`
`DEMONSTRATIVEEXHIBIT –NOT EVIDENCE
`
`Patent Owner’s Presentation
`August 11, 2021 Oral Hearing
`
`IPR2020‐01053
`
`Slayback Pharma LLC. v. Sumitomo Dainippon Pharma Co.,
`
`Ltd.
`
`1
`
`Exhibit 2143
`Slayback v. Sumitomo
`IPR2020-01053
`
`
`
`PDX-101
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`•Obviousness (Ground 3) –Claims 1‐75 are patentable over Saji, US
`
`5,532,372, a reference previously considered by the Patent Office
`
`•Because these claims are entitled to the Provisional Filing date, Grounds 1 and 2 fail as the art relied on is
`•These claims are entitled to the August 22, 2002 provisional filing date
`•These claims recite treating “manic depressive psychosis” or treating a patient with “an anti‐psychotic.”
`56‐60, 62, 64, 66, 67, 69, 71, 73, and 75.
`
`–Grounds 1 and 2 apply only to claims 8‐18, 25‐28, 30‐31, 33‐39, 40‐44, 46, 48‐55,
`
`after that date.
`
`•Priority (Grounds 1 and 2)
`
`Overview
`
`2
`
`
`
`PDX-102
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`IPR2020-01053, Ex. 1001
`
`–Without either clinically significant weight gain or weight gain
`–Administered: Once daily, oral administration of 20‐120 mg
`–To treat schizophrenia or manic depressive psychosis
`
`•Claims cover use of lurasidone as an antipsychotic
`•75 Claims (5 independent)
`
`The Patented Invention
`
`3
`
`
`
`PDX-103
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`•See IPR2020‐01053 Petition at 21.
`bipolar disorder
`person of skill to mean
`psychoses” is understood by a
`
`–“Manic depressive
`
`•Specification refers to both
`
`–See IPR2020‐01053Ex. 1001
`schizophrenia
`psychoses,” and
`“manic depressive
`
`’827 Patent col. 2, ll. 5‐10.
`
`’827 Patent Specification Discloses Both Schizophrenia and
`
`Manic Depressive Psychoses
`
`4
`
`
`
`PDX-104
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`POR at 12-13
`
`IPR2020-01053 Ex. 2022
`
`Weight Gain is a Known and Substantial Problem
`
`5
`
`
`
`PDX-105
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`POR at 6
`
`IPR2020-01053, Ex. 2027
`
`Stahl’s Essential 2013
`
`Antipsychotics are Complex
`
`6
`
`
`
`PDX-106
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`Ziprasidone –POR at 11‐12
`
`Risperidone –POR at 10‐11
`
`Quetiapine –POR at 8‐9
`
`Olanzapine –POR at 7
`
`Antipsychotics are Complex
`
`POR at 6
`
`IPR2020-01053, Ex. 2027
`
`Stahl’s Essential 2013
`
`7
`
`
`
`PDX-107
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`IPR2020-01053 Ex. 2131 ¶¶ 81-89
`
`at 81; POR at 12-13
`
`Dr. Stephen Stahl
`
`Mechanisms Underlying Weight Gain are Complex and
`
`Poorly Understood
`
`8
`
`
`
`PDX-108
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`IPR2020-01053 Ex. 2028 at 5-
`
`6; POR at 13
`
`“Weight gain . . . Difficult to Predict”
`
`9
`
`
`
`PDX-109
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`IPR2020-01053 Ex. 1001, 7:49-
`
`67
`
`Inventors Surprisingly Discovered the Novel Dosing
`
`Regimen did not Cause Weight Gain
`
`10
`
`
`
`PDX-110
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`IPR2020-01053 Ex. 1001,
`
`Claim 1
`
`Inventors Surprisingly Discovered the Novel Dosing
`
`Regimen did not Cause Weight Gain
`
`11
`
`
`
`PDX-111
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`Grounds 1 and 2 –Priority
`
`12
`
`
`
`PDX-112
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`–A POSA, reading the ’927 provisional application in light of what was known about
`
`understand that the inventors were in possession of the MDP claims –POR 27‐32
`the link between schizophrenia and manic depressive psychosis (“MDP”) would
`
`–Slayback’s priority argument is legally flawed and not properly before the Board –
`
`POR at 32‐33 et seq.
`
`•Slayback’s argument fails both legally and factually:
`
`•Grounds 1 and 2 (priority) apply only to claims 8‐18, 25‐28, 30‐31, 33‐39,
`
`“antipsychotic”
`–Claims recite treating “manic depressive psychosis” or treating a patient with an
`40‐44, 46, 48‐55, 56‐60, 62, 64, 66, 67, 69, 71, 73, and 75.
`
`’827 Patent Claims Entitled to Priority to Aug. 22, 2002
`
`13
`
`
`
`PDX-113
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`U.S.C. §311
`for the MDP claims and that is not an issue properly before the Board. 35
`•Thus, the question is purely whether there is written description support
`
`filing
`August 28, 2014 filing date as they were not part of the August 28, 2014
`•Therefore, the MDP claims cannot be legally considered “entitled” to the
`
`•The MDP claims were notfiled with the August 28, 2014 application, they
`
`were added later by amendment
`
`•Slayback argues that the MDP claims are entitled to a filing date no
`
`earlier than August 28, 2014.
`
`Slayback’s Priority Argument is Legally Flawed
`
`14
`
`
`
`PDX-114
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`•Ex. 1001, 5:1‐10:25; Ex. 1005, pp. 32‐41; see Ex. 2131 (Stahl), ¶¶ 98‐99. POR 28
`MDP specifically, without weight gain.
`claimed dosing regimen could treat psychoses generally, and schizophrenia and
`–Both describe the results of a Phase IIaclinical study that demonstrated that the
`
`•The specifications of the ’927 provisional application and the ’827 patent
`
`•Compare Ex. 1001, 2:7‐39 with Ex. 1005, p. 27, line 23 to p. 28, line 4.POR 28
`depressive psychoses, and nervous breakdown (U.S. 5,532,372)”
`especially as an agent for treatment of schizophrenia, senile insanity, manic
`of compounds “useful as an antipsychotic (c.f. neuroleptic agent, antianxiety, etc.),
`–Both describe the Saji ’372 patent (IPR2020‐01053 Ex. 1009) as disclosing a genus
`are identical in all relevant respects –POR 28
`
`The MDP Claims are Entitled to the ’927 Provisional Filing
`
`Date
`
`15
`
`
`
`Jojooy]UM
`aytuas‘eruasydoziyosfoJUaueaT)JOPJuaseueseAT][RID
`
`
`
`ayyAqpunoysemYSIS‘ePNULOFBULMOT[O}Sy]JOAANRALIOP
`
`
`
`uese[nfasnoqAPU“sIOJUDAUTJUasotddU}JOsJayJOM-09
`
`
`
`-adso“(aja“Ajarxenue“juasesydayomou“y'9)syoysAsdynue
`
`
`
`
`
`
`-yealqsnoArIeupue‘sesoyodAsdaatssoidapommeur‘Ayrmesut
`
`
`
`aptsy]WY}UMoUYydeqseyIt‘puey
`
`
`(ZLETES‘S“ON“Wd“S')UMOp
`
`
`
`
`
`ou} JOdAT}LALIOp
`Splut9Je}UMOUU20qseyHI‘pueYJoujO94}UG
`yuasaiday}Josiax1om-ooay}AqpunojsemYOoTyM‘e_NULIoJSurmoypjoy
`
`
`
`
`alas‘etuaiydoziypsJoJuauI}e901]JoyJUDEUeseATTeID0dS=a‘(Ajorxenue
`
`
`
`dSN)umopyeeigsnosisupue‘sesoyodsdaatssaidapo1ueuw‘Ayruesut
`
`
`
`
`
`‘yuaseondojoimou‘y:0)ogoyoAsdynueuese[nyasnoqAeur‘s10}U9AuT
`
`
`
`
`
`‘(ZLeTes‘s
`
`16
`
`
`
`
`
`The MDP Claims are Entitled to the ’927 Provisional Filing Date
`
`
`
`93eqBulll4J2UOISIAOIg£76,9U}0}pal}qUyaveSwe!dqWauL
`
`Gii-Xdd
`
`PDX-115
`
`8cYOd
`
`POR 28
`
`92-1uy‘ZzA‘SOOTXF
`
`Ex. 1005, p. 27, line 21 -26
`
`
`
`
`
`
`
`I1-$°7WadL78.TOOT“XA
`
`Ex. 1001,’827 Patent, 2:5-11
`
`
`
`
`
`
`
`
`
`
`
`AONAGIASLON—LIGIHX]ASAILVYLSNOWAG
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`
`
`
`
`
`
`16
`
`
`
`
`
`
`
`ZOT-LOTbb‘TETZXTzgSUIO|dUIASJOUONITIOOvsvYIOG
`
`<—
`
`17
`
`ail-XQd
`
`PDX-116
`
`Ex. 2131, ¶¶ 101-102
`
`
`
`
`
`
`
`AONAGIASLON—LIGIHX]SSAILVYLSNOWAGaw
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`
`
`
`
`
`
`
`
`
`pure[vUONUSAUOSlog‘suo}dUIASapnyoulUdstsoysAsdaatssaidapo1ueUtUOWUTUOD
`dAlssaidaporueulpueviuarydoziyosyear]0}UMOUYa1amsonoysAsdyuepeordAye
`
`
`
`
`
`
`pueviuarydoziyost10q“7¢ydeiseredulaAo0gepassndsIp|sV‘ZOL
`
`
`
`
`
`Iejodigq‘a'r)stsoysAsdaatssaidapstuewpueemoamdoziyss‘TOI
`
`
`
`
`
`
`
`
`
`
`
`
`MATA0]9]BINIIVSIOULSTJI“IOYILY“SASBASIPJOUNISIPpueayeredasjOUare(JapIOSIp
`
`
`
`
`
`pulysig‘payejasuAjouaseqq|A|pueeluasudoziuds
`
`Schizophrenia and MDP are not Unrelated, Distinct
`
`Saseasiq
`
`Diseases
`
`egJoldada1qq=sururedopay)SuNssie)AqsisoysAsd
`
`17
`
`
`
`
`PDX-117
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`–Slayback’s Expert, Dr. Kosten, agrees . . .
`
`•Ex. 2131, ¶ 102; Ex. 2140 –Surreplyat 3
`targeting the D2receptor
`–Antipsychotics were known to treat schizophrenia and the manic phase of MPD by
`–Psychotic symptoms are the result of excess dopamine
`
`•Ex. 2131, ¶¶ 37, 102; Ex. 2140 –Surreplyat 3
`
`–Both include psychotic symptoms
`
`•Schizophrenia and MDP are not unrelatedconditions
`
`Treating Schizophrenia is Treating the Manic Phase of MDP
`
`18
`
`
`
`PDX-118
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`Ex. 2134, 34:15-17
`Dr. Thomas Kosten
`
`A. That’s correct.
`
`schizophrenia and the manic phase of bipolar disorder.
`Q. So the antispsychoticcan be used to treat both
`
`Treating Schizophrenia Treats the Manic Phase of Bipolar
`
`Disorder (MDP)
`
`19
`
`
`
`PDX-119
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`Ground 3 -Obviousness
`
`20
`
`
`
`PDX-120
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`–Extrapolating From Other Chemical Structures Is Improper.
`–Receptor Binding Affinity Data Are Inconsistent and Inconclusive.
`
`•The lurasidone prior art did not disclose a weight effect.
`•Weight gain is a multifactorial process.
`•Multiple receptors are involved.
`•The relationship between pharmacological profile and weight gain was not (and is not) well understood.
`
`•A Skilled Artisan Would Have No Reasonable Expectation of Success In Achieving
`
`–The Pharmacology of Antipsychotics is Complex.
`the Claimed Invention Because the Art is Unpredictable.
`
`35 U.S.C. §103: No Reasonable Expectation of Success
`
`21
`
`
`
`PDX-121
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`•“Guideline for Industry: Dose‐Response Information to Support Drug Registration” (1994) (“ICH‐4;” Ex.
`
`1030).
`
`Drug Safety (2001) (“Wetterling;” Ex. 1042);
`(“Allison;” Ex. 1041) and Wetterling, “Bodyweight Gain with Atypical Antipsychotics: A Comparative Review,”
`•Allison, “Antipsychotic‐Induced Weight Gain: A Comprehensive Research Synthesis” Am. J. Psychiatry (1999)
`
`Various Receptors in the Brain,” Jap. J. of Neuropsychopharmacology(Dec. 1999) (“Horisawa;” Ex. 1028);
`•Horisawa, “Pharmacological Characteristics of the Novel Antipsychotic SM‐13496: Evaluation of Action on
`•“ZYPREXA® (Olanzapine) tablets.” Physicians’ Desk Reference, 55thed. (2001) (“Olanzapine;” Ex. 1039);
`•“Saji amendment” (Ex. 1026) submitted during prosecution of the Saji patent;
`the following references:
`–Although not formally part of the unpatentability ground, Slayback also relies on
`over Saji, U.S. 5,532,372 –Ex. 1009.
`
`•As the Patent Office previously determined, Claims 1‐75 are patentable
`
`Claims 1‐75 are Patentable over Saji
`
`22
`
`
`
`PDX-122
`
`POR 36‐37
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`(objections from counsel
`
`removed)
`
`Ex. 2134; 88:8-24; 89:16-
`
`90:10
`
`Dr. Thomas Kosten
`
`information. So that's not irrelevant.
`with this medication.ꞏYou need to know that
`what? I mean, they're relevant to treatment of patients
`THE WITNESS:ꞏI guess I don’t ‐‐irrelevant to
`. . .
`all of those other things are irrelevant; right?
`regimen leads to weight gain –it’s your position that
`not you give it with something else, whether or not that
`use, how often you're supposed to give it, whether or
`limitations --how much of the drug you're supposed to
`QꞏꞏSo it’s your position that all of those other
`AꞏꞏOkay.
`lurasidone molecule itself; right?
`the use of lurasidone hydrochloride are due to the
`ꞏunexpected results for any secondary consideration to
`QꞏꞏYou have a blanket statement now that any
`
`Slayback’s Expert Disagrees with Slayback
`
`23
`
`
`
`PDX-123
`
`POR 36‐37
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`(objections from counsel
`
`removed)
`
`Ex. 2134; 88:8-24; 89:16-
`
`90:10
`
`Dr. Thomas Kosten
`
`objection to them having been patented for schizophrenia.
`THE WITNESS: They were patented. I don’t have any
`A They were –
`drawn, and the claims to schizophrenia are patentable?
`QꞏꞏSo you agree that it was fair for claims to be
`BY MR. SHEAR:
`
`idea.ꞏThat was fair.
`in fact, given a patent.ꞏAnd I agree.ꞏThat’s a good
`presented for use of this in schizophrenia, which was,
`THE WITNESS:ꞏThere are data that were
`. . .
`came after that is patentable?
`after that patent published, that none of the work that
`Saji patent which covers the compound of lurasidone --
`QꞏꞏSo is it your view, Dr. Kosten, that after the
`
`Slayback’s Expert Disagrees with Slayback
`
`24
`
`
`
`PDX-124
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`IPR2020-01053 Ex. 1001,
`
`Claim 1
`
`Saji ’372 Patent does not Teach the Claimed Dosing
`
`Regimen
`
`25
`
`
`
`
`
`S2l-X0dAONAGIASLON—LIGIHX]ASAILVYLSNOWAG
`
`PDX-125
`
`
`
`
`
`
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`
`
`AjsoodpuexajdwodAjasizuaYdIUMJOSLUSIUeYDaWase
`
`
`
`
`
`
`
`
`
`
`
`•Does not teach anything about weight gain, the
`•Discloses varying dosing frequencies
`
`
`
`
`
`
`
`to lurasidone
`
`008A
`
`
`
`IGN,TERI
`
`
`
`yuayedZZE,Iles
`
`Saji ’372 Patent
`
`
`
`pal}aveYdIUMJoauOU‘s}JUNOLUeasopBUIAJeASaso}IsIq
`
`•Discloses varying dose amounts, none of which are tied
`•Discloses billions of compounds
`•Was considered by the PTO
`
`understood
`mechanisms of which are entirely complex and poorly
`
`
`
`oy}‘ulesJySIaMynogesulyyAueYydea}JOUS90q
`
`salauanbadsjSuisopSUIAJeASasojsiq
`
`
`
`SPpUNOdWODJOSUOII|IGSasojIsiq
`
`
`Old34}AqpaJapisuodse«
`QuOpIsesn|0}
`poossapun
`
`
`
`Ov-ZLEYOd
`
`POR 37‐40
`Ex. 1009
`
`6001“X7
`
`quajodTLE,10S
`
`Saji ’372 Patent
`
`eet‘ctOrwanedJo218
`
`26
`
`26
`
`
`
`
`
`PDX-126
`
`
`
`
`
`
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`
`
`AONAGIASLON—LIGIHX]ASAILVYLSNOWAG
`
`
`
`
`
`
`
`wadesnootsdnoeonseprysen‘sipesVONEppepise
`
`
`
`
`
`
`
`
`
`
`
`AILPOE[OORO(RYPuUeAMOxyeLomo]“LOayEJamo]Jos00
`
`
`
`(i\/
`
`
`
`LOVaLsay[ec]
`
`
`
`[EPMOauJOPuNodwEsspraywy
`
`(RIDLUOY2]JOnau&st
`
`WEES,
`
`
`
`UESL0PUS“OOPallljapaleSiemISqMsBYYopUE
`
`BUOYayajodnowS2sycj]
`
`
`
`‘TagAasaye
`
`FHF
`
`
`
`AjewondoJougoqumeacupAysaewore-wouFstYOONoT
`
`
`
`
`
`
`
`
`
`
`
`Pres‘WorewaiAsooe10dowdauapAyyeJamo]Fimpaipug
`
`
`
`
`
`aaa[AqeJoao,presputBuvodeopAysnelore-noU
`
`
`
`S00[se2a,TEitmpasqnsAjpeoondewoesSugdno
`
`
`
`
`
`
`
`
`
`drow?onpypsuayd&20drewAxousyd2‘dnoa®jAozuag
`
`saydig&sfJY20—YOO<Jo—HD<“A815pur
`
`
`
`SAOGE209JO[JF‘==oc61)purdonutsospcpAgyoyAg
`
`
`
`
`
`
`
`EdnaSEWwOTeayAsouaeg©doodaEROreOe51Dy
`
`
`
`Pur'730|‘Qposafaqo7urgonasuebpordpor"poysso]
`
`
`
`
`
`ISA,12WoeparniisgnsAypeuondeyesHinagsdnort
`
`
`
`
`
`
`
`
`
`SPUNOAdWOZJOSUOII|IgSAasojIsiG
`
`SajiDiscloses Billions Of Compounds
`
`Ife
`
`S
`
`
`
` 966ZLislyeating
`
`
`we'ces'sawllquayegsaqeigpayuy
`
`JOD.USQY1D6001“XH
`
`Ex. 1009 at Abstract
`
`
`
`ingsonesnséy“SBE
`
`27
`
`mornIO“Prt
`
`so6t‘teFoype
`
`ec
`
`
`
`eeeent=0NEV[ZT
`
`
`
`(eenuringZoueNOS
`
`
`
`nde"eR10
`
`
`
`
`
`Kundusqusprosmmunyy,SeoyuENS“ay[EL]
`
`
`
`
`
`
`
`ToveyPecos,aesQUEsiauNK[GL]
`
`
`
`(N000000|
`
`
`
`MISHILGN‘SAALIVAINSath
`
`lest
`
`ashanyNoman
`
`27
`
`
`
`
`
`
`
`
`L2\-XOd
`
`PDX-127
`
`
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`
`
`
`
`"SOWQIOWJOOM]UTATPAprArp
`
`
`
`A
`
` AONAGIASLON—LIGIHX]ASAILVYLSNOWAG
`
`Ss]10(J)punoduwiosapioy}Joo3esopoy)OITASI
`
`
`JOUIT]a[suIsButporfddeaqAewasoppreg‘uondafur
`
`‘BUIOOOL0}[|NoqeworjoasopAjrep&11NpeueoO}
`
`
`
`ay)ymApeoldsoueayeso[qeidaooeAypeonnaoeuneyd
`
`
`UdATSATTeIOUAS3qAPU71OMI]OY]PueApOUUOTeNsTUNUpe
`
`
`
`
`-UIWIPB[BIOJOIS¥dUl“SUIQOL01S$MogeuOIyATqerayoid
`
`
`
`
`
`
`dy)‘WLIOaBesSOpoY}‘WoTJed9y}Jo}YSIOMpuvode‘wWo}duIAs
`‘BUIOOT01[°OINogeWioIJoasopA[repeBjepueUONeNs!
`
`
`SNOSABULJOISBIUT“SUIQS01€'QINogeWwoIA[quiayoid
`
`
`
`
`
`
`
`
`llquayegsaqeigpayuy
`
`PC-ST-CII”6001XA
`
`Ex. 1009 at 12:15-24
`
`2fies
`
`28
`
`
`
`
`
`Saji Teaches Very Little About Dosing
`
`
`
`
`
`sulsogynogy9/341]Aya,sayseaytfes
`
`28
`
`
`
`
`
`PDX-128
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`Saji5,532,372
`
`SajiSilent Regarding Weight Gain
`
`29
`
`
`
`
`
`
`
`B2I-X0dAONAGIASLON—LIGIHX]SSAILVYLSNOWAGA
`
`
`
`
`
`SEMUIEDJUSIAMJO49e7JEU}USI|Ge}SZJOUS8OpeEMeSIIOH
`UarydoznyosSoaoidunl96F¢ET-NSLY}Isassnss]Nsarasaq_L.|=AL;——~—
`ATOJYNIMsjyey]|pueuonseSsurydo]qJojdasar<pH-¢pue<qeIAstoydurAs3|
`
`
`-sASSNOAIOUJMTpPOYITAI2Ivay]UOWoTIestasneIaqapuesoe||$]9ayJ2
`
`
`
`
`$]Da]J2aptsUorssaidap[enus>puewajsAs
`
`
`
`“MOULIAYLM“MOTStsto}daza1INPH-¢pue“ty“too}AyeBur
`
`
`-pulogs}IasnedaqYeamareVodeSUTsKaIDUTyYSIaMmApogpue
`
`
`
`
`
`apts[epruesAdenxasSmipa]Jey}Isassnss]pnsezay}
`"yeaSTsIo}dadar(q[PIRESBIAUI}
`
`ASopoovuLIvydoysAsdo.nan
`
`
`
`
`
`jo[vutnorasauuder
`
`
`
`30
`
`
`
`PDX-129
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`payedxXy
`
`Expected
`
`Horisawa does not Establish that Lack of Weight Gain was
`
`
`
`
`
`£9D8COlXA
`
`Ex. 1028 at 3
`
` I(GaERMNRENMEI9SES
`
`QONGEICA
`
`FrgeOrelNast
`
`
`
`30
`
`
`
`
`
`PDX-130
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`POR at 43
`
`Ex. 2028 at pp. 5-6
`
`Receptor Binding Affinity Does Not Predict Weight Gain
`
`31
`
`
`
`PDX-131
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`POR at 43
`Ex. 2035 at 1
`
`Receptor Binding Affinity Does Not Predict Weight Gain
`
`32
`
`
`
`PDX-132
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`Ziprasidone –Does Not Cause Weight Gain
`
`POR at 43
`
`IPR2020-01053, Ex. 2027
`
`Stahl’s Essential 2013
`
`Quetiapine –Causes Weight Gain
`
`Olanzapine –Causes Weight Gain
`
`Receptor Binding Affinity Does Not Predict Weight Gain
`
`33
`
`
`
`PDX-133
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`Ziprasidone
`
`Lurasidone
`
`•BUT: Lurasidone Is NotStructurally Similar To Ziprasidone. Ziprasidone
`
`has an indole structure. Lurasidonedoes not.
`
`•Slayback, relying on Allison and Wetterling, argues that lack of weight
`
`lurasidone and did not cause weight gain.
`gain was expected because ziprasidone is structurally similar to
`
`35 U.S.C. §103: Unpredictability of the Claimed Invention
`
`34
`
`
`
`PDX-134
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`–Binding affinities are quite different
`
`for treating bipolar depression.
`–Lurasidoneis indicated for treating bipolar depression. Ziprasidone is not indicated
`
`–Ziprasidone causes QT prolongation, which required a black box warning on its
`
`label. Lurasidonedoes not cause QT prolongation.
`
`•Ziprasidone and lurasidonehave very different properties:
`
`35 U.S.C. §103: Unpredictability of the Claimed Invention
`
`35
`
`
`
`PDX-135
`
`POR 49
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`Ziprasidone and Lurasidone have Different Receptor
`
`Binding Profiles
`
`36
`
`
`
`del-Xdd ADNAGIAS
`
`
`
`
`
`
`‘SMPBO}UOTIvAISISIOT[VULJIqIyXdAvUyUaTedouo‘ajdurexd10.7“Snupepnotsedv
`
`
`uosiadyY“aaIsesip[.-),SueumyJOALISJOAIpay},ay)01anpJuanedvUTUTESIYSIAM
`
`
`
`
`
`
`
`
`0}ApuarayyippuodsarAvutsquared[eNplAIpuUrVY)9ZIUSOIAIp[NOM[[L{sATeBUIPIOJO
`
`
`
`
`vJosaniadoiday)puvysiapun0}SuLyaas[[LYsAleuIpsoJouosiady‘6rl
`
`
`
`
`
`qey)19adxapynoar[[PYsAreurpsoJouossadvJey)sansieuaysoy“Iq‘Srl
`
`
`
`
`
`JOUP[NOM[[LYsAreuIpsoJouossadve‘yUaTeda[sutsvJoasuodsaloy)UOpasegqIng
`
`
`
`
`
`
`JUBSTJIUSISAT[VOTUT]SIOUTSJYSIOMSsNvdJOUP[NOMUSWIISEISUISOppouTE]Say)
`
`[[MJuatjed[enprlAipulUdAISAUBMOYSUIUIULIa}apUOpasndojaqJOUpynomSnip
`
`
`
`
`
`
`
`
`
`
`
`AjISJDAIG,,UOpasegpa}IedxqJOUSEMUleDJUSIAMJOyDe7]
`
`Lack of Weight Gain was not Expected Based on “Diversity
`
`of Humans”
`
`Ex. 2131, ¶¶ 148-149
`
`37
`
`SUBLUNHJO“l
`
`PDX-136
`
`
`
`
`
`LON—LIGIHX4SAILVYLSNOWSAG
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`“AOBILTJ210s]oayjoaptsJoyWIodpur}say)worpuodsar
`
`
`
`
`
`
`
`
`
`“IOLUL[BIDUISBSBUOTDAIS1BIA][VUBSdsNeVdSNAPdy)apnpsuo0s
`
`37
`
`
`
`Leh-XOd
`
`PDX-137
`
`AONACIAZLON—LIBIHXSAAILVYLSNOWAG
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`
`
`
`
`‘spiom
`
`ET-t-ChFEITXY
`
`‘qeAuoszedeojutqueSeue
`
`38
`
`Lack of Weight Gain is not Inherent
`
`
`
`BESONSmoAO
`
`Ex. 2134, 42:4-13
`Dr. Thomas Kosten
`
`
`Jo320s302,no04Jt--yBnoyq‘S5utteep
`
`
`
`and3,ueaeynodpue‘AzeaoostpBnape&JosTpptwuseyqut
`
`STIATT&@$,91‘seqemtadyqtmststyqgtATzeTnotqzed
`
`
`ZeyqOUTAng‘seTpNyASsjUSporAworzZyoOTperzdofAepzeYy
`
`
`
`wozjzuoTRZeWAOJUTsulos7eH[T,noApuesetpnq4sTeutue
`
`
`
`
`
`
`
`
`‘quBtempeutedstTeutueazanofAzey.eyMofseesoyy
`
` e2,noKJI5 JUSJIYU|JOUSIUIEDJUSIa\\JO9e7
`
`38
`
`
`
`
`Bel-XOd
`
`PDX-138
`
`
`
`
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`
`
`AONAGIASLON—LIGIHX]ASAILVYLSNOWAG
`
`ECSFETSFELTXA
`
`
`
`éj0u
`
`39
`
`Lack of Weight Gain is not Inherent
`
`
`
`uajsoysmuoy]tga
`
`Ex. 2134, 84:24-85:3
`Dr. Thomas Kosten
`
`
`*MouUYyY4,U0pIos‘3eYQpeqjseqAeasuAueduiodsyWw
`
`
`azo34u6TemMutedp—nomepnjeyjoswezHtTTtu90gHutyzeq
`
`
`
`euoSeUIOSJOUZOAZeyQeYyMeeptAuesaeynokog:yHbnoyy
`
`
`
`
`‘qutodotjytoeds
`
` syqoj--asnf€J‘Aazosog0 JUTIIUYU|JOUSIUlEDJUSIAa/\\JOy9e7
`
`39
`
`
`
`
`PDX-139
`
`DEMONSTRATIVE EXHIBIT –NOT EVIDENCE
`
`•Slayback’s nexus argument is contrary to established law
`
`•Slayback fails to rebut Patent Owner’s objective evidence of
`
`nonobviousness
`
`Objective Indicia
`
`40
`
`