Filed:February6,2015

U N IT EDST A T ES PA T EN T A N DT RA DEM A RK OFFIC E

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B EFORE T HE PA T EN T T RIA LA N DA PPEA LB OA RD

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M Y LA N PHA RM A C EU T IC A LS IN C .Petitioner,

v .

Y EDA RESEA RC H & DEV ELOPM EN T C O.LT D.PatentOw ner.

— — — — — — — — — — — — — — — —PatentN o.8 ,23 2,250

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PE T IT ION FOR IN T E R PA RT E S R E V IE W

ii

T A B LE OFC O N T E N T S

I. IN T RODU C T ION ...........................................................................................1

II. M A N DA T ORY N OT IC ES .............................................................................2

A . RealParties-In-Interest(3 7 C .F.R.§ 4 2.8 (b)(1))..................................2

B . Related M atters(3 7 C .F.R.§ 4 2.8 (b)(2))..............................................2

C . IdentificationofC ounsel(3 7 C .F.R.§ 4 2.8 (b)(3 )) andService Information(3 7 C .F.R.§ 4 2.8 (b)(4 )).......................................3

D. Service Information(3 7 C .F.R.§ 4 2.8 (b)(4 )).......................................3

III. GROU N DS FOR ST A N DIN GA N DPROC EDU RA LST A T EM EN T .........3

IV . IDEN T IFIC A T ION OFC HA LLEN GE A N DST A T EM EN T OFT HEPREC ISE RELIEFREQ U EST ED..................................................................3

V . T HRESHOLDREQ U IREM EN T FOR IN T ER PA RT ESREV IEW ...............4

V I. ST A T EM EN T OFREA SON S FOR T HE RELIEFREQ U EST ED...............5

A . Summaryofthe A rgument....................................................................5

B . B ackground ofthe ‘250Patent..............................................................7

1. T he ’250Patent...........................................................................7

2. T he ’250Patent’sProsecutionHistory.......................................9

a. February14 ,2012 N on-FinalOffice A ction....................9

b. A pplicant-Initiated Interv iew Summary.........................10

c. M ay14 ,2012 Response..................................................11

C . Lev elofOrdinarySkillinthe A rt.......................................................13

D. C laim C onstruction..............................................................................14

E. Patentsand Printed PublicationsRelied OnInT hisPetition.................................................................................................17

1. Pinchasi(Ex.1005)...................................................................17

2. 19 9 6 FDA SB OA (Ex.1007A ).................................................18

3 . Flechter2002A (Ex.1008 ) .......................................................20

4 . PriorA rtInformingthe GeneralKnow ledge oftheOrdinarily-Skilled A rtisan........................................................22

F. Ground 1:C laims1-13 and 19 -20A re U npatentable A sA nticipated byPinchasi.......................................................................22

iii

1. IndependentC laims1and 19 A re A nticipated byPinchasi.....................................................................................22

2. DependentC laims2-12 and 20A re A nticipated byPinchasi.....................................................................................27

a. Pinchasidisclosed the furtherlimitationsofclaims3 ,12 and 20.....................................................................27

b. Pinchasidisclosed the furtherlimitationinclaims2 and 4 -11.......................................................................27

3 . DependentC laim 13 isA nticipated byPinchasi......................3 4

G. SummaryofPetitioner’sObviousnessPositions................................3 5

1. T he Law ofObv iousness..........................................................3 5

2. T he PriorA rtRendersthe C laimsObvious..............................3 8

a. Inv estigationinto DifferentDosingProtocolsforGA T herapy....................................................................3 8

b. T he PriorA rtM otiv ated aPersonofOrdinarySkillto Inv estigate DifferentDosingProtocolsandProv ided A Reasonable ExpectationofSuccess............4 1

H. Ground 2:C laims1-20A re U npatentable A sObviousov erPinchasi.......................................................................................4 5

1. IndependentC laims1and 19 A re Obviousov erPinchasi.......4 5

2. DependentC laims2-13 and 20A re Obv iousinV iew ofPinchasi.....................................................................................4 8

3 . DependentC laim 14 IsObv iousinV iew ofPinchasi..............4 9

4 . IndependentC laim 15 and DependentC laims16-18 A reObviousinV iew ofPinchasi....................................................4 9

I. Ground 3 :C laims1-20A re U npatentable A sObviousov erPinchasiand the 19 9 6 SB OA ......................................................52

1. IndependentC laims1,15 and 19 A re Obviousov erPinchasiinview ofthe 19 9 6 FDA SB OA ................................52

2. DependentC laims2-14 ,16-18 ,and 20A re Obviousov erPinchasiand the 19 9 6 SB OA ....................................................55

J. Ground 4 :C laims1-20A re U npatentable A sObviousov erPinchasiand Flechter2002A ......................................................56

iv

1. IndependentC laims1,15,and 19 A re Obv iousinV iewofPinchasiand Flechter2002A ................................................56

2. DependentC laims2-14 ,16-18 ,and 20A re Obviousov erPinchasiand Flechter2002A ....................................................57

K. A nySecondaryC onsiderationsFailto Ov ercome theShow ingofObv iousness.....................................................................58

1. T he M ethodsRecited inthe ’250PatentProduced N oRelev antU nexpected Results...................................................58

2. T he ’250PatentSatisfied N o Long-FeltB utU nmetN eed.......59

3 . C opyingB yGenericDrugM akersIsIrrelev ant.......................60

v

T A B LE OFA U T HO R IT IE SPage(s)

C A SE S

Baldw inGraphicSys.,Inc.v.Siebert,Inc.,512 F.3 d 13 3 8 (Fed.C ir.2008 )...............................................................16,17

BayerHealthcare Pharms.,Inc.v.WatsonPharms.,Inc.,713 F.3 d 1369 (Fed.C ir.2013 ).....................................................................60

Bristol-M yersSquibb Co.v.T evaPharms.U SA ,Inc.,752 F.3 d 9 67 (Fed.C ir.2014 ) .......................................................................59

CardinalChem.Co.v.M ortonInt’l,Inc.,508 U .S.8 3 (19 9 3 ).........................................................................................17

Exparte Tanksley,26 U .S.P.Q .2d 13 8 4 (B PA I19 91).................................................................17

GaldermaLabs.v.T olmar,Inc.,73 7 F.3 d 731(Fed.C ir.2013 ) .......................................................................60

Gillette Co.v.EnergizerHoldingsInc.,4 05 F.3 d 1367 (Fed.C ir.2005).........................................................15,16,26

Graham v.JohnDeere Co.ofKan.City,3 8 3 U .S.1(1966)...........................................................................................3 5

Hoffmann-LaRoche,Inc.v.A potexInc.,74 8 F.3 d 13 26 (Fed.C irc.2014 ) .............................................................3 8 ,59

Inre BaxterTravenolLabs.,9 52 F.2d 3 8 8 (Fed.C ir.19 91).................................................................29 ,3 0

Inre Cronyn,8 90F.2d 1158 (Fed.C ir.19 8 9 ) .....................................................................20

Inre Cuozzo Speed T echs.,LLC,N o.2014 -3 1,Slipopinion(Fed.C ir.Feb.4 ,2014 ).............................................................14

Inre Kubin,561F.3 d 13 51(Fed.C ir.2009 )...............................................................3 0,3 8

Inre Lister,58 3 F.3 d 1307 (Fed.C ir.2009 ).....................................................................20

Inre PepperBallT echs.,Inc.,4 69 F.A pp’x878 (Fed.C ir.2012)..........................................................59 ,60

Inre Petering,3 01F.2d 676 (C C PA 19 62)...........................................................................3 5

v i

InvitrogenCorp.v.BiocrestM fg.,L.P.,3 27 F.3 d 1364 (Fed.C ir.2003 ).........................................................14 ,15,26

KSR Int’lCo.v.T eleflexInc.,550U .S.3 9 8 (2007).................................................................................3 5,3 6

M edichem,S.A .v.Rolabo,S.L.,3 53 F.3 d 9 28 (Fed.C ir.2003 ) .......................................................................15

Pfizer,Inc.v.A potex,Inc.,4 8 0F.3 d 13 4 8 (Fed.C ir.2007)....................................58

WarnerChilcottCo.v.T evaPharms.U SA ,Inc.,N os.2014 -14 3 9 ,14 4 1,14 4 4 -4 6,2014 W L64 3 504 2 (Fed.C irc.N ov .18 ,2014 )........3 6,3 7,3 8

ST A T U T E S

3 5 U .S.C .§ 103 (a) ...................................................................................................3 5

3 5 U .S.C .§ 3 14 (a) .................................................................................................4 ,5

R U LE S

3 7 C .F.R.§ 4 2.100(b) ..............................................................................................14

M PEP 2111.03 .........................................................................................................15

I. IN T R ODU C T IO N

Pursuant to 35 U.S.C. §§ 311-319 and 37 C.F.R. § 42, Mylan

Pharmaceuticals Inc. (�Petitioner�) petitions for Inter Partes Review (�IPR�) of

claims 1-20 of U.S. Patent No. 8,232,250 to Klinger, titled �Low Frequency

Glatiramer Acetate Therapy� (�the �250 patent,� Ex. 1001). Concurrently filed

herewith is a Power of Attorney pursuant to 37 C.F.R. § 42.10(b). Pursuant to 37

C.F.R. § 42.103, the fee set forth in § 42.15(a) accompanies this Petition.

This Petition demonstrates that a preponderance of the evidence shows a

reasonable likelihood that claims 1-20 of the �250 patent are unpatentable over the

prior art. Specifically, Teva, the commercial partner of Yeda for Copaxone®, in

2007 disclosed to the public in a published patent application to Irit Pinchasi (Ex.

1005) the claimed subject matter more than one year before Yeda filed its patent

application. This disclosure anticipated claims 1-13 and 19-20 and rendered all the

claims obvious to a person having ordinary skill in the art (�POSA�) as of the

priority date. All of the �250 patent�s claims are alternatively obvious over

Pinchasi in view of either of two additional prior art publications: the published

Summary Basis of Approval for 20 mg Copaxone® (Ex. 1007A) or a 2002 article

by Flechter, et al. (Ex. 1008).

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II. M A N DA T O R Y N O T IC E S

A . R ealParties-In-Interest(3 7 C .F.R .§ 4 2.8 (b)(1))

T he real parties-in-interestforPetitionerare M ylanPharmaceuticalsInc.,

M ylanInc.and M ylanT eoranta.

B . R elated M atters(3 7 C .F.R .§ 4 2.8 (b)(2))

Petitioner is notaw are of any reexamination certificates or pending

prosecutionconcerningthe ’250patent. Petitionerisadefendantto the follow ing

litigationsinvolvingthe ’250patent: T evaPharms.U SA ,Inc.v.M ylanPharms.

Inc.,14 -cv -01278 (D.Del.,Oct.6,2014 ); T eva Pharms.U SA ,Inc.v.M ylan

Pharms.Inc.,14 -cv-00167 (N .D.W .V a.,Oct.7,2014 ). Otherpendinglitigations

involv ingthe ’250patentinclude,T evaPharms.U SA ,Inc.,v.Sandoz,Inc.,N o.14 -

cv -01171(D.Del.Sept.10,2014 ); T evaPharms.U SA ,Inc.,v.Dr.Reddy’sLabs.,

N o.14 -cv -01172 (D.Del.Sept.10,2014 ); T evaPharms.U SA ,Inc.v.Dr.Reddy’s

Labs., N o. 14 -cv -05672 (D.N .J. Sept. 11, 2014 ); T eva Pharms. U SA , Inc. v.

SynthonPharms.Inc.,N o.14 -cv -014 19 (D.Del.N ov .18 ,2014 ); T eva Pharms.

U SA ,Inc.v.SynthonPharms.Inc.,N o.14 -cv -009 75 (M .D.N .C .N ov .19 ,2014 );

and T evaPharms.U SA ,Inc.v.A mnealPharms.,LLC,N o.15-cv -00124 (D.Del.

Feb.3 ,2015).

A patentapplicationinthe same patentfamilyispendingasU .S.Patent

A pplicationN o.13/770,677.

4

“StatementofReasonsforReliefRequested.” In accordance w ith 3 7 C .F.R.

§ 4 2.6(c),copiesofthe exhibitsare filed herew ith. Inaddition,thisPetitionis

accompanied bythe DeclarationofStephenJ.Peroutka,M .D.,Ph.D.(Ex.1003 )

and the DeclarationofA riGreen,M .D.(Ex.1004 ).

T he challenged claimsofthe ’250patentare generallydirected to methods

ofalleviatingsymptomsofrelapsing–remittingmultiple sclerosisbyadministering

atleast“three subcutaneousinjectionsofa4 0mgdose ofglatirameracetate ov era

period ofsev endaysw ithatleastone daybetw eenev erysubcutaneousinjection.”

C laims1-20ofthe ’250patentare unpatentable basedonthe follow inggrounds:

Ground 1:C laims1-13 and 19 -20are anticipated byPinchasi.

Ground 2:C laims1-20are obv iousov erPinchasi.

Ground 3 :C laims1-20are obv iousov erPinchasiinview ofthe 19 9 6 FDA

SB OA .

Ground 4 : C laims1-20 are obviousov erPinchasiin view ofFlechter

2002A .

V . T HR E SHOLDR E Q U IR E M E N T FOR INTER PARTES R E V IE W

A petitionforinterpartesrev iew mustdemonstrate “areasonable likelihood

thatthe petitionerw ould prev ailw ithrespectto atleast1ofthe claimschallenged

in the petition.” 3 5 U .S.C .§ 3 14 (a). T hisPetition meetsthisthreshold. A s

5

explained below ,there isareasonable likelihood thatPetitionerw illprevailw ith

respectto atleastone ofthe challenged claims.

V I. ST A T E M E N T OFR E A SO N S FOR T HE R E LIE FR E Q U E ST E D

A . Summaryofthe A rgument

Glatirameracetate (“GA ”) w asfirstpatented ascopolymer-1in1974 asU .S.

PatentN o.3 ,8 4 9 ,550(“the ’550patent”). Ex.1003 at¶ 4 3 . Inthe 19 80s,Y eda

partnered w ith T ev a to dev elop GA commercially and seek FDA approv al to

marketit,asC opaxone® ,to treatM ultiple Sclerosis(“M S”). T he FDA first

approv ed C opaxone® foruse intreatingM S inthe U .S.in19 9 6. Id. In19 9 6,the

FDA approv ed C opaxone® inadosingregimenof20mgdailyadministered by

subcutaneous(“SC ”) injection.Inthe 19 90s,follow ingthe expirationofthe ’550

patentand inpreparationforthe U .S.launchof20mgC opaxone® ,T evasought

additionalU .S.patentprotectionand receiv ed patentsonthe GA compound and on

methodsofmakingand usingit. In2013 ,w iththe lastofthe patentscov ering

T ev a’s20mgdailydosage form readyto expire,T ev asoughtFDA approv alofa

4 0 mg,three timesperw eek C opaxone® and upon approv al,began to sw itch

patientsfrom the old,20mgdailyproductto its“new ,”4 0mgthree timesper

w eek C opaxone® .

One ofthe patentsthatisalleged byT ev ato cov erits4 0mgdosage form is

the ’250patent. T he ’250patentisgenerallydirected to “low frequencyglatiramer

6

acetate therapy”and describesamethod of“allev iatingasymptom ofrelapsing-

remittingmultiple sclerosis.” Ex.1001,T itle,A bstract. Ingeneral,the claimsof

the ’250patentrecite anopen-ended method comprisingadministrationof4 0mg

ofGA SC atleastthree timesina7-dayperiod to treatM S. Ex.1001atcol.16,l.

3 5 -col.18 ,l.29 . A llclaims,how ev er,describe anM S treatmentregimenthat

w asalreadyknow nin,orobviousinview of,the priorart.

B efore the earliestpossible priority date (A ugust20,2009 ),v ariousGA

dosagesand injectionfrequenciesw ere tested and know n. A sexplained indetail

below , a 2007 T eva patentapplication to Pinchasi (Ex. 1005) taughtthe

administrationofa4 0mgdosage ofGA ev eryotherday,anticipatingclaims1-13

and 19 -20ofthe ’250patentunderthe broadestreasonable constructionofthe

claims.

M oreov er,allofthe claimsare obv iousinlightofthe priorart,including

Pinchasiand others. A numberofpriorartreferencestaughtadministeringGA

ev eryotherdayforinteralia improv ed patientcompliance and adherence. Ex.

1004 at¶¶ 54 -59 ; see also Ex.1003 at¶¶ 20-25,100-103 . T he priorartalso

disclosed thatno additionaladv erse side effectsare associated w ithadministering

4 0 mg ofGA perdose, ascompared to 20 mg ofGA perdose previously

administered.Ex.1004 at¶ 9 9 (citingEx.1005 atp.19 ,ll.8 -14 ); Ex.1003 at¶ 74

(citingEx.1005 atp.19 ,ll.11-14 ). A nd so,inlightofPinchasialone,orin

7

combinationw ithotherreferencesdetailed below ,the claimsofthe ’250patent

w ere obviousatthe time ofthe allegedinv ention.

B . B ackground ofthe ‘250Patent

1. T he ’250Patent

T he ’250patentissued July3 1,2012 from anapplicationfiled onN ov ember

3 0,2011.T hisapplicationisacontinuationofanearlierapplicationand claimsthe

benefitoftw o provisionalapplications. T he ’250patentnamesEtyKlingeras

inv entorand Y edaResearch& Dev elopmentC o.,Ltd.(“Y eda”) asassignee.T he

’250patent’searliestpossible prioritydate isA ugust20,2009 .

T he ’250patentissued w ith20claims. C laims1,15 and 19 are independent

claims. Independentclaim 1relatesto “[a]method ofalleviatingasymptom of

[RRM S]inahumanpatient.”Ex.1001atcol.16,ll.3 5-4 5. T he claimed method

includesthe stepof“administeringto the humanpatientatherapeuticallyeffectiv e

regimenofthree subcutaneousinjectionsofa4 0mgdose of[GA ]ov eraperiod of

sev en daysw ith atleastone day betw een ev ery subcutaneousinjection.” Id.

Independentclaims15 and 19 recite similarmethodsbutinclude astheirrespectiv e

preamblesrecitations“[a]method ofincreasingthe tolerabilityofGA treatmentin

ahumanpatient”and “[a]method ofreducingfrequencyofrelapsesinahuman

patientsuffering.” Id.atcol.17,ll.24 -30,col.18 ,ll.19 -26. A seachindependent

claim employsthe open-ended transition“comprising,”the claimsare notlimited

8

to onlythree SC injectionsper7-dayperiod.Instead,the claim recitationsafterthe

transitionserv e onlyto setthe floorforthe numberofinjectionsadministered each

7-dayperiod and aminimum time period betw eensuchinjections.

T he dependentclaimsrecite the specific“symptom”alleged to be alleviated

(claims2 and 4 -11),thatthe method employsaprefilled syringe,justlike priorart

C opaxone® (claims3 ,12,18 and 20),characteristicsofthe patient(claim 13 ),and

furtherlimitationsrelated to injectionsite reactions(claims14 and 16-17).

T he patent’sspecificationacknow ledgesthattreatingM S patientsw ithGA

isnotnew .Ex.1001atcol.2,ll.17-4 6.GA had beenknow nforyearsto be asafe

and effectiv e treatmentforM S and had beenFDA approv ed asa20mgdaily

injectiontherapyforM S patientssince 19 9 6. Id. W hile the patentacknow ledges

priorartC opaxone® ,itfailsto acknow ledge the extensiv e bodyofpriorartrelated

to alternate dosagesand dosingregimensforGA ’streatmentofM S. See e.g.,Exs.

1005,1006,1007A ,1008 ,1010,1011. M uchofthishighlyrelev antpriorartis

authored by Y eda oritscommercial partner,T ev a,orthose w orking on their

behalf.

T he patentincludesone propheticexample (Ex.1001atcol.8 ,l.55 -col.

15,l.50),butdoesnotprov ide anyactualinvitro orinvivo dataordatafrom a

concluded humanclinicaltrialto show safetyorefficacyofthe claimed method or

its purported improv ementin tolerability or reduction in side effects. N o

9

unexpected resultsare alleged inthe patent. T he patentdoesnotsuggestthatthe

claimed methodsare more efficaciousthan priorartmethods,including daily

administration of 20 mg C opaxone® . Instead, the patentstates only that

“[t]reatmentw ith4 0mgs.c.GA three timesw eeklyisatleastaseffective as20

mgs.c.GA dailyadministration”forvariousclinicalendpoints.See,e.g.,Ex.1001

atcol.13 ,l.4 6 –col.15 l.20.W hile the patentgenerallyallegesthat“due to the

complexpharmacokinetic behav ior ofa drug, v ariation in the frequency of

administrationisunpredictable and requiresempiricaltesting,”no suchempirical

testingisincluded inthe patent. Ex.1001atcol.16,ll.9-12. Instead,the patent

cites an article addressing the unrelated interferon class of drugs w ithout

correlatingthe stated propositionorthe teachingsofthe article specificallyto GA .

T hisarticle isimmaterialespeciallyinlightofthe extensiv e priorartdisclosuresof

the many differentsafe and efficaciousdosagesand dosing schedulesforGA ,

rangingfrom 20through4 0mgdailyinjectionsand from dailyto alternate-day

dosingregimens.See,e.g.,Ex.1003 at¶ 24 ; Ex.1004 at¶ 18 .

2. T he ’250Patent’sProsecutionHistory

a. February14 ,2012 N on-FinalOffice A ction

Duringprosecution,allclaimsw ere rejected under3 5 U .S.C § 112,¶1. T he

Examinerstated thatthe claimsencompassed a method hav ingasfew asthree

subcutaneousinjectionsof4 0mgofGA onalternate daysduringasingle 7-day

10

period and concluded thatthe claimsw ere notenabled oradequatelydescribed.

Ex.1002 atpp.65-66. T he Examinerrejected mostofthe claimsasbeing

anticipated byFlechter2002A . Id.atpp.66-68 . T he Examineralso rejected many

ofthe claimsasobv iousov erFlechter2002A inview ofC ohen. Id.atpp.68-69 .

T he Examinerstated thatC ohentaughtthata4 0mgdose ofGA maybe more

effectiv e thanthe currentlyapprov ed 20mgdailydose inreducingM RIactivity

and clinical relapse. T he Examinerasserted itw ould hav e been prima facie

obviousto one ofordinaryskillinthe artto combine the 4 0mgdose ofcopolymer

1described inC ohenw iththe alternate-dayregimenofFlechter2002A to reduce

the frequencyofinjectionsthatanRRM S patientissubjectto byhalf.

b. A pplicant-Initiated Interview Summary

A n A pplicant-Initiated Interview Summary w asissued onM ay10,2012.

Ex.1002 atpp.14 7-14 9 . T he Summaryindicated thatA pplicantw asadvised of

the Examiner’sv iew thatintroducing a limitation w hich indicatesthe claimed

method w asnotintended to be limited to asingle 7-dayperiod ofadministrationof

GA w ould av oid the outstandingrejectionsunder3 5 U .S.C § 112,¶1. Id. T he

Summaryalso indicated thatA pplicantw asadvised thatincludingalimitationto a

4 0mgdose w ould remov e Flechter2002A asananticipatoryreference and that

ev idence thatthe priorartdid notconsidera4 0mgdose ofGA to be superiorto a

20mgdose inthe treatmentofM S w ould av oid anobviousnessrejection.Id.

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c. M ay14 ,2012 R esponse

In response to the rejection ofthe claimsforfailing to comply w ith the

w ritten description and enablementrequirements, A pplicantargued thatthe

interpretationofthe claimsto encompassadministrationofasfew asthree dosesof

GA to anindiv idualsufferingfrom RRM S foronlyasingle 7-dayperiod w asan

unreasonablybroad interpretation.Ex.1002 atpp.157-159 . A pplicantstated that

one ofordinaryskillinthe artw ould interpretthe claimsto be directed to alonger

dosage regimenatleastbecause the claimsrecite “so asthereby[to]allev iate the

symptom.” Id. atp. 158 . A pplicantalso amended claim 1to recite the

administrationof“atherapeuticallyeffectiv e regimen”ofGA and to recite “the

regimenbeingsufficientto allev iate the symptom ofthe patient.” Id.atp.151.

A pplicantargued the claimsasamended remov ed anypurported ambiguityand

“cannotbe reasonably construed to read on only a single sev en day period of

administration,atleastbecause the claimsasamended require a‘regimen.’” Id.at

p.159 . T hus,accordingto the A pplicant,the claimsrequire asfew asthree doses

ofGA per7-dayperiod administered insuccessiv e one-w eek periods.

Inresponse to the rejectionofthe claimsasbeinganticipated byFlechter

2002A ,A pplicantasserted thatFlechter2002A taughtalternate-dayadministration

and doesnotanticipate the claimed methods.Ex.1002 atpp.161-162. A pplicant

also asserted thatFlechter2002A doesnotteachadministrationofa4 0mgdose of

12

GA asrequired bythe claimsasamended. Id.IndistinguishingFlechter2002A ,

the A pplicantstated that“Flechter[]show ed in theirresultsthatalternate day

dosing w ith 20mg GA isdemonstrably w orse therapeutically than 20mg GA

daily.” Id.atp.167. How ev er,inmakingthisargument,the A pplicantfailed to

acknow ledge thatthe 20mgGA alternate daytreatmentdataand the 20mgGA

dailytreatmentdatacame from tw o differentclinicalstudiesinvolvingdifferent

setsofpatients. See Ex.1003 at¶¶ 57-61. Flechter2002A ’suse oftw o datasets

from tw o independentstudies precludes one from reaching the conclusion

presented bythe A pplicant; the tw o datasetscannotbe used to determine w hich

dosingschedule issuperiorbetw eenthe tw o studies. See id.at¶ 58 . M oreov er,

there w ere meaningfuldifferencesinthe patientpopulationsinthe tw o studies,

includingameaningfuldifference inthe disabilitystatusofthe patientpopulations

atthe startofeachstudycited inFlechter2002A . A nanalysisofFlechter2002A

thusunderminesthe argumentsmade bythe A pplicantsduringprosecution. Id.at

¶¶ 60-61.

In response to the Examiner’srejection ofclaims1-20 asobviousov er

Flechter2002A inview ofC ohen,A pplicantargued thatthe priorartprovided no

motiv ationto combine the teachingsofthe references. A pplicantalleged thatthe

priorarttaughtthata 4 0 mg daily dose ofGA did notdemonstrate increased

efficacyov erthe 20mgdailydose and thata4 0mgdailydose ofGA w ould be

13

more expensiv e thana20mgdailydose. Ex.1002 atpp.167-169 . A pplicantalso

disputed the expressteachinginFlechter2002A thatalternate-daydosingof20mg

w astherapeuticallycomparable to dailydosing. Id. A pplicantargued thatone of

ordinaryskillinthe artw ould expectthatalternate-daydosingof4 0mgofGA

w ould be lesseffectiv e thantreatmentw ith20mgofGA daily. Id. A fterthis

response,the Examinerallow ed the claimsto issue.

C . Lev elofOrdinarySkillinthe A rt

T he field ofthe inv entionrelatesto therapeuticmethodsofadministering

GA . A personofordinaryskillinthe art(POSA )1w ould hav e had sev eralyearsof

experience inthe pharmaceuticalindustryorinpracticingmedicine. See,e.g.,Ex.

1003 at¶ 3 8 ; Ex.1004 at¶ 27. Suchapersonw ould hav e had experience w iththe

administration or formulation of therapeutic agents, dosing schedules and

frequencies,and drugdev elopmentalstudyand design. Id. Suchapersonw ould

also hav e beenw ell-v ersed inthe w orld-w ide literature thatw asavailable asofthe

priority date. Id. Such a person typically w ould hav e been a Ph.D. in

pharmacology (or a Pharm.D.) or a physician w ith experience in clinical

1A llreferenceshereinto the know ledge orunderstandingofaPOSA oraPOSA ’s

interpretationorunderstandingofapriorartreference are asofthe earliestpossible

prioritydate unlessspecificallystated otherw ise.

14

pharmacology. Id.Suchpersontypicallyw ould hav e consulted w ithone ormore

membersofateam ofexperienced professionalsinthe pharmaceuticalindustry,

includingasone example aphysicianw ithexperience inclinicalpharmacology.Id.

D. C laim C onstruction

T he claims ofthe ’250 patentare presumed to take on the “broadest

reasonable construction in lightofthe specification ofthe patentin w hich it

appears.” 3 7 C .F.R.§ 4 2.100(b); see also Inre Cuozzo Speed T echs.,LLC,N o.

2014 -31,slipopinion(Fed.C ir.Feb.4 ,2015) (affirmingthe applicationofthe

broadestreasonable constructionstandard ininterpartesreview ). A ccordingto

the broadestreasonable construction, one ofordinary skill in the artw ould

understand the follow ingclaim termsto hav e the follow ingmeanings.

Comprising. T he independentclaimsofthe ’250patentuse the open-ended

“comprising” transition. A s a transition in a patentclaim, “comprising” is

inclusiv e oropen-ended and doesnotexclude additional,unrecited elementsor

method steps. See,e.g.,InvitrogenCorp.v.BiocrestM fg.,L.P.,3 27 F.3 d 13 64 ,

1368 (Fed.C ir.2003 ) (“T he transition‘comprising’inamethod claim indicates

thatthe claim isopen-ended and allow sforadditionalsteps.”); see also M edichem,

S.A .v.Rolabo,S.L.,3 53 F.3 d 9 28 ,9 3 3 -3 4 (Fed.C ir.2003 ) (claim thatusesthe

transition“comprising”“includesnotonlythe stepslisted inthe claim,butalso

anyadditionalstepsthatmaybe added”); M PEP 2111.03 (collectingcases). For

15

example,inGillette Co.v.EnergizerHoldingsInc.,4 05 F.3 d 1367,1369 ,13 71-73

(Fed.C ir.2005),the FederalC ircuitheld thataclaim to “asafetyrazorblade unit

comprising a guard, a cap, and a group offirst, second, and third blades”

encompasses razors w ith four blades because of the open-ended phrase

“comprising”in the preamble. “T he w ord ‘comprising’transitioning from the

preamble to the bodysignalsthatthe entire claim ispresumptiv elyopen-ended.”

Id. Here,asinGillette,the claimsare openended and are thusnotlimited to

periodicadministrationofthree and onlythree injectionsina7-dayperiod. Giv en

theirbroadestreasonable construction,the claimscov er,e.g.,the addition ofa

fourthdose ev eryother7-dayperiod,asoccursw ithalternate daydosing.

In determining “w hatisorisnotexcluded” by the transitional phrase

“comprising,”M PEP 2111.03 ,the onlylimitationonthe claimed dosingschedule

inthe independentclaimsisthatthere mustbe atleastthree injectionsina7-day

period w ithatleastone daybetw eeneachinjection. T hus,the PatentOw ner’s

choice to employthe transition“comprising”allow sthe claimsto encompassthree

ormore subcutaneousinjections“ov eraperiod ofsev endaysw ithatleastone day

betw eenev erysubcutaneousinjection.” T hisincludesev ery-other-daydosing,in

w hichthree dosesare administered duringthe first7-dayperiod (e.g.,onSunday,

T uesdayand T hursday) and fourdosesare administered duringthe second 7-day

period (e.g.,onSaturday,M onday,W ednesdayand Friday).

16

Regimen. T he independentclaimsofthe ’250patentuse the term “regimen.”

T he broadestreasonable interpretationof“regimen”to apersonofskillinthe art

asofthe prioritydate is“asystemicplanoftreatment”or“aprogram oftreatment”

to attainsome result. Ex.1003 at¶ 79 ; Ex.1004 at¶ 3 2. T he specificationdoes

notdefine “regimen”and offersno expressrestrictiv e disclosure. T he use ofthe

term “regimen”inthe claimsdoesnotalterthe broadestreasonable interpretation

of“comprising”orsomehow close the claims. See Gillette,4 05 F.3 d at1374

(notingthat“‘w ordsorexpressionsofmanifestexclusion’or‘explicit’disclaimers

inthe specificationare necessaryto disav ow claim scope”and that“[d]espite the

numerouscitesto three-bladed razorsplucked from the w ritten description,no

statementin the patentsurrendersorexcludesa four-bladed razor.” (citation

omitted)). Indeed, as the indefinite article “a” is used in the phrase “a

therapeuticallyeffectiv e regimen”recited inthe independentclaims,thatindefinite

article means“one ormore.” Baldw inGraphicSys.,Inc.v.Siebert,Inc.,512 F.3 d

13 3 8 ,13 4 2 (Fed.C ir.2008 ) (T he FederalC ircuit“hasrepeatedlyemphasized that

anindefinite article ‘a’or‘an’inpatentparlance carriesthe meaningof‘one or

more’in open-ended claims containing the transitional phrase ‘comprising.’”

(quotationsomitted)). T hus,the use ofthe open-ended transition“comprising”

coupled w iththe use ofthe indefinite article “a”before “regimen”reinforcesthat

the independentclaimsare eachopen-ended and allow foradditional,unrecited

17

elementsto fallw ithinthe scope ofthe claim.

Claim 3. C laim 3 containsanuncorrected,typographicalerror. B ased onits

position,and from the language ofclaim 2 and the follow ingdependentclaims,

claim 3 dependsfrom claim 1. PT A B can,and inthisrev iew should,reachthe

meritsofclaim 3 despite itsflaw . See CardinalChem.Co.v.M ortonInt’l,Inc.,

508 U .S.8 3 ,100(19 9 3 ) (explainingstrongpresumptionforresolv inginvalidity

issuesw hen presented ratherthan dismissing forprocedural reasons); Exparte

T anksley,26 U .S.P.Q .2d 13 8 4 ,13 8 7 (B PA I19 91) (deciding priorartrejection

despite indefiniteness). W hetherclaim 3 dependsfrom claim 1orclaim 2,the

unpatentabilityofclaim 3 doesnotchange. IfY edaw antsto cure thisdefect,it

should mov e to amend claim 3 duringthe trialphase.

E . Patentsand Printed PublicationsR elied OnInT hisPetition

Petitionerreliesonthe follow ingpatentsand printed publications:

1. Pinchasi(E x.1005)

Pinchasidisclosesmethodsofallev iatingsymptomsofapatientsuffering

from RRM S byadministeringapharmaceuticalcompositioncomprising4 0mgof

GA . See,e.g.,Ex.1005 atp.5,ll.2-8 ,p.8 ,ll.2-15 and p.13 ,ll.21-23 ; Ex.1003

at¶¶ 70-75; Ex.1004 at¶ 61. C ertainembodimentsinvolv e dailyadministration

ofthisdosage,w hile otherembodimentsinvolv e ev ery-other-dayadministration.

See, e.g., Ex. 1005 atp. 8 , ll. 2-11. Pinchasidiscusses experimental data

18

demonstratingthatdailyinjectionof4 0mg(28 0mgGA w eekly) w assafe and

therapeutically effectiv e. See,e.g.,Ex.1003 at¶¶ 73-74 ; Ex.1004 at¶ 61.

Pinchasi’sdataalso formed the basisofthe C ohen2007 article inN eurology,a

preeminentpeer-review ed journalinthe field ofneurology,w hichw ould hav e led

aPOSA to considerthe dataespeciallypersuasiv e and credible. Ex.1003 at¶ 65;

Ex.1004 at¶¶ 62-64 ; Ex.1006. T reatingpatientsusingbothPinchasi’sdailyand

alternate-day embodimentsw ill hav e beneficial effectson theirsymptoms, as

show nin(amongotherthings) the reductioninthe meancumulativ e numberof

Gd-enhancinglesionsand new T 2 lesionsinthe brainofthe patients.See,e.g.,Ex.

1005 atp.5,ll.2-8 ,p.8 ,ll.2-15,p.9 ,ll.7-12; Ex.1003 at¶ 73 .

A sPinchasiw aspublished onJuly19 ,2007,more thanone yearbefore

the ’250patent’searliestpossible prioritydate,itqualifiesaspriorartto the ’250

patentatleastunderpre-A IA 3 5 U .S.C .§ 102(b).

2. 19 9 6 FDA SB O A (E x.1007A )

In19 9 6,the FDA rev iew ed T eva’snew drugapplication(N DA ) for20mg

daily C opaxone® . T hatdocument— the 19 9 6 FDA SB OA — w asdisclosed to

M ylan(and so publiclyav ailable) more thanone yearpriorto the earlierpossible

19

prioritydate ofthe ’250patent.2 T he 19 9 6 FDA SB OA explicitlyencouraged less

frequentGA injectionsand provided half-life datademonstratingthatC opaxone

treatmentsw ith injectionsasinfrequentasabout80 hoursapartw ould be as

effectiv e asdaily injections. See Ex. 1003 at¶120. In particular, one FDA

review erstated that“itisunclearto me w hyitisnecessaryto injectthe drugona

dailybasis. T hisdosingregimenseemslike itw ould subjectthe patientto an

excessiv e amountofdiscomfortifitisnotnecessaryto maintainefficacy.” Ex.

1007A at121. T he review er“recommend[ed]that[T eva]ev aluate the necessity

ofdailys.c.[subcutaneous]injectionsasopposed to more infrequentintermittent

administrationofthe drug.” T he 19 9 6 FDA SB OA therefore demonstrated the

desirabilityand effectiv enessoflessfrequentGA injectionsw hile also defininga

range ofviable choicesforthose ofordinaryskillseekingto optimize the regimen.

See Ex.1003 at¶¶ 119 -13 9 .

T o qualify asa printed publication w ithin the meaning of§ 102(b), a

reference “musthav e beensufficientlyaccessible to the publicinterested inthe art”

before the critical date. In re Cronyn,8 90 F.2d 1158 ,1160 (Fed.C ir.19 8 9 ).

2 Ex.1007,A ffidav itofM arlene S.B obkadated December9 ,2014 attachingas

Ex.A ,JohnJ.Jessup,Review and EvaluationofPharmacologyT oxicologyData:

OriginalN DA Review (19 9 6) (“the 19 9 6 FDA SB OA ”,Ex.1007A ).

20

Public accessibility isbased on the “factsand circumstancessurrounding the

reference’sdisclosure to membersofthe public.” Inre Lister,58 3 F.3 d 1307,

1311(Fed.C ir.2009 ). A reference isconsidered publicly accessible ifitis

disseminated or otherw ise made av ailable such thatinterested persons and

ordinarilyskilled artisans,exercisingreasonable diligence,canlocate it.Id.

T he 19 9 6 FDA SB OA w aspublicallyav ailable atleastasofJuly17,2007.

Ex.1007,M .B obkaA ffidavit(demonstratingav ailabilityto the publicmore than

one yearbefore the priority date). A sthe 19 9 6 FDA SB OA w aspublically

av ailable asa printed publication more than one yearbefore the ’250 patent’s

earliestpossible prioritydate (see Ex.1007),itqualifiesaspriorartto the ’250

patentatleastunderpre-A IA 3 5 U .S.C .§ 102(b).

3 . Flechter2002A (E x.1008 )

Flechter2002A 3 disclosesalternate-daytreatmentofRRM S w ith20mgof

GA . Ex.1003 at¶¶ 54 -56; Ex.1004 at¶ 66; Ex.1008 atA bstract. Inthe study,

RRM S patientsw ere sw itched from dailyadministrationof20mgto alternate-day

administrationof20mg. Ex.1008 at11-12. T he frequency ofexacerbations

3 Ex.1008 ,Flechteretal.“C opolymer1(glatirameracetate) inrelapsingformsof

multiple sclerosis: Openmulticenterstudyofalternate-dayadministration”Clin.

N europharm.,25:11-15 (2002) (“Flechter2002A ”).

21

(“relapse rate”) and Expanded DisabilityStatusScale (“EDSS”) scoringendpoints

w ere measured. Id. U singthose endpoints,Flechter2002A found similarefficacy

ratesw ith20mgdailyand 20mgalternate daytreatment. Id.at15. M oreov er,

Flechter2002A ’sresultsindicated increased compliance forpatientstreated w ith

alternate day dosing— 60.3 % of patients treated w ith alternate day dosing

completed tw o yearsoftreatmentw hile only 3 9 .7% ofpatientsreceiv ingdaily

treatmentcompleted tw o yearsoftreatment.Id.at15.

Giv enthe similarefficacyofdailyand alternate daydosing, Flechter2002A

stated that“20mgofC opolymer1onalternate daysalreadyhasamaximaleffect,

and daily injectionsare unnecessary.” Id.at15. T herefore,Flechter2002A

suggested that:

Itispossible thatthe biologiceffectofC opolymer1isnotdose-

related butisrelated to the exposure ofthe immune system to its

presence by the continuity of administering the drug w ith

rechallenging the immune system, thus making daily injections

unnecessary.

Id.T hus,Flechter2002A taughtalternate daydosage ofGA forM S patients.

A sFlechter2002A w aspublished in 2002,more than one yearbefore

the ’250patent’searliestpossible prioritydate (see Ex.1008 ),itqualifiesasprior

artto the ’250patentatleastunderpre-A IA 3 5 U .S.C .§ 102(b).

22

4 . PriorA rtInformingthe GeneralKnow ledge oftheOrdinarily-Skilled A rtisan

Inadditionto the priorartdiscussed abov e,the declarationsofDrs.Peroutka

and Green addressadditional priorartconfirming the general know ledge ofa

POSA asofthe prioritydate. T hese additionalpublicationsconfirm thataPOSA

w ould hav e recognized thatreducingthe numberofinjectionsina7-dayperiod

w ould increase patientadherence and compliance. See,e.g.,Ex.1003 at¶¶ 100-

103 ; Ex. 1004 at¶¶ 54 -59 ; see also Ex. 1010, Ex. 1011. T he additional

publications also confirm thatas ofthe priority date a POSA w ould hav e

recognized thatalternate daydosingw ould hav e equiv alentefficacyto a20mg

dose ofGA . See Ex.1003 at¶¶ 113-118 ; Ex.1004 at¶¶ 67-71; see also Ex.1008

at11; Ex.1006 at9 4 1-9 4 4 .

F. Ground 1: C laims 1-13 and 19 -20 A re U npatentable A sA nticipated byPinchasi.

1. IndependentC laims1and 19 A re A nticipated byPinchasi.

C laim 1recitesan open-ended method fortreating M S using GA that

includesthe follow ingelements:

apreamble explainingthatthe method “allev iat[es]asymptom”ofM S in

certainpatients,

23

asingle stepofadministeringaregimenincludingatleastthree injectionsof

4 0mgGA duringa7-dayperiod,w ithatleastone daybetw eeneach

injection,and

thatthe regimenis“sufficientto alleviate the symptom ofthe patient.”

C laim 19 issimilarto claim 1exceptforapreamble thatrecitesonly“a

humanpatientsufferingfrom [RRM S]”asthe treated patientand recitesthatthe

method “reduc[esthe]frequencyofrelapses”ratherthan“allev iat[es]asymptom.”

A sexplained below ,Pinchasiexpresslydiscloseseachelementofclaims1

and 19 .See Ex.1003 at¶¶ 78 -8 4 ; Ex.1004 at¶ 8 8-9 4 .

Pinchasi discloses the preambles: A sathreshold matter,M ylandoesnot

concede thatthe preamble ofclaim 1or19 islimiting. Regardless,Pinchasi

expresslydisclosesthe preamblesofclaims1and 19 .

T he preamble ofclaim 1recitesa “method ofallev iating a symptom of

[RRM S]”intw o alternativ e typesofpatients:(1) “ahumanpatientsufferingfrom

[RRM S]”or(2) “a patientw ho hasexperienced a firstclinical episode and is

determined to be athighrisk ofdev elopingclinicallydefinite [M S].” B ecause the

tw o typesofpatientsare recited usingthe disjunctiv e “or,”apriorartteachingw ith

eitherpatientmeetsthe preamble to the extentitisanaffirmativ e claim limitation.

Pinchasidisclosesa method oftreating a human patientsuffering from

RRM S –the firsttype ofpatientrecited inclaim 1and the onlytype ofpatient

24

recited inclaim 19 –that“providesamethod ofallev iatingasymptom ofapatient

sufferingfrom arelapsingform ofmultiple sclerosis.” Ex.1005 atp.8 ,ll.2-4 .

Pinchasidisclosesthatthe method can be used “to allev iate a symptom ofa

relapsingform ofmultiple sclerosisinahumanpatient,”id.atp.10,ll.26-27,and

that“[i]n yetanotherembodiment,the relapsing form ofmultiple sclerosisis

relapsing-remitting multiple sclerosis.” Id. atp. 8 , ll. 12-13 . Pinchasithus

disclosesa“method ofalleviatingasymptom of[RRM S]...”inahumanpatientas

recited inthe preamble ofclaim 1.Ex.1003 at¶ 78 ; Ex.1004 at¶¶ 8 8 -9 4 .

Pinchasialso expressly disclosesthatitstreatmentregimen reducesthe

frequencyofrelapsesinRRM S patients(Ex.1005 atp.8 ,ll.14 -15; 17).Pinchasi

thusdiscloses“reducingfrequencyofrelapses...”inahumanpatientasrecited in

the preamble ofclaim 19.Ex.1003 at¶ 8 4 ; Ex.1004 at¶ 8 8 .

Pinchasi discloses administration of the open-ended regimen: Pinchasi

discloses each aspect of the open-ended method of claim 1, including

“administeringto the humanpatientatherapeuticallyeffectiv e regimenofthree

subcutaneousinjectionsofa4 0mgdose ofglatirameracetate ov eraperiod of

sev endaysw ithatleastone daybetw eenev erysubcutaneousinjection.” See Ex.

1003 at¶¶ 79 -81; Ex.1004 at¶¶ 9 0-9 5.

First, w ith respectto the dose amount,Pinchasidiscloses“periodically

administering to the patientby subcutaneous injection a single dose of a

25

pharmaceuticalcompositioncomprising4 0mgof[GA ]so asto therebyallev iate

the symptom ofthe patient.”Ex.1005 atp.5,ll.2-8 .

Second,w ithrespectto the dose schedule,Pinchasidiscloses“periodically

administering...asingle dose ofapharmaceuticalcompositioncomprising4 0mg

of[GA ]”and statesthat“the periodicadministrationisev eryotherday”inone

specificallydisclosed embodiment. Id.atp.8 ,ll.2-11. Pinchasi’sdisclosure ofa

regimen of administering 4 0 mg of GA an ev ery-other-day basis discloses

providingatleast“three subcutaneousinjections”ofthatdose “ov eraperiod of

sev endaysw ithatleastone daybetw eenev erysubcutaneousinjection”forany

period oftreatmentgreaterthanorequalto sev endays. Ex.1003 at¶¶ 79 -81; Ex.

1004 at¶¶ 90-9 5. Injecting4 0mgGA “ev eryotherday”(asPinchasidiscloses)

results in administration ofthatdrug thatalternates betw een three and four

injections per 7-day period w ith atleastone day betw een injections, w hich

necessarilyresultsinatleastthree subcutaneousinjectionsper7-dayperiod. Ex.

1003 at¶¶ 79 -8 1; see,e.g.,Ex.1004 at¶¶ 8 9 -91.W hile Pinchasi’sdosingregimen

mayresultinfourinjectionsinone 7-dayperiod and three injectionsthe next,

neitherclaim 1norclaim 19 excludesthatpossibility,and indeed bothexpressly

allow “comprising”to be anopen-ended term. See,e.g.,Invitrogen.,3 27 F.3 d at

1368 . A spreviouslypointed out,claim 1doesnotexclude additional,unrecited

elements or method steps, and thus encompasses Pinchasi’s one additional

26

injection ev ery other7-day period. See, e.g., Gillette, 4 05 F.3 d at1371-73 .

A ccordingly,Pinchasidisclosesthe administrationstepofbothclaims1and 19 .

Ex.1003 at¶¶ 79 -81; Ex.1004 at¶ 9 4 .

Pinchasi discloses that the regimen is sufficient to alleviate symptoms and

reduce relapses: Pinchasidisclosesthatthe regimenis“sufficientto allev iate the

symptom of the patient.” Pinchasi states thatits method of periodically

administering injections of4 0 mg GA “alleviat[es]a symptom ofa patient

sufferingfrom [RRM S].”See,e.g.,Ex.1005 atp.8 ,ll.2-15.

Pinchasialso disclosesthatitsregimenis“sufficientto reduce frequencyof

relapsesinthe humanpatient.” Specifically,Pinchasistatesthatitsregimenof

periodicadministrationof4 0mgGA “reducesasymptom ofM S [including]the

frequencyofrelapses.”Id.atp.9 ,ll.13 -17.

A ccordingly,Pinchasiexpresslydisclosesaregimenrecited inbothclaims1

and 19 thatis“sufficientto allev iate [a]symptom ofthe patient”(asrecited in

claim 1) and “sufficientto reduce frequencyofrelapsesinthe humanpatient”(as

recited inclaim 19 ).

A ccordingly,atleastforthe reasonsdiscussed abov e,Pinchasidiscloses

each elementofclaims 1and 19 ofthe ’250 patentand these claims are

unpatentable asanticipated.Ex.1003 at¶¶ 78 -8 4 .

27

2. DependentC laims2-12 and 20A re A nticipated byPinchasi.

a. Pinchasidisclosed the furtherlimitationsofclaims3 ,12 and 20.

Dependentclaims3 and 12 furtherlimitclaim 1,and dependentclaim 20

furtherlimitsclaim 19 bylimitingthe claimed method to administrationofa“4 0

mgdose ofglatirameracetate [that]isinaprefilled syringe forselfadministration

bythe humanpatient.” Pinchasiexpresslydisclosesthatthe GA administered as

partofitsregimen“isinaprefilled syringe and isselfadministered bythe patient.”

See Ex.1005 at8 ,ll.24 -26 and 22,ll.3 -5. A ccordingly,Pinchasianticipates

claims3 ,12 and 20forthe reasonsstated abov e w ithrespectto claims1and 19 in

v iew ofthisfurtherdisclosure ofPinchasi.Ex.1003 at¶ 8 6; Ex.1004 at¶ 108 .

b. Pinchasidisclosed the furtherlimitationinclaims2and 4 -11.

Dependentclaims2,4 and 6-8 furtherlimitclaim 1by identifying the

symptom allegedlyalleviated bythe claimed administration.A sshow ninthe table

below , Pinchasiexpressly discloses thatits regimen alleviates the symptoms

recited inclaims2,4 and 6-8 . A ccordingly,Pinchasianticipatesclaims2,4 and 6-

8 forthe reasonsstated abov e w ithrespectto claims1and 19 inview ofthese

furtherPinchasidisclosures. Ex.1003 at¶¶ 8 5,8 7-8 9 ,91,9 3 ; Ex.1004 at¶¶ 111-

114 .

3 0

T hese beneficialtreatmenteffectsw ere presentinthe priorart,including

T ev a’sow n2001C opaxone® label. T he treatmenteffectsrecited inclaims5 and

9 -11are the directresultofPinchasi’salternate-dayinjectionsof4 0mgGA . Ex.

1003 at¶¶ 8 8-90,9 2-9 3 ; Ex.1004 at¶ 111. See Inre Kubin,561F.3 d 13 51,1357

(Fed. C ir. 2009 ) (“Ev en if no prior artof record explicitly discusses the

[limitation],the [patentapplicant’s]applicationitselfinstructsthat[the limitation]

isnotanadditionalrequirementimposed bythe claims...butratheraproperty

necessarilypresentinthe [claimed inv ention].”).

M oreov er,the treatmenteffectsdescribed inclaims5 and 9 -11w ere not

discov ered bythe inv entorsand are notimprov ed bythe claimed methods. A t

best,the patentstatesthatitsmethod resultsinatreatmenteffectthatis“atleastas

effectiv e”asthe priorartadministrationof20mgdailyC opaxone® . Ex.1001at

col.13 ,l.4 6 -col.15,l.50.

Claim 5. C laim 5 recites “w herein alleviating a symptom comprises

reducingbrainatrophyinthe patient.” Reducingbrainatrophyisthe naturalresult

ofadministeringGA asrecited inclaim 1and inPinchasi. A POSA asofthe

prioritydate w ould hav e understood thattreatingapatientw ithafirst-line therapy

suchasGA naturallyresultsinareductioninbrainatrophy. Ex.1003 at¶ 90; Ex.

1004 at¶¶ 78 ,111.Pinchasi’sdisclosure ofaGA treatmentregimenforM S w ould

hav e been understood by a POSA to necessarily resultin a reduction ofbrain

3 1

atrophy. T he PatentOw nerdoesnotallege thatitsmethodsw ere the firstto result

inthe reductioninbrainatrophyorev enthatthe claimed methodsimprov e the

reductioninbrainatrophy; the patentmerelystatesthat“[t]reatmentw ith4 0mg

s.c. GA three timesw eekly isatleastaseffectiv e as20 mg s.c. GA daily

administrationatreducingbrainatrophy.” Ex.1001atcol.13 ,l.66 -col.14 ,l.5.

T hus,the method ofclaim 1and ofPinchasinecessarilyresultinthe reductionof

brainatrophy.T hisrendersthe additionallimitationofclaim 5 the necessaryresult

oftreatinganM S patientassetforthinclaim 1. T herefore,claim 5 isanticipated

byPinchasi.Ex.1003 at¶¶ 90,9 3 ; Ex.1004 at¶¶ 111-114 .

Claim 9. C laim 9 recites “w herein alleviating a symptom comprises

reducing the numberofnew hypointense lesionson enhanced T 1scansin the

patientorreducingthe totalv olume ofhypointense lesionsonenhanced T 1scans

inthe patient.” Reducingthe numberorv olume ofhypointense lesionsasrecited

inclaim 9 isthe naturalresultoftreatinganM S patientasinclaim 1and Pinchasi.

A POSA asofthe prioritydate w ould hav e understood thattreatingapatientw itha

first-line therapysuchasGA w ould necessarilyresultinreducingthe numberof

hypointense lesionsorthe total v olume ofhypotensiv e lesionsonenhanced T 1

scansin the patient. Ex.1003 at¶¶ 9 2,9 3 ; Ex.1004 at¶ 112. Pinchasi’s

disclosure ofatreatmentregimenforanM S patientw ould hav e beenunderstood

byaPOSA to resultinreducingthe numberofnew hypotensiv e lesionsorthe total

3 2

v olume ofhypotensiv e lesionsonenhanced T 1scans. T he PatentOw nerdoesnot

allege thatitsmethodsw ere the firstto resultinsuchareductionorev enthatthe

claimed methodsimprov e the reduction; the patentmerelystatesthat“[t]reatment

w ith4 0mgs.c.GA three timesw eeklyisatleastaseffectiv e as20mgs.c.GA

daily administration atreducing the number ofnew hypointense lesions on

enhanced T 1scans[and]the totalv olume ofhypointense lesionsonT 1scans.”

Ex.1001atcol.14 ,ll.4 7-61. T hus,the method ofclaim 1and ofPinchasiw ould

necessarilyreduce boththe numberand v olume ofsuchlesions. T hisrendersthe

additionallimitationsofclaim 9 anecessaryresultoftreatinganM S patientasset

forthinclaim 1,and so claim 9 isanticipated byPinchasi. Ex.1003 at¶¶ 9 2-9 3 ;

Ex.1004 at¶¶ 111-114 .

Claim 10. C laim 10 recites“w herein alleviating a symptom comprises

reducing a lev el of disability as measured by EDSS Score, by the w ork

productiv ityand activ itiesimpairment-GeneralHealth(W PA I-GH) questionnaire,

orby EuroQ oL(EQ 5D) questionnaire in the patient.” Reducing the lev elsof

disabilityasrecited inclaim 10isthe naturalresultofthe administrationofGA as

recited in claim 1and Pinchasi. A POSA asofthe priority date w ould hav e

understood thattreating a patientw ith a first-line therapy such asGA w ould

necessarily resultin a reduction ofa lev el ofdisability asmeasured by EDSS

Score. Ex.1003 at¶¶ 8 9 ,9 2-9 3 ; Ex.1004 at¶¶ 111-112. Pinchasi’sdisclosure of

3 3

atreatmentregimenforM S w ould hav e beenunderstood byaPOSA to resultin

the reductionofalev elofdisabilityasmeasured byEDSS Score. T he Patent

Ow nerdoesnotallege thatitsmethodsw ere the firstto resultinsuchareduction

orev enthatthe claimed methodsimprov e the reduction; the patentmerelystates

that“[t]reatmentw ith4 0mgs.c.GA three timesw eeklyisatleastaseffectiv e as

20mgs.c.GA dailyadministrationatreducingthe change ...inEDSS Score[,]

the lev elofdisabilityasmeasured byEuroQ oL(EQ 5D) questionnaire [and]the

lev elofdisabilityasmeasured bythe w ork productiv ityand activitiesimpairment-

GeneralHealth(W PA I-GH) questionnaire.” Ex.1001atcol.15,ll.4 2-50. T hus,

the method ofclaim 1and ofPinchasiw ould necessarily reduce the disability

lev elsmeasured bythe recited metrics. T hisrendersthe additionallimitationsof

claim 10the necessaryresultoftreatinganM S patientassetforthinclaim 1,and

so claim 10isanticipated byPinchasi. Ex.1003 at¶¶ 9 0,9 3 -9 4 ; Ex.1004 at¶¶

111-114 .

Claim 11. C laim 11recites“w herein alleviating a symptom comprises

reducing a change in EDSS Score in the patientor reducing a change in

A mbulation Indexin the patient.” Reducing the change in EDSS Score and

A mbulationIndexasrecited inclaim 11isthe naturalresultofthe administration

ofGA asrecited inclaim 1and ofPinchasi. A POSA asofthe prioritydate w ould

hav e understood thattreatingapatientw ithafirst-line therapysuchasGA w ould

3 4

resultinareductionofachange inEDSS Score inthe patient. Ex.1003 at¶¶ 8 9 ,

9 3 -9 4 ; Ex.1004 at¶¶ 111-112. Pinchasi’sdisclosure ofatreatmentregimenfor

M S w ould hav e beenunderstood byaPOSA to resultinthe reductionofachange

inEDSS Score inthe patient. T he PatentOw nerdoesnotallege thatitsmethods

w ere the firstto resultin such a reduction orev en thatthe claimed methods

improv e the reduction; the patentmerelystatesthat“[t]reatmentw ith4 0mgs.c.

GA three times w eekly is atleastas effectiv e as 20 mg s.c. GA daily

administrationatreducingthe lev elofdisabilityasmeasured byEDSS Score.”Ex.

1001atcol.15,ll.20-51. T hus,the method ofclaim 1and ofPinchasiw ould

necessarilyreduce the recited changes. T hisrendersthe additionallimitationsof

claim 11the necessary resultoftreating an M S patient, and so claim 11is

anticipated byPinchasi.Ex.1003 at¶¶ 8 9 ,9 2-9 3 ; Ex.1004 at¶¶ 111-114 .

3 . DependentC laim 13 isA nticipated byPinchasi

Pinchasianticipatesclaim 13 ,w hichfurtherlimitsthe patientofclaim 1to a

“patient[w ho]hasnotreceiv ed glatirameracetate therapypriorto initiationofthe

regimen.” T he patientofclaim 13 istherefore naïv e to the therapy.

A POSA w ould hav e know n thatGA w asa first-line therapy forM S

treatment,and w astherefore prescribed to bothnaïv e patientsand patientsalready

receivingGA therapy. Ex.1003 at¶ 9 4 ; Ex.1004 at¶ 109 . Giv enthis,GA w ould

hav e beenavailable to patientsw hetherornottheyhad beenpreviouslytreated

3 5

w ithGA . A POSA w ould prescribe GA to eithertype ofpatientastaughtby

Pinchasi,and so Pinchasianticipatesclaim 13 . Ex.1003 at¶ 9 4 ; Ex.1004 at¶¶

109 ,119 ; see Inre Petering,301F.2d 676,681-8 2 (C C PA 19 62) (embodiment

need notbe stated ifaPOSA w ould appreciate the embodimentfrom the limited

numberofpossibilities).

G. SummaryofPetitioner’sObviousnessPositions.

1. T he Law ofObviousness

A patentclaim isinv alid asobv iousifanalleged infringerprov esthatthe

differencesbetw eenthe claimed subjectmatterand the priorartare suchthatthe

subjectmatterasaw hole w ould hav e beenobv iousatthe time ofinv entionto a

personhavingordinaryskillinthe art. 3 5 U .S.C .§ 103 (a) (2006). Obv iousnessis

ultimatelyaquestionoflaw premised onunderlyingissuesoffact,including:(1)

the scope and contentofthe priorart; (2) the lev elofordinaryskillinthe pertinent

art; (3 ) the differencesbetw eenthe claimed inv entionand the priorart; and (4 )

objectiv e evidence suchascommercialsuccess,long-feltneed,and the failure of

others. KSR Int’lCo.v.T eleflexInc.,550U .S.3 9 8 ,4 27 (2007); Graham v.John

Deere Co.ofKan.City,3 8 3 U .S.1,17-18 (1966).

InKSR,the Supreme C ourtenumerated sev eralexemplaryrationalesthat

maysupportafindingofobv iousness. Forexample,the “mere substitutionofone

elementforanotherknow ninthe field”to “yield apredictable result”maysupport

3 6

afindingofobviousness. Id.at4 16 (citationomitted). T he C ourtalso explained

thatobv iousnessmaybe show nifitw as“obviousto try”:“W henthere isadesign

need ormarketpressure to solv e a problem and there are a finite numberof

identified,predictable solutions,apersonofordinaryskill[inthe art]hasgood

reasonto pursue the know noptionsw ithinhisorhertechnicalgrasp. Ifthisleads

to the anticipated success,itislikelythe productnotofinnov ationbutofordinary

skilland commonsense.”Id.at4 21.

T he FederalC ircuithasfrequentlyinv alidated asobv iouspatentsthatseek to

claim modified dosingprotocolsforpriorartdrugs. Forexample,the Federal

C ircuitrecently affirmed a districtcourt’s grantof summary judgmentof

obviousnessoftw o patentsthatclaimed asingle monthlydose of150mgofthe

drugrisedronate,w hichbelongsto aclassofpharmaceuticalcompoundscalled

bisphosphonates. See WarnerChilcottCo.v.T evaPharms.U SA ,Inc.,N os.2014 -

14 3 9 ,14 4 1,14 4 4 -4 6,2014 W L64 3 504 2 (Fed.C irc.N ov .18 ,2014 ). T hatcase is

strikingly similar to this one. T here, the prior art products included

bisphosphonatesdosed at5 mgdaily,and one bisphosphonate dosed at3 5 mg

w eekly. T he priorartdaily dosed productsw ere know n to cause irritation to

mucousmembranesand significantadv erse esophagealand gastrointestinalside

effects, w hich resulted in noncompliance issues w ith patients on the daily

3 7

regimens. T hose problemsw ere onlysomew hatalleviated byw eeklydosingof

bisphosphonates.See id.at*1.

Inaffirmingthe inv alidityofthese patents,the FederalC ircuitheld thatthe

districtcourtcorrectlydetermined thatthe cited priorartreferencesdisclosed or

suggested each limitation,and provided both motiv ation to pursue the claimed

monthly regimen and a reasonable expectation ofsuccess in doing so. Id.

A ccordingto the FederalC ircuit,the districtcourtcorrectlyfound thatthe priorart

suggested lessfrequentdosingschedules.A ccordingto the Federal C ircuit,the

priorartalso established a reasonable expectation thatonce-monthly dosing of

risedronate could successfullytreatosteoporosis. T he FederalC ircuitfound that

“[a]slongerdosinginterv alssuitpatientconv enience and compliance,the priorart

therefore provided expressmotiv ationto pursue amonthlydosingregimen.” Id.at

* 5.

T he patentow nerargued thatuncertaintyasto the safetyand efficacyofa

once monthly150mgdosingprotocolprecluded afindingofobviousness. T he

FederalC ircuitflatlyrejected thatargument,holdingthata“[w ]hile itistrue that,

asof[the prioritydate],the highestsingle dose ofrisedronate thathad actually

beentested inapatientw as50mg,obviousnessdoesnotrequire absolute certainty

ora guarantee ofsuccess.” Id.at*6. A sforthe patentow ner’sevidence of

secondaryconsiderationsofnon-obviousness,includinganalleged long-feltneed

3 8

forand skepticism ofotherstow ard the claimed dosingregimen,the courtfound

that“lack ofcertaintydoesnotpreclude aconclusionofobv iousness.”Id.

WarnerChilcottisnotan outlier.T he Federal C ircuitreached a similar

conclusioninHoffmann-LaRoche,Inc.v.A potexInc.,74 8 F.3 d 13 26 (Fed.C irc.

2014 ),w here itinv alidated asobv iousotherpatentsrelated to modified dosing

protocolsforasimilarpharmaceuticalproduct.A longthe w ay,the courtnoted that

“[c]onclusiv e proofofefficacyisnotnecessaryto show obviousness,”and held

thatthe claimed dosingregimeninthe invalidated patentsw as“obviousto try:

T here w asaneed to solv e the problem ofpatientcompliance bylookingto less-

frequentdosingregimens.” Id.at13 31-3 2; see also Inre Kubin,561F.3 d at13 57

(“Ev enifno priorartofrecord explicitlydiscussesthe [limitation],the [patent

applicant’s]application itselfinstructsthat[the limitation]isnotan additional

requirementimposed bythe claims...butratherapropertynecessarilypresentin

the [claimed inv ention].”).

2. T he PriorA rtR endersthe C laimsObvious

a. Inv estigationinto DifferentDosingProtocolsforGAT herapy

Ithas long been know n thatthe prior artdosing protocol of20 mg

C opaxone® administered dailyw as“ratherarbitrarilyselected.” Ex.1008 at11.

Personsofskillinthe arthad extensiv e interestinoptimizingthe dosingprotocol

3 9

forC opaxone® and,asdiscussed inthe nextsection,had more thanample reasonto

do so.

T he priorartisreplete w ithinv estigationsofdifferentdosingprotocolsfor

the treatmentofM S w ithGA . T hese inv estigationsstudied differentdose amounts

and differentdosingschedulesand combinationsthereof. Forexample,sev eral

studiesexamined administering20mgofGA to RRM S patientsev eryotherday.

One studyexamined a4 0mgdailydose. Eachstudyreported encouragingresults.

T hese studies,and otherpatentsand printed publicationsinthe priorart,informed

aPOSA ofatleastthe follow ingfoundationalfacts,eachw ellknow nto aPOSA as

ofthe prioritydate and eachofw hichw ould hav e informed theirdev elopmentof

improv ed treatmentprotocols:

T he half-life ofGA w asgreaterthan 80 hoursand therefore did not

require dailyadministration. See Ex.1007A at66; Ex.1003 at¶¶ 120,

131,13 4 ;

A POSA w ould hav e know n thatpatientsuniv ersally preferred dosing

schedulesforGA treatmentthatrequired lessfrequentinjections. See Ex.

1003 at¶¶ 100-101,154 and Ex.1004 at¶¶ 54 -59 (bothdiscussingKhan

2008 (instudyofdailyv s.ev ery-other-day20mgC opaxone® injections,

“[a]fter2 years,allpatientsinthe [daily]groupopted to sw itchto [ev ery

otherday]”);

4 0

T he administrationofa4 0mgdailyinjectionofGA did notcreate any

safetyortolerabilityconcernsascompared to the dailyadministrationof

20mgGA . See,e.g.,Ex.1005 atp.19 ,ll.8 -14 (“T he increased efficacy

observ ed w ith4 0mg/dayGA … isnotaccompanied byacorresponding

increase ofadv erse reactionsw hichw ould be expected uponadoublingof

the administered dose.”);

T hat4 0mgGA administered dailyw assafe and effectiv e. See,e.g.,Ex.

1005 atp.19 ,ll.8-14 ; Ex.1006 at9 3 9 (A bstract) (“GlatiramerA cetate

(GA ) 4 0 mg w assafe and w ell tolerated. T he ov erall efficacy results

suggested thata 4 0-mg dose ofGA may be more effectiv e than the

currentlyapprov ed 20-mgdailydose inreducingM RIactiv ityand clinical

relapse.”); and

Patientadherence and compliance forchronictherapies,aseriousconcern

inthe art,isimprov ed w ithlessfrequentand more conv enientdosing

protocols.See,e.g.,Ex.1010(notingthat“[t]here isconsiderable interest

in alternate dosing regimensofGA in RRM S. Daily SC injectable

therapycanbe challengingforlong-term patientcompliance,”and finding

that“[a]fter2 years,allpatientsinthe [daily]groupopted to sw itchto

[ev eryotherday]”).

4 1

Here, the PatentOw ner may be expected to argue thatthe difference

betw eenthe claimed inv entionand the priorartisthe difference betw eenanev ery-

other-day4 0-mgdosingschedule (asdisclosed inPinchasi) and a4 0-mgdosing

schedule thatrequiresexactly three injectionsper7-day period w ith one day

betw eeneachinjection(asrecited inthe ’250patent). W hile Petitionerdoesnot

believ e there are anydifferencesbetw eenthe priorartand the claimed inv ention,

inthe scenario mostfavorable to the PatentOw ner,thisamountsto one additional

injectioninthe Pinchasiregimenev eryotherw eek ascompared to the regimenof

the ’250 patent. T hatis,the disclosure ofPinchasiisa dosing schedule that

alternatesbetw een3 injectionsper7-dayperiod w ithatleastone dayinbetw een

injectionsand 4 injectionsper7-day period w ith atleaston day in betw een

injections.

b. T he PriorA rtM otivated aPersonofOrdinarySkillto Inv estigate DifferentDosingProtocolsandProvided A R easonable ExpectationofSuccess.

A rmed w iththisextensiv e know ledge ofGA therapy,a POSA asofthe

prioritydate w ould be motiv ed to dev ise the dosingschedule ofthe ’250patentand

w ould hav e areasonable expectationofsuccessindoingso.

First,a POSA w ould hav e been motivated to eitheralterPinchasialone

(w hichdiscloses4 0mgalternate dayadministration),orcombine itw ithanother

reference (disclosing similar alternate day dosing regimens), w ith a goal of

4 2

low ering the numberofinjectionsa patientmustendure and thusoptimizing

patientadherence and compliance. Pinchasistressed the efficacy,tolerabilityand

safetyofdailyinjectionsof4 0mgGA initsclinicalstudies,findingthatthe onset

ofactionw ith4 0mgGA w asmore rapid ascompared to 20mgGA treatment.See

Ex.1005 atp.19 ,ll.8 -14 . M oreov er,thisincreased efficacyw asseeninthe

absence ofanincrease ininjectionsite reactionsw ith4 0mgGA administration.

Ex.1005 atp.19 ,ll.8 -14 ; Ex.1004 at¶¶ 57,61,120; Ex.1003 at¶¶ 74 -75.

Pinchasidemonstrated thatthe occurrence ofinjectionsite reactionsinpatients

treated w ith4 0mgGA dailyw asthe same as,ifnotslightlyless,thantreatment

w ith20mgdaily. See Ex.1005 atT able 5; Ex.1004 at¶¶ 9 9 ,119 . A saresultof

the increased efficacycombined w iththe lack ofanincrease inadv erse injection

site reactions,Pinchasiexplicitlyencouraged and motiv ated aPOSA to use 4 0mg

GA inthe treatmentofRRM S:

T he increased efficacy observ ed w ith 4 0 mg/day GA in reducing

M RI-measured disease activityand relapse rate indicatesthatitisw ell

tolerated and can improv e the treatmentofRRM S patients. T he

improv ement in efficacy, how ev er, is not accompanied by a

correspondingincrease ofadv erse reactionsw hichw ould be expected

uponadoublingofthe administered dose.

Ex.1005 atp.19 ,ll.8 -14 ; Ex.1004 at¶¶ 9 6,9 9 ,111-113 ; Ex.1003 at¶ 115.

Pinchasi,w hichT ev aow ns,isno fluke. InT ev a’s2008 pressrelease prev iew ing

4 3

resultsofitsFORT E trial— w hichcompared 4 0mgdailydosingw ith20mgdaily

dosing ofC opaxone® — T ev a reported no difference in efficacy w ith similar

tolerability.Ex.104 6.

A POSA asofthe prioritydate w ould also hav e beenmotivated to pursue

less-than-dailydosingasameansto improv e patientcompliance (the degree to

w hichpatientsregularlytake medicationasprescribed) and adherence (the extent

to w hichaperson’sbehav iorcorrespondsw itha caregiv er’sinstructions). Ex.

1004 at¶¶ 54 -59 ,116-120; Ex.1003 at¶¶ 100-103 . Pinchasiexpresslydisclosed

and claimed “periodicadministration,”including“ev eryotherday”dosing,w ith4 0

mgofGA . Ex.1005 atp.8 ,ll.10-11& p.21,ll.11-12 (claim 3 ). M oreov er,

reducingthe numberofinjectionsissimplycommonsense to aPOSA :patientsare

mostlikelyto take painfulinjectionsasprescribed w henthe injectionistakenless

often. Ex.1003 at¶ 101; Ex.1004 at¶¶ 54 -59 ,116-119 . Ev en setting this

commonsense aside,how ev er,the priorartisfilled w iththismotiv ation. Khan

noted,forexample,thatthere “isconsiderable interestinalternate dosingregimens

ofGA inRRM S”because “[d]ailySC injectable therapycanbe challengingfor

long-term patientcompliance.” Ex.1010; Ex.1004 at¶ 116. Khanalso reported

thatw hengiv enachoice,allpatientsw ho w ere treated w ithGA onadailybasis

chose to sw itchto alternate daytherapies. Ex.1010; Ex.1004 at¶ 118 . T he 19 9 6

SB OA prov ided similarmotivation. Init,the FDA review ertold T ev a:“Iw ould

4 4

recommend thatthe Sponsorev aluate the necessityofdailys.c.[subcutaneous]

injectionsasopposed to more infrequentintermittentadministrationofthe drug.”

Ex.1007A at121.

Second, a POSA asofthe priority date w ould hav e had a reasonable

likelihood ofsuccessinadministering4 0mgGA accordingto the dosingschedule

claimed inthe ’250patent. Pinchasidisclosed 4 0mgofGA administered ev ery

otherdayassafe and effectiv e,and Flechterand Khandemonstrated that20mg

ev eryotherdayw assafe and effectiv e. Ex.1005 atp.19 ,ll.8-14 ; Ex.1008 at15;

Ex. 1010. T hus, a skilled artisan w ould hav e expected that4 0 mg ofGA

administered ev eryotherday,orthree timesineach7-dayperiod w ithatleastone

daybetw eendoses,w ould be safe and effectiv e. Ex.1003 at¶¶ 113 -115; Ex.1004

at¶¶ 115-119 . M oreov er,aPOSA w ould hav e had areasonable expectationthat

suchdosingw ould improv e patientcompliance and adherence. Inadditionto the

POSA ’scommonsense,Khanhad demonstrated thatpatientsuniformlypreferred

4 5

alternate daydosing. Ex.1003 at¶ 115; Ex.1004 at¶ 118 ; Ex.1010. T he table

below comparesanembodimentofthe ’250patent— three dosesper7-dayperiod

w ithatleastone daybetw eendoses— w ithpriorartdosingschedules.

Insum,the published priorartprov ided allofthe dataaPOSA w ould need

to try— w itha reasonable expectationofsuccess— a reduced-injectionapproach

w ithinthe scope ofthe ofthe ’250patentclaims.

H. Ground 2:C laims1-20A re U npatentable A sO bv iousov erPinchasi.

1. IndependentC laims1and 19 A re Obviousov erPinchasi.

C laim 1recitesamethod fortreatingM S usingGA hav ingthe follow ing

elements:

apreamble explainingthatthe method “allev iat[es]asymptom”ofM S in

certainpatients,

asingle stepofadministeringaregimenincludingatleastthree injectionsof

4 0mgGA duringa7-dayperiod,w ithatleastone daybetw eeneach

injection,and

afinalclause statingthatthe claimed regimenis“sufficientto allev iate the

symptom ofthe patient.”

A sexplained below ,Pinchasiteacheseachelementofclaim 1.See Ex.1003

at¶ 119 ; Ex.1004 at¶¶ 9 5-107.

4 6

C laim 19 issimilarto claim 1exceptforapreamble thatrecitesonly“a

humanpatientsufferingfrom [RRM S]”asthe treated patientand recitesthatthe

method “reduc[esthe]frequencyofrelapses”ratherthan“allev iatingasymptom.”

A sexplained abov e,Pinchasidiscloseseachlimitationofclaims1and 19

w henthe administrationisunderstood to be atleastthree injectionsina7-day

period w ith one day in betw een each injection and therefore anticipatesthese

claims. Supra § F.1. Pinchasiw ould also renderadosingfrequencylimited to

onlythree doseseach7-dayperiod obv ious.

Forexample,astrictthree timesper7-dayperiod regime w ould hav e been

obviousfrom Pinchasialone because aPOSA asofthe prioritydate w ould hav e

v iew ed sixdosesov ertw o 7-dayperiodsto be therapeuticallyequiv alentto sev en

dosesov erthe same period. Ex.1004 at¶¶ 9 5-107. A POSA w ould hav e also

understood thatthree injectionsof4 0mgGA each7-dayperiod (i.e.,120mg/7-

dayperiod) and alternate-dayinjectionsof4 0mgGA (i.e.,120mg–160mg/7-

dayperiod) w ould hav e had substantiallythe same pharmacologicaleffect. Ex.

1003 at¶¶ 119 -13 9 . A POSA knew from the priorartthatadministeringata4 0

mgSC dose ofGA w assafe and effectiv e and thatadministering120mgofGA

per7-dayperiod (i.e.,three 4 0mginjections) w asinthe middle ofthe safe and

effectiv e range forGA . See § V I.G.2.b atT able,supra. M oreov er,POSA sknew

thatlessfrequentSC injectionsw ould be expected to decrease the incidence ofside

4 7

effectsassociated w ithinjectable medicines,and thatlessfrequentadv erse ev ents

w ould increase patientcompliance.

A POSA w ould also be motiv ated to modifythe dosingregimendisclosed in

Pinchasito reduce the numberofdosesto exactlythree injectionsineach7-day

period (ratherthanhav ingafourthdose ev eryotherw eek),because thisw ould

reduce the frequency ofinjectionsev ery other7-day period by one injection,

therebyreducingthe frequencyofside effects. Ex.1003 at¶¶ 100-103 ; Ex.1004

at¶¶ 9 3 -9 4 . M odifyingthe Pinchasiregimento aregimenhavingonly3 injections

perw eek also allow sforamore conv enientdosingschedule (i.e.,allow ingthe

patientto medicate onthe same daysofeachw eek) w hichw ould improv e patient

adherence to the regimen,animportantconsiderationinthe treatmentofchronic

conditions. Ex.1004 at¶¶ 9 3 -9 4 . A POSA w ould hav e predicted thatthis

modified dosing regimen w ould be safe and efficacious based on the

pharmacologicaldataand clinicaltrialsknow ninthe art. Ex.1003 at¶¶ 119 -13 4 ;

Ex.1004 at¶¶ 91-9 4 . Similarly,a POSA knew thatadministering a 4 0 mg

injectionofGA did notimpactthe tolerabilityascompared to 20mginjectionsof

GA againbased onthe pharmacologicaldataand clinicaltrialsknow ninthe art.

Ex.1003 at¶ 119 ; Ex.1004 at¶¶ 9 7-9 8 . T he w ealthofpharmacologicaland

clinical data in the artprov ided the POSA w ith a reasonable expectation of

success.

4 8

In addition to the clinical motiv ations, by 2009 there w asan industry

recognized motivation to inv estigate differentdosagesand dosing regimensfor

successfulproductsto achiev e furthermarketplace exclusiv ity. B y2009 ,priorart

C opaxone® had beenonthe marketformore thanadecade and faced competition

from lessfrequentlyinjected competitorproductsand oraltherapiesasw ellasthe

expirationofthe patentscov eringpriorartC opaxone® . Forexample,since atleast

2003 the dosingschedule forB etaseron® required SC injectionsonalternate days

and Rebif® w asinjected three timesperw eek.Ex.1003 at¶ 111; Ex.1004 at¶ 55.

T he ’250patentdid notcontribute aninv entiv e dosingM S regime to the art,but

instead adopted a predictably safe and effectiv e regimen thatmetthe market

pressuresto offeralessfrequentdosingregimenw hile also allow ingformarket

exclusivitybased onnew patents.

2. DependentC laims2-13 and 20A re ObviousinV iew ofPinchasi.

Dependentclaims2-13 eachdepend from claim 1. Ex.1001atcol.16,l.4 6

-col.17,l.19 .Eachofthese limitationsisdisclosed inPinchasi.Supra§ F.2.For

thatreason,and allofthe reasonsthatclaim 1isobv iousinv iew ofPinchasi,

dependentclaims2-13 are obviousinview ofPinchasi. Ex.1003 at¶¶ 119 -13 9 ;

Ex.1004 at¶¶ 108 -109 ,111.

Similarly,dependentclaim 20isdependentonclaim 19 .Ex.1001atcol.18 ,

ll.27-29 . A sexplained infra § F.2,the additional limitation ofclaim 20 is

4 9

disclosed inPinchasi.Forthatreason,and allofthe reasonsclaim 19 isobv iousin

v iew ofPinchasi,dependentclaim 20isalso obvious. Ex.1003 at¶¶ 119-13 9 ; Ex.

1004 at¶ 108 .

3 . DependentC laim 14 IsObv iousinV iew ofPinchasi

C laim 14 dependsfrom claim 1,addingthe limitationthat“the frequencyof

animmediate postinjectionreactionorthe frequencyofaninjectionsite reactionis

reduced relativ e to dailysubcutaneousadministrationof20mgof[GA ].” Ex.

1001atcol.17,ll.22-24 . Pinchasidisclosesthatinjectionsite reactionsoccurless

frequentlyw henadministering4 0mgGA dailyascompared to 20mgGA daily.

Ex.1005 atT able 5. M oreov er,w hile Pinchasiteachesadministeringtw ice as

muchGA inasingle injection,Pinchasiteachesthatadministrationof4 0mg“is

notaccompanied byacorrespondingincrease inadv erse reactions” Ex.1005 atp.

19 ,ll.11-15. A POSA w ould know and understand thatdecreasingthe numberof

injectionsthatapatientmustadministerw ould furtherdecrease the frequencyof

post-injectionsite reactions.Ex.1003 at¶ 176; Ex.1004 at¶¶ 110.T husclaim 14

isobv iousinv iew ofPinchasiforthe reasonsdiscussed w ithrespectto claim 1in

v iew ofthese furtherteachingsofPinchasi.

4 . IndependentC laim 15 and DependentC laims16-18 A reO bviousinV iew ofPinchasi.

Claim 15. C laim 15 issimilarto claim 1exceptthatclaim 15 recitesinits

preamble thatthe claimed method relatesto “increasing the tolerability ofGA

50

treatment”and statesthatthe claimed method increase the tolerability ofGA

treatmentin the patient. C laim 15 otherw ise recitesthe same obv iousstep of

administrationcomprisingatleast3 injectionsof4 0mgGA ina7-dayperiod as

recited inclaim 1and isobviousforthe same reasonsdiscussed w ithrespectto

claim 1.Supra§ H.1.

C hanging the preamble from “allev iating a symptom”to “increasing the

tolerability ofGA treatment”presentsno patentable distinction ofthe claimed

method ov erclaim 1ofthe ’250patentorthe priorart. A POSA asofthe priority

date w ould know and understand the decreasing the numberofsubcutaneous

injections thata patientmustendure w ould increase the tolerability ofGA

treatment. Ex.1003 at¶¶ 101-105; see also,e.g.,Ex.1004 at¶¶ 117-118 . A

decrease inthe numberofinjectionsw ould normallybe expected to increase the

tolerabilityofthe treatmentregimento apatient. Ex.1003 at¶¶ 101-105. T hus

claim 15 isobv iousinview ofPinchasi.

Claim 16. C laim 16 dependsfrom claim 15 and furtherlimitsclaim 15 by

furtherlimitingthe “increasingthe tolerabilityofGA treatment”to “increasingthe

tolerabilityof[GA ]treatmentinahumanpatientsufferingfrom arelapsingform

ofmultiple sclerosiscomprisesreducing the frequency ofan immediate post

injectionreaction.”Ex.1001atcol.18 ,ll.7-11.

51

T hisfurtherlimitationislikew ise rendered obviousinv iew ofPinchasi. A

personofskillinthe artw ould applythe same commonsense logicto immediate

postinjection reactionsasto any otherinjection reactions: reducing injections

reducesimmediate postinjectionreactions. Ex.1004 at¶ 110; see also,e.g.,Ex.

1003 at¶¶ 175-176. Forthisreason,and the same reasonsclaim 15 isobvious

ov erPinchasi,claim 16 isobviousinview ofPinchasi.

Claim 17. C laim 17 isdependentonclaim 15.Itfurtherlimitsclaim 15 by

recitingthatthe “increasingthe tolerabilityof[GA ]treatmentinthe humanpatient

suffering from a relapsing form ofmultiple sclerosiscomprisesreducing the

frequencyofaninjectionsite reaction.”

T hisfurtherlimitationissimilarlyobviousinview ofPinchasi. A gain,a

personofskillinthe artw ould applythe same logicasw ithclaims15 and 16:

reduction in subcutaneousinjectionsw ill lead to a reduction in injection site

reactions. Ex.1004 at¶ 110; see also,e.g.,Ex.1003 at¶¶ 175-176. Giv enthis

reason,and the same reasonsthatclaim 15 isobv iousov erPinchasi,claim 17 is

obviousinview ofPinchasi.

Claim 18. C laim 18 isdependentonclaim 15,furtherlimitingclaim 15 by

requiringthe pharmaceuticalcompositionadministered be “inaprefilled syringe

forselfadministration by the patient.” Ex.1001atcol.18 ,ll.16-18 . T his

limitationisexpresslydisclosed inPinchasi. Supra § F.2.A . T hus,claim 18 is

52

obviousov erPinchasiforthe reasonsstated w ithrespectto claim 15 inv iew ofthis

furtherexpressteachingofPinchasi.

I. Ground 3 :C laims1-20A re U npatentable A sO bv iousov erPinchasiand the 19 9 6 SBO A .

W hile the common know ledge and common sense ofa POSA inthe art

rendersthe ’250Patentobviousinv iew ofPinchasialone,combiningPinchasiand

the 19 9 6 SB OA confirmsthatclaims1-20ofthe ’250patentare unpatentable as

obvious.

1. IndependentC laims1,15 and 19 A re Obv iousov erPinchasiinview ofthe 19 9 6 FDA SB O A .

A ssupra§ H.1,claims1,15 and 19 are obviousinv iew ofPinchasito the

extentnotanticipated. T he common limitation among all three claims is

administering “a regimen ofthree subcutaneousinjectionsofa 4 0 mg dose of

glatirameracetate ov eraperiod ofsev endaysw ithatleastone daybetw eenev ery

injection.” Ifthe B oard determinesthatthese claimsare notanticipated and reads

thisrecitationundulynarrow ly,thatrecitationmayrequire three and onlythree

injectionsper7-day period. IfPinchasialone doesnotrenderthatobv ious,

Pinchasiinview ofthe 19 9 6 FDA SB OA confirmsthe limitationisobv ious.

A ssupra 4 6 (§ H.1),astrictthree timesper7-dayregime w ould hav e been

obviousfrom Pinchasialone forthe reasonsstated abov e. W henthe teachingsof

Pinchasiare combined w iththe teachingsofthe 19 9 6 FDA SB OA ,the motiv ation

53

to modifythe dosingregimenofPinchasito offerapatientlessfrequentinjections

and the POSA sexpectationofsuccessindoingso are unassailable.

T he 19 9 6 FDA SB OA teaches thatthe half-life for C opaxone® is

approximately8 0hoursinthe primate C ynomolgusmonkey. Ex.1003 at¶¶ 13 4 -

13 5 (citingEx.1007A at66). Pharmacokineticdata,includinghalf-life data,from

aC ynomolgusmonkeyw asareliable modelforpredictinghumanpharmacokinetic

parametersand creatingdosingschedulesforhumanadministrationofC opaxone

asofthe prioritydate. See Ex.1007A at66; Ex.1003 at¶ 120. W henFDA

review ed this data, submitted by Y eda’s partner, T eva, the review ing

pharmacologistcommented:

Inlightofthe factthatC opolymer-1ismostlikelyactingasapeptide

v accine,itisunclearto me w hyitisnecessaryto injectthe drugona

daily basis. T hisdosing regimen seemslike itw ould subjectthe

patientto anexcessiv e amountofdiscomfortifitisnotnecessaryto

maintain efficacy. Furthermore, ifthere should be a problem in

humansw ithsaturationofthe clearance mechanism,thusincreasing

the amountofintactdruginthe systemiccirculationov ertime,this

problem mightbe lessened w ith intermittentrather than daily

administration. Iw ould recommend thatthe Sponsorev aluate the

necessity ofdaily s.c. injections as opposed to more infrequent

intermittentadministrationofthe drug.

Ex.1007A at121. A POSA w ould hav e agreed w iththe review er’sanalysisbased

onthe datapresented byT ev a. T he 19 9 6 FDA SB OA notesthatmore frequent

54

injectionssubjectthe patientto discomfort,indicatingthatreducingthe frequency

ofinjectionsisgenerallydesirable “ifitisnotnecessaryto maintainefficacy.” See

Ex.1007A at121; Ex.1003 at¶ 13 7; Ex.1004 at¶¶ 102-103. A POSA w ould

hav e understood thatthe reported half-life ofC opaxone® indicated thatinjection

frequenciescould be reduced asfarasapproximatelyonce ev ery8 0hoursw hile

maintainingthe same safetyand tolerabilityprofiles. Ex.1003 at¶¶ 13 2-13 3 . T he

20mgdailydosage amountofaSC administered C opaxone® w ithapredicted

av erage half-life of80hoursw asestablished assafe and effectiv e forhumansin

19 9 6 w henthe FDA approv ed the drug. Id. at¶¶ 120,13 2. A POSA asofthe

prioritydate w ould therefore hav e understood thatdaily,alternate-day,oratleast

three dosesina7-dayperiod interv alw ere interchangeable. Id. T hus,w ellbefore

the prioritydate,aPOSA w ould hav e expected both4 0mgGA three timesov era

7-dayperiod and 20mgdailyto provide the same therapeuticprofile to apatient.

Id.at¶ 13 4 .

B ased onthese teachings,aPOSA w ould hav e recognized that(1) reducing

the frequencyofinjectionsisgenerallydesirable,(2) 4 0mgdosingthree timesper

7-dayperiod w ould provide the same therapeuticprofile w iththe potentialfora

substantiallyimprov ed safetyand tolerabilityprofile compared to the 20mgdosing

daily,and (3 ) maintainingthe efficacyestablished fordailyGA injections(i.e.

maintainingasteadystate concentration) w ould require adosinginterv alno greater

55

thanapproximately80hours. Ex.1003 at¶¶ 119 -13 9 . T herefore,asexplained

furtherbelow ,itw ould hav e been obviousto one ofordinary skill to select

Pinchasi’s alternate day injection schedule and slightly adjustthe injection

frequency to provide exactly three injections ev ery 7-day period (instead of

alternatingbetw eenthree and fourinjectionsper7-dayperiod).T hisw ould also

provide amore desirable schedule thatisatleastaseffectiv e and safe asdaily

injections.Ex.1003 at¶¶ 119 -13 9 .Inlightofthe abov e and because claims1,15

and 19 are obv iousov erPinchasi,claims1,15 and 19 are obviousov erPinchasi

and the 19 9 6 SB OA .

2. DependentC laims2-14 ,16-18 ,and 20A re O bviousov erPinchasiand the 19 9 6 SBO A .

C laims2-14 depend from claim 1. Ex.1001atcol.16,l.3 5 -col.17,l.24 .

A llofthe additionallimitationspresented throughthese claimsare obv iousov er

Pinchasi. Supra§ H.2. Forthatreasonand the reasonsdescribed abov e rendering

claim 1obv iousinview ofPinchasiand the 19 9 6 SB OA ,claims2-14 are obvious

inv iew ofPinchasiandthe 19 9 6 SB OA .

C laims16-18 depend from claim 15. Ex.1001atcol.17,l.25 -col.18 ,l.

18 . A llofthe additionallimitationsare obviousov erPinchasi. Supra§ H.4 For

thatreasonand the reasonsdescribed abov e renderingclaim 15 obviousinv iew of

Pinchasiand the 19 9 6 SB OA ,claims16-18 are obv iousinview ofPinchasiand the

19 9 6 SB OA .

56

C laim 20 dependsfrom claim 19 . Ex.1001atcol.18 ,ll.19 -29 . T he

additionallimitationisobv iousov erPinchasi. Supra § H.2. Forthatreasonand

the reasonsdescribed abov e renderingclaim 20obviousinview ofPinchasiand

the 19 9 6 SB OA ,claim 19 isobviousinview ofPinchasiand the 19 9 6 SB OA .

J. Ground 4 :C laims1-20A re U npatentable A sO bv iousov erPinchasiand Flechter2002A .

1. IndependentC laims1,15,and 19 A re Obv iousinV iew ofPinchasiand Flechter2002A .

A ssupra,all limitationsofclaims1,15 and 19 are obviousin v iew of

Pinchasi. One ofthose limitationsincludesadministering “a regimen ofthree

subcutaneousinjectionsofa4 0mgdose ofglatirameracetate ov eraperiod of

sev endaysw ithatleastone daybetw eenev eryinjection.” Ifread narrow lythat

limitationmayrequire onlythree injectionseach7-dayperiod. IfPinchasialone

doesnotrenderthatobvious,Pinchasiinv iew ofFlechter2002A does.

Pinchasidisclosed alternate-day treatmentofRRM S w ith 4 0 mg ofGA .

Flechter2002A disclosed alternate-daytreatmentofRRM S w ith20mgofGA and

also disclosed thatthe alternate-day regimen had similarefficacy asthe daily

regimenand thatdailyadministrationw astherefore notnecessary. Ex.1003 at¶¶

14 2-14 5; Ex.1004 at¶ 65; Ex.1008 atA bstract. A POSA w ould hav e recognized

thatthe dosage amountof120mgina7-dayperiod (i.e.,three 4 0mginjectionsin

a7-dayperiod) fellsquarelyw ithinthe safe and effectiv e rangesestablished by

57

Pinchasiand Flechter2002A . See supra§§ I.A ,V I.G.2.b atT able; Ex.1003 at¶

14 6; Ex.1004 at¶¶ 115-119 . M oreov er,settingacourse oftreatmentforthe same

dayeachw eek,forexample onM onday,W ednesdayand Friday,w ould hav e been

recognized by a POSA as increasing compliance and adherence to a dosing

regimen. Ex.1004 at¶¶ 116,119 . Inlightofthe reasonsabov e and because

claims1,15,and 19 are obv iousov erPinchasi,claims1,15 and 19 are obv ious

ov erPinchasiand Flechter2002A .

2. DependentC laims2-14 ,16-18 ,and 20A re O bviousov erPinchasiand Flechter2002A .

C laims2-14 depend from claim 1. Ex.1001atcol.16,l.3 5 -col.17,l.24 .

A llofthe additionallimitationsare obviousov erPinchasi.Supra§§ H.2-H.3 . For

thatreasonand the reasonsdescribed abov e renderingclaim 1obv iousinview of

Pinchasiand the 19 9 6 SB OA ,claims2-14 are obviousinv iew ofPinchasiand

Flechter2002A .

C laims16-18 depend from claim 15.Ex.1001atcol.17,l.25-col.18 l.18 .

A llofthe additionallimitationsare obviousov erPinchasi. Supra § H.4 . W ith

respectto claim 16,Flechter2002A also providesthattolerabilityisimprov ed in

alternate daydosage,w hichdirectlyteachesthe additionallimitationofclaim 16.

Ex.1003 at¶ 177. Forthose reasonsand the reasonsdescribed abov e rendering

claim 15 obv iousin view ofPinchasiand Flechter2002A ,claims16-18 are

obviousinview ofPinchasiand Flechter2002A .

58

C laim 20 dependsfrom claim 19 . Ex.1001atcol.18 ,ll.19 -29 . T he

additionallimitationisobv iousov erPinchasi. Supra § H.2. Forthatreasonand

the reasonsdescribed abov e renderingclaim 20obviousinview ofPinchasiand

Flechter2002A ,claim 19 isobviousinview ofPinchasiand Flechter2002A .

K. A nySecondaryC onsiderationsFailto O v ercome the Show ingofObviousness.

T o counterthe ov erw helmingevidence thatallclaimsofthe ’250patentare

obvious, the PatentOw ner may try to rely on secondary considerations of

nonobviousness, despite no show ing ofsuch secondary considerations in the

patent. W hile anysuchev idence w ould be “insufficient”to “ov ercome the strong

[case]ofobviousness”here (Pfizer,Inc.v.A potex,Inc.,4 8 0F.3 d 13 4 8 ,1372 (Fed.

C ir.2007)),Petitionernonethelesspreliminarilyaddressessome ofthese alleged

secondary considerations below , and reserv es the rightto respond to any

argumentsbythe PatentOw nerasserted inthisproceeding.

1. T he M ethodsR ecited inthe ’250PatentProduced N oR elevantU nexpected R esults.

T he ’250 patentmakesno claim thatthe methodsrecited in itsclaims

achiev e anyunexpected result.Q uite to the contrary,the bestthe ’250patentcould

claim isthatitsmethods“are atleastaseffectiv e”asthe priorart. Ex.1001atcol.

13 ,l.4 6 –col.15,l.50. A nd ev enthese statementsare unsupported byanydata.

N onetheless,inview ofthe extensiv e disclosuresinthe priorartasdiscussed in

59

thisPetition,the efficacyofthe administrationofGA asrecited inthe ’250patent’s

claimsisnotsurprising,and iscertainlynotunexpected. Ex.1003 at¶¶ 66,74 -75;

Ex.1004 at¶¶ 9 5-9 8 ,115.

Ev en assuming thatthe methods claimed in the ’250 patenthav e

“unexpected properties,”they“do[]notupsetanalreadyestablished motiv ationto

treatpatientsw ithglatirameracetate “based on[its]expected properties.” Bristol-

M yersSquibb Co.v.T evaPharms.U SA ,Inc.,752 F.3 d 9 67,9 76 (Fed.C ir.2014 ).

A sdiscussed supra,aPOSA w ould hav e beenmotivated to treatpatientsw ith4 0

mginjectionsofGA three timesperw eek w ithareasonable expectationthatit

w ould alleviate symptomsofRRM S and w ould be w elltolerated w ithfew erside

effects.T hus,any “ev idence of[the claimed method’s]superiorefficacy does

nothingto undercutthe show ingthatthere w asareasonable expectationofsuccess

...,ev enifthe lev elofsuccessmayhav e turned outto be somew hatgreaterthan

w ould hav e beenexpected.”Hoffmann-LaRoche,74 8 F.3 d at13 3 4 .

2. T he ’250PatentSatisfied N o Long-FeltB utU nmetN eed.

T he PatentOw nermayalso claim thatthere w asalong-feltbutunmetneed

for a method of treating patients suffering from RRM S w ith less frequent

injectionsand thatthe ’250patentmetthatneed. Y et,ifthere w asanylong-felt

need w asitw asmetlongago byPinchasi,amongotherreferences. T herefore,

“othershad previously solv ed”any “long-feltneed”alleged to be metby the

60

claimsofthe ’250patent. See Inre PepperBallT echs.,Inc.,4 69 F.A pp’x878 ,

8 8 2-8 3 (Fed.C ir.2012). M oreov er,asofthe prioritydate,there w ere anumberof

effectiv e M S treatmentsonthe marketand approv ed bythe FDA thatresulted in

lessfrequentinjections. Ex.1003 at¶ 112; Ex.1004 at¶ 50. Finally,the factthat

no one else had made and commercialized amethod oftreatmentasinthe ’250

patentasofthe prioritydate isirrelev ant. B ecause the ’250patentrecitesmethods

ofusingGA ,acompound thatw ascov ered byotherU .S.patentsatthe priority

date,“no entityotherthan”the PatentOw ner“could hav e successfullybrought[the

claimed methods]to market.” GaldermaLabs.v.T olmar,Inc.,73 7 F.3 d 73 1,74 0

(Fed.C ir.2013 ).

3 . C opyingB yGenericDrugM akersIsIrrelev ant.

Finally,to the extentthe PatentOw nerarguesthatPetitionerand other

generic drug companies seek to copy the inv ention of the ’250 patentby

commercializinggenericv ersionsofglatirameracetate,thistoo failsto support

non-obviousness. A s“copying”“isrequired forFDA approv al”ofgenericdrugs,

any “ev idence ofcopying in the [generic drug]contextis notprobativ e of

nonobviousness.” BayerHealthcare Pharms.,Inc.v.WatsonPharms.,Inc.,713

F.3 d 1369 ,13 77 (Fed.C ir.2013 ).