UNITED STATES PATENT AND TRADEMARK OFFICE
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`SLAYBACK PHARMA LLC,
`Petitioner,
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`v.
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`SUMITOMO DAINIPPON PHARMA CO., LTD.,
`Patent Owner.
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`_________________
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`Case IPR2020-01053
`U.S. Patent 9,815,827
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`PATENT OWNER’S SUR-REPLY
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`SLAYBACK PHARMA LLC,
`Petitioner,
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`v.
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`SUMITOMO DAINIPPON PHARMA CO., LTD.,
`Patent Owner.
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`_________________
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`Case IPR2020-01053
`U.S. Patent 9,815,827
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`PATENT OWNER’S SUR-REPLY
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`Attorney Docket No.: 46094-0002IP1
`Case No.: IPR2020-01053
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`TABLE OF CONTENTS
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`INTRODUCTION ............................................................................................... 1
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`
`I.
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`II. THE ’927 PROVISIONAL APPLICATION PROVIDES WRITTEN
`DESCRIPTION SUPPORT FOR THE MANIC DEPRESSIVE CLAIMS ...... 2
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`III. CLAIMS 1-75 ARE PATENTABLE .................................................................. 9
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`A. Slayback’s Obviousness Analysis Improperly Focuses on Individual Claim
`Elements and Misrepresents the Experts’ Testimony .................................... 9
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`1. Slayback Wants To Retract Dr. Kosten’s Admissions ............................... 10
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`2. Slayback Mischaracterizes Dr. Stahl’s Testimony...................................... 11
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`B. Slayback Ignores Evidence Demonstrating That Lurasidone’s Lack of
`Weight Gain Was Unexpected ...................................................................... 15
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`C. Slayback Fails to Rebut Sumitomo’s Objective Evidence of Nonobviousness
` ....................................................................................................................... 16
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`D. Slayback Misconstrues the Role of Patient Populations in the Context of
`Weight Gain and Obviousness ...................................................................... 19
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`E. Slayback Fails to Prove That Lack of Weight Gain is Inherent in the Prior
`Art .................................................................................................................. 21
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`F. Wong Teaches Away From Dosing Regimens in Which Lurasidone Was the
`Sole Active Ingredient (Claims 40-75) .......................................................... 22
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`IV. SLAYBACK OPTED NOT TO FILE A MOTION FOR ADDITIONAL
`DISCOVERY RELATED TO EXPERT REPORTS FROM EARLIER
`DISTRICT COURT LITIGATION ................................................................. 25
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`V. CONCLUSION .................................................................................................. 26
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`Attorney Docket No.: 46094-0002IP1
`Case No.: IPR2020-01053
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`I.
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`INTRODUCTION
`Sumitomo’s Patent Owner Response carefully and meticulously sets forth
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`how Slayback’s arguments fundamentally failed to show that the ’827 patent is not
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`entitled to its priority date or that the patent claims are obvious. In its Reply,
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`Slayback fails to address any of Sumitomo’s arguments head on. Instead,
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`Slayback:
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` takes statements completely out of context;
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` cherry picks data from the prior art in a failed attempt to support its
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`obviousness position;
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` inconsistently argues that Saji ’372 is too broad to support priority, all
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`the while relying on it for obviousness;
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` illogically argues that Sumitomo waived certain positions by failing to
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`respond to arguments that Slayback never made;
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` outright fails to respond to both the facts and many of the arguments
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`that Sumitomo made; and
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` continues to ignore the complexity of atypical antipsychotics.
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`
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`The reason for Slayback’s approach is simple. As set forth below, it is clear
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`to a person of skill in the art that the ’827 patent is entitled to its priority date and
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`that its claims are not obvious.
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`1
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`II. THE ’927 PROVISIONAL APPLICATION PROVIDES WRITTEN
`DESCRIPTION SUPPORT FOR THE MANIC DEPRESSIVE
`CLAIMS
`Slayback fundamentally misunderstands and mischaracterizes the written
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`
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`description issue. Slayback repeatedly notes that the ’927 provisional only
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`mentions manic depressive psychosis in the background section and presents data
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`only for schizophrenia.1 In doing so, Slayback ignores evidence demonstrating
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`how a POSA would interpret that disclosure. For example, at his deposition Dr.
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`Stahl testified that a POSA would recognize that the claimed dosing regimen could
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`treat manic depressive psychosis without weight gain on the basis of the
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`schizophrenia data disclosed in the ’927 provisional specification:
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`Q. Is there any mention in the ’927 provisional application of no
`weight gain when treating manic depressive psychosis?
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`A. Yes.
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`Q. Where?
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`A. I don’t know how many times we have to go through this, sir,
`because when you mentioned it first [sic] schizophrenia you are
`mentioning it for bipolar. People don’t gain weight because they have
`schizophrenia. They gain weight because of some undetermined
`property of certain drugs. If you give the same drug that doesn’t
`cause weight gain in A, it won’t cause weight gain in B. There is
`nothing magic about schizophrenia that makes you gain weight on
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`1 Reply, 13-16.
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`2
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`antipsychotics as far as we know. Clearly you prefer to have certain
`things in certain places in certain explicit language certain ways, and
`maybe because it’s not explicit you don’t agree with me that these
`things are there, but I’m the POSA. I look at it. I see it.2
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`Dr. Stahl specifically explained how a person of ordinary skill would link
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`the disclosure relating to schizophrenia with manic depressive psychosis because
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`the conditions are not unrelated. Rather, both can include psychotic symptoms.3
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`Psychotic symptoms, in turn, are the result of excess dopamine
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`(“hyperdopaminergic”). Both conventional and atypical antipsychotics were
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`known to treat schizophrenia and manic depressive psychosis by targeting the
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`dopamine D2 receptor.4 Thus, a POSA, reading the ’927 provisional application
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`and ’827 patent, would recognize that the claimed dosing regimen could treat
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`psychoses generally, and schizophrenia and manic depressive psychosis
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`specifically, without weight gain based on the data demonstrating successful
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`treatment of schizophrenia without weight gain. As Dr. Stahl explained at his
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`deposition:
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`Q. Is it your testimony that when the ’827 patent says schizophrenia
`what it really means is schizophrenia or manic depressive psychosis?
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`2 Ex. 1054, 151:4-23.
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`3 Ex. 2131, ¶¶ 37, 102; Ex. 2140.
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`4 Ex. 2131, ¶ 102; Ex. 2140.
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`3
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`A. No, it means psychosis. It’s a proxy for any kind of psychosis, so
`it should work in senile, or whatever they call it, age-related
`psychosis. It should work in depressive psychosis. It should even
`work in drug-induced psychosis. Psychosis is too much dopamine.
`Schizophrenia is an illness of symptoms, and it’s not symptoms that
`cross across other diagnoses, so you can divide schizophrenia
`categorically by delusions, hallucinations and thought disorder, but
`the hallucinations are the part of psychosis that will cross over other
`diagnostic categories of different types of psychosis which are highly
`related in the fact that they are both hyperdopaminergic and are
`treated by the same drugs but have some differences in terms of some
`of the other dimensions of the psychopathology and sometimes the
`outcome.5
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`Slayback’s expert, Dr. Kosten, agreed.6 Furthermore, Dr. Kosten admitted
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`that a POSA, reading Saji ’372 and its prosecution history, would recognize that
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`lurasidone could successfully treat psychoses generally, and schizophrenia and
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`manic depressive psychosis specifically.7 Therefore, a POSA reading the ’927
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`application, including the reference to Saji ’372 and the data for treating
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`schizophrenia without weight gain, would understand that the application was
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`5 Ex. 1054, 153:6-154:1; see also id., 125:17-129:20.
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`6 Ex. 2134, 34:15-17; see also id., 32:8-34:10.
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`7 Ex. 1002, ¶¶ 111-116; Ex. 2131, ¶ 105.
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`teaching administration of lurasidone according to the claimed regimens to treat
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`schizophrenia and manic depressive psychosis without weight gain.
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`Simply put, the known relationship between D2 binding affinity and the
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`ability to treat psychoses provides the “blazemarks” informing a POSA that, on the
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`basis of the schizophrenia data, the claimed dosing regimen could also treat manic
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`depressive psychosis without weight gain.
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`Slayback has no rational response. Dr. Kosten’s second declaration does not
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`rebut Sumitomo’s evidence regarding the relationship between D2 binding affinity
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`and the ability to treat psychoses generally. In fact, Dr. Kosten’s second
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`declaration is silent on the written description issue. Importantly, he never recants
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`his earlier testimony regarding lurasidone’s ability to treat psychoses generally,
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`and manic depressive psychosis and schizophrenia specifically.
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`It also is of no consequence that the ’927 provisional does not explicitly
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`disclose the common link (excess dopamine) among the various psychoses. The
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`law does not require that a patent explicitly disclose information that would have
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`been known to a POSA. See Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802
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`F.2d 1367, 1384 (Fed. Cir. 1986) (“a patent need not teach, and preferably omits,
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`what is well known in the art.”). This is also not a case, as Slayback alleges, of
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`conflating written description and obviousness.8 Rather, it relates to the way in
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`8 Reply, 17-18.
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`which a POSA, armed with knowledge available to skilled artisans, would interpret
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`the disclosure of the ’927 provisional. On this point, Dr. Stahl’s deposition
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`testimony could not have been more clear: a POSA would interpret the ’927
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`provisional as describing that the claimed dosing regimen could treat manic
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`depressive psychosis without weight gain.
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` Equally unavailing is Slayback’s argument regarding the breadth of Saji
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`’372’s genus of compounds to which the ’927 provisional refers.9 It is irrelevant
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`whether the genus includes a large number of compounds – tellingly, when it
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`comes to obviousness, Slayback is emphatic that it “is undisputed that lurasidone
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`hydrochloride is a preferred compound of the Saji Patent.”10
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`A POSA reading Saji ’372 would have recognized that the specific chemical
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`compound recited in the ’927 provisional, which is now known as lurasidone,
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`corresponded to Compound 105 of Saji ’372, and fell within Saji ’372’s genus.11
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`A POSA also would have appreciated, based on Saji ‘372, that Compound 105
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`binds to the D2 receptor.12 For the reasons stated above, a POSA, on the basis of
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`the D2 binding activity, would have known that lurasidone (Compound 105) could
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`9 Reply, 15-16.
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`10 Reply, 10.
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`11 See Ex. 1009, 30:30-32:22; Ex. 2131, ¶¶ 93, 98-99, 104, 115-118.
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`12 See id., 13:5-10 (Table 2) and 30:30-32:32; Ex. 2131, ¶ 119.
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`treat both schizophrenia and manic depressive psychosis. Even Dr. Kosten
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`admitted that a POSA, reading Saji ’372 and its prosecution history, would
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`recognize that lurasidone could successfully treat both schizophrenia and manic
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`depressive psychosis, and based his obviousness opinion on this fact.13
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`Slayback’s reliance on Dr. Stahl’s testimony that antipsychotics exhibit
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`complex behavior is of no help.14 They do indeed exhibit complex behavior,
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`which is why, as both Dr. Stahl and Dr. Kosten testified, it is not possible to
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`predict side effect profiles such as weight gain until the drugs are actually tested in
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`patients.15 However, for the reasons discussed above, it was well-known that an
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`agent that exhibited D2 binding affinity could successfully treat psychoses,
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`including schizophrenia and manic depressive psychosis, because psychoses as a
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`class are characterized by excess dopamine. That much was entirely predictable
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`and known. As even Dr. Kosten recognized, anti-psychotics such as olanzapine
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`and lurasidone shared this property, and olanzapine was indicated for treating both
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`schizophrenia and manic depressive psychosis (specifically, manic episodes
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`associated with bipolar I disorder).16
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`13 Ex. 1002, ¶¶ 111-116; Ex. 2131, ¶ 105.
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`14 Reply, 14.
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`15 Ex. 2131, ¶¶ 88, 139; Ex. 2134, 42:4-13.
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`16 Ex. 2131, ¶ 103; Ex. 1002, ¶¶ 117, 122, 143.
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`Slayback further argues that even if the ’927 provisional describes using
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`lurasidone to treat manic depressive psychosis, Sumitomo somehow waived its
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`written description argument by not addressing “a method with all limitations of
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`the manic depressive claims.”17 This argument makes no sense.
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`First, it is expressly contradicted by Patent Owner’s Response, which details,
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`for example, how “[a]s Dr. Stahl explains, a person of ordinary skill, reading the
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`passage regarding Saji ’372, as well as the Phase II clinical data reported in both
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`the ’827 patent and the ’927 provisional application, would recognize that the
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`claimed lurasidone dosing regimen could treat psychoses generally, and
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`schizophrenia and manic depressive psychosis specifically, without causing
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`weight gain.”18 It goes without saying that “the claimed lurasidone dosing
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`regimen” means “the claimed method with all limitations.” Second, Slayback
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`does not challenge the claims limited to treating schizophrenia on the basis of
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`written description, thereby admitting that these claims are entitled to the ’927
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`provisional filing date. A POSA would understand, as Dr. Stahl testified during
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`deposition, that if the claimed dosing regimen treated schizophrenia without weight
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`gain, it also would treat manic depressive psychosis without weight gain.19
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`17 Reply, 16-17 (emphasis in original).
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`18 Response, 28-29.
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`19 Ex. 1054, 151:4-23.
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`Slayback is simply wrong—Sumitomo did address all limitations of the
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`challenged claims and the ’927 application does provide written description
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`support for the ’827 claims.
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`III. CLAIMS 1-75 ARE PATENTABLE
`A.
`Slayback’s Obviousness Analysis Improperly Focuses on
`Individual Claim Elements and Misrepresents the Experts’
`Testimony
`Slayback’s flawed obviousness analysis focuses on whether Saji ’372
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`
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`teaches individual elements of the ’827 patent claims.20 But Slayback misses the
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`point.
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`Here, the inventors invented a novel dosing regimen for treating psychoses,
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`including schizophrenia and manic depressive psychosis, where patients so treated
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`surprisingly did not gain weight. There is no dispute that the claimed dosing
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`regimen is novel, for Slayback’s challenge is based on obviousness, not
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`anticipation. However, Slayback mischaracterizes what Saji ’372 teaches and fails
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`to rebut Sumitomo’s extensive evidence of unexpected results.
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`Saji ’372 teaches a genus of compounds for treating psychoses, including
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`schizophrenia and manic depressive psychosis.21 This genus includes “Compound
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`20 Reply, 20-24.
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`21 Ex. 1009, Abstract; Ex. 2131, ¶¶ 115-116.
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`105,” which is now known as lurasidone.22 Saji ’372 further provides D2 binding
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`affinity data demonstrating to a POSA that Compound 105 could effectively treat
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`psychoses.23 The Saji Amendment (Ex. 1026), upon which Slayback relies,
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`similarly teaches that Compound 105 could successfully treat psychoses. Because
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`the data in the Saji ’372 specification demonstrated that Compound 105 could
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`successfully treat psychoses, it may be considered a preferred embodiment of Saji
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`’372. But that in no way establishes that the ’827 claims would have been obvious
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`over Saji ’372.
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`1.
`Slayback Wants To Retract Dr. Kosten’s Admissions
`Slayback’s own expert, Dr. Kosten, admitted during his deposition that the
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`’827 patent claims directed towards treating schizophrenia would not have been
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`obvious over Saji ’372.24 Slayback now submits a second declaration from Dr.
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`Kosten in which Dr. Kosten backtracks and says what he really meant is that “the
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`clinical data in the ’827 Patent demonstrated the safety and efficacy of using
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`lurasidone to treat schizophrenia.”25 But Dr. Kosten said much more than that.
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`Here is what he said:
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`22 Ex. 1009, 30:30-32:23; Ex. 2131, ¶ 118.
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`23 Ex. 1009, 13:5-10, 30:30-32:23; Ex. 2131, ¶ 119.
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`24 Ex. 2134, 89:16-90:10 (objections from counsel removed).
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`25 Ex. 1051, ¶ 4.
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`Qꞏ ꞏ So is it your view, Dr. Kosten, that after the
`Saji patent which covers the compound of lurasidone --
`after that patent published, that none of the work that
`came after that is patentable?
`. . .
`
`THE WITNESS:ꞏ There are data that were
`presented for use of this in schizophrenia, which was,
`in fact, given a patent.ꞏ And I agree.ꞏ That’s a good
`idea.ꞏ That was fair.
`
`ꞏBY MR. SHEAR:
`ꞏQꞏ ꞏ So you agree that it was fair for claims to be
`ꞏdrawn, and the claims to schizophrenia are patentable?
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`ꞏAꞏ ꞏ They were –
`ꞏTHE WITNESS:ꞏThey were patented. I don’t have
`ꞏany objection to them having been patented for
`schizophrenia.26
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`Dr. Kosten’s deposition testimony is unambiguous. In his opinion, the ’827
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`patent claims directed to treating schizophrenia are patentable over Saji ’372.
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`2.
`Slayback Mischaracterizes Dr. Stahl’s Testimony
`Slayback desperately makes much of Dr. Stahl’s deposition testimony where
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`
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`he stated that a POSA reading Saji ’372 would recognize that lurasidone could
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`26 Ex. 2134, 88:8-24; 89:16-90:10 (objections from counsel removed).
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`successfully treat schizophrenia, calling it a “profound statement of the obvious.”27
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`But what Dr. Stahl simply meant, when viewed in context, was that a POSA,
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`seeing the D2 binding affinity data for Compound 105 in Saji ’372, would
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`immediately recognize that Compound 105 could treat schizophrenia and
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`psychoses generally. As explained above, this is because psychoses are
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`characterized by excess dopamine. Accordingly, Dr. Stahl acknowledged that it
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`was obvious to a POSA that if a compound acts as a dopamine (D2) antagonist, it
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`will treat psychosis. However, it was not at all obvious from Saji ’372 that the
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`specific dosing regimen for lurasidone claimed in the ’827 patent could treat
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`psychoses without weight gain.28
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`Dr. Stahl’s testimony that the ’827 patent was the “logical outcome” of Saji
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`’372 was also made in the context of Compound 105’s ability to act as a D2
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`antagonist and treat psychosis. Slayback takes Dr. Stahl’s statement out of context
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`in order to misconstrue it as an admission that the ’827 patent would have been
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`obvious over Saji ’372.29
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`As an initial matter, there is no “logical outcome” test for obviousness, as
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`Slayback proposes. More importantly, when Dr. Stahl’s testimony is viewed in
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`27 Reply, 20-21; Ex. 1054, 129:22-130:12; 98:19-99:2.
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`28 See Ex. 1054, 168:21-169:20.
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`29 Reply, 22.
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`context, it is apparent he was not conceding obviousness but rather explaining why
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`the ’927 provisional and ’827 patent provided written description support for the
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`manic depressive psychosis claims. Specifically, in response to the question “But
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`how do you know just looking at this document that the named inventors of the
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`’827 patent even knew about D2 antagonism?” Dr. Stahl responded: “Because this
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`patent is a logical outcome of that property.…”30—i.e., the disease states being
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`treated are based on the D2 antagonism disclosed by Saji ’372.
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`
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`It is evident that Dr. Stahl was explaining why the ’927 provisional and ’827
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`patent provided written description support for the manic depressive psychosis
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`claims. In no way was he opining as to obviousness, as Slayback would have the
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`Board believe.
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`Dr. Stahl has consistently testified that Saji ’372 fails to teach or suggest the
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`claimed dosing regimen or anything about weight gain.31 Saji ’372 generically
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`states that the compounds covered by its genus may be provided in any of four
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`broad dose ranges: a “dose of from about 1 to 1000 mg,” a dose “from about 5 to
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`100 mg,” a dose “from about 0.1 to 100 mg,” and a dose “from about 0.3 to 50
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`mg,” but includes nothing to suggest which dose range might work for which
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`compounds, or which route of oral administration or intravenous injection might
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`30 Ex. 1054, 127:20-24.
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`31 Ex. 2131, ¶¶ 121-123; Ex. 1054, 121:8-122:2, 131:4-16, 133:6-134:18.
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`work for which compounds.32 Thus, it is not true, as Slayback alleges, that Saji
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`’372 teaches orally administering lurasidone at a dose from 5 to 100 mg.
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`Moreover, while Saji ’372 says that the dose for these compounds may be applied
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`as a single dose, it also says it may be divided in two or more times.33 Thus,
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`without the use of hindsight, Saji ’372 fails to teach or suggest the ʼ827 patent’s
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`specific dosing range of 20-120 mg administered orally once a day for any
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`compound, let alone for lurasidone.34 Saji ’372 simply is not that specific. As Dr.
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`Stahl noted during his deposition, Slayback is cherrypicking from Saji ’372’s
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`disclosure:
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`Q. In the ’372 patent it did say preferably from 5 to a hundred
`milligrams orally per day, correct?
`
`A. Well, I mean it also said one to a thousand, and it also said I.V.,
`and it also said more than once a day, but in hindsight you are kind of
`cherrypicking what the other one said, but it did say that, but until
`you’ve tested it you don’t know which of the various proposed things
`is actual.35
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`32 Ex. 1009, 12:19-22; Ex. 2131, ¶ 121.
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`33 Ex. 1009, 12:24-25.
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`34 Ex. 2131, ¶ 123.
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`35 Ex. 1054, 121:17-122:2 (objection omitted).
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` Slayback’s cherrypicking of Saji ’372’s disclosure exposes Slayback’s
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`
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`obviousness ground as pure hindsight. See ATD Corp. v. Lydall, Inc., 159 F.3d
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`534, 546 (Fed. Cir. 1998) (obviousness “can not be based on the hindsight
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`combination of components selectively culled from the prior art to fit the
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`parameters of the patented invention.”). Even more significantly, as explained
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`below, Slayback entirely fails to offer any rebuttal to Sumitomo’s evidence that
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`lack of weight gain associated with the claimed dosing regimen was unexpected.
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`B.
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`Slayback Ignores Evidence Demonstrating That Lurasidone’s
`Lack of Weight Gain Was Unexpected
`In its Reply, Slayback incorrectly argues that because Sumitomo did not
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`
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`swear behind WO 01/76557 (Ex. 1040), Sumitomo admitted that a POSA would
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`have known that SM-13496 was lurasidone as of the publication date of WO
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`01/76557.36 Not so. Sumitomo disputed this point but then said it did not matter
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`because a POSA would not have been able to predict lack of weight gain based on
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`the receptor data reported in Horisawa for SM-13496.37 In support, Sumitomo
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`cited numerous scientific publications, as well as Dr. Stahl’s testimony and Dr.
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`Kosten’s deposition testimony, which illustrated the inability to predict lack of
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`36 Reply, 26.
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`37 POR, 41-42.
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`Attorney Docket No.: 46094-0002IP1
`Case No.: IPR2020-01053
`weight gain based on receptor data.38 But Slayback ignores all of this evidence.
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`Slayback did not even question Dr. Stahl about Horisawa during his deposition nor
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`did Slayback submit arguments or evidence in its Reply to rebut Sumitomo’s
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`extensive evidence. Even though Dr. Kosten submitted a second declaration, he
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`never addressed Sumitomo’s arguments distinguishing Horisawa, tacitly admitting
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`that Sumitomo is correct.
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`
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`At the end of the day, Slayback has no answer. Its conclusory statements, in
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`the face of Sumitomo’s unrebutted evidence regarding the unreliability of receptor
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`data with respect to weight gain, fail to prove unpatentability.
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`C.
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`Slayback Fails to Rebut Sumitomo’s Objective Evidence of
`Nonobviousness
`Sumitomo introduced evidence, in the form of documents and the
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`declarations of Drs. Stahl and Reisetter, demonstrating that the claimed dosing
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`regimen was commercially successful and satisfied a long-felt but unmet need for
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`an antipsychotic that was effective against schizophrenia and bipolar disorder,
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`including bipolar depression, and that had an acceptable side effect profile,
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`including lack of weight gain.39 Sumitomo also submitted evidence of industry
`
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`38 POR, 42-45; Ex. 2131, ¶¶ 81-89; Ex. 2134, 42:4-13; Exs. 2022, 2027-2029;
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`2036-2039; 2046; 1042.
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`39 POR, 53-58 and exhibits cited therein.
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`16
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`
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`Attorney Docket No.: 46094-0002IP1
`Case No.: IPR2020-01053
`skepticism on the part of leading pharmaceutical manufacturers regarding the
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`claimed lurasidone dosing regimen’s ability to fulfill this need, which further
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`supports non-obviousness.40
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`Slayback’s only response is to argue lack of nexus on the ground that neither
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`of Sumitomo’s experts was able to articulate “the novel aspects of the claims,” by
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`which Slayback meant pointing to individual claimed features that allegedly were
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`novel.41 But Slayback’s position is contrary to law. “[I]f the marketed product
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`embodies the claimed features, and is co-extensive with them, then a nexus is
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`presumed and the burden shifts to the party asserting obviousness to present
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`evidence to rebut the presumed nexus.” Brown & Williamson Tobacco Corp. v.
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`Philip Morris Inc., 229 F.3d 1120, 1130 (Fed. Cir. 2000).
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`Slayback does not dispute that the ’827 claims cover and are co-extensive
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`with LATUDA®. Therefore, it was incumbent on Slayback to rebut the
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`presumption of nexus by introducing evidence demonstrating that commercial
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`success, satisfaction of long felt need, and skepticism of experts were due to
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`factors other than the merits of the claimed invention. See id. (“The presumed
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`nexus cannot be rebutted with mere argument; evidence must be put forth.”).
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`Slayback has not done this. Both Dr. Stahl and Dr. Reisetter established that each
`
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`40 POR, 58-59 and exhibits cited therein.
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`41 Reply, 28-29.
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`17
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`
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`Attorney Docket No.: 46094-0002IP1
`Case No.: IPR2020-01053
`of these objective factors was attributable to the merits of the claimed invention—
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`specifically, the ability of the claimed lurasidone dosing regimen to treat
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`schizophrenia and bipolar disorder, including bipolar depression, with an
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`acceptable side effect profile, including lack of weight gain.42 Dr. Stahl explained
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`that this was why psychiatrists such as himself prescribed LATUDA®.43 Dr.
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`Reisetter explained in detail why other factors such as advertising did not account
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`for LATUDA®’s commercial success, and noted that LATUDA® remained
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`commercially successful despite the availability of cheaper generic and newer
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`branded alternatives.44
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`Slayback did not offer expert testimony to rebut Dr. Reisetter’s thorough
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`analysis of nexus. Dr. Kosten did not address Sumitomo’s objective evidence at
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`all, even though he submitted a second declaration. In fact, Slayback has done
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`nothing to rebut Sumitomo’s objective evidence of nonobviousness.
`
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`42 Ex. 2131, ¶ 76; Ex. 2132, ¶¶ 42-59; Ex. 1054, 168:24-169:9 (“the ’827 patent . . .
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`identified a dose range actually that worked in a human being which had efficacy
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`in a type of psychosis which was an indicator of a proof of confidence it would
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`work in all kinds of psychosis, and it also surprisingly didn't have a weight gain to
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`it.”)
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`43 Ex. 2131, ¶ 76.
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`44 Ex. 2132, ¶¶ 42-59.
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`18
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`
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`D.
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`Attorney Docket No.: 46094-0002IP1
`Case No.: IPR2020-01053
`Slayback Misconstrues the Role of Patient Populations in the
`Context of Weight Gain and Obviousness
`There is no dispute that “a patient,” as recited in the ’827 claims, refers to
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`“one or more patients.” Nevertheless, how a patient population behaves is relevant
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`to the issue of obviousness—in particular, to whether a POSA would have had a
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`reasonable expectation that a patient treated with lurasidone according to the
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`claimed dosing regimen would not gain weight. During his deposition, Dr. Stahl
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`succinctly explained this concept:
`
`Q. So as of August of 2021 the person of ordinary skill in the
`art understood that in at least one study of risperidone approximately
`60 percent of the patients administered the risperidone did not gain a
`clinically significant amount of weight, right?
`
`A. Yes, that’s what ended up happening, but again as I say you
`don’t practice in hindsight. Before you give a patient you have to
`have expectations and predictions, and so the practice of medicine is
`taking multi-center trials for the population and treating the
`individual, and as you know nobody treats populations. People treat
`individuals so the art is trying to figure out what does this mean to a
`patient. What this means to a person of ordinary skill in the art is that
`you expect weight gain. You just don’t know who is going to have
`it.45
`
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`45 Ex. 1054, 48:1-18.
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`19
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`Attorney Docket No.: 46094-0002IP1
`Case No.: IPR2020-01053
`In other words, how a patient population behaves with respect to weight gain
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`is relevant to whether a POSA would expect weight gain for a patient. The fact
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`that some individual patients ultimately do not gain weight is irrelevant to a
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`POSA’s reasonable expectations. And it is the reasonable expectation of success
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`that matters in the obviousness context. As Dr. Stahl repeatedly testified, it was
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`indeed surprising and unexpected that, when compared to other atypical
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`antipsychotics such as olanzapine and risperidone, patient populations treated with
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`the claimed lurasidone dosing regimens did not gain weight:
`
`Q. And that’s what a person would expect from giving a drug
`to a population of people, right, some would gain and some would not
`gain?
`
`A. No. You expect everybody to gain weight on drugs that
`have a lot of weight gain associated with it before you give it, and you
`expect nobody to gain weight today on this drug [LATUDA®],
`although at the time it was invented, we’ll get to that, everybody
`would have expected that this one, too, would cause weight gain in
`everybody.46
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`Dr. Stahl’s declaration is consistent: “There is nothing to suggest that [the
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`claimed] dose range and dose regimen would successfully treat those disorders
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`without causing weight gain or clinically significant weight gain.”47 Because a
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`46 Ex. 1054, 57:7-16.
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`47 Ex. 2131, ¶ 126.
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`20
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`Attorney Docket No.: 46094-0002IP1
`Case No.: IPR2020-01053
`POSA’s reasonable expectations are formed based on the population, Slayback’s
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`argument with respect to individual patients are not relevant to obviousness.
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`E.
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`Slayback Fails to Prove That Lack of Weight Gain is Inherent in
`the Prior Art
`Slayback again wrongly asserts that lack of weight gain in one or more
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`patients is inherent because at least one patient will not gain weight as a result of
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`practicing the claimed methods.48 Such a hindsight-based assertion that practicing
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`the claimed method will produce the claimed result does not establish obviousness.
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`As noted in
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