPR2018-00347, 2018 WL 3203408 (P.T.A.B. Jun. 27, 2018) .......................... 10
`Am. Well Corp. v. Teladoc Health, Inc.,
`IPR2022-00038, 2022 WL 1265771 (P.T.A.B. Apr. 19, 2022) ........................... 4
`Apple Inc. v. Fintiv, Inc.,
`IPR2020-00019, 2020 WL 2126495 (P.T.A.B. Mar. 20, 2020) ..................passim
`Apple Inc. v. Fintiv,
`IPR2020-00019, 2020 WL 2486683 (P.T.A.B. May 13, 2020) ......................... 15
`Apple Inc. v. Koss Corp.,
`IPR2021-00679, 2021 WL 4865225 (P.T.A.B. Oct. 12, 2021) ............................ 7
`Bio-Rad Lab’ys, Inc. v. 10X Genomics Inc.,
`967 F.3d 1353 (Fed. Cir. 2020) .......................................................................... 24
`Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp.,
`320 F.3d 1339 (Fed. Cir. 2003) .................................................................... 22, 62
`Braintree Lab’ys, Inc. v. Novel Lab’ys, Inc.,
`749 F.3d 1349 (Fed. Cir. 2014) .......................................................................... 40
`Bristol-Myers Squibb Co. v. Ben Venue Lab’ys, Inc.,
`246 F.3d 1368 (Fed. Cir. 2001) .......................................................................... 23
`Canon Inc. v. Optimum Imaging Techs. LLC,
`IPR2020-01321, 2021 WL 786624 (P.T.A.B. Mar. 1, 2021) ............................. 14
`Cisco Sys., Inc. v. Oyster Optics, LLC,
`IPR2021-00238, 2021 WL 2221615 (P.T.A.B. Jun. 1, 2021) ............................ 15
`City of Elizabeth v. Am. Nicholson Pavement Co.,
`97 U.S. 126 (1877) .............................................................................................. 47
`
`
`
`
`–v–
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`
`Cont’l Can Co. USA v. Monsanto,
`948 F.2d 1264 (Fed. Cir. 1991) .......................................................................... 47
`E.I. Du Pont de Nemours & Co. v. Monsanto Tech. LLC,
`IPR2014-00333, 2014 WL 3507803 (P.T.A.B. July 11, 2014) .......................... 23
`Eli Lilly & Co. v. Teva Pharms. Int’l GmbH,
`8 F.4th 1331 (Fed. Cir. 2021) ................................................................. 22, 23, 64
`Eli Lilly & Co. v. Teva Pharms. Int’l GmbH,
`IPR2018-01710, 2020 WL 1540364 (P.T.A.B. Mar. 31, 2020),
`aff’d 8 F.4th 1331 (Fed. Cir. 2021) ............................................................... 38, 63
`Endo Pharms. Sols., Inc. v. CustoPharm Inc.,
`894 F.3d 1374 (Fed. Cir. 2018) .................................................................... 51, 53
`Fenner Invs., Ltd. v. Cellco P’ship,
`778 F.3d 1320 (Fed. Cir. 2015) .......................................................................... 29
`General Plastic Indus. Co. v. Canon Kabushiki Kasha,
`IPR2016-01357, 2017 WL 3917706 (P.T.A.B. Sept. 6, 2017) ...................passim
`Gilead Scis., Inc. v. U.S.,
`IPR2019-01455, 2020 WL 582380 (P.T.A.B. Feb. 5, 2020) ................. 23, 32, 33
`GlaxoSmithKline LLC v. Fibrogen, Inc.,
`IPR2016-01318, 2017 WL 379248 (P.T.A.B. Jan. 11, 2017) ............................ 40
`GlaxoSmithKline LLC v. Glenmark Pharms. Inc., USA,
`No. 14-877-LPS-CJB, 2017 WL 8948972 (D. Del. May 24, 2017) .................. 37
`Griffin v. Bertina,
`285 F.3d 1029 (Fed. Cir. 2002) .......................................................................... 23
`Guest-Tek Interactive Ent. Ltd. v. Nomadix, Inc.,
`IPR2018-01668, 2019 WL 1751093 (P.T.A.B. Apr. 16, 2019) ......................... 11
`Hulu, LLC v. Sound View Innovations, LLC,
`IPR2018-01039, 2019 WL 7000067 (P.T.A.B. Dec. 20, 2019) ......................... 20
`In Re: Copaxone Consol. Cases,
`906 F.3d 1013 (Fed. Cir. 2018) .......................................................................... 23
`
`
`
`
`–vi–
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`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule
`Patent Litig.,
`676 F.3d 1063 (Fed. Cir. 2012) .......................................................................... 65
`In re Distefano,
`808 F.3d 845 (Fed. Cir. 2015) ...................................................................... 41, 43
`In re Ngai,
`367 F.3d 1336 (Fed. Cir. 2004) .......................................................................... 43
`In re Oelrich,
`666 F.2d 578 (C.C.P.A. 1981) ............................................................................ 52
`INO Therapeutics LLC v. Praxair Distrib. Inc.,
`782 F. App’x 1001 (Fed. Cir. 2019) ................................................................... 42
`Jansen v. Rexall Sundown, Inc.,
`342 F.3d 1329 (Fed. Cir. 2003) .......................................................................... 40
`Keyme, LLC v. Hillman Grp.,
`IPR2020-01485, 2021 WL 1236002 (P.T.A.B. Mar. 31, 2021) ......................... 17
`King Pharms., Inc. v. Eon Labs, Inc.,
`616 F.3d 1267 (Fed. Cir. 2010) .......................................................................... 43
`Meds. Co. v. Mylan, Inc.,
`853 F.3d 1296 (Fed. Cir. 2017) .......................................................................... 31
`Microsoft Corp. v. Uniloc 2017 LLC,
`IPR2019-01251, 2019 WL 7000081 (P.T.A.B. Dec. 20, 2019) ....................... 4, 5
`Mylan Lab’ys Ltd. v. Aventis Pharma S.A.,
`IPR2016-00712, 2019 WL 5430242 (P.T.A.B. Oct. 22, 2019) .................... 37, 63
`Mylan Pharms. Inc. v. Regeneron Pharms., Inc.,
`IPR2021-00881, Paper 21 (P.T.A.B. Nov. 10, 2021) ..................................passim
`Nature Simulation Sys. Inc. v. Autodesk, Inc.,
`23 F.4th 1334 (Fed. Cir. 2022) ........................................................................... 33
`Nautilus, Inc. v. Biosig Instruments, Inc.,
`572 U.S. 898 (2014) ............................................................................................ 35
`
`
`
`
`–vii–
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`
`Nevro Corp. v. Bos. Sci. Corp.,
`955 F.3d 35 (Fed. Cir. 2020) .............................................................................. 36
`Nichia Corp v. Document Security Sys., Inc.,
`IPR2019-00398, 2019 WL 1749299 (P.T.A.B. Apr. 15, 2019) ....................... 8, 9
`Nine Energy Serv. Inc. v. NCS Multistage Inc.,
`IPR2020-01615, 2021 WL 1131566 (P.T.A.B. Mar. 24, 2021) ......................... 15
`Oticon Med. AB v. Cochlear Bone Anchored Sols. AB,
`IPR2017-01018, Paper 52 (P.T.A.B. Aug. 21, 2018) ......................................... 33
`Perricone v. Medicis Pharm. Corp.,
`432 F.3d 1368 (Fed. Cir. 2005) .......................................................................... 50
`Pitney Bowes, Inc. v. Hewlett-Packard Co.,
`182 F.3d 1298 (Fed. Cir. 1999) .......................................................................... 32
`Praxair Distrib., Inc. v. Mallinckrodt Hospital Products IP Ltd.,
`890 F.3d 1024 (Fed. Cir. 2018) ...................................................................passim
`Rapoport v. Dement,
`254 F.3d 1053 (Fed. Cir. 2001) .................................................................... 40, 41
`Regeneron Pharms., Inc. v. Mylan Pharms. Inc.,
`1:22-cv-00061-TSK (N.D.W.Va.) ...................................................................... 12
`Salix Pharms. Ltd. v. Norwich Pharms., Inc.,
`No. 20-430-RGA, 2022 WL 3225381 (D. Del. Aug. 10, 2022) ......................... 36
`Samsung Elecs. Co. v. Elm 3DS Innovations, LLC,
`IPR2017-01305, 2017 WL 4708081 (P.T.A.B. Oct. 17, 2017) ............................ 5
`Sanofi v. Glenmark Pharms. Inc.,
`204 F. Supp. 3d 665 (D. Del. 2016), aff’d sub nom. Sanofi v.
`Watson Lab’ys Inc., 875 F.3d 636 (Fed. Cir. 2017) ..................................... 37, 64
`Shenzhen Silver Star Intelligent Tech. Co. v. iRobot Corp.,
`IPR2018-00882, 2018 WL 4773438 (P.T.A.B. Oct. 1, 2018) ............................ 12
`Teva Pharms. USA, Inc. v. Corcept Therapeutics, Inc.,
`PGR2019-00048, 2020 WL 6809812 (P.T.A.B. Nov. 18, 2020) ....................... 63
`
`
`
`
`–viii–
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`
`Transclean Corp. v. Bridgewood Servs., Inc,
`290 F.3d 1364 (Fed. Cir. 2002) .......................................................................... 47
`Victoria’s Secret Stores LLC v. Andra Grp.,
`IPR2020-00853, 2020 WL 4719300 (P.T.A.B. Aug. 13, 2020) ......................... 20
`Statutes
`35 U.S.C. §102 ......................................................................................................... 17
`35 U.S.C. §103 ......................................................................................................... 17
`35 U.S.C. §311 ........................................................................................................... 7
`35 U.S.C. §313 ........................................................................................................... 1
`35 U.S.C. §314 ........................................................................................................... 5
`35 U.S.C. §324 ........................................................................................................... 5
`42 U.S.C. §262 ....................................................................................... 12, 13, 14, 16
`Other Authorities
`37 C.F.R. §42.107 ...................................................................................................... 1
`
`
`
`
`
`
`–ix–
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`APOTEX V. REGENERON IPR2022-01524
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`
`
`TABLE OF EXHIBITS
`
`Description
`Ex. No.
`2001 Expert Declaration of Dr. Diana Do
`2002 Curriculum Vitae of Dr. Diana Do
`2003 Exhibit Number Unused
`2004 Exhibit Number Unused
`2005 Exhibit Number Unused
`2006 Exhibit Number Unused
`2007 Declaration of Rachel Watters
`2008 Regeneron Pharms., Inc. v. Mylan Pharms. Inc., 1:22-cv-00061-TSK,
`D.I. 1 (N.D. W.Va. Aug. 2, 2022)
`2009 Regeneron Pharms., Inc. v. Mylan Pharms. Inc., 1:22-cv-00061-TSK,
`D.I. 26 (N.D. W.Va. Aug. 19, 2022)
`2010 Federal Court Management Statistics (Jun. 30, 2022)
`2011 Regeneron Pharms., Inc. v. Mylan Pharms. Inc., 1:22-cv-00061-TSK,
`D.I. 7 (N.D. W.Va. Aug. 5, 2022)
`2012 Regeneron Pharms., Inc. v. Mylan Pharms. Inc., 1:22-cv-00061-TSK,
`D.I. 47 (N.D. W.Va. Aug. 25, 2022)
`2013 Regeneron Pharms., Inc. v. Mylan Pharms. Inc., 1:22-cv-00061-TSK,
`D.I. 75, including Exhibits A and B (N.D. W.Va. Aug. 25, 2022)
`2014 Exhibit Number Unused
`2015 Exhibit Number Unused
`2016 Exhibit Number Unused
`2017 Exhibit Number Unused
`2018
`IPR2021-00881 Ex.2120, Press Release, Genentech, Inc. Submits
`Biologics License Application For FDA Review Of Lucentis(TM) In Wet
`Age-Related Macular Degeneration (December 30, 2005), available at
`https://www.biospace.com/article/releases/genentech-inc-
`submitsbiologics-license-application-for-fda-review-of-lucentis-tm-in-
`wetage-related-macular-degeneration-/
`2019 McGregor N. Lott et al., Bevacizumab in Inflammatory Eye Disease,
`148 AM. J. OPHTHALMOL. 148 (2009)
`2020 Ahmad M. Mansour et al., Long-term Visual Outcomes of Intravitreal
`Bevacizumab in Inflammatory Ocular Neovascularization, 148 AM. J.
`OPHTHALMOL. 310 (2009)
`IPR2021-00881 Ex.2130, Transcript of Deposition of Thomas Albini,
`M.D. (January 20, 2022)
`
`2021
`
`
`
`
`–x–
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`
`
`2022
`
`IPR2021-00881 Ex.2287, Transcript of Deposition of Thomas Albini,
`M.D. (June 22, 2022)
`2023 Matthew Ohr et al., Aflibercept in wet age-related macular
`degeneration: a perspective review, 3 THER. ADV. CHRONIC DIS. 153
`(2012)
`IPR2021-00881 Ex.1085, U.S. Publication No. 2007/0190058 A1
`(“Shams”)
`IPR2021-00881 Ex.2217, Drugs@FDA, Macugen Label, 12/2004,
`available at
`https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/021756lbl.p
`df
`IPR2021-00880 Ex.1114 (REDACTED COPY), Expert Declaration of
`Dr. Thomas A. Albini in Support of Petitioner’s Reply (May 27, 2022)
`IPR2021-00881 Ex.2290, Patent Owner’s Demonstratives for Oral
`Argument (August 10, 2022)
`IPR2021-00880 Ex.1002, Expert Declaration of Dr. Thomas A. Albini
`in Support of Petition for Inter Partes Review of U.S. Patent No.
`9,669,069 B2
`IPR2021-00881 Ex.1037, Robert Steinbrook, The Price of Sight —
`Ranibizumab, Bevacizumab, and the Treatment of Macular
`Degeneration, 355 N. ENGL. J. MED. 1409 (2006)
`2030 Side-by-side comparison of the exclusion criteria of VIEW and the
`exclusion criteria of ANCHOR/MARINA
`2031 Center For Drug Evaluation & Research, NDA 21-756, Macugen
`Medical Review
`IPR2021-00881 Ex.2039, Press Release, Regeneron, Regeneron Reports
`Fourth Quarter and Full Year 2012 Financial and Operating Results,
`dated February 14, 2013
`IPR2021-00881 Ex.2040, Press Release, Regeneron, Regeneron Reports
`Fourth Quarter and Full Year 2019 Financial and Operating Results,
`dated February 6, 2020
`IPR2021-00881 Ex.2194, FiercePharma, The Top 20 Drugs by
`Worldwide sales in 2020 (May 3, 2021), available at
`https://www.fiercepharma.com/special-report/top-20-drugs-by-2020-
`sales
`IPR2021-00881 Ex.2098, CDER, Statistical Review for Application
`Number 125387 (November 18, 2011)
`IPR2021-00881 Ex.1110, Transcript of Deposition of David M. Brown,
`M.D. (April 26, 2022)
`
`2024
`
`2025
`
`2026
`
`2027
`
`2028
`
`2029
`
`2032
`
`2033
`
`2034
`
`2035
`
`2036
`
`
`
`
`–xi–
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`
`
`2037
`
`2038
`
`2039
`
`2040
`
`2041
`
`2042
`
`2043
`
`2044
`
`IPR2021-00881 Ex.2280, Regeneron, ATU Sales Share Data: Wet
`AMD, c. 2021
`IPR2021-00881 Ex.2281, Regeneron, ATU Sales Share Data: DME, c.
`2021
`IPR2021-00881 Ex.2137, Regeneron, Eylea Marketing Material,
`11/2013
`IPR2021-00881 Ex.2133, Regeneron, Earnings Call Transcript,
`2/13/2012
`IPR2021-00881 Ex.2289 (REDACTED COPY), Transcript of
`Deposition of Ivan Hofmann (June 23, 2022)
`IPR2021-00881 Ex.1002, Expert Declaration of Dr. Thomas A. Albini
`in Support of Petition for Inter Partes Review of U.S. Patent No.
`9,254,338 B2
`IPR2021-00881 Ex.1003, Declaration of Mary Gerritsen, Ph.D. in
`Support of Petition for Inter Partes Review of U.S. Patent No.
`9,254,338 B2
`IPR2021-00881 Ex.2288, Transcript of Deposition of Mary Gerritsen,
`Ph.D. (June 17, 2022)
`
`
`
`
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`
`Regeneron Pharmaceuticals, Inc. (“PO” 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” or “Mylan”) 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. 10,130,681 (“the ’681 Patent,” Ex.1001).
`
`I.
`
`INTRODUCTION
`Petitioner’s challenge to the ’681 Patent is the latest in its series of
`
`challenges against Regeneron’s patents covering the FDA-recommended dosing
`
`regimen for EYLEA®. Because the Petition is both procedurally and substantively
`
`deficient, institution should be denied.
`
`First, Petitioner strategically delayed filing this Petition for over a year after
`
`it challenged what Petitioner calls “identical” claims of a related EYLEA® dosing
`
`patent in IPR2021-00881, filed May 5, 2021.1 Consequently, Petitioner used the
`
`roadmap from its previously-filed IPR challenge to modify and bolster its
`
`arguments here, even while relying on essentially the same grounds. At the same
`
`time, Petitioner’s delay ensures that the same validity challenge to the ’681 Patent
`
`presented in the Petition will proceed in parallel before the district court.
`
`Petitioner’s unjustified delay presents inefficiencies and risks inconsistent
`
`determinations in this IPR and the district court, as well as inconsistent (and
`
`1 Challenging claims of U.S. Patent No. 9,254,338 (“the ’338 Patent”).
`
`
`
`
`–1–
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`
`
`piecemeal) decisions on related patents before the Board, which alone warrants
`
`discretionary denial.
`
`Second, Petitioner attempts to pass off an unauthenticated compilation
`
`(Ex.1058) as a single prior art reference that it purports to rely on for obviousness.
`
`Petitioner appears to have combined pages from two different sources and
`
`presented them as a single publication without comment or acknowledgement, let
`
`alone evidence that Ex.1058 is an authentic copy of “Rosenfeld-2006” or that it
`
`was publicly accessible as of the 2011 priority date of the ’681 Patent.
`
`Petitioner’s submission of this doctored exhibit requires rejection of its
`
`obviousness Ground 5, and is yet another example of the gamesmanship that
`
`warrants denial of the Petition.
`
`Third, Petitioner fails to carry its burden on anticipation Grounds 1-3.
`
`Petitioner urges the Board to ignore the patient exclusion criteria limitation recited
`
`in every claim of the ’681 Patent. But this limitation, which is undisputedly
`
`absent from the express disclosures of Petitioner’s Grounds 1-3 prior art, defines
`
`the scope of the claimed method of treatment and cannot simply be “read out” of
`
`the Challenged Claims. Likewise, Petitioner’s back-up argument—that the
`
`exclusion criteria employed in the non-prior-art VIEW trials are somehow
`
`inherent in the limited disclosures of its asserted art—is wrong as a matter of fact
`
`and law.
`
`
`
`
`–2–
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2019 PAGE 015
`
`

`

`
`
`Finally, Petitioner fails to carry its burden on obviousness for any of
`
`Grounds 4-6. Petitioner argues that it would have been obvious to use the
`
`exclusion criteria from MARINA (an earlier Lucentis clinical trial) to practice the
`
`claimed dosing regimen, but fails to appreciate that Challenged Claims have
`
`different exclusion criteria than MARINA. Petitioner also fails to demonstrate the
`
`person of ordinary skill in the art (“POSA”) would have had a reasonable
`
`expectation of success in treating patients with a disclosed prospective Q8 dosing
`
`regimen from Regeneron’s Phase 3 trials. Petitioner’s expert has admitted that
`
`before Regeneron’s trials, no one used Q8 dosing and, further, that an existing
`
`dosing regimen with monthly monitoring, while more burdensome, would have
`
`been considered a “better dosing strategy” given the failures with fixed, extended
`
`dosing in the art. IPR2021-00881, Ex.2021, 283:13-284:7, 285:15-286:3. Thus,
`
`Petitioner’s suggestion that Regeneron’s claimed Q8 dosing regimen was obvious
`
`is undermined by the great uncertainty that existed as to whether a Q8 extended,
`
`fixed dosing regimen would work until Regeneron’s Phase 3 clinical trial results
`
`proved that it could.
`
`For these reasons, and as explained further below, Regeneron respectfully
`
`requests that the Board deny institution of the Petition.
`
`
`
`
`–3–
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2019 PAGE 016
`
`

`

`
`
`II. THE BOARD SHOULD DENY INSTITUTION UNDER
`35 U.S.C. §314(A)
`A.
`Institution Should Be Denied under General Plastic
`Petitioner’s strategic delay in filing the Petition is a transparent attempt to
`
`leverage information acquired during the course of IPR2021-00881, to polish and
`
`bolster arguments in this follow-on Petition. These tactics warrant discretionary
`
`denial under General Plastic. General Plastic Indus. Co. v. Canon Kabushiki
`
`Kasha, IPR2016-01357, 2017 WL 3917706 (P.T.A.B. Sept. 6, 2017); see also Am.
`
`Well Corp. v. Teladoc Health, Inc., IPR2022-00038, 2022 WL 1265771, *4-10
`
`(P.T.A.B. Apr. 19, 2022) (denying institution when petitioner “incrementally”
`
`bolstered its second petition using learning from prior, instituted IPR).
`
`Notably, Petitioner argues that the Exclusion Criteria—the only limitation
`
`that differentiates the Challenged Claims from those previously-challenged in
`
`IPR2021-00881—should be ignored, rendering the ’681 Patent identical to the
`
`previously-challenged ’338 Patent. Moreover, while General Plastic explicitly
`
`addresses circumstances where a petitioner serially challenges the same patent, it is
`
`not so limited. The Board has signaled a willingness to consider a General Plastic
`
`argument when, e.g., a second petition challenges a related patent with a common
`
`specification to the first challenged patent. See Microsoft Corp. v. Uniloc 2017
`
`
`
`
`–4–
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2019 PAGE 017
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`

`

`
`
`LLC, IPR2019-01251, 2019 WL 7000081, *3 (P.T.A.B. Dec. 20, 2019)2; see also
`
`Abiomed, Inc. v. Maquet Cardiovascular, LLC, IPR2017-02134, 2018 WL
`
`1840065, *2-6 (P.T.A.B. Apr. 16, 2018) (denying institution when new petition
`
`challenged claims similar in scope to those challenged in earlier IPRs of the same
`
`and related patents, and petitioner had benefit of previous POPRs); Samsung Elecs.
`
`Co. v. Elm 3DS Innovations, LLC, IPR2017-01305, 2017 WL 4708081, *6-9
`
`(P.T.A.B. Oct. 17, 2017) (denying institution and finding that petitioner’s use of
`
`information from earlier IPRs of related patents weighed strongly in favor of
`
`denial).
`
`Because institution imposes a tremendous burden on the Board and a patent
`
`owner, “[t]here may be other reasons besides the ‘follow-on’ petition context
`
`where,” as is the case here, “the ‘effect … on the … integrity of the patent
`
`system’… favors denying a petition even though some claims meet the threshold
`
`standards for institution under 35 U.S.C. §§ 314(a) and 324(a).” Patent Trial and
`
`Appeal Board Consolidated Trial Practice Guide 58 (Nov. 2019) (“TPG”).
`
`
`2 After applying the General Plastic factors in Microsoft, the Board ultimately
`
`instituted based on the specific facts of that case. 2019 WL 7000081, *5.
`
`
`
`
`–5–
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2019 PAGE 018
`
`

`

`
`
`1.
`
`Petitioner Previously Challenged Substantially Similar
`Claims of a Related Patent Using the Same References
`(General Plastic Factors One and Two)
`Petitioner requested IPR of the ’338 Patent on May 5, 2021. IPR2021-
`
`00881, Paper 1. Nearly fourteen months later, it filed a new petition on the
`
`related ’681 Patent using the same references that were asserted in the ’338 IPR.3
`
`Petition, 3-4. Petitioner concedes that the ’681 and ’338 Patents share the same
`
`specification and, according to Petitioner, the challenged claims in this proceeding
`
`“mimic those” in the related ’338 Patent. Petition, 1, 4-5, 21. In fact, Petitioner
`
`argues (incorrectly) that the ’681 Patent claims are “identical” to the previously
`
`challenged ’338 Patent claims. Petition, 21, 25. Even rejecting Petitioner’s
`
`flawed claim construction argument, a cursory comparison of the ’681 and ’338
`
`Challenged Claims reveals their substantial similarity. Either way, General Plastic
`
`factor one weighs heavily against institution.
`
`
`3 The only “new” references in Petitioner’s grounds here are Ex.1058 and
`
`Heimann-2007, which Petitioner relies on solely for its Grounds 5 and 6
`
`obviousness arguments relating to the patient exclusion criteria recited in the
`
`Challenged Claims. Moreover, under Petitioner’s incorrect world view—i.e., that
`
`the exclusion criteria are not patentable limitations—Ex.1058 and Heimann-2007
`
`are irrelevant.
`
`
`
`
`–6–
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2019 PAGE 019
`
`

`

`
`
`General Plastic factor two also favors denial of institution. Petitioner was
`
`aware of all of the primary references it asserts here, and used these same
`
`references for its grounds in the earlier-filed IPR2021-00881:
`
`’338 IPR
`
`’681 IPR
`
`(anticipation)—Dixon,
`Grounds 1-4
`Adis, Regeneron (8-May-2008), NCT-
`795
`
`in
`Ground 6 (obviousness)—Dixon
`combination with the ’758 Patent or
`Dix
`
`(anticipation)—Dixon,
`Grounds 1-3
`Adis, Regeneron (8-May-2008)
`
`in
`Ground 4 (obviousness)—Dixon
`combination with the ’758 Patent or
`the ’173 Patent4
`
`IPR2021-00881, Paper 1, 6; Petition, 12-13. Dixon is also the primary reference
`
`for Grounds 5-6, and Petitioner does not contend that its Grounds 5-6 secondary
`
`references were newly-discovered. Thus, factor two weighs against institution.
`
`See, e.g., Apple Inc. v. Koss Corp., IPR2021-00679, 2021 WL 4865225, at *6
`
`(P.T.A.B. Oct. 12, 2021).
`
`
`4 While Petitioner has traded Dix (Ex.1033) for the ’173 Patent (Ex.1008), it was
`
`well-aware of the ’173 Patent, which was Petitioner’s Ex.1008 in IPR2021-00881.
`
`Rather than supporting institution this substitution is a clear example of road-
`
`mapping and further favors denial under General Plastic factor three. See infra
`
`II.A.2.
`
`
`
`
`–7–
`
`APOTEX V. REGENERON IPR2022-01524
`REGENERON EXHIBIT 2019 PAGE 020
`
`

`

`
`
`2.
`
`Petitioner Uses the Prior Proceeding to Roadmap Its
`Arguments (General Plastic Factor Three)
`A Petitioner should not be permitted to “strategically stage [its] prior art and
`
`arguments,” by using prior proceedings “as a roadmap” for future patent
`
`challenges. See General Plastic, IPR2016-01357, 2017 WL 3917706, *7. Such
`
`road-mapping is “unfair to patent owners and is an inefficient use of the inter
`
`partes review process.” Id.
`
`Here, Petitioner waited to challenge the ’681 Patent until it benefitted from
`
`the nearly complete record in IPR2021-00881. Nichia Corp v. Document Security
`
`Sys., Inc., IPR2019-00398, 2019 WL 1749299, *7 (P.T.A.B. Apr. 15, 2019)
`
`(denying institution where Petitioner leveraged a nearly complete record from the
`
`prior proceeding). And Petitioner has