`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________________________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`________________________________________________
`
`HOPEWELL PHARMA VENTURES, INC.,
`Petitioner,
`
`v.
`MERCK SERONO SA,
`Patent Owner.
`_________________________________________________
`Case IPR2023-00481
`Patent 8,377,903
`____________________________________________________
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`PATENT OWNER’S PRELIMINARY RESPONSE
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`TABLE OF CONTENTS
`Introduction ...................................................................................................... 1
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`IPR2023-00481
`U.S. Patent No. 8,377,903
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`Background ...................................................................................................... 4
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`I.
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`II.
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`III. Person Of Ordinary Skill In The Art ............................................................... 6
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`IV. Claim Construction .......................................................................................... 6
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`V.
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`Petitioner Is Not Reasonably Likely To Prevail On Ground I ...................... 16
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`A.
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`Petitioner Fails To Establish That Bodor And Stelmasiak
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`Disclose Or Suggest All Claim Limitations ........................................ 17
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`1.
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`Neither Bodor Nor Stelmasiak Discloses Or Suggests
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`The Claimed Weight-Based Oral, Induction Or
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`Maintenance Dosing ................................................................. 17
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`2.
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`Neither Bodor Nor Stelmasiak Discloses Or Suggests A
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`Maintenance Period As Claimed .............................................. 21
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`B.
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`Petitioner Has Not Established Any Motivation To Combine
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`Bodor With Stelmasiak To Arrive At The Challenged Claims .......... 29
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`1.
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`A POSA Would Not Have Been Motivated To Adopt
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`Weight-Based Dosing ............................................................... 29
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`2.
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`A POSA Would Not Have Been Motivated To Combine
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`Bodor With Stelmasiak To Arrive At The Claimed
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`Induction Doses ......................................................................... 30
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`i
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`A POSA Would Not Have Been Motivated To
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`3.
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`Re-Treat Patients After Bodor’s 10-Month
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`Cladribine-Free Period .............................................................. 37
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`4.
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`A POSA Would Not Have Been Motivated To Combine
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`Bodor With Stelmasiak To Arrive At The Claimed 1.7
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`Mg/Kg Maintenance Dose ........................................................ 38
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`5.
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`Petitioner’s Routine Optimization Arguments Fail To
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`Explain How A POSA Would Have Been Motivated To
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`Arrive At Claimed Dosing Methods ......................................... 40
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`C.
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`Petitioner Has Not Established Any Reasonable Expectation
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`Of Success In Combining Bodor’s Method With Stelmasiak
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`To Arrive At The Challenged Claims ................................................. 45
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`1.
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`A POSA Would Not Have Reasonably Expected To
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`Arrive At The Claimed Weight-Based Dosing ......................... 46
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`2.
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`A POSA Would Not Have Reasonably Expected To
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`Arrive At The Claimed 1.7-3.5 Mg/Kg Total Induction
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`Dose By Modifying Bodor’s Method In View Of
`
`Stelmasiak ................................................................................. 46
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`3.
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`A POSA Would Not Have Reasonably Expected To
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`Treat RRMS Or Early SPMS Using The Claimed About
`ii
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`8-10- Or 10-Month Cladribine-Free Period By
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`U.S. Patent No. 8,377,903
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`Modifying Bodor’s Method In View Of Stelmasiak ................ 47
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`4.
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`A POSA Would Not Have Reasonably Expected To
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`Arrive At The Claimed About 1.7 Mg/Kg Maintenance
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`Dose By Modifying Bodor’s Method In View Of
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`Stelmasiak ................................................................................. 49
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`5.
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`A POSA Would Not Have Reasonably Expected To
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`Arrive At A Safe And Effective Method Of Treating
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`RRMS Or Early SPMS As Claimed By Modifying
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`Bodor’s Method In View Of Stelmasiak .................................. 50
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`VI. Objective Indicia Support Non-Obviousness ................................................ 52
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`VII. The Petition Should Be Denied Under 35 U.S.C. § 325(d) ........................... 53
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`A.
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`The Office Already Considered Petitioner’s Alleged Prior
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`Art And Arguments ............................................................................. 53
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`1.
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`Becton Dickinson Factors (a) And (b): Asserted Art
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`Was Considered During Examination ...................................... 54
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`2.
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`Becton Dickinson Factor (d): Petitioner’s And The
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`Examiner’s Arguments Are Not Materially Different .............. 55
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`B.
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`Petitioner Has Not Identified A Material Error By The
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`Examiner ............................................................................................. 58
`iii
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`Becton Dickinson Factor (c): Asserted Art Was
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`1.
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`Evaluated During Examination ................................................. 59
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`2.
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`Becton Dickinson Factor (e): Petitioner Has Not
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`Identified Material Examiner Error .......................................... 60
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`3.
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`Becton Dickinson Factor (f): Additional Evidence
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`Does Not Warrant Reconsideration .......................................... 63
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`VIII. Conclusion ..................................................................................................... 64
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`TABLE OF AUTHORITIES
`
` Page(s)
`
`CASES
`Advanced Bionics, LLC v. Med-El Elektromedizinische Gerate GmbH,
`IPR2019-01469, Paper 6 (P.T.A.B. Feb. 13, 2020) .....................................passim
`Agrofresh Solutions, Inc. v. Lytone Enterprise, Inc.,
`IPR2021-00451, Paper 11 (P.T.A.B. Jul. 27, 2021) ........................................... 62
`ATD Corp. v. Lydall, Inc.,
`159 F.3d 534 (Fed. Cir. 1998) ............................................................................ 26
`Becton, Dickinson & Co. v. B. Braun Melsungen AG,
`IPR2017-01586, Paper 8 (P.T.A.B. Dec. 15, 2017) ....................................passim
`Belden Inc. v. Berk-Tek LLC,
`805 F.3d 1064 (Fed. Cir. 2015) .......................................................................... 41
`Biogen Idec, Inc. v. GlaxoSmithKline LLC,
`713 F.3d 1090 (Fed. Cir. 2013) .......................................................................... 11
`Dafron Elecs. Corp. v. Shipman,
`IPR2022-01008, Paper 11 (P.T.A.B. Dec. 2, 2022) ..................................... 57, 63
`Epistar Corp. v. Int’l Trade Comm’n,
`566 F.3d 1321 (Fed. Cir. 2009) .......................................................................... 10
`
`In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Pat.
`Litig., 676 F.3d 1063 (Fed. Cir. 2012) ................................................................ 43
`In re Enhanced Sec. Research, LLC,
`739 F.3d 1347 (Fed. Cir. 2014) .......................................................................... 26
`In re Gurley,
`27 F.3d 551 (Fed. Cir. 1994) .............................................................................. 30
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) .......................................................................... 40
`
`
`
`v
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`U.S. Patent No. 8,377,903
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`Invitrogen Corp. v. Biocrest Mfg., L.P.,
`327 F.3d 1364 (Fed. Cir. 2003) .......................................................................... 11
`Omega Eng’g, Inc. v. Raytek Corp.,
`334 F.3d 1314 (Fed. Cir. 2003) .......................................................................... 11
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) (en banc) ...................................................... 6, 15
`R.J. Reynolds Vapor Co. v. Fontem Holdings 1 B.V.,
`IPR2017-01642, Paper 10 (P.T.A.B. Jan. 16, 2018) .......................................... 59
`Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd.,
`492 F.3d 1350 (Fed. Cir. 2007) .......................................................................... 43
`TWi Pharms. Inc. v. Merck Serono SA,
`IPR2023-00050, Paper 8 (P.T.A.B. Mar. 28, 2023) ....................................passim
`Unigene Lab’ys, Inc. v. Apotex, Inc.,
`655 F.3d 1352 (Fed. Cir. 2011) .......................................................................... 52
`Vudu Inc. v. Ideahub, Inc.,
`IPR2020-01689, Paper 16 (P.T.A.B. Apr. 19, 2021) ......................................... 63
`Ziegmann v. Stephens,
`IPR2015-01860, Paper 13 (P.T.A.B. Sept. 6, 2017) ........................................... 59
`STATUTES, RULES, AND REGULATIONS
`35 U.S.C. § 314(a) ................................................................................................... 16
`35 U.S.C. § 325(d) ............................................................................................... 3, 64
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`
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`vi
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`
`
`INTRODUCTION
`The Board should deny institution of inter partes review of claims 17, 19-
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`IPR2023-00481
`U.S. Patent No. 8,377,903
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`
`I.
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`20, and 22-27 of U.S. Patent No. 8,377,903 (“challenged claims”) because
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`Petitioner fails to show any reasonable likelihood of prevailing.
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`Before the ’903 patent’s invention, numerous multiple sclerosis (“MS”)
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`clinical trials concluded that high doses equivalent to at least 4.1 mg/kg oral
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`cladribine (i.e., intravenous or subcutaneous doses of 2.1, 2.8, or 3.65 mg/kg, based
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`on highest reported bioavailability) were “not found to be effective against MS
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`clinical deterioration[.]” See Ex. 1015, 17541; Ex. 1016, 425 (Table III). Further,
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`there were significant long-term safety concerns about using cladribine to treat
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`MS, and the art provided no guidance on which specific combination of doses and
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`dosing periods would be safe and effective. Ex. 1001, 2:59-3:2, 3:22-30; Ex. 1031,
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`43-44; Ex. 1014, 1720; Ex. 1016, 430-431. The ’903 patent claims a dosing
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`regimen for treating relapsing-remitting MS (“RRMS”) or early secondary
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`progressive MS (“SPMS”) based on the inventors’ surprising discovery of a
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`specific combination of (a) cladribine dosing periods, (b) low oral cladribine
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`weight-based doses, and (c) cladribine-free periods. The claimed method
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`1 Hereinafter, all emphasis is added unless otherwise noted.
`1
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`overcame the challenges of the cladribine clinical studies and provides a safe and
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`effective method for treating MS, now approved by the FDA in MAVENCLAD®.
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`Petitioner’s one ground is based solely on art teaching flat dosing—neither
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`Bodor (Ex. 1022) nor Stelmasiak (Ex. 1013) teaches or suggests weight-based
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`dosing—and thus it is even more deficient than the ground asserted against the
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`’903 patent in TWi Pharmaceuticals Inc. v. Merck Serono SA, in which the Board
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`denied institution. See IPR2023-00050, Paper 8 at 21-27 (P.T.A.B. Mar. 28,
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`2023). In that proceeding, the ground relied on Bodor and a different secondary
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`reference, Rice, that taught subcutaneous weight-based dosing. Id. at 6, 17.
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`Nonetheless, the Board found that “Bodor already considered Rice prior to
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`envisioning its orally administered flat dosage” and concluded “the motivation to
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`modify Bodor’s method of dosing to a weight-based dosage or to achieve a total
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`dose based on weight remains missing.” Id. at 26. Petitioner here cannot establish
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`that Bodor or Stelmasiak discloses or suggests any weight-based dosing, let alone
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`the claimed weight-based induction or maintenance period dosing, and thus the
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`Petition must fail.
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`Petitioner’s Ground also fails because Petitioner does not establish why a
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`person of ordinary skill in the art (“POSA”) would have been motivated to shift
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`from Bodor or Stelmasiak’s flat dosing method to a weight-based one, or to modify
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`Bodor’s method in view of Stelmasiak to arrive at the claimed about 1.7-3.5 mg/kg
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`or 1.7 mg/kg induction period dose, or the claimed about 1.7 mg/kg maintenance
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`period dose. Particularly in view of Petitioner’s argument that cladribine causes
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`“suppression of lymphocyte counts” (Pet. 36 (citations omitted)), where a decrease
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`in lymphocyte levels to ≤1000 cells/μL constitutes “suppression” and a “positive
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`response” (Ex. 1002, ¶32; Pet. 16, n.6), and its declarant’s opinion that “a direct
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`correlation exists between the dose and length of administration of cladribine and
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`level of lymphocyte suppression” (Ex. 1002, ¶91), a POSA considering Bodor and
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`Stelmasiak would not have been motivated to modify Bodor’s method in view of
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`Stelmasiak to arrive at the claimed induction or maintenance period, or have any
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`reasonable expectation of success in doing so.
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`Further, Petitioner’s routine-optimization argument fails to explain why a
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`POSA would have been motivated to select the claimed specific dosing method
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`from the infinite number of potential combinations of doses, dosing period length
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`and number, and drug-free period length and number, or have any reasonable
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`expectation of success in doing so, when the prior art provides no guidance
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`regarding which combination would result in a safe and effective method to treat
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`RRMS or early SPMS.
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`The Petition also should be denied under § 325(d). Petitioner does not
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`dispute that it presents the same art and arguments already evaluated and overcome
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`during prosecution. But rather than demonstrating any material error, Petitioner
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`merely disagrees with the Examiner’s evaluation of the art and allowance of the
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`challenged claims so institution should be denied under Advanced Bionics.
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`For at least the foregoing reasons, institution of inter partes review should
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`be denied.
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`II. BACKGROUND
`MS is a chronic inflammatory demyelination disease of the central nervous
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`system. Ex. 1001, 1:26-28. Clinically defined MS types include RRMS and
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`SPMS. Id., 1:48-50.
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`The ’903 patent specification describes five FDA-approved disease
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`modifying treatments (“DMTs”) for MS: three beta interferons (Betaseron®;
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`Avonex®; Rebif®), glatiramer acetate (Copaxone®), and mitoxantrone
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`(Novantrone®). Id., 2:14-21. Other than mitoxantrone, these drugs are
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`administered parenterally in a continuous, single-dosing phase at flat (i.e., not
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`weight-based), fixed doses without any extended drug-free period. Ex. 1006, 947
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`(Table 2). Mitoxantrone is administered intravenously based on body surface area
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`every 3 months. Id. Thus, a POSA would have understood that as of December
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`2004, most FDA-approved MS drugs used a continuous, single-dosing phase
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`without any extended drug-free period and that none of these drugs used oral or
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`weight-based dosing.
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`4
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`By December 2004, several clinical trials had investigated the use of
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`cladribine for treating MS. Most of these trials used a single, high intravenous- or
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`subcutaneous-dose dosing phase (e.g., total doses of 2.1, 2.8, or 3.65 mg/kg per
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`dosing period); achieving the same cladribine exposure would be expected to
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`require even higher doses when administered orally. See Ex. 1016, 425 (Table III);
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`Ex. 1001, 2:37-42; Ex. 1047, 295; Ex. 1031, 36. A limited number of cladribine
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`trials used more than one dosing phase. See Ex. 1013, 5; Ex. 1014, 1716; Ex.
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`1018, 1146-47.
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`Despite the numerous clinical trials, “cladribine was not found to be
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`effective against MS clinical deterioration[.]” Ex. 1015, 1754. Further, there were
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`significant long-term safety concerns about using cladribine to treat MS, including
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`increased cancer risk, hematologic toxicity, and bone marrow suppression. Ex.
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`1001, 2:59-3:2, 3:22-30; Ex. 1031, 40-41; Ex. 1014, 1720; Ex. 1016, 430. And
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`while these clinical trials used varying dosing periods and doses, nothing in the
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`prior art taught a POSA how the combination of the different dosing variables—
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`dose, length and number of dosing period or length of drug-free periods—would
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`impact the treatment of MS or what specific combination (if any) would result in a
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`safe and effective MS treatment method. Indeed, the art taught “[t]here is still
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`more to be learned about optimal cladribine dosages, ideal timing for retreatment
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`and how cladribine compares with other agents used to treat MS.” Ex. 1016, 431.
`5
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`III. PERSON OF ORDINARY SKILL IN THE ART
`Patent Owner (“PO”) reserves the right to challenge Petitioner’s definition at
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`IPR2023-00481
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`a later stage in this proceeding, should the Board institute trial.
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`IV. CLAIM CONSTRUCTION
`Petitioner contends the claim term “a maintenance period” should be
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`construed as “a period during which a total dose of cladribine is lower than the
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`total dose of cladribine administered in an induction period.” Pet. 30-31.
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`Petitioner argues that “the specification supports [such] a construction” (id.) even
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`though Petitioner’s declarant states, “[t]he ’903 patent does not explicitly define
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`‘maintenance period[.]’” Ex. 1002, ¶70. The Board should reject Petitioner’s
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`construction because (1) it disregards the plain and ordinary meaning of the term
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`“maintenance period,” as informed by the ’903 patent claims and specification; and
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`(2) Petitioner fails to show that PO disclaimed subject matter directed to using the
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`same dose for the maintenance and induction periods.
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`It has long been held that the “words of a [patent] claim are generally given
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`their ordinary and customary meaning” “in the context of the entire patent,
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`including the specification.” Phillips v. AWH Corp., 415 F.3d 1303, 1312-13 (Fed.
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`Cir. 2005) (en banc) (internal citations and quotations omitted).
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`First, a POSA considering the plain language of the ’903 patent claims and
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`specification would have understood a “maintenance period” means “a treatment
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`period that follows an induction period and a cladribine-free period.” For example,
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`claim 17 recites a “method of treating [RRMS] … following the sequential steps
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`… [of] (i) an induction period …, (ii) a cladribine-free period …, (iii) a
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`maintenance period …, (iv) a cladribine-free period[.]” Ex. 1001, 18:7-26; see
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`also id., 16:52-17:5 (claim 1). Similarly, Example 1 of the ’903 patent discloses a
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`study in which the “maintenance period” occurs “at month 13,” after an “induction
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`period” and a cladribine-free period. Id., 15:47-67. Thus, a POSA considering the
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`claims and specification would have understood that a maintenance period is a
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`treatment period that follows an induction period and a cladribine-free period.
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`Contrary to Petitioner’s assertion, a POSA would not understand the term
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`“maintenance period” itself to require administration of any particular dose of
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`cladribine. Instead, other language in the claims specifies the exact dose to be
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`administered during the maintenance period. See, e.g., id., 18:7-26 (claim 17,
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`reciting “the total dose of cladribine reached at the end of the maintenance period
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`is about 1.7 mg/kg”). Thus, Petitioner’s attempt to read a dosing amount into the
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`construction of “maintenance period” is improper.
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`Indeed, Petitioner’s argument that a maintenance period requires a lower
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`total dose than the induction period dose is directly contradicted by the claim
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`language, which makes clear that the total cladribine dose administered during a
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`maintenance period can be either the same as or lower than that administered
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`during the induction period. For example, independent claim 1 expressly recites
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`“wherein the total dose of cladribine reached at the end of the maintenance period
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`is lower than the total dose of cladribine reached at the end of the induction
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`period” (i.e., the “lower than” limitation). Id., 16:52-17:5. On the other hand,
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`independent claim 17 recites “the total dose of cladribine reached at the end of the
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`induction period is from about 1.7 mg/kg to about 3.5 mg/kg” and “the total dose
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`of cladribine reached at the end of the maintenance period is about 1.7 mg/kg[.]”
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`Id., 18:7-26. That is, if the total dose administered during the induction period
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`were about 1.7 mg/kg (the low end of the claimed range), then the total dose
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`administered during the maintenance period would be the same as the total dose
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`administered during the induction period. In fact, claim 20, which depends from
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`claim 17, expressly recites that “the total dose of cladribine reached at the end of
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`the induction period is about 1.7 mg/kg.” Id., 18:30-32. A POSA would thus have
`
`understood that claim 20 requires the total cladribine dose during the induction
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`period to be the same as the total cladribine dose during the maintenance period,
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`i.e., “about 1.7 mg/kg” in each case. Thus, reading the claims as a whole, a POSA
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`would have understood that the total dose of cladribine administered during the
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`maintenance period could be either the same as or lower than the total dose
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`administered during the induction period.
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`8
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`Consistent with the claims, the specification describes embodiments wherein
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`the total cladribine dose administered during a maintenance period is the same as
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`or lower than the total dose of cladribine administered during the induction period.
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`Example 1 discloses a study in which patients in Groups 2 and 3 receive a total
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`induction period dose of 1.75 and 3.5 mg/kg cladribine, respectively. Id., 14:6-
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`15:61. After a cladribine-free period, Groups 2 and 3 both “receive re-treatment
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`with Cladribine … for 2 months (maintenance period) with the lower dose,” i.e.,
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`the lower of the two induction period doses—1.75 mg/kg. Id., 15:62-67; see also
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`id., 14:49-15:19 (“[A]dministration schemes for the induction period … are given
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`below in Tables 3 and 4 for the target doses of 1.75 mg/kg and 3.5 mg/kg
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`respectively. For the maintenance period, the example of administration scheme of
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`Table 3 is applicable,” which discloses a target dose of “1.75 mg/kg”); 16:1-6.
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`Thus, for Group 3, the total cladribine dose during the maintenance period is lower
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`than that administered during the induction period, whereas for Group 2, the total
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`doses administered for each of the induction and maintenance periods are the
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`same, i.e., 1.75 mg/kg.
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`The ’903 patent further describes embodiments wherein the total cladribine
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`dose administered during a maintenance period is the same as that administered
`
`during the induction period. For example, “[i]n a further preferred embodiment,”
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`“the total dose of Cladribine reached at the end of the induction period is about 1.7
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`mg/kg” and “the total dose of Cladribine reached at the end of the maintenance
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`period is about 1.7 mg/kg.” Id., 12:65-67, 13:13-15.
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`Thus, a POSA reading the claim term “maintenance period” in the context of
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`the claims and the specification would have understood that its plain and ordinary
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`meaning is “a treatment period that follows an induction period and a cladribine-
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`free period,” without requiring administration of a particular dose. Instead, the
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`total doses for the maintenance period are clearly recited in the claims, e.g., “lower
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`than the total dose of cladribine reached at the end of the induction period” in
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`claim 1; or “about 1.7 mg/kg” in claim 17. The claims and specification clearly
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`describe and support that the total cladribine dosing during a maintenance period
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`can be either the same as or lower than the total dose of cladribine administered
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`during the induction period.
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`Second, Petitioner fails to show that PO disclaimed a maintenance period
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`dosing that was the same as the induction period dosing and thus cannot overcome
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`the plain and ordinary meaning of a “maintenance period” as claimed.
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`Courts have declined to apply the doctrine of prosecution disclaimer where
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`an alleged infringer’s arguments fail to “show the patentee expressly relinquished
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`claim scope,” and thus are insufficient to “overcome [the] heavy presumption that
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`claim terms carry their full ordinary and customary meaning[.]” Epistar Corp. v.
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`Int’l Trade Comm’n, 566 F.3d 1321, 1334 (Fed. Cir. 2009). “[F]or prosecution
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`disclaimer to attach, [Federal Circuit] precedent requires that the alleged
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`disavowing actions or statements made during prosecution be both clear and
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`unmistakable.” Omega Eng’g, Inc. v. Raytek Corp., 334 F.3d 1314, 1325-26 (Fed.
`
`Cir. 2003); see also Invitrogen Corp. v. Biocrest Mfg., L.P., 327 F.3d 1364, 1369
`
`(Fed. Cir. 2003) (same).
`
`Here, Petitioner’s estoppel arguments are not supported by the prosecution
`
`history. See Pet. 31, n.8.
`
`Petitioner first argues that “Merck is bound by accepting the Examiner’s
`
`statement” that neither Bodor nor Grieb teaches that the total maintenance period
`
`dose is lower than the total induction period dose, citing Biogen Idec, Inc. v.
`
`GlaxoSmithKline LLC, 713 F.3d 1090 (Fed. Cir. 2013). Id. But the present
`
`situation is far different than in Biogen, where the Court found the patentees had
`
`disclaimed subject matter when patentees “did not directly challenge the
`
`examiner’s characterization” of the disputed term but also “adopted that
`
`characterization when applicants limited their claims.” 713 F.3d at 1096-97& n.6.
`
`Here, PO did not “accept” an alleged characterization that all claims required a
`
`lower maintenance period dose, and instead argued that “nowhere” in Bodor “is
`
`there any discussion about repeating a treatment course at any point in time at
`
`either the original dosage or at a lower dosage in a manner that could be
`
`construed as a ‘maintenance period.’” Ex. 1004, 121, 151 (same); see also Pet. 12
`11
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`IPR2023-00481
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`(Petitioner acknowledging PO argued that Bodor did not teach a “maintenance
`
`period” dose that was the same or lower than the original dose). Further, in
`
`contrast to the patentees in Biogen, who limited their claims to match the
`
`examiner’s characterization and therefore “adopted” that characterization, PO here
`
`made no amendments with either of its Responses, which addressed some claims
`
`reciting the “lower than” limitation and others allowing the total maintenance
`
`period dose to be the same or lower. Ex. 1004, 117-127, 147-153. This directly
`
`contradicts Petitioner’s purported acquiescence. Under these circumstances, there
`
`can be no “clear and unmistakable disavowal.”
`
`Petitioner’s additional arguments concerning the prosecution history are
`
`similarly misplaced. After rebutting the Examiner’s rejection of all claims (claims
`
`1-29) by arguing that Bodor did not teach a maintenance period at all—either the
`
`same dosage as or lower than the total induction period dosage—PO further
`
`argued that “[e]ven if one were to accept [the] ‘implied’ teaching in Bodor et al.,”
`
`i.e., “that following these 10 months, treatment with cladribine is resumed,” “the
`
`teachings of the reference would not lead [a POSA] to the claimed invention” and
`
`“[s]pecifically, a [POSA] would not have had any reason to reduce the dosage of
`
`cladribine administered during the ‘maintenance period’[.]” Id., 151. PO
`
`concluded that “the combined teachings of the references would not have led [a
`
`POSA] to a dosing regimen and/or total dosages recited in claims 1, 4, 5, 9, 10, 17,
`12
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`IPR2023-00481
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`20 or 21.” Id. Thus, PO never argued the maintenance period must always use a
`
`total dose lower than the induction period dose.
`
`To the contrary, PO repeatedly distinguished Bodor on the grounds that it
`
`failed to teach a maintenance period dosage that was either the same as or lower
`
`than the total induction period dosage. See Ex. 1004, 121 (“nowhere in … [Bodor]
`
`is there any discussion about repeating a treatment course at any point in time at
`
`either the original dosage or at a lower dosage”), 151 (same). As such, PO made
`
`clear that the then-pending claims included claims directed to not just a lower
`
`maintenance period dosage relative to the induction period dosage, but also claims
`
`allowing the same total dosages for both periods (e.g., claims 17 and 20).
`
`Likewise, the prosecution history shows the Examiner recognized the
`
`application included claims directed to a method having the same total cladribine
`
`dosage for the maintenance and induction periods. During prosecution, the
`
`Examiner stated:
`
`[A] woman weighing approximately 58 kg and treated for
`2 months with 10 mg cladribine daily for 5 days per month
`would reach a total dose of 1.72 mg/kg, which would be
`on point to claims 4 and 20 (i.e., the total dose of
`cladribine reached at the end of the induction period is
`about 1.7 mg/kg).
`
`
`
`13
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`Id., 101. Then claim 20, through dependency from claim 17, recites “the total dose
`
`of cladribine reached at the end of the maintenance period is about 1.7 mg/kg[,]”
`
`thus reciting the same dose of about 1.7 mg/kg for both the induction and
`
`maintenance periods. Ex. 1001, 18:7-26, 18:30-33. The Examiner’s specific
`
`reference to claim 20 and discussion of the recited doses show her appreciation of
`
`certain claims directed to a method having the same total cladribine dosage for the
`
`maintenance and induction periods.
`
`Petitioner also asserts that the prosecution history of the parent patent (U.S.
`
`Patent No. 7,713,947) supports Petitioner’s proposed construction. Pet. 31-33.
`
`But the only evidence identified by Petitioner is PO’s argument that Bloom did not
`
`teach “lowering treatment dosages with each successive use of the drug.” Id., 32
`
`(quoting Ex. 1025, 251). Regardless, during prosecution of the ’947 patent, PO’s
`
`arguments regarding the art reflected the scope of then-pending claims 18-37,
`
`which contained an express limitation that the total dose during the maintenance
`
`period was “lower than” the total induction period dose. Ex. 1025, 3-6, 237-255.
`
`PO then added claims specifying that the maintenance period dosing may be the
`
`same as the induction period dosing. Id., 243-245. These circumstances do not
`
`“show the patentee expressly relinquished claim scope” regarding the maintenance
`
`period dosing.
`
`
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`14
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`Accordingly, nowhere in the file histories of the ’947 or ’903 patents is there
`
`a “clear and unmistakable” disavowal of a total maintenance period dose that is the
`
`same as the total induction period dose. Instead, PO’s statements during
`
`prosecution of both patents show the maintenance and induction period doses can
`
`be the same in the challenged claims.
`
`Thus, Petitioner fails to show that PO disclaimed a maintenance period
`
`dosing that was the same as the induction period dosing and cannot overcome the
`
`plain and ordinary meaning of a “maintenance period,” as a POSA reading the
`
`claim term in the context of the challenged claims, the specification, and the file
`
`histories would have understood it. See Phillips, 415 F.3d at 1312-13. The Board
`
`should thus reject Petitioner’s proposed construction of “maintenance period.”
`
`Petitioner similarly asserts that “the term ‘induction period’ should be
`
`construed as a period during which a total dose of cladribine is higher than the
`
`total dose of cladribine administered in maintenance period.” Pet. 30. For the
`
`same reasons discussed above with respect to “maintenance period,” a POSA
`
`would have understood that the plain meaning of “induction period” does not
`
`require a particular dose, and the total cladribine induction period dose can be
`
`either the same as or higher than the total cladribine maintenance period dose.
`
`The Board should reject Petitioner’s construction of “induction period” as
`
`requiring a higher dose than the “maintenance period.” PO reserves the right to
`15
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`further address construction of “induction period” and “maintenance period”
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`should the Board institute trial.
`
`Lastly, regardless of how “maintenance period”/”induction period” is
`
`construed, Petitioner is not reasonably likely to prevail on its sole Ground. See
`
`Section V, infra.
`
`V.
`
`PETITIONER IS NOT REASONABLY LIKELY TO PREVAIL ON
`GROUND I
`The Petition should not be instituted because Petitioner has not
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