Trials@uspto.gov
`571.272.7822
`
`Paper 15
`Date: December 20, 2023
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`TWI PHARMACEUTICALS, INC.,
`Petitioner,
`
`v.
`
`MERCK SERONO SA,
`Patent Owner.
`_______________
`
`IPR2023-00049
`Patent 7,713,947 B2
`_______________
`
`
`Before ULRIKE W. JENKS, ZHENYU YANG, and TINA E. HULSE,
`Administrative Patent Judges.
`
`JENKS, Administrative Patent Judge.
`
`
`
`
`DECISION
`Granting Petitioner’s Request for Rehearing
`37 C.F.R. § 42.71(d)
`Granting Institution of Inter Partes Review
`35 U.S.C. § 314
`
`
`
`
`571.272.7822
`
`Paper 15
`Date: December 20, 2023
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`TWI PHARMACEUTICALS, INC.,
`Petitioner,
`
`v.
`
`MERCK SERONO SA,
`Patent Owner.
`_______________
`
`IPR2023-00049
`Patent 7,713,947 B2
`_______________
`
`
`Before ULRIKE W. JENKS, ZHENYU YANG, and TINA E. HULSE,
`Administrative Patent Judges.
`
`JENKS, Administrative Patent Judge.
`
`
`
`
`DECISION
`Granting Petitioner’s Request for Rehearing
`37 C.F.R. § 42.71(d)
`Granting Institution of Inter Partes Review
`35 U.S.C. § 314
`
`
`
`
`
`IPR2023-00049
`Patent 7,713,947 B2
`
`INTRODUCTION
`I.
`TWi Pharmaceuticals, Inc. (“Petitioner”) requests rehearing of our
`Institution Decision (“Decision”) denying inter partes review of claims 36,
`38, 39, and 41–48 of U.S. Patent No. 7,713,947 B2 (Ex. 1001, “the ’947
`patent”) entered on March 28, 2023 (Paper 10, “Dec.”). Paper 11 (“Req.
`Reh’g”). Petitioner requested institution of inter partes review on the basis
`of anticipation by Bodor1 under 35 U.S.C. § 102(e), obviousness under
`35 U.S.C. § 103(a) over Bodor and the knowledge of a person of ordinary
`skill in the art, and obviousness under 35 U.S.C. § 103(a) over Bodor and
`Rice.2 Paper 1 (“Pet.”).
`In its Request for Rehearing, Petitioner contends that the Board
`overlooked or misapprehended that the inventors of the ’947 patent did not
`invent weight-based dosing, overlooked or misapprehended the scope of the
`prior art references and materials incorporated by reference therein, and
`misinterpreted the claims. See generally Req. Reh’g.
`For the following reasons, Petitioner’s Request for Rehearing is
`granted, and we institute trial on all challenged claims on all grounds raised
`in the Petition. See Pet. 27–55.
`
`STANDARD OF REVIEW
`II.
`A party requesting rehearing has the burden to show a decision should
`be modified by specifically identifying all matters the party believes were
`misapprehended or overlooked, and the place where each matter was
`
`
`1 US 7,888,328 B2, issued Feb. 15, 2011 (Ex. 1029, “Bodor”).
`2 Rice et al., Cladribine and progressive MS: Clinical and MRI outcomes of
`a multicenter controlled trial, NEUROLOGY, 54(5):1145–1155 (2000) (Ex.
`1008, “Rice”).
`
`2
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`IPR2023-00049
`Patent 7,713,947 B2
`
`addressed previously in a motion, opposition, or a reply. 37 C.F.R.
`§ 42.71(d). When rehearing a decision on institution, we review the decision
`for an abuse of discretion. 37 C.F.R. § 42.71(c). An abuse of discretion may
`arise if a decision is based on an erroneous interpretation of law, if a factual
`finding is not supported by substantial evidence, or if the decision represents
`an unreasonable judgment in weighing relevant factors. Star Fruits S.N.C. v.
`United States, 393 F.3d 1277, 1281 (Fed. Cir. 2005); Arnold P’ship v. Dudas,
`362 F.3d 1338, 1340 (Fed. Cir. 2004); In re Gartside, 203 F.3d 1305, 1315–
`16 (Fed. Cir. 2000).
`
`III. ANALYSIS
`Independent claim 36 recites, “[a] method of treating multiple
`sclerosis comprising the oral administration of a formulation comprising
`cladribine” following the sequential steps of administrating cladribine during
`an induction period, followed by a cladribine-free period, followed by a
`cladribine maintenance period, followed by a cladribine-free period.
`Ex. 1001, 19:14–30. The total amount of cladribine administered during the
`induction period is in a range from 1.7–3.5 mg/kg, while the total amount of
`cladribine administered during the maintenance period is about 1.7 mg/kg.
`Id.
`
`In the Decision, we found that Petitioner has not shown that the
`dosage of cladribine administered in Bodor’s maintenance period “would
`necessarily be” the same dosage administered in the first round because
`Bodor instructs that its methods are to be used with continuous clinical
`evaluations for beneficial effect to determine any need for adjusting a
`particular treatment dose, instead of remaining silent on the dosage for
`subsequent rounds. Dec. 13–14. Specifically, we found that Bodor’s teaching
`3
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`Patent 7,713,947 B2
`
`to adjust the dosage of cladribine does not involve considerations based on
`patient weight, but instead focuses on “the particular exigencies specific to a
`given mammal” and “concurrent evaluation of beneficial effect.” Ex. 1029,
`13:31–40; Dec. 12, see also id. at 16.
`In its Request for Rehearing, Petitioner argues that we overlooked or
`misapprehended the scope of Patent Owner’s claims because “the
`Challenged Claims do not require the maintenance period to be at the same
`dosage—the issue is that they allow the maintenance period to be at the
`same dosage.” Req. Reh’g 13 (emphasis omitted). Petitioner argues that we
`overlooked or misapprehended its evidence because the claims do not
`exclude “flat dosing,” or dosing with the same amount of cladribine every
`day during the induction and maintenance period cycles. Req. Reh’g 14
`(citing Pet. 42–48). Petitioner contends that instead, the claims require that
`the total dosage of cladribine reaches the claimed amounts, and Bodor
`discloses those amounts when the drug is administered to a patient of
`average weight. Id.
`Having reconsidered the record before us, we are persuaded that
`Petitioner has met its burden under 37 C.F.R. §§ 42.71(c) and (d) and
`presented sufficient evidence to support a reasonable likelihood that Bodor
`either alone or in combination with Rice renders obvious the method of
`treating multiple sclerosis by administering cladribine to a patient in the
`same claimed total amount for both the induction period and maintenance
`period to support Petitioner’s challenge to claim 36.
`To summarize, Bodor teaches two treatment regimens for treating
`multiple sclerosis with a cladribine-cyclodextrin complex.
`
`4
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`IPR2023-00049
`Patent 7,713,947 B2
`
`10 mg of cladribine in the instant complex cladribine-
`cyclodextrin complex . . . would be administered [orally] once
`per day for a period of five to seven days in the first month,
`repeated for another period of five to seven days in the second
`month, followed by ten months of no treatment. Alternatively the
`patient would be treated with 10 mg of cladribine in the instant
`complex cladribine-cyclodextrin complex in the instant dosage
`form once per day for a period of five to seven days per month
`for a total of six months, followed by eighteen months of no
`treatment.
`
`Ex. 1029, 13:20–30. Petitioner acknowledges that Bodor does not explicitly
`suggest applying the same regimen again after a cladribine-free period but
`finds that repeating the treatment protocol is reasonably inferred. Pet. 33
`(citing Ex. 1005 ¶¶ 109, 111–113), see id. at 48 (citing Ex. 1005
`¶¶ 168–170); Ex. 1029, 18:45–19:3, 20:1–20 (Examples 4 and 5 each
`describing that treatment days are separated by cladribine-free days); Ex.
`1003 at 389; Ex. 1004 at 141. Bodor also teaches that the dosing regimen
`can be tailored to suit the needs of the patient. Specifically, Bodor teaches
`that “one of skill will appreciate that the therapeutically effective amount of
`cladribine administered . . . may be lowered or increased by fine tuning
`and/or by administering cladribine . . . with another active ingredient.” Ex.
`1029, 13:31–35, see also id. 13:37–40 (“Therapeutically effective amounts
`may be easily determined . . . empirically by starting at relatively low
`amounts and by step-wise increasing with concurrent evaluation of
`beneficial effect.”). Based on these disclosures, we agree with Petitioner that
`it would be reasonable to infer from Bodor’s teachings in conjunction with
`the knowledge of the ordinary artisan that the cladribine dosing protocol in
`Bodor is repeated. Pet. 33; see also Ex. 1005 ¶¶ 109–123, 119 (“common
`practice in the industry when prescribing a second round of an
`
`5
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`IPR2023-00049
`Patent 7,713,947 B2
`
`immunosuppressant was to utilize the same dosing regimen as in the
`induction phase”).
`In its Request for Rehearing, Petitioner argues that we misinterpreted
`the claims. “All that is required is that the total dose reach a stated level in
`each period, and Bodor discloses a total dose within that range for what a
`person of ordinary skill in the art would understand to be an average
`patient.” Req. Reh’g 14 (emphasis omitted) (citing Pet. 42–48).
`Dr. Greenberg testifies that Bodor’s total dosage of cladribine ranges from
`100–140 mg in the two-month treatment period. Ex. 1005 ¶ 104. The issue,
`as presented by Petitioner, is that the ’947 patent claims simply use a
`different way of reciting a total dose of cladribine administered during the
`treatment phase when compared to the methods and dosage taught by Bodor.
`We agree with Petitioner that the method and cladribine dosage in the ’947
`patent claims overlap with the method and dosage taught by Bodor.
`To determine the total amount of cladribine administered as claimed
`in the ’947 patent requires knowledge of the weight of the patient. In the
`Petition, Petitioner relied on a patient weighing 70 kilograms (≈ 154 pounds)
`to be an acceptable average human weight as understood in the medical
`community. Pet. 31 (citing Ex. 1005 ¶ 105). Patients, however, come in all
`shapes and sizes as recognized in the ’947 patent disclosure and further
`supported by Dr. Greenberg’s testimony and referenced exhibit. See
`Ex. 1001, 3:8 (“patients of about 52 and about 75 kilos); see also Ex. 1005
`¶ 106 (“the average weight of individuals in the United States is higher than
`the global average, with an overall average weight (men and women
`combined) of roughly 177 lbs in 2002.”); Ex. 1030 (“the average weight for
`men aged 20-74 years rose dramatically from 166.3 pounds in 1960 to 191
`
`6
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`IPR2023-00049
`Patent 7,713,947 B2
`
`pounds in 2002, while the average weight for women the same age increased
`from 140.2 pounds in 1960 to 164.3 pounds in 2002.”). To arrive at the
`average weight of 177 pounds means that there are patients in the population
`that are above and below that average. See generally Ex. 1030.
`Dr. Greenberg provides calculations for the total cladribine dose
`administered based on the method disclosed in the ’947 patent claims.
`Dr. Greenberg’s calculations are based on a patient weighing either
`70 kilograms or 80.28 kilograms. Ex. 1005 ¶¶ 105– 106. Applying the lowest
`claimed dosage of 1.7 mg/kg as recited in the ’947 patent claims, the
`70-kilogram patient would receive a total dose of 119 mg while the
`80.28-kilogram patient would receive 136 mg cladribine. Ex. 1001,
`19:17-28; Ex. 1005 ¶¶ 104 (“10 mg oral tablet may be administered to a
`patient (10 –14 days), and the resulting range of total dosages (100 mg–140
`mg in 10 mg increments)”), 107 (“the dosing regimen of Bodor would
`recognize that it disclosed oral administration of 10 mg doses of cladribine
`over a two-month period, with the total dose achieved at the end of that
`period being about 1.7 mg/kg for a sizeable amount of the patient
`population, which is within the claimed range of about 1.7 mg/kg to about
`3.5 mg/kg.”).
`In our Decision, we found that “Petitioner’s examples involve a
`strategic selection of patient weights and treatment durations that support
`calculations resulting in a 1.7 mg/kg total dosage for the treatment period . . .
`[however, this] demonstrates only the total dose that is possible for some
`patients.” Dec. 13, see also 18 (“It is only by employing a strategy that
`exemplifies treatment of patients having specifically selected weights and
`specifically selected treatment durations that Petitioner is able to show that
`
`7
`
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`IPR2023-00049
`Patent 7,713,947 B2
`
`Bodor’s method of treating MS with 10 mg of the cladribine complex daily
`arrives at about a total dosage of 1.7 mg/kg at the end of a treatment
`period.”). Upon review of Petitioner’s arguments, our focus in the Decision
`on that single 70 kg patient as being insufficient was in error. Here, Bodor’s
`treatment method of administering 100– 140 mg of cladribine to a patient
`population ranging anywhere in size from 70–80.28 kilograms would
`reasonably overlap with the dosage as recited in the ’947 patent. See Pet. 45
`(“These teachings arrive at 1.7 mg/kg for numerous patients and a large
`section of the patient population.”); Ex. 1005 ¶ 107 (a person of ordinary
`skill in the art “reading the dosing regimen of Bodor would recognize that it
`disclosed oral administration of 10 mg doses of cladribine over a two-month
`period, with the total dose achieved at the end of that period being about 1.7
`mg/kg for a sizeable amount of the patient population.”), see also id. at
`¶¶ 105-106. “[W]here there is a range disclosed in the prior art, and the
`claimed invention falls within that range, there is a presumption of
`obviousness.” Iron Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317,
`1322 (Fed. Cir. 2004).
`As for the remaining arguments in the Request regarding Bodor either
`alone or in the combination with Rice, we will revisit those issues after the
`record has been fully developed. Req. Reh’g 9–15.
`
`IV. 35 U.S.C. § 325(d)
`
`Section 325(d) provides that the Director3 may “reject the petition” if
`“the same or substantially the same prior art or arguments previously were
`
`
`3 The Board institutes trial on behalf of the Director. 37 C.F.R. § 42.4(a).
`8
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`IPR2023-00049
`Patent 7,713,947 B2
`
`presented to the Office.” The Board analyzes this issue under a two-part
`framework:
`
`(1) [determining] whether the same or substantially the same art
`previously was presented to the Office or whether the same or
`substantially the same arguments previously were presented to
`the Office; and (2) if either condition of [the] first part of the
`framework is satisfied, [determining] whether the petitioner has
`demonstrated that the Office erred in a manner material to the
`patentability of challenged claims.
`
`Advanced Bionics, Paper 6 at 8.
`The first prong of the Advanced Bionics framework requires us to
`determine whether the Petition advances the same or substantially the same
`art or arguments that were previously presented to the Office. Advanced
`Bionics, 8.
`Patent Owner argues that we should exercise our discretion under
`§ 325(d) and deny institution. Prelim. Resp. 8–21. Specifically, Patent
`Owner argues that the same or substantially the same prior art and arguments
`that Petitioner relies on for its grounds of unpatentability—namely, “Bodor’s
`counterpart—Bodor ’101 (Ex. 1007), which Petitioner states has the same
`disclosure as Bodor (Pet., 24–25, n.4)—and Rice were considered by the
`Examiner during prosecution.” Id. at 9.
`Petitioner acknowledges that “Bodor was present during prosecution.”
`Pet. 12; see also id. at 25 n.4 (“Bodor was also published as WO
`2004/087101 A2, which was published on October 14, 2004, and therefore
`prior art under § 102(a). Ex. 1007. Both references have the same
`disclosure.”). Petitioner also acknowledges that Rice was considered during
`prosecution. Pet. 18 (“The Examiner considered Rice (submitted via an
`IDS)”).
`
`9
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`IPR2023-00049
`Patent 7,713,947 B2
`
`Here, both Petitioner and Patent Owner agree that Bodor and Rice
`were before the Office, therefore, the first part of the framework is satisfied.
`See Pet. 12, 18; Prelim Resp. 9.
`Next, we consider “whether the petitioner has demonstrated that the
`Office erred in a manner material to the patentability of challenged claims.”
`Advanced Bionics, 8. Patent Owner argues that “Petitioner fails to identify
`any error by the Examiner.” Prelim. Resp. 15 (citing Advanced Bionics, 8– 9,
`n.9). Patent Owner contends that “[t]he Examiner made the same argument
`that Petitioner currently makes in alleging that Bodor discloses a specific
`dose within the claimed dose range, thus reading on the claimed range.”
`Prelim. Resp. 16 (emphasis removed). Patent Owner contends that they
`“repeatedly argued that Bodor did not teach a maintenance dosage as
`claimed—neither the same as nor lower than the total induction dosage.” Id.
`at 19 (emphasis removed).
`Petitioner contends that under the second prong of the Advanced
`Bionics framework the Office erred in allowing the broader claim 36.
`
`[C]laim 36 recites a total dosage range for the induction period
`(about 1.7 mg/kg to about 3.5 mg/kg) and a total dosage range[]
`for the maintenance period (about 1.7 mg/kg). Ex. 1001 at 12,
`col. 19, ℓℓ. 14–30. While most of the claimed dosage range for
`the induction period is higher than the claimed total dosage
`during the maintenance period, the claimed dosage range
`includes a value that is equivalent to the claimed total dosage
`during the maintenance period (1.7 mg/kg). As such, the literal
`language of claim 36 is not limited to a treatment regime where
`the total dose of cladribine during the maintenance period is
`lower than the total dose of cladribine during the induction
`period, and in fact, claim 36 covers an embodiment where the
`
`10
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`IPR2023-00049
`Patent 7,713,947 B2
`
`total dose of cladribine during the maintenance period is equal
`to the total dose of cladribine during the induction period.
`
`Pet. 12–13. Petitioner contends that “the equal dosages embodiment [of
`claim 36] was never properly examined during prosecution” and urges us to
`institute. Pet. 17. Petitioner contends that “Examiner either misapprehended
`the scope of claim 36 or overlooked it.” Pet. 14.
`Petitioner contends that both “Examiner and Patent Owner understood
`Bodor to teach the equivalent dosages embodiment.” Pet. 14 (citing Ex.
`1003, 389 (Office Action mailed Aug. 3, 2009) (“Bodor teaches that for the
`treatment of multiple sclerosis, 10 mg of cladribine in solid dosage form is
`to be administered orally once per day for a period of five to seven days in
`the first month, repeated for a period of five to seven days in the second
`month, followed by 10 months of no treatment.”); Ex. 1004, 141); see also
`Ex. 1004, 156 (Office Action Response in child ’173 application) (“Rather,
`the teaching of the reference [Bodor] would suggest that the same dosing
`regime be applied to the patient. . . . This would have resulted in the same
`total dose of cladribine being administered to the patient in both the
`induction phase and the maintenance phase.”). Petitioner contends that
`because Examiner understood Bodor to teach administering the same dose of
`cladribine during the induction and maintenance phase, the only reasonable
`explanation for allowing claim 36 is that Examiner understood “claim 36 to
`mean that the total cladribine dosage in the induction phase must be one of
`the numbers higher than 1.7 mg/kg (misconstruing the claim term in a way
`that impacts patentability).” Pet. 15.
`Having considered the record, we agree with Petitioner that the Office
`erred in its evaluation of the cited art (now asserted) as required by
`
`11
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`IPR2023-00049
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`
`Advanced Bionics. Advanced Bionics cautions that “[i]f reasonable minds
`can disagree regarding the purported treatment of the art or arguments, it
`cannot be said that the Office erred in a manner material to patentability.”
`Paper 6, 9. Here, both Examiner and Patent Owner interpret Bodor to
`disclose administering the same dose of cladribine in both the induction and
`maintenance phase. Claim 36 encompasses administering the same dose of
`cladribine – 1.7 mg/kg – in both the induction and maintenance phase. By
`interpreting claim 36 as requiring a maintenance dose that is lower than the
`induction dose, we agree with Petitioner that Examiner misapprehended the
`scope of claim 36.
`We, therefore, decline to exercise our discretion to deny institution
`under § 325(d).
`
`V. CONCLUSION
`After considering the evidence and arguments presented in the current
`record, we determine that Petitioner has demonstrated a reasonable
`likelihood of success in proving that at least one of the challenged claims of
`the ’947 patent is unpatentable. Patent Owner has not persuaded us to
`exercise our discretion to deny institution of trial. We, therefore, institute
`trial on all challenged claims and on all grounds raised in the Petition.
`At this stage of the proceeding, we have not made a final
`determination as to the patentability of any challenged claim or as to the
`construction of any claim term. Any final determination will be based on the
`record developed during trial. We place Patent Owner on express notice that
`any argument not asserted in a timely-filed Response to the Petition, or in
`another manner permitted during trial, shall be deemed waived, even if that
`argument was presented in the Preliminary Response.
`12
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`
`VI. ORDER
`ORDERED that Petitioner’s Request for Rehearing is granted;
`FURTHER ORDERED that, pursuant to 35 U.S.C. § 314(a), an inter
`partes review of claims 36, 38, 39, and 41–48 of the ’947 patent is instituted
`with respect to the grounds set forth in the Petition; and
`FURTHER ORDERED that, pursuant to 35 U.S.C. § 314(c) and
`37 C.F.R. § 42.4(b), inter partes review of the ’947 patent shall commence
`on the entry date of this Order, and notice is hereby given of the institution
`of a trial.
`
`
`13
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`IPR2023-00049
`Patent 7,713,947 B2
`
`FOR PETITIONER:
`Philip Segrest
`Nathan Sportel
`Stephen Howe
`HUSCH BLACKWELL, LLP
`philip.segrest@huschblackwell.com
`nathan.sportel@huschblackwell.com
`steve.howe@huschblackwell.com
`
`FOR PATENT OWNER:
`
`Emily Whelan
`Deric Geng
`Cindy Kan
`WILMER CUTLER PICKERING HALE AND DORR LLP
`emily.whelan@wilmerhale.com
`deric.geng@wilmerhale.com
`cindy.kan@wilmerhale.com
`
`14
`
`
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