`
`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 IPR2023-00480
`Patent 7,713,947
`____________________________________________________
`
`PATENT OWNER’S PRELIMINARY RESPONSE
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`
`TABLE OF CONTENTS
`
`I.
`
`II.
`
`Introduction ...................................................................................................... 1
`
`Background ...................................................................................................... 4
`
`III.
`
`Person Of Ordinary Skill In The Art ............................................................... 5
`
`IV. Claim Construction .......................................................................................... 6
`
`V.
`
`Petitioner Is Not Reasonably Likely To Prevail On Ground I ...................... 16
`
`A.
`
`Petitioner Fails To Establish That Bodor And Stelmasiak
`
`Disclose Or Suggest All Claim Limitations ........................................ 16
`
`1.
`
`Neither Bodor Nor Stelmasiak Discloses Or Suggests
`
`The Claimed Weight-Based Oral, Induction Or
`
`Maintenance Dosing ................................................................. 16
`
`2.
`
`Neither Bodor Nor Stelmasiak Discloses Or Suggests A
`
`Maintenance Period As Claimed .............................................. 21
`
`B.
`
`Petitioner Has Not Established Any Motivation To Combine
`
`Bodor With Stelmasiak To Arrive At The Challenged Claims .......... 29
`
`1.
`
`A POSA Would Not Have Been Motivated To Adopt
`
`Weight-Based Dosing ............................................................... 29
`
`2.
`
`A POSA Would Not Have Been Motivated To Combine
`
`Bodor With Stelmasiak To Arrive At The Claimed
`
`Induction Doses ......................................................................... 30
`i
`
`
`
`
`
`A POSA Would Not Have Been Motivated To Re-Treat
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`
`3.
`
`Patients After Bodor’s 10-Month Cladribine-Free Period ....... 36
`
`4.
`
`A POSA Would Not Have Been Motivated To Combine
`
`Bodor With Stelmasiak To Arrive At The Claimed 1.7
`
`Mg/Kg Maintenance Dose ........................................................ 38
`
`5.
`
`Petitioner’s Routine Optimization Arguments Fail To
`
`Explain How A POSA Would Have Been Motivated To
`
`Arrive At Claimed Dosing Methods ......................................... 39
`
`C.
`
`Petitioner Has Not Established Any Reasonable Expectation Of
`
`Success In Combining Bodor’s Method With Stelmasiak To
`
`Arrive At The Challenged Claims ....................................................... 44
`
`1.
`
`A POSA Would Not Have Reasonably Expected To
`
`Arrive At The Claimed Weight-Based Dosing ......................... 45
`
`2.
`
`A POSA Would Not Have Reasonably Expected To
`
`Arrive At The Claimed 1.7-3.5 Mg/Kg Total Induction
`
`Period Dose By Modifying Bodor’s Method In View Of
`
`Stelmasiak ................................................................................. 46
`
`3.
`
`A POSA Would Not Have Reasonably Expected To
`
`Treat MS Using The Claimed About 8-10- Or 10-Month
`
`
`
`ii
`
`
`
`Cladribine-Free Period By Modifying Bodor’s Method In
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`
`View Of Stelmasiak .................................................................. 47
`
`4.
`
`A POSA Would Not Have Reasonably Expected To
`
`Arrive At The Claimed About 1.7 Mg/Kg Maintenance
`
`Dose By Modifying Bodor’s Method In View Of
`
`Stelmasiak ................................................................................. 48
`
`5.
`
`A POSA Would Not Have Reasonably Expected To
`
`Arrive At A Safe And Effective Method Of Treating MS
`
`As Claimed By Modifying Bodor’s Method In View Of
`
`Stelmasiak ................................................................................. 49
`
`VI. Objective Indicia Support Non-Obviousness ................................................ 52
`
`VII. The Petition Should Be Denied Under 35 U.S.C. § 325(d) ........................... 52
`
`A.
`
`The Office Already Considered Petitioner’s Alleged Prior Art
`
`And Arguments ................................................................................... 52
`
`1.
`
`Becton Dickinson Factors (a) And (b): Asserted Art Was
`
`Considered During Examination............................................... 53
`
`2.
`
`Becton Dickinson Factor (d): Petitioner’s And The
`
`Examiner’s Arguments Are Not Materially Different .............. 54
`
`B.
`
`Petitioner Has Not Identified A Material Error By The
`
`Examiner ............................................................................................. 57
`iii
`
`
`
`
`
`Becton Dickinson Factor (c): Asserted Art Was Evaluated
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`
`1.
`
`During Examination .................................................................. 58
`
`2.
`
`Becton Dickinson Factor (e): Petitioner Has Not
`
`Identified Material Examiner Error .......................................... 60
`
`3.
`
`Becton Dickinson Factor (f): Additional Evidence Does
`
`Not Warrant Reconsideration ................................................... 63
`
`VIII. Conclusion ..................................................................................................... 64
`
`
`
`
`
`iv
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`
`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) ................................ 56, 62
`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) ........................................................... 42
`In re Enhanced Sec. Research, LLC,
`739 F.3d 1347 (Fed. Cir. 2014) ............................................................... 25-26
`In re Gurley,
`27 F.3d 551 (Fed. Cir. 1994) ......................................................................... 30
`In re Peterson,
`315 F.3d 1325 (Fed. Cir. 2003) ............................................................... 39, 40
`Invitrogen Corp. v. Biocrest Mfg., L.P.,
`327 F.3d 1364 (Fed. Cir. 2003) ..................................................................... 11
`
`
`
`v
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`
`Omega Eng’g, Inc. v. Raytek Corp.,
`334 F.3d 1314 (Fed. Cir. 2003) ............................................................... 10-11
`Phillips v. AWH Corp.,
`415 F.3d 1303 (Fed. Cir. 2005) ................................................................. 6, 15
`R.J. Reynolds Vapor Co. v. Fontem Holdings 1 B.V.,
`IPR2017-01642, Paper 10 (P.T.A.B. Jan. 16, 2018) ..................................... 58
`Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd.,
`492 F.3d 1350 (Fed. Cir. 2007) ............................................................... 42-43
`TWi Pharms. Inc. v. Merck Serono SA,
`IPR2023-00049, Paper 10 (P.T.A.B. Mar. 28, 2023) .............................passim
`Unigene Lab’ys, Inc. v. Apotex, Inc.,
`655 F.3d 1352 (Fed. Cir. 2011) ..................................................................... 51
`Vudu Inc. v. Ideahub, Inc.,
`IPR2020-01689, Paper 16 (P.T.A.B. Apr. 19, 2021) .................................... 62
`Ziegmann v. Stephens,
`IPR2015-01860, Paper 13 (P.T.A.B. Sept. 6, 2017) ..................................... 58
`STATUTES, RULES, AND REGULATIONS
`35 U.S.C. § 314(a) ................................................................................................... 16
`35 U.S.C. § 325(d) ............................................................................................... 3, 63
`
`
`
`vi
`
`
`
`INTRODUCTION
`The Board should deny institution of inter partes review of claims 36, 38-
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`
`I.
`
`39, and 41-46 of U.S. Patent No. 7,713,947 (“challenged claims”) because
`
`Petitioner fails to show any reasonable likelihood of prevailing.
`
`Before the ’947 patent’s invention, numerous multiple sclerosis (“MS”)
`
`clinical trials concluded that high doses equivalent to at least 4.1 mg/kg oral
`
`cladribine (i.e., intravenous or subcutaneous doses of 2.1, 2.8, or 3.65 mg/kg, based
`
`on highest reported bioavailability) were “not found to be effective against MS
`
`clinical deterioration[.]” See Ex. 1015, 17541; Ex. 1016, 425 (Table III). Further,
`
`there were significant long-term safety concerns about using cladribine to treat
`
`MS, and the art provided no guidance on which specific combination of doses and
`
`dosing periods would be safe and effective. Ex. 1001, 2:59-3:2, 3:22-30; Ex. 1031,
`
`43-44; Ex. 1014, 1720; Ex. 1016, 430-431. The ’947 patent claims an MS dosing
`
`regimen based on the inventors’ surprising discovery of a specific combination of
`
`(a) cladribine dosing periods, (b) low oral cladribine weight-based doses, and (c)
`
`cladribine-free periods, which overcame the challenges of the cladribine clinical
`
`studies and provides a safe and effective method for treating MS, now approved by
`
`the FDA in MAVENCLAD®.
`
`
`1 Hereinafter, all emphasis is added unless otherwise noted.
`1
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`Petitioner’s one ground is based solely on art teaching flat dosing—neither
`
`Bodor (Ex. 1022) nor Stelmasiak (Ex. 1013) teaches or suggests weight-based
`
`dosing—and thus it is even more deficient than the ground asserted against the
`
`’947 patent in TWi Pharmaceuticals Inc. v. Merck Serono SA, in which the Board
`
`denied institution. See IPR2023-00049, Paper 10 at 20-26 (P.T.A.B. Mar. 28,
`
`2023). In that proceeding, the ground relied on Bodor and a different secondary
`
`reference, Rice, that taught subcutaneous weight-based dosing. Id. at 5, 21.
`
`Nonetheless, the Board found that “Bodor already considered Rice prior to
`
`envisioning its orally administered flat dosage” and concluded “the motivation to
`
`modify Bodor’s method of dosing to a weight-based dosage or to achieve a total
`
`dose based on weight remains missing.” Id. at 25. Petitioner here cannot establish
`
`that Bodor or Stelmasiak discloses or suggests any weight-based dosing, let alone
`
`the claimed weight-based induction or maintenance period dosing, and thus the
`
`Petition must fail.
`
`Petitioner’s Ground also fails because Petitioner does not establish why a
`
`person of ordinary skill in the art (“POSA”) would have been motivated to shift
`
`from Bodor or Stelmasiak’s flat dosing method to a weight-based one, or to modify
`
`Bodor’s method in view of Stelmasiak to arrive at the claimed about 1.7-3.5 mg/kg
`
`or 1.7 mg/kg induction period dose, or the claimed about 1.7 mg/kg maintenance
`
`period dose. Particularly in view of Petitioner’s argument that cladribine causes
`2
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`“suppression of lymphocyte counts” (Pet. 35 (citations omitted)), where a decrease
`
`in lymphocyte levels to ≤1000 cells/μL constitutes “suppression” and a “positive
`
`response” (Ex. 1002, ¶32; Pet. 16, n.6), and its declarant’s opinion that “a direct
`
`correlation exists between the dose and length of administration of cladribine and
`
`level of lymphocyte suppression” (Ex. 1002, ¶91), a POSA considering Bodor and
`
`Stelmasiak would not have been motivated to modify Bodor’s method in view of
`
`Stelmasiak to arrive at the claimed induction or maintenance period, or have any
`
`reasonable expectation of success in doing so.
`
`Further, Petitioner’s routine-optimization argument fails to explain why a
`
`POSA would have been motivated to select the claimed specific dosing method
`
`from the infinite number of potential combinations of doses, dosing period length
`
`and number, and drug-free period length and number, or have any reasonable
`
`expectation of success in doing so, when the prior art provides no guidance
`
`regarding which combination would result in a safe and effective MS treatment
`
`method.
`
`The Petition also should be denied under § 325(d). Petitioner does not
`
`dispute that it presents the same art and arguments already evaluated and overcome
`
`during prosecution. But rather than demonstrating any material error, Petitioner
`
`merely disagrees with the Examiner’s evaluation of the art and allowance of the
`
`challenged claims so institution should be denied under Advanced Bionics.
`3
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`For at least the foregoing reasons, institution of inter partes review should
`
`be denied.
`
`II. BACKGROUND
`MS is a chronic inflammatory demyelination disease of the central nervous
`
`system. Ex. 1001, 1:24-26. Clinically defined MS types include relapsing
`
`remitting MS (“RRMS”) and secondary progressive MS (“SPMS”). Id., 1:47-50.
`
`The ’947 patent specification describes five FDA-approved disease
`
`modifying treatments (“DMTs”) for MS: three beta interferons (Betaseron®;
`
`Avonex®; Rebif®), glatiramer acetate (Copaxone®), and mitoxantrone
`
`(Novantrone®). Id., 2:14-21. Other than mitoxantrone, these drugs are
`
`administered parenterally in a continuous, single-dosing phase at flat (i.e., not
`
`weight-based), fixed doses without any extended drug-free period. Ex. 1006, 947
`
`(Table 2). Mitoxantrone is administered intravenously based on body surface area
`
`every 3 months. Id. Thus, a POSA would have understood that as of December
`
`2004, most FDA-approved MS drugs used a continuous, single-dosing phase
`
`without any extended drug-free period and that none of these drugs used oral or
`
`weight-based dosing.
`
`By December 2004, several clinical trials had investigated the use of
`
`cladribine for treating MS. Most of these trials used a single, high intravenous- or
`
`subcutaneous-dose dosing phase (e.g., total doses of 2.1, 2.8, or 3.65 mg/kg per
`
`
`
`4
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`dosing period); achieving the same cladribine exposure would be expected to
`
`require even higher doses when administered orally. See Ex. 1016, 425 (Table III);
`
`Ex. 1001, 2:37-42; Ex. 1047, 295; Ex. 1031, 36. A limited number of cladribine
`
`trials used more than one dosing phase. See Ex. 1013, 5; Ex. 1014, 1716; Ex.
`
`1018, 1146-47.
`
`Despite the numerous clinical trials, “cladribine was not found to be
`
`effective against MS clinical deterioration[.]” Ex. 1015, 1754. Further, there were
`
`significant long-term safety concerns about using cladribine to treat MS, including
`
`increased cancer risk, hematologic toxicity, and bone marrow suppression. Ex.
`
`1001, 2:59-3:2, 3:22-30; Ex. 1031, 40-41; Ex. 1014, 1720; Ex. 1016, 430. And
`
`while these clinical trials used varying dosing periods and doses, nothing in the
`
`prior art taught a POSA how the combination of the different dosing variables—
`
`dose, length and number of dosing period or length of drug-free periods—would
`
`impact the treatment of MS or what specific combination (if any) would result in a
`
`safe and effective MS treatment method. Indeed, the art taught “[t]here is still
`
`more to be learned about optimal cladribine dosages, ideal timing for retreatment
`
`and how cladribine compares with other agents used to treat MS.” Ex. 1016, 431.
`
`III. PERSON OF ORDINARY SKILL IN THE ART
`Patent Owner (“PO”) reserves the right to challenge Petitioner’s definition at
`
`a later stage in this proceeding, should the Board institute trial.
`
`
`
`5
`
`
`
`IV. CLAIM CONSTRUCTION
`Petitioner contends the claim term “a maintenance period” should be
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`
`construed as “a period during which a total dose of cladribine is lower than the
`
`total dose of cladribine administered in an induction period.” Pet. 30-31.
`
`Petitioner argues that “the specification supports [such] a construction” (id.) even
`
`though Petitioner’s declarant states, “[t]he ’947 patent does not explicitly define
`
`‘maintenance period[.]’” Ex. 1002, ¶70. The Board should reject Petitioner’s
`
`construction because (1) it disregards the plain and ordinary meaning of the term
`
`“maintenance period,” as informed by the ’947 patent claims and specification; and
`
`(2) Petitioner fails to show that PO disclaimed subject matter directed to using the
`
`same dose for the maintenance and induction periods.
`
`It has long been held that the “words of a [patent] claim are generally given
`
`their ordinary and customary meaning” “in the context of the entire patent,
`
`including the specification.” Phillips v. AWH Corp., 415 F.3d 1303, 1312-13 (Fed.
`
`Cir. 2005) (en banc) (internal citations and quotations omitted).
`
`First, a POSA considering the plain language of the ’947 patent claims and
`
`specification would have understood a “maintenance period” means “a treatment
`
`period that follows an induction period and a cladribine-free period.” For example,
`
`claim 36 recites a “method of treating [MS] … following the sequential steps …
`
`[of] (i) an induction period …, (ii) a cladribine-free period …, (iii) a maintenance
`
`
`
`6
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`period …, (iv) a cladribine-free period[.]” Ex. 1001, 19:13-30; see also id., 16:53-
`
`17:4 (claim 1), 18:7-24 (claim 20). Similarly, Example 1 of the ’947 patent
`
`discloses a study in which the “maintenance period” occurs “at month 13,” after an
`
`“induction period” and a cladribine-free period. Id., 15:50-16:3. Thus, a POSA
`
`considering the claims and specification would have understood that a maintenance
`
`period is a treatment period that follows an induction period and a cladribine-free
`
`period.
`
`Contrary to Petitioner’s assertion, a POSA would not understand the term
`
`“maintenance period” itself to require administration of any particular dose of
`
`cladribine. Instead, other language in the claims specifies the exact dose to be
`
`administered during the maintenance period. See, e.g., id., 19:13-30 (claim 36,
`
`reciting “the total dose of cladribine reached at the end of the maintenance period
`
`is about 1.7 mg/kg”). Thus, Petitioner’s attempt to read a dosing amount into the
`
`construction of “maintenance period” is improper.
`
`Indeed, Petitioner’s argument that a maintenance period requires a lower
`
`total dose than the induction period dose is directly contradicted by the claim
`
`language, which makes clear that the total cladribine dose administered during a
`
`maintenance period can be either the same as or lower than that administered
`
`during the induction period. For example, independent claims 1 and 20 expressly
`
`recite “wherein the total dose of cladribine reached at the end of the maintenance
`7
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`period is lower than the total dose of cladribine reached at the end of the induction
`
`period” (i.e., the “lower than” limitation). Id., 16:53-17:4, 18:7-24. On the other
`
`hand, independent claim 36 recites “the total dose of cladribine reached at the end
`
`of the induction period is from about 1.7 mg/kg to about 3.5 mg/kg” and “the total
`
`dose of cladribine reached at the end of the maintenance period is about 1.7
`
`mg/kg[.]” Id., 19:13-30. That is, if the total dose administered during the
`
`induction period were about 1.7 mg/kg (the low end of the claimed range), then the
`
`total dose administered during the maintenance period would be the same as the
`
`total dose administered during the induction period. In fact, claim 39, which
`
`depends from claim 36, expressly recites that “the total dose of cladribine reached
`
`at the end of the induction period is about 1.7 mg/kg.” Id., 20:5-7. A POSA would
`
`thus have understood that claim 39 requires the total cladribine dose during the
`
`induction period to be the same as the total cladribine dose during the maintenance
`
`period, i.e., “about 1.7 mg/kg” in each case. Thus, reading the claims as a whole, a
`
`POSA would have understood that the total dose of cladribine administered during
`
`the maintenance period could be either the same as or lower than the total dose
`
`administered during the induction period.
`
`Consistent with the claims, the specification describes embodiments wherein
`
`the total cladribine dose administered during a maintenance period is the same as
`
`or lower than the total dose of cladribine administered during the induction period.
`8
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`Example 1 discloses a study in which patients in Groups 2 and 3 receive a total
`
`induction period dose of 1.75 and 3.5 mg/kg cladribine, respectively. Id., 14:18-
`
`15:64. After a cladribine-free period, Groups 2 and 3 both “receive re-treatment
`
`with Cladribine … for 2 months (maintenance period) with the lower dose,” i.e.,
`
`the lower of the two induction period doses—1.75 mg/kg. Id., 15:65-16:3; see also
`
`id., 14:63-15:22 (“[A]dministration schemes for the induction period … are given
`
`below in Tables 3 and 4 for the target doses of 1.75 mg/kg and 3.5 mg/kg
`
`respectively. For the maintenance period, the example of administration scheme of
`
`Table 3 is applicable,” which discloses a target dose of “1.75 mg/kg”); 16:4-9.
`
`Thus, for Group 3, the total cladribine dose during the maintenance period is lower
`
`than that administered during the induction period, whereas for Group 2, the total
`
`doses administered for each of the induction and maintenance periods are the
`
`same, i.e., 1.75 mg/kg.
`
`The ’947 patent further describes embodiments wherein the total cladribine
`
`dose administered during a maintenance period is the same as that administered
`
`during the induction period. For example, “[i]n a further preferred embodiment,”
`
`“the total dose of Cladribine reached at the end of the induction period is about 1.7
`
`mg/kg” and “the total dose of Cladribine reached at the end of the maintenance
`
`period is about 1.7 mg/kg.” Id., 13:10-12, 13:25-27.
`
`
`
`9
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`Thus, a POSA reading the claim term “maintenance period” in the context of
`
`the claims and the specification would have understood that its plain and ordinary
`
`meaning is “a treatment period that follows an induction period and a cladribine-
`
`free period,” without requiring administration of a particular dose. Instead, the
`
`total doses for the maintenance period are clearly recited in the claims, e.g., “lower
`
`than the total dose of cladribine reached at the end of the induction period” in
`
`claims 1 and 20; or “about 1.7 mg/kg” in claim 36. The claims and specification
`
`clearly describe and support that the total cladribine dosing during a maintenance
`
`period can be either the same as or lower than the total dose of cladribine
`
`administered during the induction period.
`
`Second, Petitioner fails to show that PO disclaimed a maintenance period
`
`dosing that was the same as the induction period dosing and thus cannot overcome
`
`the plain and ordinary meaning of a “maintenance period” as claimed.
`
`Courts have declined to apply the doctrine of prosecution disclaimer where
`
`an alleged infringer’s arguments fail to “show the patentee expressly relinquished
`
`claim scope,” and thus are insufficient to “overcome [the] heavy presumption that
`
`claim terms carry their full ordinary and customary meaning[.]” Epistar Corp. v.
`
`Int’l Trade Comm’n, 566 F.3d 1321, 1334 (Fed. Cir. 2009). “[F]or prosecution
`
`disclaimer to attach, [Federal Circuit] precedent requires that the alleged
`
`disavowing actions or statements made during prosecution be both clear and
`10
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`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 Beutler 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 had no reason to challenge the Examiner’s characterization with
`
`respect to the then-pending claims 18-37, because those claims contained an
`
`express limitation that the total dose during the maintenance period was “lower
`
`than” the induction period dose. See Ex. 1004, 3-6; Pet. 10. Thus, the Examiner’s
`
`characterization aligned with the scope of the then-pending claims. 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
`11
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`added claims specifying that the maintenance period dosing may be the same as the
`
`induction period dosing—thus directly contradicting Petitioner’s purported
`
`acquiescence. Ex. 1004, 238-245; see also Pet. 10 (Petitioner acknowledging the
`
`scope of the “already-pending” and new claims). Under these circumstances, there
`
`can be no “clear and unmistakable disavowal.”
`
`Petitioner’s arguments concerning the child patent’s prosecution history
`
`(U.S. Patent No. 8,377,903) are similarly misplaced. In the case of the ’903 patent,
`
`PO rebutted 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. Ex. 1025, 151 (“Turning to the first
`
`dosing regimen and the argument that ‘it is implied that following these 10 months,
`
`treatment with cladribine is resumed’, … nowhere in the teachings of [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’”). PO further argued that “[e]ven if one were to accept
`
`this ‘implied’ teaching in Bodor et al., 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. PO concluded that “the combined teachings of the
`
`references would not have led [a POSA] to a dosing regimen and/or total dosages
`12
`
`
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`recited in claims 1, 4, 5, 9, 10, 17, 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. 1025, 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 of the ’903
`
`patent).
`
`Likewise, the prosecution history shows the Examiner recognized the
`
`application leading to the ’903 patent included claims directed to a method having
`
`the same total cladribine dosage for the maintenance and induction periods.
`
`During prosecution, the Examiner stated:
`
`
`
`13
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`[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).
`
`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. 1025, 52-53. 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.
`
`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
`
`
`
`14
`
`
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`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
`
`further address construction of “induction period” and “maintenance period”
`
`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.
`
`
`
`15
`
`
`
`V.
`
`IPR2023-00480
`U.S. Patent No. 7,713,947
`
`PETITIONER IS NOT REASONABLY LIKELY TO PREVAIL ON
`GROUND I
`The Petition should not be instituted because Petitioner has not established a
`
`reasonable likelihood that it will prevail on Ground I, its only ground asserted. See
`
`35 U.S.C. § 314(a).
`
`The Petition challenges claims 36, 38-39, and 41-46 of the ’947 patent as
`
`unpatentable over Bodor and Stelmasiak. Pet. 33. The Petition fails at least
`
`because Petitioner fails to show that the references, even in combination, teach or
`
`suggest all limitations of the challenged claims. Neither reference teaches or
`
`suggests either an induction period as claimed or a maintenance period as claimed.
`
`In particular, neither reference teaches or suggests weight-based dosing as claimed.
`
`Furthermore, Petitioner fails to establish any motivation to modify Bodor’s flat-
`
`dosing regimen in view of Stelmasiak’s high-dose, flat-dosing method