Trials@uspto.gov
`Tel: 571-272-7822
`
`
`
`
`
`Paper: 109
`Entered: July 11, 2018
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`APOTEX INC. and APOTEX CORP.,
`ARGENTUM PHARMACEUTICALS LLC, ACTAVIS ELIZABETH LLC,
`TEVA PHARMACEUTICALS USA, INC., SUN PHARMACEUTICAL
`INDUSTRIES, LTD., SUN PHARMACEUTICAL INDUSTRIES, INC.,
`and SUN PHARMA GLOBAL FZE,
`Petitioners,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`_______________
`
`
`
`Case IPR2017-008541
`Patent US 9,187,405 B2
`_______________
`
`Before CHRISTOPHER M. KAISER, ROBERT A. POLLOCK, and
`KRISTI L. R. SAWERT,2 Administrative Patent Judges.
`
`POLLOCK, Administrative Patent Judge.
`
`
`
`FINAL WRITTEN DECISION
`Claims 1–6 Not Shown to Be Unpatentable
`35 U.S.C. § 318(a); 37 C.F.R. § 42.73
`
`
`
`
`1 Cases IPR2017-01550, IPR2017-01946, and IPR2017-01929 have been
`joined with this proceeding.
`2 Replacing Judge Lora M. Green, who has left the Board.
`
`
`
`
`Tel: 571-272-7822
`
`
`
`
`
`Paper: 109
`Entered: July 11, 2018
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`_______________
`
`APOTEX INC. and APOTEX CORP.,
`ARGENTUM PHARMACEUTICALS LLC, ACTAVIS ELIZABETH LLC,
`TEVA PHARMACEUTICALS USA, INC., SUN PHARMACEUTICAL
`INDUSTRIES, LTD., SUN PHARMACEUTICAL INDUSTRIES, INC.,
`and SUN PHARMA GLOBAL FZE,
`Petitioners,
`
`v.
`
`NOVARTIS AG,
`Patent Owner.
`_______________
`
`
`
`Case IPR2017-008541
`Patent US 9,187,405 B2
`_______________
`
`Before CHRISTOPHER M. KAISER, ROBERT A. POLLOCK, and
`KRISTI L. R. SAWERT,2 Administrative Patent Judges.
`
`POLLOCK, Administrative Patent Judge.
`
`
`
`FINAL WRITTEN DECISION
`Claims 1–6 Not Shown to Be Unpatentable
`35 U.S.C. § 318(a); 37 C.F.R. § 42.73
`
`
`
`
`1 Cases IPR2017-01550, IPR2017-01946, and IPR2017-01929 have been
`joined with this proceeding.
`2 Replacing Judge Lora M. Green, who has left the Board.
`
`
`
`
`
`IPR2017-00854
`Patent US 9,187,405 B2
`
`
`
`
` INTRODUCTION
`This is a Final Written Decision in an inter partes review challenging
`the patentability of claims 1–6 of U.S. Patent No. US 9,187,405 B2
`(Ex. 1001, “the ’405 patent”). We have jurisdiction under 35 U.S.C. § 6.
`For the reasons that follow, we determine that Petitioners have failed
`to show, by a preponderance of the evidence, that claims 1–6 of the
`’405 patent are unpatentable.
`
`A.
`
`Procedural History
`Apotex Inc. and Apotex Corp. (“Apotex”) filed a Petition requesting
`an inter partes review of claims 1–6 the ’405 patent. Paper 2 (“Pet.”).
`Novartis AG3 (“Novartis”), filed a Preliminary Response to the Petition.
`Paper 8 (“Prelim. Resp.”). We instituted inter partes review of each of the
`challenged claims. Paper 11, 27 (“Dec.”).
`Three parties filed Petitions substantially the same as Apotex’s
`Petition along with requests for joinder: 1) Argentum Pharmaceuticals LLC
`(“Argentum”) (IPR2017-01550, Papers 1 and 3); 2) Actavis Elizabeth LLC
`and Teva Pharmaceuticals USA, Inc. (collectively, “Teva”) (IPR2017-
`01946, Papers 2 and 3); and 3) Sun Pharmaceutical Industries, Ltd., Sun
`Pharmaceutical Industries, Inc., and Sun Pharma Global FZE (collectively,
`“Sun”) (IPR2017-01929, Papers 2 and 3). We granted each Petition and
`
`
`3 According to Patent Owner, “Novartis AG has assigned its rights in U.S.
`Patent 9,187,405 to Novartis Pharmaceuticals Corporation (see Assignment
`at Reel 043314/Frame 0800). The real party in interest is Novartis
`Pharmaceuticals Corporation. Novartis AG and other Novartis subsidiaries
`may also have an interest.” Paper 22.
`
`2
`
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`IPR2017-00854
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`associated requests for joinder to IPR2017-00854. See IPR2017-01550,
`Paper 10; IPR2017-01946, Paper 9; IPR2017-01929, Paper 7, respectively.
`Because our grants of joinder were conditioned on Apotex taking the lead
`role in the joined proceeding, we refer to Apotex, Argentum, Teva, and Sun,
`collectively, as “Petitioners.”
`After institution of trial and our grants of joinder, Patent Owner filed a
`Patent Owner Response (Paper 26, “PO Resp.”); Petitioners filed a
`responsive Reply (Paper 49, “Pet. Reply”); and Patent Owner filed an
`authorized Sur-Reply (Paper 63, “PO Sur-Reply”).
`Patent Owner also filed a Corrected Contingent Motion to Amend.
`Paper 61. Petitioners opposed (Paper 51), and Patent Owner responded with
`a Reply in support of its motion (Paper 64).
`Petitioners rely on the declaration of Dr. Barbara S. Giesser
`(Ex. 1002), first submitted with Apotex’s Petition, and on the later-submitted
`Reply Declaration of Leslie Z. Benet, Ph.D. (Ex. 1047).
`Patent Owner relies on the declarations of Fred D. Lublin, M.D.
`(Exs. 2003, 2025, 2107, 2097), William J. Jusko, Ph.D. (Exs. 2005, 2024,
`2095), Lawrence Steinman, M.D. (Exs. 2022, 2096), and Jerold
`Chun, M.D., Ph.D, (Ex. 2098). Patent Owner further relies on the
`declaration of named inventor Christian Schnell. Ex. 2026.
`Petitioners filed motions for observations on depositions of
`Drs. Lublin, Jusko, Steinman, and Chun (Papers 77, 79, 76, and 78,
`respectively); Patent Owner filed responses to each of those motions
`(Papers 90, 93, 91, 92, respectively).
`We heard oral argument on May 11, 2018. A transcript of that
`proceeding is entered as Paper 108 (“Tr.”).
`
`3
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`IPR2017-00854
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`
`The parties filed the following motions. Petitioners filed a motion to
`exclude evidence (Paper 82); Patent Owner opposed (Paper 89); and
`Petitioners submitted a reply in support of its first motion to exclude
`(Paper 98). Patent Owner filed a first motion to exclude evidence
`(Paper 80); Petitioners opposed (Paper 94); and Patent Owner submitted a
`reply in support of its first motion to exclude (Paper 97). Patent Owner filed
`a supplemental motion to exclude evidence (Paper 102); Petitioners opposed
`(Paper 101); and Patent Owner submitted a reply in support of its
`supplemental motion to exclude (Paper 103). The parties have also filed six
`motions to seal. (Papers 36, 50, 83, 99 (by Petitioners); Papers 29, 37 (by
`Patent Owner)).
`
`B.
`
`Related Proceedings
`According to Patent Owner, there are no other judicial or
`administrative matters that would affect, or be affected by, a decision in this
`proceeding. Paper 4, 2. Petitioners note that in IPR2014-00784, the Board
`issued a Final Written Decision relating to U.S. Patent No. 8,324,283 B2,
`and that “[a]lthough not from the same patent family as the ’405 patent, the
`’283 patent included claims to pharmaceutical compositions of fingolimod,
`or a pharmaceutically acceptable salt thereof, that is suitable for oral
`administration, as well as claims directed to the treatment of multiple
`sclerosis using S1P receptor agonists.” Pet. 20; see id. at 13–14; Paper 49, 7.
`We are not persuaded, however, that the Board’s prior decision with respect
`to the ’283 patent is probative of the instant proceeding.
`
`C.
`
`The ’405 Patent and Relevant Background
`The ’405 patent, titled “S1P Receptor Modulators for Treating
`Relapsing-Remitting Multiple Sclerosis,” issued to Peter C. Hiestand and
`
`4
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`IPR2017-00854
`Patent US 9,187,405 B2
`
`Christian Schnell from U.S. Application No. 14/257,342 (“the
`’342 application”), filed April 21, 2014. Ex. 1001, at [21], [60], [71], [72].
`The ’342 application is a divisional of Application No. 13/149,468 (“the
`’468 application”) (now U.S. Pat. No. 8,741,963). Id. at [60]. The
`’468 application, in turn, is a continuation of Application No. 12/303,765
`(“the ’765 application.”), which is the U.S. entry of PCT/EP2007/005597,
`filed June 25, 2007. Id.; Ex. 1009, 21, 40. PCT/EP2007/005597 claims
`priority to foreign application GB0612721.1 (Ex. 1012), filed on June 27,
`2006. Ex. 1001, at [30]; see Ex. 1009, 57–58.
`The instant “invention relates to the use of an S1P4 receptor modulator
`in the treatment or prevention of neo-angiogenesis associated with a
`demyelinating disease, e.g. multiple sclerosis.” Ex. 1001, 1:5-8.
`“Characteristic pathological features of demyelinating diseases include
`inflammation, demyelination and axonal and oligodendrocyte loss. In
`addition[,] lesions can also have a significant vascular component. A firm
`link has recently been established between chronic inflammation and
`angiogenesis and neovascularization seems to have a significant role in the
`progression of disease.” Id. at 9:6–12. According to the inventors, “[i]t has
`now been found that S1P receptor modulators have an inhibitory effect on
`neo-angiogenesis associated with demyelinating diseases, e.g. MS.” Id. at
`9:13–15.
`“Multiple sclerosis (MS) is an immune-mediated disease of the central
`nervous system with chronic inflammatory demyelination leading to
`progressive decline of motor and sensory functions and permanent
`
`
`4 S1P refers to sphingosine-1 phosphate, a natural serum lipid. Ex. 1001,
`1:13–14.
`
`5
`
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`IPR2017-00854
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`disability.” Ex. 1001, 8:61–64. The inventors state that S1P receptor
`agonists or modulators may be useful in the treatment of MS, including the
`Relapsing-Remitting form (RR-MS), which accounts for 85% of patients’
`initial experience with the disease and is the precursor to the more
`debilitating Secondary-Progressive form (SPMS). Id. at 9:64–10:21; see
`also id. at 10:3–5 (noting that within 10 years of onset about half of RR-MS
`patients will develop SPMS); Ex. 1005,5 159–60, Fig. 1 (discussing the
`pathophysiology, classification, and clinical course of MS).
`“S1P receptor agonists or modulators are known as having
`immunosuppressive properties or anti-angiogenic properties in the treatment
`of tumors . . . .” Ex. 1001, 8:56–60. Preferred compounds stimulate
`lymphocyte homing, thereby “elicit[ing] a lymphopenia resulting from a re-
`distribution, preferably reversible, of lymphocytes from circulation to
`secondary lymphatic tissue, without evoking a generalized
`immunosuppression.” Id. at 2:17–23. “A particularly preferred S1P
`receptor agonist . . . is FTY720, i.e., 2-amino-2-[2-(4-octyphenyl)ethyl]
`propane-1, 3-diol . . . .” Id. at 8:17–30. This compound, also known as
`fingolimod, is the active ingredient in Novartis’s Gilenya product
`(fingolimod hydrochloride) approved for the treatment of RR-MS. See
`Ex. 2040, 11; Ex. 2024 ¶ 38.
`
`D.
`
`The Challenged Claims
`Illustrative claim 3 recites (paragraphing added):
`3. A method for treating Relapsing-Remitting multiple sclerosis
`in a subject in need thereof, comprising
`
`
`5 Thomson, “FTY720 in Multiple Sclerosis: The Emerging Evidence of
`its Therapeutic Value,” 1(3) CORE EVIDENCE 157-167 (2006). Ex. 1005.
`
`6
`
`
`
`IPR2017-00854
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`
`
`orally administering to said subject 2-amino-2-[2-(4-
`octylphenyl)ethyl]propane-1, 3-diol, in free form or in a
`pharmaceutically acceptable salt form,
`at a daily dosage of 0.5 mg,
`absent an immediately preceding loading dose regimen.
`The remaining independent claims differ only in the language of the
`preamble, such that the “treating” language of claim 3 is replaced with
`“reducing or preventing or alleviating relapses” (claim 1) or “slowing
`progression” of RR-MS (claim 5).
`Depending from claims 1, 3, and 5, respectively, claims 2, 4, and 6
`specify that the 2-amino-2-[2-(4-octylphenyl)ethyl]propane-1, 3-diol is the
`hydrochloride salt form—i.e., fingolimod hydrochloride.
`
`E. Grounds of Unpatentability
`We instituted trial to review the patentability of the challenged claims
`on each of the three grounds asserted in the Petition:
`Basis
`Ground Claims
`References
`§ 103
`1
`1–6
`Kovarik6 and Thomson7
`2
`1–6
`Chiba,8 Kappos 2005,9 and Budde10 § 103
`
`6 Kovarik and Appel-Dingemanse, WO 2006/058316, published
`June 1, 2006. Ex. 1004. (“Kovarik”).
`7 Thomson, “FTY720 in Multiple Sclerosis: The Emerging Evidence of its
`Therapeutic Value,” 1(3) Core Evidence 157-167 (2006). Ex. 1005.
`(“Thomson”).
`8 Chiba et al., US 6,004,565, issued Dec. 21, 1999. Ex. 1006. (“Chiba”).
`9 Kappos et al., “FTY720 in Relapsing MS: Results of a Double-Blind
`Placebo-Controlled Trial with a Novel Oral Immunomodulator,” 252 (Suppl
`2) J. Neurology Abstract O141 (2005). Ex. 1007. (“Kappos 2005”).
`10 Budde, et al., “First Human Trial of FTY720, a Novel Immunomodulator,
`in Stable Renal Transplant Patients,” 13 J. Am. Soc. Nephrology 1073-1083
`(2002). Ex. 1008. (“Budde”).
`
`7
`
`
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`IPR2017-00854
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`
`Ground Claims
`3
`1–6
`
`Paper 11, 27.
`
`References
`Kappos 201011
`
`Basis
`§ 102
`
` ANALYSIS
`
`A.
`
`Legal Principles
`To anticipate a claim under 35 U.S.C. § 102,12 “a single prior art
`reference must expressly or inherently disclose each claim limitation.”
`Finisar Corp. v. DirecTV Group, Inc., 523 F.3d 1323, 1334 (Fed. Cir. 2008).
`That “single reference must describe the claimed invention with sufficient
`precision and detail to establish that the subject matter existed in the
`prior art.” Verve, LLC v. Crane Cams, Inc., 311 F.3d 1116, 1120 (Fed. Cir.
`2002).
`A claim is unpatentable under 35 U.S.C. § 103(a) if the differences
`between the subject matter sought to be patented and the prior art are such
`that the subject matter as a whole would have been obvious at the time the
`invention was made to a person having ordinary skill in the art to which that
`subject matter pertains. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406
`(2007). The question of obviousness is resolved on the basis of underlying
`
`
`11 Kappos et al., “A Placebo-Controlled Trial of Oral Fingolimod in
`Relapsing Multiple Sclerosis,” 362(5) N. Engl. J. Med. 387–401 (2010).
`Ex. 1038. (“Kappos 2010”).
`12 The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284
`(2011) (“AIA”), amended 35 U.S.C. §§ 102 and 103. Because the
`challenged claims of the ’405 patent have an effective filing date before the
`effective date of the applicable AIA amendments, throughout this Final
`Written Decision we refer to the pre-AIA versions of 35 U.S.C. §§ 102 and
`103.
`
`8
`
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`IPR2017-00854
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`
`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) objective evidence of
`nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966).
`A precise teaching directed to the specific subject matter of a
`challenged claim is not necessary to establish obviousness. KSR, 550 U.S. at
`418. Rather, “any need or problem known in the field of endeavor at the
`time of invention and addressed by the patent can provide a reason for
`combining the elements in the manner claimed.” Id. at 420. Accordingly, a
`party that petitions the Board for a determination of unpatentability based on
`obviousness must show 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.” In re Magnum Oil Tools Int’l, Ltd., 829
`F.3d 1364, 1381 (Fed. Cir. 2016) (internal quotations and citations omitted);
`see also Belden Inc. v. Berk–Tek LLC, 805 F.3d 1064, 1073 (Fed. Cir. 2015)
`(“[O]bviousness concerns whether a skilled artisan not only could have
`made but would have been motivated to make the combinations or
`modifications of prior art to arrive at the claimed invention.”).
`
`B.
`
`Person of Ordinary Skill in the Art
`Petitioners propose that a person of ordinary skill in the art as of the
`date of the invention
`would typically include a person with a medical degree (M.D.)
`and several years of experience treating multiple sclerosis
`patients. . . . would be familiar with administering therapeutic
`agents for the treatment of multiple sclerosis, including RR-MS,
`and dosing regimens of the various therapeutic agents available
`for treating RR-MS. . . . [and] would be knowledgeable about the
`
`9
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`IPR2017-00854
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`
`multiple sclerosis medical literature available at the relevant
`time.
`
` Pet. 18–19 (citing Ex. 1002 ¶¶ 39–40). Petitioners’ proposal is consistent
`with the definition offered during prosecution that, “[t]he relative skill of
`those in the art is high, generally that of an M.D. or Ph.D. with expertise in
`the area of neurology.” Ex. 1009, 13. We further note, in focusing on the
`MS disease state and the conduct of a prophetic clinical trial of fingolimod
`(“Compound A”) in treating RR-MS, the Specification suggests that one of
`ordinary skill in the art would possess a medical or related doctoral degree
`and have experience in the field of MS treatment and clinical research. See,
`e.g., Ex. 1001, 8:61–9:12, 9:64–10:16, 11:4–12:13.
`In the Preliminary Response, Patent Owner argues that Apotex’s
`proposed definition “is plainly incorrect” because “a person of skill in other
`dosing patent cases almost always includes a pharmacologist,” the
`’405 Patent and relevant references include pharmacologists as “essential
`contributing authors,” and “[p]harmacologists would have to interpret that
`data before reaching any conclusions about the obviousness of a 0.5 mg
`daily dose.” Prelim. Resp. 39–43.
`In our Decision instituting trial, we agreed with Patent Owner that in
`the context of this proceeding, expertise in pharmacology would be useful in
`determining obviousness. Dec. 8. We further noted that it was not
`necessary to decide between the hypothetical medical doctor proposed by
`Petitioners and the pharmacologist proposed by Patent Owner, as courts and
`tribunals have frequently identified the hypothetical person of ordinary skill
`as a composite or team of individuals with complementary backgrounds and
`skills. Dec. 8–9 (citing AstraZeneca Pharm. LP v. Anchen Pharm., Inc., No.
`
`10
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`10-CV-1835 JAP TJB, 2012 WL 1065458, at *19, *22 (D.N.J.
`Mar. 29, 2012), aff’d, 498 F. App’x 999 (Fed. Cir. 2013) (collecting cases);
`Helsinn Healthcare S.A. v. Dr. Reddy’s Labs. Ltd., No. CV 11-3962 (MLC),
`2016 WL 832089, at *72 (D.N.J. Mar. 3, 2016) (reversed on other grounds
`by Helsinn Healthcare S.A. v. Teva Pharm. USA, Inc., 855 F.3d 1356 (Fed.
`Cir. 2017), cert. granted, --- S. Ct. ----, 2018 WL 1142984 (June 25, 2018));
`Merial, Inc. v. Fidopharm Inc., IPR2016-01182, Paper 11 at 9 (PTAB Nov.
`7, 2016)).
`Accordingly, we determined that one of ordinary skill in the art could
`be part of a multi-disciplinary research team including 1) a Ph.D. with
`expertise in the area of neurology and/or an M.D. having several years of
`clinical experience treating multiple sclerosis patients, and who would be
`knowledgeable about the multiple sclerosis medical literature, and 2) a
`pharmacologist with experience in drug development. Id. at 9.
`Neither party argues that this determination is incorrect. Nor, upon
`consideration of the complete record, do we find reason to modify our prior
`determination.
`
`C.
`
`Claim Construction
`In an inter partes review, claim terms in an unexpired patent are
`interpreted according to their broadest reasonable construction in light of the
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b);
`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–46 (2016)
`(upholding the use of the broadest reasonable interpretation standard).
`“Under a broadest reasonable interpretation, words of the claim must be
`given their plain meaning, unless such meaning is inconsistent with the
`specification and prosecution history.” Trivascular, Inc. v. Samuels, 812
`
`11
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`F.3d 1056, 1062 (Fed. Cir. 2016). Any special definition for a claim term
`must be set forth in the specification with reasonable clarity, deliberateness,
`and precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
`
`i. Whether the Preambles are Limiting
`The preambles of the independent claims recite methods for “reducing
`or preventing or alleviating relapses in” (claim 1), “treating” (claim 3), and
`“slowing progression of” (claim 5) RR-MS “in a subject in need thereof.”
`This “subject in need thereof” is then reflected in the body of each claim as
`it recites the step of orally administering fingolimod “to said subject.”
`Petitioners argue that the preambles of the independent claims should
`be accorded no patentable weight as they “at most merely describe[] the
`intended purpose of the method and that the subject receiving fingolimod is
`a subject with RR-MS.” Pet. 24–25; Ex. 1002 ¶¶ 43–45. As we understand
`the argument, Petitioners propose that “said subject” is any subject with
`RR-MS, as such persons inherently are, or will be, “in need of a treatment
`that reduces, prevents or alleviates relapses and slows the progression of
`RR-MS.” Id. at 22–23; Ex. 1002 ¶¶ 43–45. Thus, Petitioners argue, the
`preambles “are not required to breathe life into the claim[s].” Id. at 24.
`Petitioners’ argument, however, conflates the etiology and
`progression of multiple sclerosis with the plain language of the claims.
`Thus, for example, Petitioners may be correct that because patients accrue
`neurologic disability with each relapse episode, “an RR-MS patient is in
`need of a treatment that reduces, prevents or alleviates relapses and slows
`the progression of RR-MS,” depending on that patient’s disease state. See
`Pet. 23. But “[i]n the absence of any evidence to the contrary, we must
`presume that the use of these different terms in the claims connotes different
`
`12
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`meanings.” CAE Screen Plates, Inc. v. Heinrich Fiedler GMBH & Co. KG,
`224 F.3d 1308, 1317 (Fed. Cir. 2000). In the present case, Petitioners do not
`direct us to sufficient evidence that “reduc[ing], prevent[ing] or alleviat[ing]
`relapses,” as set forth in claim 1, is necessarily the same as the arguably
`broader language, “treating,” recited in claim 3.
`In contrast to Petitioners’ position, Patent Owner contends that the
`preambles of independent claims 1, 3, and 5, limit the scope of the
`challenged claims, and are necessary to provide understanding to what the
`inventors actually invented. Prelim Resp. 29–35. Relying on the testimony
`of its expert, Dr. Lublin, Patent Owner presents evidence that “a person of
`skill would not understand reducing relapses, treating the disease, and
`slowing its progression to mean the same thing.” Id. at. 32–33 (citing
`Ex. 2003 ¶¶ 5–7, 43–55). As noted above, we do not ascertain where, on
`this record, Petitioners or Petitioners’ experts argue or present evidence that
`these three terms are synonymous.
`Patent Owner also points out that failing to accord meaning to the
`differences in the preambles “would eliminate any differences among
`claims 1–2, 3–4, and 5–6.” Id. at 30–31. On balance, we agree with Patent
`Owner that the presumption against claim redundancy weighs against
`Petitioners’ proposed construction.
`We also find persuasive Patent Owner’s argument that the words in
`the preambles inform the scope of “said subject” in the body of each claim.
`Prelim. Resp. 29–35. In particular, the preambles of claims 1, 3 and 5:
`provide[] an antecedent basis for terms used in the body of each
`claim, specifying the needs of the “subject” alluded to later. This
`is a classic example of the preamble defining a term—the
`“subject in need” of certain effects—which then is subsequently
`used in the body of the claim—“to said subject.”
`
`13
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`
`Id. at 34.
`Because the three preamble terms, “reducing or preventing or
`alleviating relapses in” (claim 1), “treating” (claim 3), and “slowing
`progression of” (claim 5) RR-MS have different meanings, and each informs
`the scope of the “subject” in the body of the claims, we concluded that the
`preambles give life and meaning to the balance of the claim. See Pitney
`Bowes Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305 (Fed. Cir. 1999).
`Accordingly, we construed the preambles of claims 1, 3, and 5 as limiting,
`and accord the ordinary and customary meaning to the claim language
`“reducing or preventing or alleviating relapses in,” “treating,” and “slowing
`progression of” RR-MS “in a subject in need thereof.” Dec. 12. We further
`construed the terms “reducing or preventing or alleviating relapses” and
`“slowing progression” as subsumed within the genus of “treating” RR-MS.13
`Id. Upon consideration of the complete record, we find no reason to modify
`our construction.
`
`ii. Whether the Preambles Invoke an Efficacy Element
`The parties do not appear to argue that our construction of the
`preambles is incorrect, but disagree as to whether they invoke an efficacy
`element. According to Patent Owner, we should construe the claims to
`require that administering 0.5 mg fingolimod daily provides the effects
`recited in the preambles or, in the alternative, require that the drug “be given
`for the ‘intentional purpose for which the method must be performed.’” PO
`Reply 9; Sur-Reply 3–4 (quoting Janssen v. Rexall Sundown, Inc., 342 F. 3d
`
`
`13 Unless specifically indicated otherwise, we refer herein to the more
`generic “treating” as a matter of convenience.
`
`14
`
`
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`
`1329, 1333 (Fed. Cir. 2003)); Ex. 2095 ¶¶ 9–17. Petitioners, by contrast,
`contend that the preambles do not create an efficacy requirement but merely
`inform the scope of “said subject” in the body of the claims, or “describe the
`intended purpose of the method.” Pet. 24–25; Pet. Reply 7–8 (citing In re
`Montgomery, 677 F.3d, 1375, 1380 (Fed. Cir. 2012)); Opp. 5–6.
`Consistent with our determination in section II(C)(i), above,
`administration of fingolimod to “said subject” in the claim body clearly
`refers to “a subject in need” of treatment of RR-MS in the preambles.
`Accordingly, at a minimum, we agree with Patent Owner that the claims
`require that the 0.5 mg daily dosage of fingolimod is given for the purpose
`of treating RR-MS. Although an understanding that the claims refer to the
`administration of fingolimod for the purpose of treating RR-MS provides
`context for understanding Grounds 1–3, counsel for Patent Owner points out
`that whether the preambles further demand that the orally administered
`dosage is efficacious is “more important for the motion to amend.” Tr.
`45:5–10. We agree with Patent Owner. And, as we do not reach the
`substance of Patent Owner’s motion to amend (see section II(A), below), we
`need not further construe the preambles. See Wellman, Inc. v. Eastman
`Chem. Co., 642 F.3d 1355, 1361 (Fed. Cir. 2011) (“[C]laim terms need only
`be construed ‘to the extent necessary to resolve the controversy.’” (quoting
`Vivid Techs., Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir.
`1999))).
`
`iii. Daily Dosage
`Illustrative claim 3 recites a method for treating RR-MS in a subject
`comprising “orally administering to said subject [fingolimod] . . . at a daily
`
`15
`
`
`
`IPR2017-00854
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`
`dosage of 0.5 mg.” The parties disagree as to whether “daily dosage”
`requires administration over a course of treatment for more than one day.
`Relying on the testimony of Dr. Benet, Petitioners argue that “the
`broadest reasonable construction of a ‘daily dosage of 0.5 mg’ includes a
`total dose of 0.5 mg in 24 hours regardless of what unit doses are used or
`whether the same dose is repeated on consecutive days.” Pet. Reply 8–9
`(citing Ex. 1047 ¶¶ 107–116).
`According to Patent Owner, considered in context, “‘daily’ does not
`mean ‘once.’ It means 0.5 mg per day for more than one day . . . . [because]
`therapies like fingolimod require continuous administration to be effective.
`Giving the drug only once would be meaningless.” PO Sur-Reply 3–4. As
`Dr. Steinman explains, “[a] person of skill with any familiarity with RRMS
`or disease-modifying therapies like fingolimod would understand that these
`[disease modifying therapies] are never proposed as a single-dose cure, but
`are always envisioned to be taken on a regular basis over an extended
`period.” Ex. 2089 ¶ 22; see Ex. 2024 ¶ 114. Thus, “[a] skilled person would
`understand ‘daily dosage’ to refer to once a day for a number of days.”
`Ex. 2096 ¶ 21; see also id. (further noting that “[a] single, one-time dose can
`be referred to by the phrase ‘a dosage’ and the word ‘daily’ is not needed.”).
`Consistent with Dr. Steinman’s testimony, the Specification states that
`“[d]aily dosages required in practicing the method of the present
`invention . . . will vary depending upon, for example, the compound used,
`the host, the mode of administration and the severity of the condition
`treated . . . . [and] may alternatively be administered intermittently, e.g., at a
`dose of 0.5 to 30 mg every other day or once a week.” Ex. 1001, 11:20–38;
`see Ex. 2089 ¶ 23. Accordingly, the Specification presents intermittent
`
`16
`
`
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`
`dosing (i.e., not every day) as an alternative to daily dosing and, in so doing,
`indicates that either regimen entails administration for more than one day.
`As an initial matter, we credit Dr. Benet’s testimony that a daily
`dosage need not be administered as a single unit dose and, thus, refers to the
`total dose administered in 24 hours. See Ex. 1047 ¶¶ 110–111; Ex. 1001,
`11:24–25 (“daily dosage” includes “as a single dose or in divided doses”).
`On balance, however, we find that Patent Owner has the better position with
`respect to the length of treatment implicit in the claim term. The ’405 Patent
`is directed to the treatment of a chronic and progressively debilitating
`disease. See Ex. 1001, 8:61–9:5, 9:64-10:5; Ex. 1005, 159; see generally
`Ex. 1023, 193–202.14 As Dr. Steinman indicates, such patients are in need
`of treatment “on a regular basis over an extended period of time.” Ex. 2089
`¶ 22. This is consistent with our reading of the Specification as disclosing
`daily or intermittent treatment for more than one day. See Ex. 1001, 11:20–
`38; see Ex. 2089 ¶ 23.
`Moreover, with respect to Petitioners’ argument in their Reply brief
`that the claim language is broad enough to encompass both single
`administration and administration on consecutive days (see Pet. Reply 8–9),
`we conclude that, in the context of the ’405 patent, Petitioners’ proposed
`definition renders the word “daily” superfluous. Accordingly, we construe
`“daily dosage of 0.5 mg” as referring to the amount of fingolimod
`administered per day over the course of a multi-day treatment.15
`
`
`14 MCALPINE’S MULTIPLE SCLEROSIS, 4th Ed., Compston, ed.
`(Elsevier, Inc., December 2005).
`15 Although our construction of “daily dosage” is helpful to understanding
`the claims as a whole, our determination with respect to Petitioners’
`obviousness grounds would be the same under either construction.
`
`17
`
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`D. Ground I: Obviousness in view of Kovarik and Thomson
`Petitioners challenge claims 1–6 under 35 U.S.C. § 103 as obvious in
`view of Kovarik and Thomson. Pet. 21, 32–48. Patent Owner opposes. We
`begin with an overview of the asserted references.
`
`i. Overview of Kovarik
`Kovarik relates to an improved loading dosage regimen of S1P
`receptor modulators or agonists for the treatment of transplant patients
`suffering from autoimmune diseases or disorders, including multiple
`sclerosis. Ex. 1004, 1, 14. Preferred S1P receptor modulators or agonists
`“elicit a lymphopenia resulting from a re-distribution, preferably reversible,
`of lymphocytes from circulation to secondary lymphatic tissue, without
`evoking a generalized immunosuppression.” Id. at 2. In a particularly
`preferred embodiment, the S1P receptor agonist is FTY720 (i.e.,
`fingolimod). Id. at 13.
`Kovarik teaches that S1P receptor modulators or agonists are used in
`combination with cyclosporine A and everolimus in transplantation
`experiments and “[d]ue to their immune-modulating potency . . . are also
`useful for the treatment of inflammatory and autoimmune diseases.” Id. at 1.
`According to Kovarik, “[i]t has now surprisingly been found that a specific
`dosage regimen, e.g. a loading dose, will provide further unexpected
`benefits.” Id. In particular, an “S1P receptor modulator or agonist . . . is
`administered in such a way that during the initial 3 to 6 days . . . of treatment
`the dosage of said S1P receptor modulator or agonist is raised so that in total
`the R-fold (R being the accumulation factor) standard daily dosage of said
`S1P receptor modulator or agonist is administered and thereafter the
`treatment is continued with the standard or a lower daily dosage . . . .” Id. at
`
`18
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`13–14. “[T]he standard daily dosage (also called maintenance dose) refers
`to the dosage of an S1P receptor modulator or agonist necessary for a
`steady-state trough blood level of the medication or its active metabolite(s)
`providing effective treatment.” Id. at 14.
`According to Kovarik:
`A particularly preferred dosage of . . . the preferred S1P
`rece
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