Trials@uspto.gov
`571-272-7822
`
`Paper 10
`Entered: September 22, 2023
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`HOPEWELL PHARMA VENTURES, INC.,
`Petitioner,
`v.
`MERCK SERONO S.A.,
`Patent Owner.
`
`IPR2023-00480
`Patent 7,713,947 B2
`
`
`
`
`
`
`
`
`
`Before ZHENYU YANG, ROBERT A. POLLOCK, and TIMOTHY G.
`MAJORS, Administrative Patent Judges.
`MAJORS, Administrative Patent Judge.
`
`DECISION
`Granting Institution of Inter Partes Review
`35 U.S.C. § 314
`
`
`
`
`
`
`
`
`571-272-7822
`
`Paper 10
`Entered: September 22, 2023
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`HOPEWELL PHARMA VENTURES, INC.,
`Petitioner,
`v.
`MERCK SERONO S.A.,
`Patent Owner.
`
`IPR2023-00480
`Patent 7,713,947 B2
`
`
`
`
`
`
`
`
`
`Before ZHENYU YANG, ROBERT A. POLLOCK, and TIMOTHY G.
`MAJORS, Administrative Patent Judges.
`MAJORS, Administrative Patent Judge.
`
`DECISION
`Granting Institution of Inter Partes Review
`35 U.S.C. § 314
`
`
`
`
`
`
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`
`INTRODUCTION
`I.
`Hopewell Pharma Ventures, Inc. (“Petitioner” or “Hopewell”) filed a
`Petition (Paper 2, “Pet”) requesting inter partes review of claims 36, 38, 39,
`and 41–46 of U.S. Patent No. 7,713,947 B2 (Ex. 1001, “the ’947 patent”).
`Pet. 1, 33. Merck Serono S.A. (“Patent Owner” or “Merck”) filed a
`Preliminary Response (Paper 8, “Prelim. Resp.”).
`Under 35 U.S.C. § 314(a), an inter partes review may not be instituted
`unless it is determined that there is a reasonable likelihood that the petitioner
`will prevail with respect to at least one of the claims challenged in the
`petition. Considering the parties’ arguments and evidence, for the reasons
`set forth below, we conclude that Petitioner demonstrates a reasonable
`likelihood of prevailing with respect to at least one of the ’947 patent’s
`challenged claims. We decline to deny the Petition on the basis of discretion
`under 35 U.S.C. § 325(d) as sought by Patent Owner. We therefore institute
`an inter partes review on all challenged claims. See SAS Inst. Inc. v. Iancu,
`138 S. Ct. 1348, 1355 (2018).
`Any findings and conclusions at this stage are preliminary and based
`on the current record. This is not a final decision on the patentability of the
`challenged claims. Any such final decision will be based on a complete
`record developed through trial.
`II. BACKGROUND
`Real Parties-in-Interest
`A.
`Petitioner identifies itself and the following entities as real parties-in-
`interest: Hopewell Pharma Ventures LLC; Levy SPV, LLC; GLS Capital
`Partners Fund I, LP; GLS Capital Partners GP, LLC; and GLS Capital, LLC.
`Pet. 68–69. Merck identifies itself along with Merck KGaA and Ares
`Trading SA as the real parties-in-interest. Paper 3, 1.
`
`2
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`
`Related Matters
`B.
`The parties identify the following lawsuits involving assertions of the
`’947 patent: Merck KGaA et al. v. Accord Healthcare, Inc. et al., 1-22-cv-
`00974 (D. Del.); Merck KGaA et al. v. Hopewell Pharma Ventures, Inc., 1-
`22-cv-01365 (D. Del); Merck KGaA et al v. Aurobindo Pharma USA, Inc. et
`al., 1-23-cv-00039 (D. Del.). Pet. 69; Paper 3, 1.
`The parties also identify other related matters before the Board.
`Pet. 69–70; Paper 3, 1–2. Those matters include IPR2023-00481, filed by
`Hopewell, challenging U.S. Patent No. 8,377,903 (“the ’903 patent”), in
`which we institute trial concurrent with this decision.1 Paper 3, 1.
`Additionally, the parties identify IPR2023-00049 and IPR2023-00050,
`which were filed by a different petitioner (TWi Pharmaceuticals, Inc.
`(“TWi”)), challenging the ’947 and ’903 patents.2 Id. at 1–2; Pet. 69.
`The ’947 Patent & Technology Background
`C.
`The ’947 patent, titled “Cladribine Regimen for Treating Multiple
`Sclerosis,” issued on May 11, 2010. Ex. 1001, codes (45), (54). The
`application that matured into the ’947 patent was filed December 20, 2005,
`and claims the priority benefit of a provisional patent application filed
`December 22, 2004. Id. at codes (22), (60).3
`
`
`1 IPR2023-00482 involved the same parties (or their RPIs) and a patent on
`related subject matter, but that case terminated on August 16, 2023, before
`institution due to settlement. IPR2023-00482, Paper 12.
`2 The Board denied institution on the TWi-filed petitions. See IPR2023-
`00049, Paper 10; IPR2023-00050, Paper 8.
`3 Although not conceding that the ’947 patent is entitled to claim priority to
`the date this provisional application was filed (Pet. 7–8 n.3), Petitioner
`applies that date (December 22, 2004) in explaining the state of the art at
`that time and for its obviousness analysis. Id. at 2–4, 13–28. In determining
`
`3
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`According to the ’947 patent, the “invention relates to the use of
`multiple doses of Cladribine for the treatment of multiple sclerosis,
`especially relapsing-remitting multiple sclerosis or early secondary
`progressive multiple sclerosis.” Ex. 1001, 1:17–20.
`Cladribine is a chlorinated purine analogue, 2-chloro-
`2´deoxyadenosine (also known as 2-CdA). Id. at 2:24–27. Cladribine was
`known in the prior art, as were oral, i.v., and subcutaneous formulations
`including it. See, e.g., id. at 6:20–25 (noting oral formulations described in,
`for example, WO 2004/087101, which is the Bodor reference asserted in this
`proceeding). As background, the ’947 patent also notes that cladribine has
`been suggested previously as useful for treating multiple sclerosis. Id. at
`2:24–3:21 (discussing prior studies on cladribine’s use, in various forms
`including delivery via oral and subcutaneous routes, in patients with multiple
`sclerosis); see also Pet. 19–21; Ex. 1002 ¶¶ 33–52 (testimony of Dr. Aaron
`Miller on studies by Beutler, Stelmasiak, Rice, and others).
`As described in the ’947 patent, “[m]ultiple sclerosis (MS) is the most
`known chronic inflammatory demyelinating disease of the central nervous
`system in humans.” Ex. 1001, 1:25–27. “Over time, MS may result in the
`accumulation of various neurological disabilities” and “[c]linical disability
`in MS is presumed to be a result of repeated inflammatory injury with
`subsequent loss of myelin and axons, leading to tissue atrophy.” Id. at 1:30–
`34. The patent states that “MS is manifested in physical symptoms (relapses
`and disability progression), Central Nervous System (CNS) inflammation,
`brain atrophy and cognitive impairment.” Id. at 1:35–37.
`
`
`whether Petitioner has shown a reasonable likelihood that it would prevail
`herein, we will likewise apply that date.
`
`4
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`Before December 2004, it was known that lymphocytes (or T cells),
`which cells are part of the body’s acquired immune system, play a role in the
`pathophysiology of MS. Ex. 1002 ¶¶ 28–29. According to Dr. Miller,
`“[p]atients with MS ‘harbor T cells that react with CNS autoantigens’” and,
`“[a]lthough these T cells (a type of lymphocyte) may ‘remain dormant for
`decades, at some point they are activated in the periphery,’” allowing the
`cells to “‘migrate through the blood-brain barrier to the brain and spinal
`cord.’” Id. (citing Ex. 1044, 1–3; Ex. 1007, 131). “Once these T cells are
`reactivated in the CNS . . . they ‘release pro-inflammatory Th1 cytokines
`and orchestrate the destruction of the myelin sheath by various types of
`immune cells.’” Id. (citing Ex. 1007, 131). As Dr. Miller further explains,
`inflammation and resulting demyelination creates “lesions” in the affected
`tissues that can be detected and monitored. Ex. 1002 ¶¶ 15, 24, 27
`(discussing detection of active/enhancing lesions using MRI).
`According to the ’947 patent, MS is “considered to be a multi-phasic
`disease and periods of clinical quiescence (remissions) occur between
`exacerbations. Remissions vary in length and may last several years but are
`infrequently permanent.” Ex. 1001, 1:43–46. Moreover, the patent states,
`“[f]our courses of the disease are individualized: relapsing-remitting (RR),
`secondary progressive (SP), primary progressive (PP) and progressive
`relapsing (PR) multiple sclerosis.” Id. at 1:47–50. “More than 80% of
`patients with MS will initially display a RR course with clinical exacerbation
`of neurological symptoms, followed by recovery that may or may not be
`complete.” Id. at 1:51–56 (noting that disability arises from incomplete
`recovery from relapses). “Approximately, half of the patients with RRMS
`switch to a progressive course, called SPMS, 10 years after the disease[]
`onset.” Id. at 1:57–62 (noting that worsening of disability in the progressive
`
`5
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`phase results from “accumulation of residual symptoms after exacerbation
`but also from insidious progression between exacerbations”).
`There is no known cure for MS. Ex. 1002 ¶ 22 (citing Ex. 1024, 35).
`Because MS is a chronic autoimmune disease, Dr. Miller explains, patients
`ordinarily require ongoing care and repeated treatments designed to alter or
`suppress the immune system. Ex. 1002 ¶ 53 (citing Ex. 1008, 211–213).
`Dr. Miller identifies Figure 1 of Weiner (Ex. 1008), which is reproduced
`below.
`
`
`
`Ex. 1008, 212, Fig. 1. Figure 1, above, is titled a “clinical course and
`treatment of multiple sclerosis” and shows a common MS disease course,
`with the horizontal axis representing time and the vertical axis the level of
`disability. Id. (capitalization omitted). The figure includes an early “attack”
`followed by multiple “relapses,” shown by vertical bars of different heights
`on the left half of the figure; then, at the time represented by a vertical
`dashed line near the middle of the figure, the onset of a progressive phase of
`the disease with persistent disability steadily increasing as shown by the
`upwardly sloping line as one moves to the figure’s right. Id. (including,
`below the horizontal axis, a treatment strategy (e.g., improve recovery from
`
`6
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`attack, etc.) for the disease stage). According to Dr. Miller, as reflected in
`the figure above, “different therapies are designed to treat acute attacks,
`prevent or decrease the number of relapses, and prevent onset of or halt the
`progressive phase.” Ex. 1002 ¶ 53 (citing Ex. 1008, 212–213).
`As Dr. Miller further explains, “[b]ecause of the role the immune
`system plays in the underlying pathophysiology of MS, [administering]
`immunosuppressive drugs was ‘[t]he most common therapeutic approach’
`for treating MS before December 2004.” Id. ¶ 16 (citing Ex. 1013, 4;
`Ex. 1007, 131); see also id. ¶ 30 (“Because of the role autoantigen-specific
`T lymphocytes were known to play in MS, suppressing these lymphocytes
`was a target of [prior] MS therapies”). According to Dr. Miller, “[b]ecause
`cladribine caused ‘prolonged, profound suppression of lymphocyte counts,’
`researchers began studying it in MS.” Id. ¶ 16 (citing Ex. 1016, 420).
`Indeed, Dr. Miller testifies that “[i]n early studies, cladribine was shown to
`‘modulat[e] autoimmune processes involving lymphocyte abnormalities
`such as MS’ and ‘impressively decrease[]’ relapse rates” in MS patients. Id.
`(citing Ex. 1018, 1146; Ex. 1013, 5, 7). Dr. Miller testifies that, “[d]uring
`treatment, neurologists commonly assessed the therapeutic effect of
`cladribine by monitoring a patient’s lymphocyte count, with a sustained
`reduction of lymphocytes, e.g., below 1000 [cells]/µL, being characteristic
`of a treatment response.” Id. (citing Ex. 1018, 1146; Ex. 1013, 5; Ex. 1014,
`1717).
`The ’947 patent describes, in an example, a treatment regimen for
`patients with MS. Ex. 1001, 14:19–16:23 (Example 1). In a study on sixty
`patients with relapsing forms of MS, the patients were sorted into three
`groups: for the first year, Group 1 patients received placebo for 4 months
`followed by 8 months of no treatment; Group 2 patients received daily oral
`
`7
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`administration of cladribine (10 mg tablets) for about 5 days a month for
`2 months, followed by placebo for 2 months, and 8 months of no treatment
`(“total dose of about 1.75 mg/kg”); and Group 3 patients received daily oral
`administration of cladribine (10 mg tablets, as above) for about 5 days a
`month for 4 months followed by 8 months of no treatment (“total dose of
`about 3.5 mg/kg”). Id. In the second year (starting month 13), the patent
`discloses that all three groups received oral cladribine for about 5 days a
`month for 2 months at the lower dose (i.e., total of “about 1.75 mg/kg” over
`the 2 months) followed by 10 months of no treatment.4 Id. (disclosing, inter
`alia, that lymphocyte markers are monitored and that “[p]atients in Groups 2
`and 3 have a decrease in brain lesions”); see also Ex. 1001, 5:52–6:12
`(disclosing that “[e]fficacy” of cladribine for MS treatment can be measured
`by, for example, frequency of relapses, reduction of MRI-detectable lesions,
`or improvements in clinical assessments, like the “Expanded Disability
`Status Scale (EDSS)”).
`
`Illustrative Claims
`D.
`Claim 36, reproduced below, is the only independent claim challenged
`in this proceeding. It reads:
`36. A method of treating multiple sclerosis comprising the oral
`administration of a formulation comprising cladribine following
`the sequential steps below:
`
`(i) an induction period lasting from about 2 months to
`about 4 months wherein said formulation is orally administered
`and wherein 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;
`
`(ii) a cladribine-free period lasting from about 8 months to
`about 10 months, wherein no cladribine is administered;
`
`4 The ’947 patent indicates that the course of treatment continues into a third
`year (starting at month 25) that essentially repeats the regimen given during
`the second year. Ex. 1001, 16:4–9.
`
`8
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`
`(iii) a maintenance period lasting from about 2 months to
`about 4 months, wherein said formulation is orally administered
`and wherein the total dose of cladribine reached at the end of the
`maintenance period is about 1.7 mg/kg; [and]
`(iv) a cladribine-free period wherein no cladribine is
`administered.
`Ex. 1001, 19:14–30. Illustrating some of the challenged dependent claims,
`claim 39 depends from claim 36 and adds “wherein the total dose of
`cladribine reached at the end of the induction period is about 1.7 mg/kg,”
`claim 41 depends from claim 36 and adds “wherein the cladribine-free
`period (ii) lasts about 10 months,” and claim 45 depends from claim 36 and
`adds “wherein the formulation is orally administered at a daily dose of
`10 mg cladribine.” Id. at 20:5–7, 20:11–12, 20:20–22.
`Prior Art and Asserted Ground
`E.
`Petitioner asserts that claims 36, 38, 39, and 41–46 are unpatentable
`based on the following ground:
`Claims Challenged
`35 U.S.C. §5
`
`References/Basis
`
`
`36, 38, 39, 41–46
`
`
`103
`
`Bodor, 6 Stelmasiak7
`
`Petitioner also submits testimony from Aaron E. Miller, M.D., in
`support of its challenge. Ex. 1002 (Miller Decl.).
`
`
`5 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29, 125
`Stat. 284, 285–88 (2011), revised 35 U.S.C. §§ 102, 103 effective March 16,
`2013. The ’947 patent issued from an application filed before March 16,
`2013, so pre-AIA §§ 102 and 103 apply. Ex. 1001, code (22).
`6 Bodor et al., WO 2004/087101 A2, published Oct. 14, 2004 (“Bodor”
`(Ex. 1022)).
`7 Zbigniew Stelmasiak, A pilot trial of cladribine (2-chlorodeoxyadenosine)
`in remitting-relapsing multiple sclerosis, 41:1 Med. Sci. Monit. (March 1,
`1998) (“Stelmasiak” (Ex. 1013)).
`
`9
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`
`III. ANALYSIS
`Legal Standards
`A.
`“In an [inter partes review], the petitioner has the burden from the
`onset to show with particularity why the patent it challenges is
`unpatentable.” Harmonic Inc. v. Avid Tech., Inc., 815 F.3d 1356, 1363 (Fed.
`Cir. 2016) (citing 35 U.S.C. § 312(a)(3)).
`A claim is unpatentable under 35 U.S.C. § 103 if the differences
`between the claimed invention and the prior art are such that the claimed
`invention as a whole would have been obvious at the time the invention was
`made to a person having ordinary skill in the relevant art. KSR Int’l Co. v.
`Teleflex Inc., 550 U.S. 398, 406 (2007). The question of obviousness is
`resolved on the basis of underlying factual determinations including: (1) the
`scope and content of the prior art; (2) any differences between the claimed
`subject matter and the prior art; (3) the level of ordinary skill in the art; and
`(4) secondary considerations of nonobviousness when presented. Graham v.
`John Deere Co., 383 U.S. 1, 17–18 (1966).
`Moreover, “[a]n obviousness determination requires finding both that
`a skilled artisan would have been motivated to combine the teachings of the
`prior art references to achieve the claimed invention, and that the skilled
`artisan would have had a reasonable expectation of success in doing so.”
`CRFD Research, Inc. v. Matal, 876 F.3d 1330, 1340 (Fed. Cir. 2017)
`(internal quotation marks and citation omitted).
`Level of Ordinary Skill in the Art
`B.
`In determining the level of skill in the art, we consider the problems
`encountered in the art, the art’s solutions to those problems, the rapidity with
`which innovations are made, the sophistication of the technology, and the
`
`10
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`educational level of active workers in the field. Custom Accessories, Inc. v.
`Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962 (Fed. Cir. 1986).
`Petitioner proposes that the person of ordinary skill in the art
`(“POSA”) would have a “high” level of skill. Pet. 28. In more detail,
`Petitioner contends:
`A POSA here would have drawn upon the knowledge and
`experience of related disciplines of a multi-disciplinary team that
`might lie outside the POSA’s primary training. . . . A POSA for
`the ’947 patent would have the knowledge of multiple
`disciplines, such as immunology, biochemistry, and human
`physiology and anatomy, and also typically [would] be a
`clinician with experience and/or training in neurology. . . . The
`POSA typically would be a medical doctor with a specialty in
`neurology, specifically in treating autoimmune disorders of the
`nervous system, such as multiple sclerosis, and typically at least
`2 years of experience with administering treatments to patients
`and evaluating results of such treatments, as well as experience
`or knowledge in related research and development.
`Id. at 28–29 (citing Ex. 1002 ¶¶ 20–21).
`Patent Owner does not contest Petitioner’s definition for the POSA.
`Prelim. Resp. 5. For purposes of this decision, we apply Petitioner’s
`proposed POSA level, which appears consistent with the skill level reflected
`in the prior art.
`
`C. Claim Construction
`In inter partes review, we construe claims using the same claim
`construction standard used to construe claims in a civil action before the
`courts under 35 U.S.C. § 282(b), including construing claims in accordance
`with the ordinary and customary meaning as understood by the POSA and
`the patent’s prosecution history. 37 C.F.R. § 42.100(b). We need only
`construe terms that are in controversy and only as needed to resolve the
`
`11
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`matters in dispute. Realtime Data, LLC v. Iancu, 912 F.3d 1368, 1375 (Fed.
`Cir. 2019).
`Petitioner proposes constructions for the following terms: (a) “total
`dose of cladribine”; (b) “an induction period”; and (c) “maintenance period.”
`Pet. 29–33. There is no dispute at this stage that turns on interpretation of a
`“total dose of cladribine,” and we see, as pointed out by Petitioner, that
`“total dose” is defined in the ’947 patent. Ex. 1001, 4:19–26 (defining “total
`dose” as the “cumulative dose,” i.e., “the total dose of Cladribine
`administered during the treatment, i.e. the dose reached at the end of the
`treatment that is calculated by adding the daily doses”). We need not further
`address the interpretation of this term at this time.
`We discuss the terms “induction period” and “maintenance period” in
`greater detail below, starting with the “maintenance period,” which is the
`focus of the parties’ claim construction arguments.
`maintenance period
`1.
`The parties’ argument on the term “maintenance period” concerns a
`comparison between the total amount of cladribine reached at the end of the
`induction and maintenance periods. More specifically, whether
`“maintenance period” should be construed as a retreatment period “during
`which the total dose of cladribine is lower than the total dose in the
`induction period”—Petitioner’s position. Pet. 30–33 (emphasis added). Or,
`whether 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”—Patent Owner’s argument. Prelim. Resp. 10.
`The parties cite intrinsic evidence that allegedly supports their respective
`interpretations. Pet. 30–33; Prelim. Resp. 6–15.
`
`12
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`It is not wholly clear that “maintenance period” must be further
`interpreted to resolve Petitioner’s challenge. Patent Owner’s interpretation
`is broader and encompasses Petitioner’s interpretation. Nevertheless, to
`address the arguments made and give guidance for trial, we determine that
`the weight of the evidence on this preliminary record supports Patent
`Owner’s interpretation, and we conclude that the dosing of cladribine given
`during the “maintenance period” can be same as or lower than the total dose
`given during the induction period. We explain below.
`First, the language of the claims supports Patent Owner’s
`interpretation. Claim 36 expressly recites that the total dose reached at the
`end of the induction period (step (i)) “is from about 1.7 mg/kg to about
`3.5 mg/kg.” See supra Section II(D). Claim 36, step (iii), recites that the
`total dose of cladribine reached at the end of the maintenance period “is
`about 1.7 mg/kg.” The plain language of claim 36, thus, indicates that the
`cladribine dosing given during the induction period and the maintenance
`period can be the same—each “about 1.7 mg/kg.” Claim 36 also
`encompasses regimens where the maintenance period dosing (e.g.,
`1.7 mg/kg) is lower compared to the induction period dosing (e.g.,
`3.5 mg/kg). But the plain language of the claims does not require a lower
`total dose in the maintenance period. Petitioner’s construction narrows the
`claims and, in effect, asks us to rewrite the lower bound of the range recited
`in claim 36’s induction period step to be some value higher than “about
`1.7 mg/kg.” We decline to do so.
`Petitioner’s interpretation is also at odds with dependent claim 39,
`which specifies that the total dose of cladribine reached at the end of the
`induction period “is about 1.7 mg/kg.” Thus, in claim 39, the same dosing
`amount is recited for the induction and maintenance periods (“about
`
`13
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`1.7 mg/kg,” given the dependency from claim 36). Petitioner does not
`explain how its proposed “lower than” construction can be reconciled with
`the express language of claim 39.
`In addition, other claims (not challenged in this proceeding) expressly
`require that the “total dose of cladribine is lower than the total dose of
`cladribine reached at the end of the induction period.” See, e.g., Ex. 1001,
`18:7–24 (claim 20, which is otherwise substantially identical to claim 36,
`apart from using the “lower than” language not the language “about 1.7
`mg/kg” for the maintenance period) (emphasis added). The patent applicant,
`thus, knew how to draft independent claims requiring the maintenance
`period dosing be lower. But that language was not used in independent
`claim 36, which instead sets forth the amount of cladribine reached at the
`end of the maintenance period using different, numerical terms. Under such
`circumstances, Petitioner does not persuade us that we should construe claim
`36 to insert a “lower than” requirement.
`Second, the Specification of the ’947 patent supports Patent Owner’s
`interpretation. Petitioner cites a definition of “Maintenance Treatment” that
`describes a maintenance period in which the total cladribine dosage is
`“orally administered at a lower dose than the Cladribine dose orally
`administered during the induction treatment.” Ex. 1001, 5:6–11.8 That the
`maintenance period dosing may be lower than the induction period dosing is
`uncontroversial. The question is whether it must always be so. And the
`Specification answers this question: “no.” Indeed, the ’947 patent includes
`an example where the cladribine dose reached at the end of the induction
`
`
`8 Petitioner’s declarant, Dr. Miller, testifies that “[t]he ’947 patent does not
`explicitly define ‘maintenance period.’” Ex. 1002 ¶ 70.
`
`14
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`period and the maintenance period is the same (1.75 mg/kg in both periods)
`or it may alternatively be lower (1.75 mg/kg in the maintenance period and
`3.5 mg/kg in induction). Ex. 1001, 15:50–16:3 (describing the dosing
`regimen for Group 2 and Group 3 patients versus a placebo group).
`Petitioner’s claim construction argument never addresses this disclosure in
`the ’947 patent. There is no adequate basis on this record to construe
`“maintenance period” in claim 36 such that it would exclude the broader
`maintenance period dosing in the patent’s example.
`Lastly, the prosecution history does not, on balance, justify
`interpreting “maintenance period” in the manner urged by Petitioner.
`Petitioner argues that, during prosecution of the ’947 patent, Patent Owner
`accepted the Examiner’s finding that the applied prior art did not “teach that
`the total dose of cladribine reached at the end of the maintenance phase is
`lower than the total dose reached at the end of the induction phase.” Pet.
`31–32 (citing Ex. 1004, 2489). According to Petitioner, the Examiner’s
`finding and Patent Owner’s alleged acceptance of it reflect Patent Owner’s
`own understanding of the claimed invention. Id. The flaw with Petitioner’s
`argument is that “the Examiner’s characterization [of the art and claims]
`aligned with the scope of the then-pending claims” that were subject to the
`Examiner’s rejection. Prelim. Resp. 11 (citing Ex. 1004, 3–6 (pending
`claim 18, for example, expressly included the “lower than” language)).
`Claim 36 was added via a proposed amendment (as application claim 54)
`and was not, at any time during the ’947 patent’s prosecution, rejected by the
`Examiner. Ex. 1004, 243 (proposed amendment adding new claim 54, dated
`
`
`9 Citations to the prosecution histories of the ’947 and ’903 patents use the
`page numbering added to the exhibit copy, not the native pagination.
`
`15
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`Dec. 18, 2009); see also id. at 298 (Notice of Allowance dated Mar. 22,
`2010, following applicant’s Dec. 18, 2009, proposed amendment and
`remarks). The Examiner, thus, never characterized claim 36 as requiring a
`“lower” maintenance period dose compared to the induction period dose.
`Petitioner also cites statements made during prosecution of the child
`application that matured into the related ’903 patent. Pet. 31–32. According
`to Petitioner, Patent Owner “argued that the maintenance period is
`characterized by administration of a lower total dose of cladribine compared
`to the induction period (even for the pending claims that did not expressly
`require a lower dose, e.g., claim 17 and 20).” Id. at 32. Petitioner highlights
`argument raised during prosecution that “one skilled in the art would not
`have had any reason to reduce the dosage of cladribine administered
`during the ‘maintenance period’ as recited in the claims,” and that Patent
`Owner made this argument for the group of “claims 1, 4, 5, 9, 10, 17, 20 or
`21.” Id. (quoting Ex. 1025, 151) (emphasis added by Petitioner). Here, the
`prosecution colloquy cited by Petitioner comes closer to supporting
`Petitioner’s claim construction position. Immediately before applicant made
`the argument cited above, however, it argued “that nowhere in the teachings
`of the reference 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’ as defined by the
`subject application.” Ex. 1025, 151 (emphasis added); Prelim. Resp. 12–13
`(citing same and contending “PO never argued the maintenance period must
`always use a total dose lower than the induction period dose”). The
`prosecution history of the related ’903 patent is, at best for Petitioner,
`ambiguous on revealing any narrowed meaning of the “maintenance period.”
`This record does not, overall, support Petitioner’s interpretation on the basis
`
`16
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`of any alleged disclaimer, disavowal, or estoppel. Continental Circuits LLC
`v. Intel Corp., 915 F.3d 788, 798 (Fed. Cir 2019) (“[T]o operate as a
`disclaimer, the statement in the prosecution history must be clear and
`unambiguous, and constitute a clear disavowal of scope.”).
`Considering the totality of the intrinsic evidence and argument of
`record, we conclude that, as recited in claim 36, the total dose of cladribine
`reached at the end of the “maintenance period” need not be lower than the
`total dose reached at the end of the induction period. It may be the same
`(i.e., about 1.7 mg/kg) for both periods as discussed above.
`induction period
`2.
`The parties’ dispute about the meaning of “induction period” flows
`inescapably from their arguments about the maintenance period. That is, if
`the maintenance period dose must be lower, the induction period dose is
`“higher,” according to Petitioner. Pet. 29–30. Patent Owner, conversely,
`contends that the induction period’s total cladribine dose may be higher, but
`it may also be the same as the maintenance period dose. Prelim. Resp. 15.
`On this record, we agree with Patent Owner for the same reasons discussed
`above concerning the maintenance period.
`D. Obviousness over Bodor and Stelmasiak
`Petitioner contends that claims 36, 38, 39, and 41–46 would have been
`obvious over the combined teachings of Bodor and Stelmasiak. Pet. 33–61.
`Petitioner contends that Bodor and Stelmasiak are prior art to the
`’947 patent and Patent Owner provides no argument otherwise. Id. at 22, 24.
`On this record, we agree that Bodor and Stelmasiak qualify as prior art.
`We summarize the asserted prior art below before turning to the
`parties’ further arguments and our analysis.
`
`17
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`
`Bodor (Ex. 1022)
`1.
`Bodor is an international patent application that was filed March 26,
`2004, and published October 14, 2004. Ex. 1022, codes (22), (43). Bodor
`relates to “compositions of cladribine and cyclodextrin which are especially
`suited for the oral administration of cladribine.” Id. at Abstr.
`Bodor teaches that “[o]ral delivery of drugs is often preferred to
`parenteral delivery for a variety of reasons.” Id. at 2:9–10. “[F]oremost,”
`among the reasons given by Bodor, is “patient compliance.” Id. “Patient
`compliance is enhanced insofar as oral dosage forms alleviate repeated
`health care provider visits, or the discomfort of injections or prolonged
`infusion times associated with some active drugs.” Id. at 2:11–13.
`“However,” Bodor teaches, “to date the oral delivery of cladribine has
`been plagued by low bioavailability . . . and suboptimal interpatient
`variation.” Id. at 2:22–25. Bodor teaches that “[i]t has now been found that
`amorphous cyclodextrins can be combined to form a particularly
`advantageous product which can be incorporated into a solid oral dosage
`form.” Id. at 5:2–4. “This product is a [] cladribine-cyclodextrin complex,
`and solid oral dosage form containing it improves oral bioavailability and/or
`achieves lower interpatient and/or intrapatient variation of the drug.” Id. at
`5:4–7; see also id. at 11:27–12:3 (describing a cladribine and cyclodextrin
`complex “associated with improved cladribine absorption, as reflected by
`higher bioavailability and/or lower interpatient variation”).
` Bodor teaches that cladribine has “been used as an
`immunosuppressive agent and as a modality for the treatment of a variety of
`autoimmune conditions including . . . multiple sclerosis.” Id. at 2:1–5.
`Bodor discloses that “an effective amount of the complex cladribine-
`cyclodextrin . . . is used (e.g., an amount affective for the treatment of
`
`18
`
`
`
`IPR2023-00480
`Patent 7,713,947 B2
`multiple sclerosis[)].” Id. at 22:11–15. Bodor further teaches that
`“[t]herapeutically effective dosages described in the literature include those
`for . . . multiple sclerosis (from about 0.04 to about 1.0 mg/kg/day (see U.S.
`Patent No. 5,506,214)).” Id. at 22:17–22 (defining “therapeutically effective
`amount
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
