`
` Paper 32
`
`Trials@uspto.gov
`Entered: January 20, 2022
`
`571-272-7822
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`SLAYBACK PHARMA LLC,
`Petitioner,
`
`v.
`
`SUMITOMO DAINIPPON PHARMA CO., LTD.,
`Patent Owner.
`____________
`
`IPR2020-01053
`Patent 9,815,827 B2
`____________
`
`Before SUSAN L. C. MITCHELL, ZHENYU YANG, and
`KRISTI L. R. SAWERT, Administrative Patent Judges.
`
`YANG, Administrative Patent Judge.
`
`
`JUDGMENT
`
`Final Written Decision
`Determining All Challenged Claims Unpatentable
`35 U.S.C. § 318(a)
`
`Granting Patent Owner’s Motion to Seal
`37 C.F.R. § 42.55
`
`Dismissing Petitioner’s Motion to Seal
`37 C.F.R. § 42.55
`
`
`
`
`
`
`
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`Patent 9,815,827 B2
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`INTRODUCTION
`I.
`Slayback Pharma LLC (“Petitioner”) filed a Petition (Paper 2
`(“Pet.”)), seeking an inter partes review of claims 1–75 of U.S. Patent
`No. 9,815,827 B2 (Ex. 1001, “the ’827 patent”). We instituted trial to review
`the challenged claims. Paper 7 (“Dec.” or “Decision to Institute”).
`Thereafter, Sumitomo Dainippon Pharma Co., Ltd. (“Patent Owner”) filed a
`Response to the Petition (Paper 14, “PO Resp.”), Petitioner filed a Reply
`(Paper 21), and Patent Owner filed a Sur-reply (Paper 25). An oral hearing
`for this proceeding was held on August 11, 2021, and the transcript of that
`hearing is of record. See Paper 28 (“Tr.”).
`The Board has jurisdiction under 35 U.S.C. § 6 and issues this final
`written decision pursuant to 35 U.S.C. § 318(a) and 37 C.F.R. § 42.73. For
`the reasons provided below, we conclude Petitioner has established by a
`preponderance of the evidence that claims 1–75 of the ’827 patent are
`unpatentable.
`
`A. Related Matters
`According to the parties, the ’827 patent is the subject of the
`following district-court litigations: 2:18-cv-02065 (NJD); 1:18-cv-00256
`(DED); 2:18-cv-02620 (NJD); 1:18-cv-02107 (NYSD); 1:18-cv-01444
`(NYED); 1:18-cv-00185 (NCMD); 1:18-cv-00369 (DED); 2:18-cv-13478
`(NJD); 2:18-cv-13833 (NJD); 2:18-cv-14787 (NJD). Pet. 64; Paper 5, 2.
`Petitioner is not a party to any of those cases. Pet. 19. Patent Owner
`represents that “[n]one of the litigations is pending.” Paper 5, 2.
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`B. The ’827 Patent and Related Background
`The ’827 patent is titled “[a]gent for treatment of schizophrenia.”
`Ex. 1001, Code (54). It relates to “a method for improving schizophrenia
`without being accompanied by extrapyramidal symptoms by orally
`administering a prescribed dose of a specific bicycloheptane dicarboximide
`derivative once a day, and a therapeutic agent used in said method.” Id.
`at 1:15–20.
`There are 75 claims in the ’827 patent. Petitioner divides them into
`two groups: (1) claims comprising treating manic depressive psychosis1
`(“manic depressive claims”), including claims 8–18, 25–28, 30, 31, 33–44,
`46, 48–60, 62, 64, 66, 67, 69, 71, 73, and 75; and (2) claims limited to
`treating schizophrenia (“schizophrenia claims”), including claims 1–7,
`19–24, 29, 32, 45, 47, 61, 63, 65, 68, 70, 72, and 74. Pet. 13. Patent Owner
`adopts these groupings. See PO Resp. 27 (discussing “manic depressive
`claims”). For consistency, we do the same.
`Patent Owner explains that schizophrenia and manic depressive
`psychosis, both chronic and severe mental disorders, “can have symptoms in
`common.” PO Resp. 3–4, 29. According to the ’827 patent, schizophrenia is
`mainly treated with medication, and the treatment should be continued for a
`long time. Ex. 1001, 1:37–39. Thus, “any side effects of medication may
`always be serious problems, and based on this perspective, it has been
`
`
`1 The parties agree that “manic depressive psychosis” is now known as
`“bipolar disorder.” Pet. 21; PO Resp. 3. We use the two terms
`interchangeably in this Decision.
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`desired to develop a medicine being suitable for prolonged medication.” Id.
`at 1:42–45.
`The ’827 patent explains that antipsychotics have been used to treat
`schizophrenia. Id. at 1:46–56. According to Patent Owner, “antipsychotics
`were known to treat schizophrenia and manic depressive psychosis by
`targeting the dopamine D2 receptor.” PO Resp. 29. The antipsychotics,
`however, have various drawbacks: the first generation, or “typical”
`antipsychotics are linked to severe side effects, such as extrapyramidal
`symptoms; whereas the second generation, or “atypical” antipsychotics are
`associated with substantial weight gain. PO Resp. 4–6. The ’827 patent
`states “it has been desired to develop a safe medicament which exhibits an
`excellent effect on various schizophrenia as an antipsychotic without causing
`side effects.” Ex. 1001, 2:1–4.
`The ’827 patent states that prior art teaches a genus of imide
`derivatives that “may be useful as an antipsychotic (c.f., neuroleptic agent,
`antia[n]xiety, etc.), especially as an agent for treatment of schizophrenia,
`senile insanity, manic depressive psychoses, and nervous breakdown.” Id.
`at 2:5–39 (citing Ex. 10092).
`According to the ’827 patent, its inventors found that a compound in
`this genus, (1R,2S,3R,4S)-N-[(1R,2R)-2-[4-(1,2-benzoisothiazol-3-yl)-1-
`piperazinylmethyl]-1-cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptane-
`dicarboximide or a pharmaceutically acceptable salt thereof, “is effective for
`
`
`2 U.S. Patent No. 5,532,372, issued July 2, 1996 (Ex. 1009, “Saji”). Saji is
`one of the prior-art references asserted in this proceeding.
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`relieving the wide-ranging symptoms of schizophrenia, and may treat
`schizophrenia quite safely without being accompanied by extrapyramidal
`symptoms by orally administering a prescribed dose thereof once a day.” Id.
`at 2:50–3:6. The parties agree this compound is lurasidone.
`The ’827 patent contains results from a Phase II clinical trial where
`patients with schizophrenia were treated with SM-13496, i.e., lurasidone
`hydrochloride. Ex. 1001, 4:47–10:25.
`C. Illustrative Claims
`Claim 1 is illustrative of the schizophrenia claims, and is
`reproduced below:
`A method for treating schizophrenia in a patient without
`1.
`a clinically significant weight gain, comprising:
`administering orally to the patient (1R,2S,3R,4S)-N-[(1R,2R)-
`2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinylmethyl]-1-
`cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptanedicarboximide or a
`pharmaceutically acceptable salt thereof at a dose of from 20 to
`120 mg/day such that the patient does not experience a
`clinically significant weight gain.
`Ex. 1001, 10:51–59.
`Claim 8 is illustrative of the manic depressive claims, and is
`reproduced below:
`A method for treating manic depressive psychosis in a
`8.
`patient without a clinically significant weight gain, comprising:
`administering orally to the patient (1R,2S,3R,4S)-N-[(1R,2R)-
`2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinylmethyl]-1-
`cyclohexylmethyl]-2,3-bicyclo[2.2.1]heptanedicarboximide or a
`pharmaceutically acceptable salt thereof at a dose of from 20 to
`
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`Reference(s)
`Latuda Information4
`
`120 mg/day such that the patient does not experience a
`clinically significant weight gain.
`Id. at 11:12–21.
`Claims 25, 40, and 56 are also independent claims. Each is directed to
`a method of “treating a patient with an antipsychotic,” comprising orally
`administering lurasidone “once daily” at a dose of from 20 to 120 mg. Id.
`at 11:59–12:2, 12:34–43, 13:34–42. Claims 40 and 56 further require
`lurasidone is the “sole active ingredient.” Id. at 12:34–43, 13:34–42.
`D. Instituted Grounds of Unpatentability
`We instituted trial to determine whether the challenged claims are
`unpatentable based on the following grounds:
`Claims Challenged
`35 U.S.C.
`§3
`102
`
`8–18, 25–28, 30, 31, 33–44, 46, 48–60,
`62, 64, 66, 67, 69, 71, 73, 75
`8–18, 25–28, 30, 31, 33–44, 46, 48–60,
`62, 64, 66, 67, 69, 71, 73, 75
`
`3 The Leahy-Smith America Invents Act (“AIA”), Pub. L. No. 112-29,
`125 Stat. 284, 287–88 (2011), amended 35 U.S.C. §§ 102 and 103, effective
`March 16, 2013 (“AIA date”). The parties dispute whether the manic
`depressive claims are entitled to a priority date earlier than the AIA date.
`Pet. 26–31; PO Resp. 27–32. We do not need to resolve this issue because,
`as explained below, we find all challenged claims obvious over Saji. See
`infra, Section II.E. Saji predates the earliest possible priority date on the face
`of the ’827 patent, and thus, qualifies as prior art regardless. For purposes of
`this Decision, we apply the pre-AIA version of § 103. Our conclusion,
`however, remains the same under the AIA version of § 103.
`4 Latuda, Information published in American Journal of Psychiatry,
`Vol. 170, No. 8, August 2013 (Ex. 1007).
`5 Loebel et al., Lurasidone Monotherapy for the Treatment of Bipolar
`
`103
`
`Latuda Information,
`Loebel5
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`Claims Challenged
`
`35 U.S.C.
`Reference(s)
`§3
`Saji
`103
`1–75
`To support their respective arguments, Petitioner relies on the
`Declarations of Thomas R. Kosten, M.D. (Exs. 1002, 1051); and Patent
`Owner relies on the Declarations of Stephen Stahl, Ph.D. (Ex. 2131) and
`Brian C. Reisetter, RPh, M.B.A., Ph.D. (Ex. 2132).
`
`II. ANALYSIS
`A. Principles of Law
`To prevail in this inter partes review, Petitioner “shall have the
`burden of proving a proposition of unpatentability by a preponderance of the
`evidence.” 35 U.S.C. § 316(e); 37 C.F.R. § 42.1(d) (2019).
`A patent claim is unpatentable under 35 U.S.C. § 103(a) if the
`differences between the claimed subject matter 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 said
`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
`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 skill in the art; and (4) objective evidence of nonobviousness.
`Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966); KSR, 550 U.S. at 406.
`
`
`Depression: Results of the 6-Week, Double-blind, Placebo-controlled
`PREVAIL-2 Study, 38 NEUROPSYCHOPHARM. 109–10 (2012) (Ex. 1008).
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`When the prior art discloses a range that overlaps with the claimed
`range, there is a presumption of obviousness. E.I. DuPont de Nemours & Co.
`v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018). This presumption may
`be rebutted by showing the criticality of the claimed range, that the prior art
`taught away from the claimed range, or that the parameter was not
`recognized as “result-effective.” Id.
`We analyze the instituted grounds of unpatentability in accordance
`with these principles.
`
`B. Level of Ordinary Skill in the Art
`Petitioner contends that an ordinarily skilled artisan would have “the
`education and experience of a medical doctor trained in psychiatry who
`spent several years using psychiatric medications to treat patients with
`schizophrenia and bipolar disorders and had several years[’] experience
`developing or investigating psychiatric medications and was familiar with
`the literature on drugs for schizophrenia and bipolar disorders.” Pet. 23.
`Patent Owner argues that an ordinarily skilled artisan
`is a person with a scientific degree (either M.D., Ph.D., or
`Pharm. D.), who has at least 2-3 years of experience developing
`or investigating methods for treating patients with psychiatric
`disorders such as schizophrenia or bipolar disorder. The
`POSITA may also work in collaboration with other scientists
`and/or clinicians who have experience developing or
`characterizing antipsychotic drugs, running clinical trials
`related to such drugs, treating patients with such drugs, or
`researching the effects of such drugs. Collaborators of the
`POSITA could include, for example, pharmacologists and /or
`neuropharmacologists, psychiatrists, endocrinologists,
`statisticians and/or biostatisticians and analytical and/or
`medicinal chemists.
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`PO Resp. 24–25.
`We do not discern an appreciable difference in the parties’ respective
`definitions of the level of ordinary skill in the art, and any perceived
`distinction does not impact our Decision. Indeed, as Patent Owner
`acknowledges, the parties’ proposed definitions of the ordinary skill level do
`“not differ significantly.” Id. at 25. Nevertheless, for purposes of this
`Decision, we adopt Patent Owner’s definition of the skill level, as it is
`consistent with the ’827 patent disclosures and the prior art of record, and
`more inclusively describes the suitable experience for one of ordinary skill
`in the art.
`We further note that, in this case, the prior art itself demonstrates the
`level of skill in the art at the time of the invention. See Okajima v. Bourdeau,
`261 F.3d 1350, 1355 (Fed. Cir. 2001).
`C. Claim Construction
`In an inter partes review, we construe a claim term “using the same
`claim construction standard that would be used to construe the claim in a
`civil action under 35 U.S.C. [§] 282(b).” 37 C.F.R. § 42.100(b). Under that
`standard, the words of a claim “are generally given their ordinary and
`customary meaning,” which is “the meaning that the term would have to a
`person of ordinary skill in the art in question at the time of the invention, i.e.,
`as of the effective filing date of the patent application.” Phillips v. AWH
`Corp., 415 F.3d 1303, 1312–13 (Fed. Cir. 2005) (en banc).
`Petitioner proposes the following constructions:
`Term(s)
`Proposed Construction
`“a patient”/“the patient”
`“one or more patients”
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`Term(s)
`
`“treating a patient with an
`antipsychotic”
`(claims 25, 40, and 56)
`
`“manic depressive psychosis”
`“a pharmaceutical composition
`comprising…a sole active
`ingredient” (claims 40 and 56)
`
`Proposed Construction
`includes both “treating a patient for
`schizophrenia with an
`antipsychotic” and “treating a
`patient for manic depressive
`psychosis with an antipsychotic”
`“bipolar disorders”
`limits the “pharmaceutical
`composition” of claims 40 and 56 to
`a “sole active ingredient”
`
`Pet. 18–23.
`Patent Owner states that it “does not concede that [Petitioner]
`Slayback’s proposed constructions are correct and submits that no
`construction is necessary.” PO Resp. 24.
`On this record, we find Petitioner’s proposed constructions are
`supported by intrinsic and extrinsic evidence. See Pet. 18–23. We agree with
`Petitioner here that “a patient” or “the patient” should have its ordinary and
`customary meaning of “one or more patients,” as opposed to a “patient
`population” as Patent Owner has previously argued in a district court
`litigation involving another party. See id. at 19–20. Indeed, Patent Owner
`agrees. See Reply 19 (“There is no dispute that ‘a patient,’ as recited in the
`’827 claims, refers to ‘one or more patients.’”).
`We also agree with Petitioner that the dependent claims requiring
`treating patients with schizophrenia and manic depressive psychosis
`supports the conclusion that “treating a patient with an antipsychotic” in
`independent claims 25, 40, and 56 includes treatment of a patient with these
`particular diseases. See Pet. 20–21.
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`On this record, we further agree with Petitioner that “manic
`depressive psychosis” would be interpreted by a person or ordinary skill in
`the art as “bipolar disorder,” which includes Bipolar I Disorder, Bipolar II
`Disorder, Cyclothymia, and Bipolar Disorder Not Otherwise Specified. See
`id. at 21–22 (citations omitted); see also PO Resp. 3 (“Bipolar disorder, once
`known as manic depressive psychosis.”). Thus, for purposes of this
`Decision, we adopt Petitioner’s proposed constructions.
`On this record and for purposes of this Decision, we see no need to
`construe any other term expressly. See Wellman, Inc. v. Eastman Chem. Co.,
`642 F.3d 1355, 1361 (Fed. Cir. 2011) (stating that claim terms need only be
`construed to the extent necessary to resolve the controversy).
`D. Saji
`Saji teaches an imide compound of the formula:
`
`
`
`The figure above shows the chemical structure of compound (I) of Saji.
`Ex. 1009, 3:3–8. Saji further specifies the formula of groups Z, D, and Ar of
`compound (I). Id. at 3:10–44.
`Saji teaches that the novel imide compounds and their acid addition
`salts of its invention can be used “as anti-psyc[h]otic agents (neuroleptic
`agents, anti-anxiety agents), especially for therapy of schizophrenia, senile
`insanity, manic-depressive psychosis, neurosis, etc.” Id. at 1:8–12.
`According to Saji, for the therapeutic use as an anti-psychotic agent, the
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`imide compound (I) and its pharmaceutically acceptable salt may be
`formulated into tablets for oral administration. Id. at 11:66–12:6. According
`to Saji,
`While the dosage of the imide compound (I) or its
`pharmaceutically acceptable salt varies greatly with the
`symptom, age and weight of the patient, the dosage form, the
`administration mode and the like, it may be generally given to
`an adult at a daily dose of from about 1 to 1000 mg, preferably
`from about 5 to 100 mg, in case of oral administration . . . Said
`dose may be applied in a single time or dividedly in two or
`more times.
`Id. at 12:15–24.
`
`E. Obviousness over Saji
`Petitioner argues that claims 1–75 of the ’827 patent would have been
`obvious over Saji. Pet. 50–63. Petitioner argues that Saji teaches or suggests
`each limitation of the challenged claims. Pet. 54–63. According to
`Petitioner:
`a) Lurasidone HCl was disclosed in Saji Patent . . . to be
`effective for the treatment of schizophrenia and manic
`depressive psychosis;
`b) Oral dosing is preferred and disclosed in Saji Patent;
`b) The preferred oral daily dose was disclosed in Saji Patent to
`be “from about 5 to 100 mg;[”]
`c) Treatment without a second antipsychotic was preferred and
`Saji Patent discloses tablets with one active ingredient;
`d) Once daily dosing is preferred and lurasidone’s 18 hour half
`life led naturally to once a day dosing; and
`e) No weight gain in at least a patient was expected;
`Id. at 62. Petitioner also contends that “given the disclosed range in Saji
`Patent (‘about 5 to 100 mg’) a POSA was motivated to conduct dose ranging
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`studies and would find the claimed dosing regimens,” and would have “had
`a reasonable expectation that all the claimed dosing regimens would be
`effective for the intended purpose.” Id. at 62–63.
`After reviewing the entire record developed at trial, and as explained
`below, we determine Petitioner has shown, by a preponderance of the
`evidence, that Saji teaches or suggests each limitation of the challenged
`claims. Petitioner has also shown that an ordinarily skilled artisan would
`have had a reason to modify the dose range taught in Saji, and would have
`had a reasonable expectation of success when doing so.
`Patent Owner counters that Saji does not suggest the claimed dosing
`regimen, which “unexpectedly does not cause weight gain.”
`PO Resp. 37–52. According to Patent Owner, lack of weight gain is not
`inherent either. Id. at 52–53. Patent Owner further asserts that “[o]bjective
`evidence demonstrates that the claimed dosing regimen would not have been
`obvious.” Id. at 53–59. We address these contentions below.
`For our discussion, we divide the challenged claims into five groups
`as follows.
`
`1. Group 1 Claims
`Group 1 claims include claims 1–3, 5, and 8–11. These claims are
`directed to a method of treating either schizophrenia or manic depressive
`psychosis in a patient with lurasidone at a dose of 20–120 mg/day, wherein
`the patient does not experience clinically significant weight gain. Some of
`these claims require no weight gain after six weeks of administering
`lurasidone.
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`Saji Teaches Lurasidone as a Preferred Embodiment
`i.
`As a preliminary matter, we note that the parties refer to different
`named compounds in Saji as lurasidone. According to Petitioner, the
`compound of claim 14 and Compound No. 101 in Saji are lurasidone.
`Pet. 56. Patent Owner argues that Compound No. 105 is lurasidone, whereas
`Compound No. 101 is “a racemic mixture of enantiomers.” PO Resp. 38.
`Patent Owner contends that Compound No. 101 and Compound No. 105
`have different “structure[s] and properties,” and “[f]or this reason alone,
`Slayback’s challenge,” which focuses on Compound No. 101, “fails because
`it produces no evidence relating to the claimed dosing regimen, which
`requires lurasidone, not the racemic mixture.” Id. We disagree.
`When previously asserting Saji against certain entities, Patent Owner
`made a different argument and explained that Saji “illustrates a series of
`preferred embodiments, including lurasidone hydrochloride (Compound
`No. 105), lurasidone’s enantiomer in a hydrochloride salt form (Compound
`No. 104), and a mixture of this enantiomeric pair in a hydrochloride salt
`form (Compound No. 101).” Ex. 1052, 12; see also Ex. 1053, 4–5 (the
`same). In the previous proceedings, Patent Owner argued that “Claim 14 [of
`Saji] is not narrowly drawn to a racemic mixture. Rather, Claim 14
`encompasses lurasidone, lurasidone’s enantiomer, and mixtures thereof.” Id.
`at 13. The district court, apparently persuaded by Patent Owner’s argument,
`“construed the two-dimensional drawing in Claim 14 [of Saji] to mean
`‘lurasidone, lurasidone’s enantiomer, as well as mixtures of these
`enantiomers.’” Ex. 1053, 6. Patent Owner argued to the Federal Circuit that
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`“the district court’s construction was correct and should be affirmed.” Id.
`at 16.
`
`Claim 14 of Saji is directed to an imide compound with the following
`formula, or an acid addition salt thereof:
`
`
`The figure above shows the chemical structure of the compound of claim 14.
`Id., claim 14.
`Saji also teaches Compound No. 101, which has the following
`structure:
`
`The figure above shows the chemical structure of Compound No. 101.
`Ex. 1009, col. 30, at the bottom.
`The compound of claim 14 and Compound 101 in Saji are the same,
`with Compound 101 showing the addition of HCl in the two-dimensional
`drawing, and claim 14 reciting “an acid addition salt” in the body of the
`
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`claim. Thus, based on Patent Owner’s previous argument that “Claim 14
`encompasses lurasidone, lurasidone’s enantiomer, and mixtures thereof,” we
`find Compound 101, contrary to Patent Owner’s argument in this
`proceeding, “is not narrowly drawn to a racemic mixture.” See Ex. 1053, 13.
`Moreover, as Patent Owner acknowledges, Compound 105 is a
`preferred embodiment of Saji. Sur-reply 10; see also Ex. 1054, 93:15–18
`(Dr. Stahl, Patent Owner’s expert, testifying that an ordinarily skilled artisan
`“would be focused on” Compound 105 after reading Saji). Dr. Kosten,
`Petitioner’s expert, explained during his deposition that, although he
`“indicate[d] compound No. 101” in his declaration, “it might be compound
`105. They’re both there, and either one would be fine.” Ex. 2134, 75:18–20.
`Indeed, Saji teaches the binding affinity of both Compound 101 and
`Compound 105 for the D2 receptor. Ex. 1009, 13:5–10. Patent Owner does
`not dispute this. See PO Resp. 37 (“For Compound No. 105, Saji ’372
`discloses its in vitro binding affinity for the D2 receptor, a receptor
`commonly targeted by antipsychotic drugs.”). Thus, we disagree with Patent
`Owner that Petitioner’s evidence relates to only the racemic mixture, and not
`lurasidone.
`Patent Owner also argues that “[l]urasidone is identified as one of
`many compounds within Saji ’372’s genus, not as ‘lurasidone’ but as
`‘Compound No. 105.’” PO Resp. 37 (citing Ex. 1009, 30:30–32:23). This
`emphasis, although correct, is incomplete and insignificant. Saji may
`disclose many compounds; it, however, only claims six specific compounds
`(see Ex. 1009, claims 14–19), one of which is lurasidone (id., claim 14). And
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`because Saji discloses the chemical structure of lurasidone, it matters not
`what name it is given in Saji.
`In sum, we find Saji teaches lurasidone as a preferred embodiment.
`Saji Teaches Treating Schizophrenia and Manic Depressive Psychosis
`Petitioner refers to Saji for teaching that the disclosed novel imide
`compounds and their acid addition salts can be used as anti-psychotic agents
`for therapy of schizophrenia and manic depressive psychosis. Pet. 54 (citing
`Ex. 1009, 1:8–13).
`Petitioner also relies on the Saji Amendment, which is a response to
`an office action filed on December 29, 1994, during the prosecution of Saji.
`Id. at 50–51 (citing Ex. 1026). In the Saji Amendment, the applicant pointed
`out that Saji’s specification shows Compound Nos. 101 and 105 “have high
`affinity to the dopamine D2 receptors.” Ex. 1026, 4. According to Saji
`applicant, “these test results would be sufficient to one skilled in the art to
`establish that the claimed compounds have anti-psychotic activity and would
`be useful for the treatment of schizophrenia.” Id.
`Saji applicant also argued that “[i]t is well known to those skilled in
`the art that anti-psychotic drugs, i.e., neuroleptics, are generally effective in
`treatment of manic-depressive psychosis.” Id. at 6. Based on the test results
`in Saji’s specification, Saji applicant argued “it would be understood to
`those skilled in the art that the claimed compounds would be useful as
`anti-psychotic agents for therapy of manic depressive psychosis with
`minimal side effects.” Id. at 7.
`Patent Owner does not dispute, and we agree, that Saji teaches
`treating schizophrenia and manic depressive psychosis with lurasidone, a
`
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`preferred compound of its invention. See Sur-reply 9–10 (“[T]he data in the
`Saji ’372 specification demonstrated that Compound 105 could successfully
`treat psychoses,” including schizophrenia and manic depressive psychosis).
`Saji’s Preferred Dose Range Overlaps with the Claimed Dose Range
`iii.
`Patent Owner contends that Saji does not suggest the claimed dosing
`regimen. PO Resp. 38; Sur-reply 13. According to Patent Owner, Saji
`“generically states that the compounds covered by its genus may be provided
`in any of four broad dose ranges . . . but includes nothing to suggest which
`dose range might work for which compounds, or which route of oral
`administration or intravenous injection might work for which compounds.”
`Sur-reply 13–14; PO Resp. 38–39. Patent Owner’s arguments are
`unavailing.
`Saji lists three routes to administer the compounds of its invention:
`oral, intravenous, and rectal. Ex. 1009, 12:5–7. Dr. Kosten testifies that
`“[o]ral is a preferred route to administer an antipsychotic.” Ex. 1002 ¶ 123
`(citing Ex. 1039, 1788). Neither Patent Owner nor Dr. Stahl points to any
`evidence or argues otherwise. Thus, we credit Dr. Kosten’s unrebutted
`testimony that an ordinarily skilled artisan would have had a reason to
`administer lurasidone orally. See id.
`For oral administration, only two of Saji’s four dose ranges Patent
`Owner refers to are relevant, and only one is preferred. Ex. 1009, 12:18–21
`(teaching the compounds of its invention may be given to an adult at a “daily
`dose” of “preferably from about 5 to 100 mg, in case of oral
`administration”). Given that lurasidone is admittedly a preferred
`
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`embodiment of Saji (see Sur-reply 10), we are persuaded that an ordinarily
`skilled artisan would have started from this preferred dose range.
`The challenged ’827 patent discloses treating schizophrenia by orally
`administering lurasidone “at a daily dose of 5 mg to 120 mg” (Ex. 1001,
`3:56–62), a range broader than the “from about 5 to 100 mg” preferred range
`taught in Saji. According to Dr. Stahl, neither range is “a lucky guess,”
`because “every antipsychotic . . . out there is basically working, except for
`maybe [one], in the five to 100 [mg] range.” Ex. 1054, 104:20–105:1, see
`also id. at 104:23–105:3 (“I think it’s basically an extrapolation from what is
`known about agents in this class.”). Dr. Stahl’s testimony, thus, confirms our
`determination that an ordinarily skilled artisan would have started from
`Saji’s preferred dose range.
`Based on Saji’s preferred dose range of 5 to 100 mg/day, which
`overlaps with the “from 20 to 120 mg/day” range required by each
`challenged independent claim, Petitioner argues that an ordinarily skilled
`artisan would have been “motivated to conduct dose ranging studies and
`would find the claimed dosing regimens.” Pet. 62; see also id. at 55
`(contending that “dose ranging was a routine part of drug development”
`(citing Ex. 1030)). Dr. Stahl’s testimony supports Petitioner’s argument.
`Indeed, Dr. Stahl testifies that, although with some drugs, it can be
`difficult to find a safe and effective dose, or to get an effective dose into the
`patient, neither is the case with lurasidone. Ex. 1054, 141:3–14; see also id.
`at 142:2–6 (“Q. [A]re you aware of any particular difficulties with
`lurasidone hydrochloride and finding a safe and effective dose for
`schizophrenia and manic depressive psychosis? A. No.”); 135:18–25
`
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`(Dr. Stahl testifying that he is “not aware of anything unusual about
`[lurasidone’s] dose range”). Thus, we agree with Petitioner that an ordinarily
`skilled artisan, starting from Saji’s preferred dosing range, would have
`conducted routine dose ranging studies and identified the claimed dosing
`regimens.
`
`Lack of Weight Gain Is Not Unexpected
`iv.
`Acknowledging that “the prior art discloses a range that encompasses
`the claim,” Patent Owner asserts that “a relevant inquiry is whether there
`would have been a motivation to select the claimed composition from the
`prior art ranges.” PO Resp. 39–40 (quoting Allergan, Inc. v. Sandoz Inc.,
`796 F.3d 1293, 1304-05 (Fed. Cir. 2015)). Patent Owner contends that the
`claimed dosing regimen produces unexpected results, because it
`“unexpectedly does not cause weight gain.” Id. at 40.
`Petitioner argues that “[n]o clinically significant weight gain in one or
`more patients is inherent.” Id. at 55, 56, 57, 59. Relying on Horisawa6 and
`other prior art, Petitioner also contends that lack of weight gain was not an
`unexpected result of treatment. Pet. 55, 56, 57, 59. We agree with Petitioner,
`
`
`6 Horisawa et al. Pharmacological Characteristics of the Novel
`Antipsychotic SM-13496: Evaluation of Action on Various Receptors in the
`Brain, 19 JPN. J. NEUROPSYCHOPHARMACOL. 363 (1999). Petitioner submits
`Exhibit 1028, which includes a certified English translation of Horisawa.
`Patent Owner disputes the accuracy of this translation and provides
`Exhibit 2040, “a correct translation” of Horisawa that “the parties agreed
`to.” PO Resp. 44 n.144. For purposes of this Decision, we cite to
`Exhibit 2040.
`
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`and find Patent Owner’s evidence and argument insufficient to rebut the
`presumption of obviousness created by the overlapping ranges.
`Horisawa teaches the pharmacological characteristics of SM-13496.
`Ex. 2040, 7. Horisawa does not provide the chemical structure of SM-13496.
`According to Petitioner, however, during the prosecution of the challenged
`’827 patent, the applicant admitted SM-13496 was known as lurasidone.
`Pet. 51–52 (citing Ex. 1014–1016). Patent Owner contends that it “never
`admitted that ‘SM-13496’ was known in the prior art to be lurasidone.” PO
`Resp. 41–42. We do not need to resolve this issue because, as Petitioner
`points out and Patent Owner does not dispute, “SM-13496 was identified as
`lurasidone no later than October 18, 2001,” before the earliest possible
`priority date on the face of the challenged ’827 patent. Pet. 53
`(citing Ex. 1040, 22).
`Horisawa reports that its “results suggest that SM-13496 [i.e.,
`lurasidone] ameliorates symptoms of schizophrenia via D2 and 5-HT2
`receptor blocking effects and also has low binding affinity for α1, H1 and
`
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