P aperN o.____
`D ate filed :September28 ,2017
`
`Filed O n B ehalf O f:
`N ovartis A G
`
`B y:
`N icholas N .Kallas
`N Kallas@ fchs.com
`ZortressA finitorIP R@ fchs.com
`(212)218 -2100
`
`UN ITE D S TA TE S P A TE N T A N D TRA D E M A RK O FFIC E
`
`B EFO RE TH E P A TEN T TRIA L A N D A P P EA L B O A RD
`
`P A R P H A RM A C EUTIC A L ,IN C .,
`A RGEN TUM P H A RM A C EUTIC A L L L C ,A N D
`W EST-W A RD P H A RM A C EUTIC A L S
`IN TERN A TIO N A L L IM ITED
`P etitioners,
`
`v.
`
`N O V A RTIS A G,
`P atentO wner.
`
`C ase IP R2016-0147 91
`P atentN o.9,006,224
`
`P A TE N T O W N E R’S E X H IB IT L IS T 9
`
`1 A rgentu m P harmaceu ticalL L C was joined as apartyto this proceed ingviaa
`M otion forJoind erin IP R2017 -01063;W est-W ard P harmaceu ticals International
`L imited was joined as apartyviaaM otion forJoind erin IP R2017 -0107 8 .
`
`
`D ate filed :September28 ,2017
`
`Filed O n B ehalf O f:
`N ovartis A G
`
`B y:
`N icholas N .Kallas
`N Kallas@ fchs.com
`ZortressA finitorIP R@ fchs.com
`(212)218 -2100
`
`UN ITE D S TA TE S P A TE N T A N D TRA D E M A RK O FFIC E
`
`B EFO RE TH E P A TEN T TRIA L A N D A P P EA L B O A RD
`
`P A R P H A RM A C EUTIC A L ,IN C .,
`A RGEN TUM P H A RM A C EUTIC A L L L C ,A N D
`W EST-W A RD P H A RM A C EUTIC A L S
`IN TERN A TIO N A L L IM ITED
`P etitioners,
`
`v.
`
`N O V A RTIS A G,
`P atentO wner.
`
`C ase IP R2016-0147 91
`P atentN o.9,006,224
`
`P A TE N T O W N E R’S E X H IB IT L IS T 9
`
`1 A rgentu m P harmaceu ticalL L C was joined as apartyto this proceed ingviaa
`M otion forJoind erin IP R2017 -01063;W est-W ard P harmaceu ticals International
`L imited was joined as apartyviaaM otion forJoind erin IP R2017 -0107 8 .
`
`
`
`E xhibit
`
`D escription
`
`ExpertD eclaration O f M atthew H .Ku lke,
`M .D .,M .M .Sc.(N ovember18 ,2016)
`
`A bbreviation
`
`Ku lke D ecl.
`
`2001
`
`2002
`
`2003
`
`Curriculum Vitae ofM atthew H .Ku lke,
`M .D .,M .M .Sc.(M ay 20,2016)
`
`Ku lke C .V .
`
`Seeley,R.R.,Stephens,T.D .,& Tate,P .,
`Anatomy & Physiology,3rd Ed ition,
`pages 58 5–58 6 (1995)
`
`S eeley
`
`2004
`
`Reserved
`
`2005
`
`L au ghlin,E.H .,Coming To Terms With
`Cancer: A Glossary Of Cancer-Related
`Terms,page 4 (2002)
`
`L au ghlin
`C ancerGlossary
`
`2006
`
`Reserved
`
`2007
`
`Reserved
`
`2008
`
`M otzer,R.J.& Ru sso,P .,“Systemic
`TherapyForRenalC ellC arcinoma,”J.
`Urology 163:408 -417 (2000)
`
`M otzer
`
`2009
`
`Reserved
`
`2010
`
`P azd u r,R.,et al. (ed s.),C hapters 6,11,
`14-16,19,25,Cancer Management: A
`Multidisciplinary Approach: Medical,
`Surgical, & Radiation Oncology,9th
`Ed ition (2005)
`
`P azdu r
`
`1
`
`
`
`2011
`
`2012
`
`2013
`
`2014
`
`2015
`
`Kou varaki,M .A .et al.,“Flu orou racil,
`D oxoru bicin,A nd Streptozocin In The
`TreatmentO f P atients W ithL ocally
`A d vanced A nd M etastatic P ancreatic
`End ocrine C arcinomas,”J. Clin. Oncol.
`22(23):47 62-47 7 1 (2004)
`
`D elau noit,Th.,et al.,“The D oxoru bicin-
`Streptozotocin C ombination ForThe
`TreatmentO f A d vanced W ell-
`D ifferentiated P ancreatic End ocrine
`C arcinoma:A Ju d iciou s O ption?,”Eur. J.
`Cancer 40:515-520 (2004)
`
`Ku lke,M .H .,C hapter110,
`“N eu roend ocrine C ancer,”Clinical
`Hematology and Oncology: Presentation,
`Diagnosis and Treatment (Fu rie,B .,et al.
`ed s.2003)
`
`Ku lke,M .H .et al.,“A P hase IITrialO f
`Gemcitabine ForM etastatic
`N eu roend ocrine Tu mors,”Cancer
`101(5):934-939 (2004)
`
`M argolin,K.et al.,“C C I-7 7 9 In
`M etastatic M elanoma:A P hase IITrial
`O f The C aliforniaC ancerC onsortiu m,”
`Cancer 104(5):1045-1048 (2005)
`
`Kou varaki
`
`D elau noit
`
`Ku lke 2003a
`
`Ku lke 2004
`
`M argolin
`
`2
`
`
`
`2016
`
`2017
`
`2018
`
`2019
`
`2020
`
`2021
`
`2022
`
`“N ovartis D ru gA finitorIs First
`TreatmentForA d vanced P ancreatic N ET
`To P rovid e O verallSu rvivalO f M ore
`Than 3.5Y ears In P hase IIITrial,”
`Novartis Institutes For Biomedical
`Research (September27 ,2014)
`
`N ovartis P ress
`Release
`
`Ritschel,W .A .,Handbook of Basic
`Pharmacokinetics,4thEd ition,pages 6-7 ,
`264-267 (1992)
`
`Ritschel
`
`H eitz,P h.U.,et al.,C hapter4,“Tu mou rs
`O f The End ocrine P ancreas,”World
`Health Organization Classification of
`Tumours, Pathology and Genetics,
`Tumours of Endocrine Organs,pages
`17 7 -18 2 (D eL ellis,R.A .et al.,ed s.2004)
`
`W H O 2004
`
`P hysicians’D eskReference,59thEd ition
`(2005),pages 18 44-18 49 (Entryfor
`Gemzar® (Gemcitabine H C l))
`
`Gemzar®
`P rescribing
`Information 2005
`
`Ku lke,M .H .& M ayer,R.J.,“C arcinoid
`Tu mors,”N. Eng. J. Med. 340(11):8 58 -
`8 68 (1999)
`
`Ku lke 1999
`
`Gennaro,A .R.(Ed .),Remington’s,18 th
`Ed ition,pages 7 26-7 30 (1990)
`
`Remington’s
`
`Y ao,J.C .et al.,“Everolimu s For
`A d vanced P ancreatic N eu roend ocrine
`Tu mors,”N. Eng. J. Med. 364(6):514-
`523(2011)
`
`Y ao 2011
`
`3
`
`
`
`2023
`
`2024
`
`2025
`
`2026
`
`2027
`
`2028
`
`L and is,J.,“C an The
`Kola,I.&
`P harmaceu ticalInd u stryRed u ce A ttrition
`Rates?,”Nat. Rev. Drug Discov.,3:7 11-
`7 15(2004)
`
`Excerpts of Transcriptof TrialTestimony
`of M .Ratain,Pfizer Inc. et al. v. Mylan
`Pharms. Inc.,(C .A .N o.10-528 -GM S),
`(D .D el.N ovember29,2012),P ages 7 7 8 -
`7 9,950,995
`
`Excerpts of Transcriptof TrialTestimony
`of M .Ratain,Novartis v. Breckenridge,
`Roxane and Par (C .A .N os.14-1043-
`RGA ,14-1196-RGA and 14-128 9-RGA )
`(D .D el.A u gu st31,2016),P ages 7 69-
`7 7 2,957 ,993-94,1003,1010,1012,1014
`
`Excerpts of Transcriptof D eposition of
`M .Ratain,Novartis v. Breckenridge,
`Roxane and Par (C .A .N os.14-1043-
`RGA ,14-1196-RGA and 14-128 9-RGA )
`(D .D el.A pr.11,2016),P ages 1-5,34,
`156,340
`
`D ancey,J.E.,“Inhibitors O f The
`M ammalian TargetO f Rapamycin,”
`Expert Opin. Investig. Drugs 14(3):313-
`328 (2005)
`
`D u ran,I,et al.,“A P hase IIC linicalA nd
`P harmacod ynamic Stu d yO f
`Temsirolimu s In A d vanced
`N eu roend ocrine C arcinomas,”British J.
`of Cancer 95(9):1148 -1154 (2006)
`
`Kola&
`
`L andis
`
`Ratain TrialTr.I
`
`Ratain TrialTr.II
`
`Ratain D ep.Tr.I
`
`D ancey2005
`
`D u ran 2006
`
`4
`
`
`
`2029
`(served
`bu tnot
`filed)
`
`D eclaration of N icholas N .Kallas
`Regard ing Exhibits 2016,2022,A nd
`2028
`
`2030
`(served
`bu tnot
`filed)
`
`The New England Journal of Medicine,
`P u blication P rocess,available at
`http://www.nejm.org/page/med ia-
`center/pu blication-process
`
`2031
`(served
`bu tnot
`filed)
`
`British Journal of Cancer,A ims and
`Scope,available at
`http://www.natu re.com/bjc/abou t/aims_sc
`ope.html
`
`2032
`(served
`bu tnot
`filed)
`
`Transcriptof TrialTestimonyof M .
`Ratain,Pfizer Inc. et al. v. Mylan
`Pharms. Inc.,(C .A .N o.10-528 -GM S),
`(D .D el.N ovember29,2012)
`
`2033
`(served
`bu tnot
`filed)
`
`Transcriptof TrialTestimonyof M .
`Ratain,Novartis v. Breckenridge, Roxane
`and Par (C .A .N os.14-1043-RGA ,14-
`1196-RGA and 14-128 9-RGA )(D .D el.
`A u gu st31,2016)
`
`Transcriptof D eposition of M .Ratain,
`Novartis v. Breckenridge, Roxane and
`Par (C .A .N os.14-1043-RGA ,14-1196-
`RGA and 14-128 9-RGA )(D .D el.A pr.
`11,2016)
`
`D eclaration O f Ju lie M asow P u rsu antto
`Fed .R.Evid .902(11)
`
`2034
`(served
`bu tnot
`filed)
`
`2035
`(served
`bu tnot
`filed)
`
`5
`
`
`
`2036
`
`P hysicians’D eskReference,58 thEd ition
`(2004),pages 18 12-18 17 (Entryfor
`Gemzar® (Gemcitabine H C l))
`
`2004 P D R
`
`2037
`
`2038
`
`2039
`
`2040
`
`2041
`
`2042
`
`2043
`
`2044
`
`D eclaration in Su pportof P atentO wner
`N ovartis’s M otion forPro Hac Vice
`A d mission of C harlotte Jacobsen Und er
`37 C .F.R.§ 42.10
`
`L ongnecker,D .S.et al.,“Transplantation
`of A zaserine-Ind u ced C arcinomas O f
`P ancreas In Rats,”Cancer Letters,7 :197 -
`202 (197 9)
`
`C u rphey,T.J.,
`L ongnecker,D .S.&
`“A d enocarcinomaO f The P ancreas In
`A zaserine-Treated Rats,”Cancer Res.,
`35:2249-2258 (197 5)
`
`L ongnecker197 9
`
`L ongnecker197 5
`
`TranscriptO f The A pril17 ,2017
`D eposition O f M arkJ.Ratain
`
`Ratain Tr.
`
`ExpertD eclaration O f M atthew H .Ku lke,
`M .D .,M .M .Sc.(M ay 11,2017 )
`
`Ku lke
`
`Curriculum Vitae ofM atthew H .Ku lke,
`M .D .,M .M .Sc.(Febru ary1,2017 )
`
`Ku lke 2017 C .V .
`
`A d jei,A .A .,“SignalTransd u ction
`P athwayTargets ForA nticancerD ru g
`D iscovery,”Current Pharm. Design 6(4):
`361-37 8 (2000)
`A finitor® FD A Su pplementalA pproval
`L etterTo N ovartis P harmaceu ticals
`C orporation,d ated M ay5,2011
`
`A djei
`
`A finitor® S u pp.
`A pprovalL etter
`
`6
`
`
`
`2045
`
`2046
`
`2047
`
`2048
`
`2049
`
`2050
`
`2051
`
`A nsell,S.M .,et al.,“A P hase IIStu d yO f
`H igh-D ose P aclitaxelIn P atients W ith
`A d vanced N eu roend ocrine Tu mors,”
`Cancer 91(8 ):1543-48 (2001)
`
`A nsell,S.M .,et al.,“Topotecan In
`P atients W ithA d vanced N eu roend ocrine
`Tu mors:A P hase IIStu d y W ith
`SignificantH ematologic Toxicity,”Am.
`J. Clin. Oncol. 27 (3):232-235(2004)
`
`B ajetta,E.,et al.,“TreatmentO f
`M etastatic C arcinoid s A nd O ther
`N eu roend ocrine Tu mors W ith
`RecombinantInterferon-A lpha-2a,”
`Cancer 7 2(10):3099-3105(1993)
`
`B akker,W .H .,et al.,“In V ivo
`A pplication O f [111In-D TP A -D -P he1]-
`O ctreotid e ForD etection O f Somatostatin
`Receptor-P ositive Tu mors In Rats,”Life
`Sciences 49(22):1593-1601 (1991)
`
`C arr,K.,et al.,“A P hase IITrialO f
`Imatinib In P atients W ithA d vanced
`C arcinoid Tu mor,”J. Clin. Oncol., ASCO
`Procs. 22:14S (A bs.4124)(Ju ly15
`Su pplement)(2004)
`
`C hang,S.M .,et al.,“P hase IIStu d yO f
`C C I-7 7 9 In P atients W ithRecu rrent
`GliobstaomaM u ltiforme,”Investig. New
`Drugs 23(4):357 -361 (2005)
`
`C heng,J.Q .,et al.,“The A kt/P KB
`P athway:M olecu larTargetForC ancer
`D ru gD iscovery,”Oncogene 24:7 48 2-
`7 492 (2005)
`
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`
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`
`A nsell2004
`
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`C arr
`
`C hang
`
`C heng
`
`
`
`2052
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`2053
`
`2054
`
`2055
`
`2056
`
`C reaven,P .J.& Raghavan,D .,C hapter8 ,
`“P rinciples O f C hemotherapyFor
`Genitou rinaryC ancer:Implications For
`D evelopmentO f N ew A nticancerD ru gs,”
`Principles And Practice Of Genitourinary
`Oncology (Raghavan,D .,et al. ed s.1997 )
`
`D oran,H .,et al.,C hapter1,
`“Epid emiologyO f P ancreatic
`N eu roend ocrine Tu mou rs,”Pancreatic
`Disease: Basic Science And Clinical
`Management (Johnson,C .D .& Imrie,
`C .W .ed s.2004)
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`Endpoints For The Approval Of Cancer
`Drugs And Biologics,US D epartmentO f
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`12/9/2016)
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`Foster,B .J.,et al.,“A StrategyForThe
`D evelopmentO f Two C linicallyA ctive
`C isplatin A nalogs:C B D C A A nd
`C H IP ,”Cancer Chemotherapy
`Pharmacology 25:395-404 (1990)
`
`H id algo,M .,et al.,“A P hase IA nd
`P harmacokinetic Stu d yO f Temsirolimu s
`(C C I-7 7 9)A d ministered Intravenou sly
`D ailyFor5D ays Every2 W eeks To
`P atients W ithA d vanced C ancer,”
`Clinical Cancer Res. 12(19):57 55-57 63
`(2006)
`
`C reaven
`
`D oran
`
`FD A Gu idance
`
`Foster
`
`H idalgo 2006
`
`8
`
`
`
`2057
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`2062
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`2063
`
`Jacobsen,W .,et al.,“C omparison O f The
`In V itro M etabolism O f The M acrolid e
`Immu nosu ppressants Sirolimu s A nd
`RA D ,”Transplant. Procs. 33:514-515
`(2001)
`Kokkinakis,D .M .,et al.,“Role O f O6-
`M ethylgu anine-D N A M ethyltransferase
`In The Resistance O fP ancreatic Tu mors
`To D N A A lkylatingA gents,”Cancer
`Research 57 :5360-5368 (1997 )
`
`Ku lke,M .H .,“RecentD evelopments In
`The P harmacologicalTreatmentO f
`A d vanced P ancreatic C ancer,”Expert
`Opin. Investig. Drugs 12(6):98 3-992
`(2003)
`
`L au ghlin,E.H .,Coming To Terms With
`Cancer: A Glossary Of Cancer-Related
`Terms,pages 157 -159 (2002)
`
`M arx,J.,“Encou ragingResu lts For
`Second -Generation A ntiangiogenesis
`D ru gs,”Science 308 :1248 -1249 (2005)
`
`C aplin,M .E.,C hapter4,
`M cStay,M .&
`“GIH ormone P rod u cingTu mou rs:
`Synd romes A nd TreatmentO ptions,”
`Pancreatic Disease: Basic Science And
`Clinical Management (Johnson,C .D .&
`Imrie,C .W .ed s.2004)
`
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`N eu roend corine C arcinomas W ith
`C ombined Etoposid e A nd C isplatin,”
`Cancer 68 :227 -232 (1991)
`
`Jacobsen
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`Kokkinakis
`
`Ku lke 2003b
`
`L au ghlin C ancer
`Glossary
`
`M arx
`
`M cS tay
`
`M oertel1991
`
`9
`
`
`
`2064
`
`2065
`
`2066
`
`2067
`
`2068
`
`2069
`
`207 0
`
`207 1
`
`M ossman,B .T.,et al.,“C hlorozocin:A
`D iabetogenic A nalogu e O f Streptozocin
`W ithD issimilarM echanisms O f A ction
`O n P ancreatic B etaC ells,”Diabetes 34:
`602-610 (198 5)
`
`M otzer,R.J.& V ogelzang,N .J.,C hapter
`8 5,“C hemotherapyForRenalC ell
`C arcinoma,”Principals And Practice
`Genitourinary Oncology (Raghavan,D .,
`et al. ed s.1997 )
`
`M u ggia,F.M .& Green,M .D .,“N ew
`A nthracycline A ntitu mor
`A ntibiotics,”Crit. Rev. Oncol./Hematol.
`11:43-64 (1991)
`
`P azd u r,R.,et al.,“P hase IITrialO f
`Intravenou s C I-98 0 (N SC 37 0147 )In
`P atients W ithM etastatic C olorectal
`C arcinoma:M od elForP rospective
`Evalu ation O f N eu rotoxicity,”Am. J.
`Clin. Oncol. 20(6):57 3-57 6 (1997 )
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`(2013),pages 258 9-2594 (Entryfor
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`
`P hysicians’D eskReference,46thEd ition
`(1992),pages 2024-2027 (Entryfor
`Sand immu ne® (cyclosporin))
`P hysicians’D eskReference,49thEd ition
`(1995),pages 2034-2036 (Entryfor
`flu orou racil)
`
`P hysicians’D eskReference,54thEd ition
`(2000),pages 8 8 1-8 8 7 (EntryforTaxol®
`(paclitaxel))
`
`M ossman
`
`M otzer&
`V ogelzang
`
`M u ggia& Green
`
`P azdu r1997
`
`2013P D R
`
`1992 P D R
`
`1995P D R
`
`2000 P D R
`
`10
`
`
`
`207 2
`
`207 3
`
`207 4
`
`207 5
`
`207 6
`
`207 7
`
`P hysicians’D eskReference,58 thEd ition
`(2004),pages 67 2-67 4 (EntryforIressa®
`(gefitinib)),8 94-8 96 (Entryfor
`A d riamycin® (d oxoru bicin)),1355-1358
`(EntryforH erceptin® (trastu zu mab)),
`2268 -227 3(EntryforGleevec® (imatinib
`mesyate)),2305-2311 (Entryfor
`Sand ostatin® (octreotid e acetate)),348 3-
`3490 (EntryforRapamu ne® (sirolimu s))
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`O f D acarbazine (D TIC )In A d vanced
`P ancreatic IsletC ellC arcinoma.Stu d yO f
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`Grou p-E628 2,”Annals Oncology 12:
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`
`Raymond ,E.,et al.,“C C I-7 7 9,A
`Rapamycin A nalogW ithA ntitu mor
`A ctivity:A P hase IStu d yUtilizingA
`W eeklySched u le,”Proc. ASCO 19:18 7 a
`(A bs.7 28 )(2000)
`
`Raymond ,E.,et al.,“C C I-7 7 9,A n Ester
`A nalogu e O f Rapamycin ThatInteracts
`W ithP TEN /P I3Kinase P athways:A
`P hase IStu d yUtilizingA W eekly
`Intravenou s Sched u le,”Clinical Cancer
`Res. 6:4549s (A bs.414)(N ovember
`Su pplement)(2000)
`
`11
`
`2004 P D R
`
`2016 P D R
`
`Ramanathan
`
`Ratain 2005
`
`Raymond 2000a
`
`Raymond 2000b
`
`
`
`207 8
`
`207 9
`
`208 0
`
`208 1
`
`208 2
`
`208 3
`
`Raymond ,E.,et al.,“SafetyA nd
`P harmacokinetics O f Escalated D oses O f
`W eeklyIntravenou s Infu sion O f C C I-
`7 7 9,A N ovelmTO R Inhibitor,In
`P atients W ithC ancer,”J. Clin. Oncol.
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`
`2112
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`
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`
`Transcriptof D eposition of M .Ratain,
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`D ecember16,2016)
`
`2114
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`
`Torisel® (temsirolimu s)L abel(Ju ly
`2017 ),available at
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`a_d ocs/label/2016/02208 8 s019lbl.pd f
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`
`17
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`2116
`
`Emailchain between A nd rew Kellogg,
`Su pervisoryP aralegal,USP TO and Jared
`L .Stringham,A ttorney,Fitzpatrick,
`C ella,H arper& Scinto (Sept.20-25,
`2017 )
`
`18
`
`
`
`C E RTIFIC A TE O FS E RV IC E
`
`Icertifythatacopyof the foregoingP atentO wner’s ExhibitL ist9 was
`
`served on September28 ,2017 bycau singitto be sentbyemailto cou nselfor
`
`P etitioners atthe followingemailad d resses:
`
`D anielG.B rown (d aniel.brown@ lw.com)
`
`Jonathan M .Strang(jonathan.strang@ lw.com)
`
`B rend aL .D anek(brend a.d anek@ lw.com)
`
`Kevin L au rence (klau rence@ lpiplaw.com)
`
`M atthew P hillips (mphillips@ lpiplaw.com)
`
`TylerC .L iu (tliu @ agpharm.com)
`
`KeithA .Zu llow (kzu llow@ good winprocter.com)
`
`M artaE.D elsignore (md esignore@ good winprocter.com)
`
`D ated :September28 ,2017
`
`/N icholas N .Kallas/
`N icholas N .Kallas
`Registration N o.31,530
`L ead C ou nselforP atentO wner
`FITZP A TRIC K,C EL L A ,H A RP ER
`& SC IN TO
`1290 A venu e ofthe A mericas
`N ew Y ork,N Y 10104-38 00
`Tel.212-218 -2100
`
`19
`
`
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