Endo Pharmaceuticals Inc. v. Mylan Pharmaceuticals Inc., Civ. No. 11-717 (RMB/KW) (D. Del. Jan. 28,...

8/13/2019 Endo Pharmaceuticals Inc. v. Mylan Pharmaceuticals Inc., Civ. No. 11-717 (RMB/KW) (D. Del. Jan. 28, 2014).

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IN THE UNITED STATES DISTRICT COURT

FOR THE DISTRICT OF DELAWARE

ENDO PHARMACEUTI CALS I NC. ,

Pl ai nt i f f , Ci vi l No. 11- CV- 00717 ( RMB/ KW)

v. OPI NI ON

MYLAN PHARMACEUTI CALS I NC. , eta l . ,

Def endant s.

Appearances

J ack B. Bl umenf el dJ er emy A. Ti ganJ ul i a HeaneyMor r i s, Ni chol s, Ar sht & Tunnel l LLP1201 Nor t h Market St r eetP. O. Box 1347Wi l mi ngt on, DE 19899

At t or neys f or Pl ai nt i f f

J ef f r ey I . D. Lewi sRi char d Mai dmanSean Marshal lEdwar d R. Tempest aPat t er son Bel knap Webb & Tyl er LLP1133 Avenue of t he Amer i casNew Yor k, NY 10036

Of Counsel f or Pl ai nt i f f

Ri char d L. Hor wi t z

Bi ndu Ann George Pal apuraDavi d El l i s Moor ePot t er Anderson & Corr oon, LLP1313 N. Market St .Her cul es Pl aza, 6t h Fl oorWi l mi ngt on, DE 19899

At t or neys f or Def endant s

1

Case 1:11-cv-00717-RMB-KW Document 226 Filed 01/28/14 Page 1 of 108 PageID #: 7459


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Dougl as Carst enKat her i ne Van GunstEl ham F. St ei nerMat t hew J . Br esnahanWi l son Sonsi ni Goodr i ch & Rosat i PC

12235 El Cami no Real , Sui t e 200San Di ego, CA 92130

T. O. KongWi l son Sonsi ni Goodr i ch & Rosat i PCOne Market St r eetSpear Tower , Sui t e 3300San Fr anci sco, CA 94105

Of Counsel f or Def endant s

BUMB, Uni t ed St at es Di st r i ct J udge:

INTRODUCTION

Thi s i s an act i on f or pat ent i nf r i ngement brought by

Pl ai nt i f f Endo Phar maceut i cal s I nc. ( Endo or Pl ai nt i f f )

agai nst Def endant s Myl an Phar maceut i cal s I nc. and Myl an, I nc.

( col l ect i vel y, Myl an or Def endant s) pur suant t o 35 U. S. C.

271( e) ( 2) ( A) , and 271( a) , ( b) , and ( c) . Speci f i cal l y, Endo

al l eges t hat Myl an has i nf r i nged and/ or wi l l i nf r i nge U. S.

Pat ent Nos. 5, 464, 864 ( f i l ed Nov. 7, 1995) ( t he 864 Pat ent ) ,

5, 637, 611 ( f i l ed J une 10, 1997) ( t he 611 Pat ent ) , and

5, 827, 871 ( f i l ed Oct . 27, 1998) ( t he 871 Pat ent )

( col l ect i vel y, t he Ki ng Pat ent s) i n connect i on wi t h Myl an s

submi ss i on of Abbr evi at ed New Dr ug Appl i cat i on ( ANDA) number202931 seeki ng t he appr oval of t he U. S. Food & Dr ug

Admi ni st r at i on ( FDA) t o mar ket i t s gener i c ANDA Product pr i or

t o t he expi r at i on of t he Ki ng Pat ent s.

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On J ul y 18, 2013, t he Honor abl e J oseph E. I r enas hel d a

hear i ng pur suant t o Markman v. West vi ew I nst r ument s, I nc. , 517

U. S. 370 ( 1996) , and subsequent l y i ssued a cl ai m const r uct i on

opi ni on addr essi ng t hr ee di sput ed cl ai m t er ms of t he Ki ng

Pat ent s ( t he Cl ai m Const r uct i on Opi ni on) . ( Dkt . Ent . 167. )

Al t hough Myl an di sput es t he cl ai m const r uct i on adopt ed by t he

Cour t , i t conceded pr i or t o t r i al t hat , under t he Cour t s cl ai m

const r uct i on, Myl an i nf r i nges or wi l l i nf r i nge t he asser t ed

cl ai ms of t he Ki ng Pat ent s. ( Not i ce of Concessi on of

I nf r i ngement , Dkt . Ent . 182. ) However , Myl an mai nt ai ned t hat t he

Ki ng Pat ent s ar e i nval i d under t he doct r i nes of ant i ci pat i on,

obvi ousness, wr i t t en descr i pt i on, and enabl ement . The Cour t hel d

a bench t r i al f r om November 12 t hr ough November 21, 2013, af t er

whi ch i t per mi t t ed t he par t i es t o submi t pr oposed f i ndi ngs of

f act and concl usi ons of l aw. 1

Af t er consi der at i on of t he evi dence and t he par t i es post -

t r i al submi ssi ons, and f or t he r easons set f or t h bel ow, t he

Cour t f i nds t hat ( 1) Endo has wai ved and i s now j udi ci al l y

est opped her e f r om pur sui ng cl ai ms agai nst Myl an r el at ed t o t he

1 Myl an subsequent l y f i l ed a l et t er r equest i ng t hat t heCour t st r i ke cer t ai n por t i ons of Endo s openi ng br i ef andpr oposed f i ndi ngs of f act , whi ch i ncl uded i nt er al i a cer t ai ni r r el evant or conf i dent i al i nf or mat i on. ( See Dkt . Ent . 201. )Myl an s r equest i s moot i n l i ght of t he deci si on set f or t hher ei n and f or t he f ur t her r eason t hat Endo s mat er i al s wer ef i l ed under seal .

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871 and 611 Pat ent s i n t hi s l i t i gat i on, and ( 2) t he asser t ed

cl ai ms of t he 864 Pat ent ar e val i d. Accor di ngl y, t he Cour t

ent ers j udgment agai nst Myl an and i n f avor of Endo. Thi s Opi ni on

const i t ut es t he Cour t s f i ndi ngs of f act and concl usi ons of l aw

pur suant t o Feder al Rul e of Ci vi l Pr ocedur e 52( a) . 2

I. BACKGROUNDA.The Drug Approval Process

Under t he Federal Food, Dr ug, and Cosmet i c Act , 21 U. S. C.

301 et seq. , t he FDA must appr ove al l new dr ugs bef ore they

may be di st r i but ed i n i nt er st at e commer ce. 21 U. S. C. 355( a) .

To secur e appr oval f or a new dr ug, an appl i cant may f i l e a New

Dr ug Appl i cat i on ( NDA) t hat i ncl udes, i nt er al i a, t he number

and expi r at i on dat e of any pat ent s whi ch cl ai m t he dr ug or a

met hod of usi ng t he dr ug i f a cl ai m of pat ent i nf r i ngement coul d

r easonabl y be assert ed. I d. 355( b) ( 2) . The FDA publ i shes t he

names of appr oved dr ugs and t hei r associ at ed patent i nf ormat i on

i n t he Appr oved Dr ug Product s wi t h Therapeut i c Equi val ence

Eval uat i ons l i st , commonl y ref er r ed t o as t he Or ange Book.

Ast r aZeneca LP v. Apot ex, I nc. , 633 F. 3d 1042, 1045 ( Fed. Ci r .

2010) . An appl i cant seeki ng appr oval t o market a gener i c ver si on

2 Endo s oral mot i on made dur i ng t r i al , f or j udgment onpar t i al f i ndi ngs pur suant t o Rul e 52( c) , i s DI SMI SSED as moot .Rul e 52( c) per mi t s such mot i ons af t er a par t y has been f ul l yhear d on an i ssue dur i ng a nonj ur y t r i al . As per mi t t ed undert he r ul e, t he Cour t exer ci sed i t s di scret i on t o r eser ve on t hemot i on when i t was made dur i ng t r i al . ( Tr . 1176: 11- 12. )

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of a dr ug t hat has al r eady been appr oved may f i l e an ANDA, whi ch

al l ows an appl i cant t o r el y on t he saf et y and ef f i cacy

i nf or mat i on f or t he l i st ed dr ug i f t he appl i cant can show t hat

t he gener i c dr ug i s bi oequi val ent t o t he l i st ed dr ug. I d.

( ci t i ng 21 U. S. C. 355( b) ( 2) , ( j ) ) .

[ F] or each pat ent l i st ed i n t he Or ange Book that cl ai ms

ei t her t he l i st ed dr ug or a use of t he l i st ed dr ug f or whi ch t he

appl i cant i s r equest i ng appr oval , an ANDA must i ncl ude ei t her

one of f our cer t i f i cat i ons or a sect i on vi i i stat ement .

Ast r aZeneca LP, 633 F. 3d at 1046. I f an appl i cant submi t s a

cer t i f i cat i on, t he appl i cant must cer t i f y ( I ) t hat . . . pat ent

i nf or mat i on has not been f i l ed, ( I I ) t hat such pat ent has

expi r ed, ( I I I ) . . . t he dat e on whi ch such pat ent wi l l expi r e,

or ( I V) t hat such pat ent i s i nval i d or wi l l not be i nf r i nged by

t he manuf act ur e, use, or sal e of t he new dr ug. 21 U. S. C.

355( j ) ( 2) ( A) ( vi i ) ( I ) - ( I V) . The l ast of t hese i s known as a

par agr aph I V cer t i f i cat i on. I f an ANDA appl i cant submi t s a

par agr aph I V cer t i f i cat i on and a pat ent i nf r i ngement sui t i s

commenced wi t hi n 45 days, t hen t he FDA may not approve t he ANDA

appl i cat i on unt i l expi r at i on of a 30- mont h st at ut or y per i od. I d.

355( c)( 3) ( C) .

B.FrovaOn November 8, 2001, t he FDA appr oved NDA No. 21- 006 f or

Fr ova ( f r ovat r i pt an succi nat e) or al t abl et s. ( St i pul at ed Facts

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( SF) , Dkt . Ent . 172 8. ) Frova i s i ndi cat ed f or t he acut e

t r eat ment of mi gr ai ne at t acks wi t h or wi t hout aur a i n adul t s.

( I d. 10; see al so J ohn Campbel l ( Campbel l ) Tr . 29: 8- 20,

29: 25- 30: 10. ) 3 Physi ci ans al so pr escri be Fr ova of f - l abel f or

t he t r eat ment of menst r ual mi gr ai ne. 4 ( Dr . Br i an Gr osber g

( Gr osberg) Tr . 1374: 12- 1376: 2; see al so Campbel l Tr . 46: 22-

47: 6. ) The Or ange Book associ at es t he Ki ng Pat ent s wi t h

f r ovat r i pt an succi nat e. 5 ( Answer , Dkt . Ent . 9 36. )

Endo commerci al l y mar ket s Fr ova, whi ch cont ai ns a compound

chemi cal l y desi gnated as ( R) - ( +) - 3- methyl ami no- 6- carboxami do-

1, 2, 3, 4- t et r ahydr ocar bazol e monosucci nate monohydr ate, known as

f r ovat r i pt an monosucci nat e monohydr ate, as the act i ve

phar maceut i cal i ngr edi ent ( API ) . ( SF 5; Dr . Vi ncent Rocco

( Rocco) Tr . 126: 8- 10; see al so Dr . Gr aham J ohnson ( J ohnson)

Tr . 1024: 4- 6. ) The l abel f or Fr ova r ef er s t o t he API as

3 Tr . r ef er s t o t he t r i al t r anscr i pt s, and i s pr eceded byt he name of t he t est i f yi ng wi t ness.

4 An of f - l abel use means a use beyond t hose speci f i cal l yappr oved of by the FDA. ( Gr osberg Tr . 1375: 19- 1376: 2; Campbel lTr . 46: 22- 47: 6. )

5 The Or ange Book al so l i st s U. S. Pat ent Nos. 5, 616, 603 ( t he 603 Pat ent ) ( DTX- 1399) and 5, 962, 501 ( t he 501 Pat ent )( col l ect i vel y, t he Bor r et t Pat ent s) . ( Pl ai nt i f f s Answer t ot he Count er cl ai ms of Def endant s ( Answer t o Count er cl ai ms) ,Dkt . Ent . 17 9. ) However , t he par t i es ent er ed i nt o a covenant -not - t o- sue wi t h r espect t o t hese pat ent s. ( St i pul at i on ofDi smi ssal , Dkt . Ent . 18 ( st i pul at i ng t o di smi ssal ofcount er cl ai m r el at ed t o t hese pat ent s) . )

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f r ovat r i pt an succi nat e. ( Rocco Tr . 125: 8- 10; Campbel l Tr . 28: 10-

12; PX- 0008; PX- 0009; PX- 0059. )

The empi r i cal f or mul a f or f r ovat r i pt an monosucci nat e

monohydrat e i s C14H17N3O C4H6O4 H2O, and i t has a mol ecul ar wei ght

of 379. 4. ( SF 6; PX- 0008; PX- 0059. ) Frova t abl et s cont ai n 3. 91

mg f r ovat r i pt an monosucci nat e monohydr at e, equi val ent t o 2. 5 mg

of f r ovat r i pt an f r ee base. ( SF 9; PX- 0008; PX- 0009. ) Thi s

di f f er ence i n wei ght i s account ed f or by t he wei ght of t he

succi nat e and water mol ecul es added t o t he f r ee base. ( Rocco Tr .

128: 3- 15. )

Chemi cal compounds may exi st i n a var i et y of f orms,

i ncl udi ng f r ee base f or ms, sal t s, sol vat es, hydr at es, sal t -

hydr at es, and sal t - sol vat es. Frovat r i pt an monosucci nat e

monohydr at e i s a hydr at ed sal t f or m of f r ovat r i pt an. ( Rocco Tr .

99: 15- 101: 22. ) A sal t i s f ormed t hr ough a r eact i on between an

aci d and a f r ee base ( Rocco Tr . 99: 15- 17; Dr . Al ber t Lee ( Lee)

Tr . 389: 4- 23) ; here, succi ni c aci d r eact s wi t h t he f r ovat r i pt an

f r ee base t o f or m t he sal t ( Rocco Tr . 99: 18- 100: 8) . A sal t may

be hydrous or anhydrous, dependi ng on whet her t he mol ecul e has

wat er associ at ed wi t h i t . ( Rocco Tr . 101: 3- 12. ) Frovat r i pt an

monosucci nat e monohydr at e i s a hydr at e, whi ch means t hat i t i s a

cr yst al l i ne f or m of a compound i n whi ch wat er i s par t of t he

cryst al l at t i ce. ( Lee Tr . 390: 4- 6; Rocco Tr . 100: 24- 101: 6. ) Li ke

a hydr at e, a sol vat e i s a cryst al l i ne f or m of a compound wi t h

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sol vent mol ecul es t hat f or m par t of t he cryst al l at t i ce. ( Lee

Tr . 390: 12- 13; see al so Rocco Tr . 102: 13- 15. ) As such, a hydrat e

can be consi der ed a sol vat e i n whi ch wat er i s t he speci f i c

sol vent . ( Lee Tr . 390: 13- 15; see al so Rocco 102: 18- 20. )

Cer t ai n mol ecul es may exi st i n di f f er ent or i ent at i ons i n

t hr ee- di mensi onal space. ( SF 30. ) A mol ecul e s t hr ee-

di mensi onal conf i gur at i on i s r ef er r ed t o as i t s st er eochemi st r y.

( See Rocco Tr . 94: 14- 23. ) Compounds may have t he same mol ecul ar

f or mul a but di f f er ent t hr ee- di mensi onal conf i gur at i ons, or

st er eoi somer s. ( See Rocco Tr . 94: 19- 23. ) Wher e t he st er eoi somer s

ar e rel at ed to each ot her , and f or m non- super i mposabl e mi r r or

i mages of one anot her , t hey ar e known as enant i omers. ( Rocco Tr .

94: 24- 95: 25. )

A mol ecul e s st er eochemi st r y i s i ndi cat ed by cer t ai n nami ng

convent i ons, such as i ncl usi on of an ( R) or ( S) bef or e t he

mol ecul ar f or mul a, and may al so be r ef l ect ed i n a di agr am of t he

chemi cal st r uct ur e. ( SF 32- 33; see al so Rocco Tr . 96: 4- 97: 9. )

I n a di agr am, a l i ne connect i ng t wo at oms r epr esent s a chemi cal

bond l ocat ed on t he pl ane of t he paper . A sol i d t r i angl e

r epr esent s a bond ext endi ng out i n f r ont of t he paper ( i . e. ,

t owar ds t he reader ) , and a hat ched t r i angl e r epr esent s a bond

ext endi ng behi nd t he paper ( i . e. , away f r om t he reader ) . ( SF

33; Rocco Tr . 96: 4- 97: 9. )

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There ar e t wo enant i omer s f or f r ovat r i pt an, based upon

whet her t he NHCH3 component at t he 3- posi t i on i s ext endi ng

t owar ds or away f r om t he reader . ( Rocco Tr . 96: 4- 97: 9. ) The

speci f i c f r ovat r i pt an enant i omer used as t he API i n Frova i s t he

( R) - ( +) enant i omer , whi ch has t he f ol l owi ng chemi cal st r uct ur e:

( PX- 0008 at 1 ( Frova pr oduct l abel ) ; see al so SF 5, 20. )

C.Migraine and Migraine TreatmentFrova i s i ndi cat ed f or t he acut e t r eat ment of mi gr ai ne.

Mi gr ai nes ar e a neur ol ogi c ( i . e. , cent r al ner vous system)

syndr ome character i zed by epi sodes of sever e cephal i c ( head)

pai n, whi ch may be associ at ed wi t h neur ol ogi cal , aut onomi c,

and/ or gast r oi nt est i nal sympt oms and whi ch ar e f r equent l y

accompani ed by nausea, vomi t i ng, and/ or sensi t i vi t y t o l i ght or

sound. ( SF 15- 16; see al so Dr . St ephen Per out ka ( Per out ka)

Tr . 534: 9- 536: 1; Gr osberg Tr . 1336: 14- 22; J ohnson Tr . 659: 7-

661: 21. ) The ar t had a si mi l ar under st andi ng as of t he pr i or i t y

dat e. I f unt r eat ed or unsuccessf ul l y t r eat ed, a mi gr ai ne at t ack

t ypi cal l y l ast s f r om 4 t o 72 hour s, wi t h a medi an dur at i on of 24

hour s. ( Gr osber g Tr . 1336: 15- 22. ) The causes of mi gr ai ne ar e

unknown. ( Gr osber g Tr . 1338: 9- 10. )

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Medi cat i on used to t r eat acut e mi gr ai ne at t acks i ncl ude

bot h speci f i c and nonspeci f i c t r eat ment s. A nonspeci f i c

t r eat ment f or mi gr ai ne i s a t r eat ment t hat addr esses t he

sympt oms of mi gr ai ne, and i ncl udes acet ami nophen or Tyl enol ,

aspi r i n, non- st er oi dal ant i - i nf l ammat or y dr ugs l i ke i bupr of en,

and combi nat i on anal gesi cs. ( Gr osber g Tr . 1339: 15- 19. )

Nonspeci f i c t r eat ment s ar e somet i mes avai l abl e wi t hout

pr escr i pt i on and may be ef f ect i ve i n l ess sever e at t acks, but

t hey ar e suscept i bl e t o over use and have pot ent i al si de ef f ect s.

( Gr osber g Tr . 1339: 25- 1340: 5. ) A speci f i c t r eat ment f or mi gr ai ne

r ef er s t o a t r eat ment t hat addr esses t he mechani sm of mi gr ai ne,

and i ncl udes ergot ami nes and t r i pt ans. ( Gr osber g Tr . 1339: 19-

1340: 14. ) Speci f i c t r eat ment s ar e gener al l y pr escr i pt i on

medi cat i ons t hat ar e mor e ef f i caci ous but have l ower r ecur r ence6

and pot ent i al f or over use. ( I d. )

Er got ami nes, or er got s, wer e an ear l y f or m of speci f i c

t r eat ment f or mi gr ai ne that became avai l abl e i n t he 1920s. ( SF

18; Per out ka Tr . 537: 5- 9. ) Er got s wer e non- sel ect i ve, 7 and had

6 Recur r ence ref er s t o t he reappear ance of t he mi gr ai ne

headache af t er t he i ni t i al t r eat ment was successf ul i nal l evi at i ng t he pai n. ( Gr osber g Tr . 1340: 18- 21. )7 Sel ect i vi t y r ef er s t o t he degr ee t o whi ch a compound

di f f er ent i at es bet ween di f f er ent r ecept or s subt ypes. ( Dr .Davi d Nel son ( Nel son) Tr . 1185: 5- 21; see al so Rocco Tr .1645: 7- 9. ) A sel ect i ve dr ug r eact s pr i mar i l y wi t h desi r edr ecept or s, wher eas a non- sel ect i ve dr ug al so i nt er act s wi t hot her r ecept or s. ( See Rocco Tr . 116: 23- 117: 12; Nel son Tr .

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l ow t ol er abi l i t y and not abl e si de ef f ect s, such as t he

cont r act i on of bl ood vessel s i n t he l eg l eadi ng i n some cases t o

gangr ene. ( Per out ka Tr . 553: 21- 554: 12; J ohnson Tr . 662: 5- 663: 13;

Gr osberg Tr . 1340: 14- 17. ) Compounds i n t he ergot f ami l y i ncl ude

di hydr oer gotami ne ( DHE) , ergotami ne, and methysergi de. ( Rocco

Tr . 1687: 24- 1688: 20 ( r ef er r i ng t o Sl i de 3) . )

The t r i pt an f ami l y of compounds, a cl ass of t r ypt ami ne

der i vat i ve compounds used to t r eat mi gr ai ne, were an i mpr ovement

over er got ami nes. ( SF 19- 20; PX- 0219 at 83. ) Frovat r i pt an i s

a member of t he t r i pt an f ami l y, and i s one of seven t r i pt ans

cur r ent l y on t he mar ket . ( SF 20; Campbel l Tr . 29: 15- 24. )

Sumat r i pt an was a pr i or ar t t r i pt an. ( SF 22. ) The ot her s are

l i st ed bel ow wi t h t he chemi cal st r uct ur e, year of FDA appr oval ,

mar ket i ng company, and t r ade name.

Sumat r i pt an ( 1993) ,Gl axo Smi t hKl i ne,

"I mi t r ex"

Zol mi t r i pt an ( 1997) ,Ast r aZeneca, "Zomi g" Ri zat r i pt an

( 1998) , Mer ck,"Maxal t "

1185: 8- 1186: 5. ) A dr ug s sel ect i vi t y i mpact s t he pot ent i al si deef f ect s of t hat dr ug. ( Rocco Tr . 115: 17- 21, 116: 23- 117: 12. )

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Nar at r i pt an ( 1998) ,Gl axo Smi t hKl i ne,

"Amer ge"

Al mot r i pt an ( 2001) ,J anssen, "Axer t "

El et r i pt an( 2002) , Pf i zer ,

"Rel pax"

( SF 22, 25- 29; Campbel l Tr . 25: 21- 22; PX- 01218 at 62. )

Frovat r i pt an i s t he onl y FDA- appr oved t r i pt an wi t h a f used

t hr ee- r i ng or t r i cycl i c cor e st r uct ur e, known as a 1, 2, 3, 4-

t et r ahydr ocar bazol e. ( Rocco Tr . 123: 15- 17, 1696: 3- 11. ) The ot her

t r i pt ans have onl y a 2- r i ng cor e st r uctur e. ( I d. ) I n addi t i on,

f r ovat r i pt an i s t he onl y FDA- appr oved t r i pt an wi t h an

unsubst i t ut ed car boxami do subst i t uent at i t s 6- posi t i on and a

met hyl ami no i n i t s 3- posi t i on. ( See Rocco Tr . 1697: 8- 1699: 17. )

Serot oni n i s a member of t he t r ypt ami ne cl ass of compounds

t hat , as of t he pr i or i t y dat e, was bel i eved t o af f ect mi gr ai ne

t r eat ment . ( SF 14; Rocco Tr . 110: 10- 25. ) Ser ot oni n i s a

nat ur al l y- occur r i ng mol ecul e t hat can f unct i on as a

neur ot r ansmi t t er ; i t s chemi cal name i s 5- hydr oxyt r ypt ami ne or

5- HT and i t bear s t he f ol l owi ng chemi cal st r uct ur e:

8 Pet er De Vr i es et al . , Revi ew: Phar macol ogi cal aspect s ofexper i ment al headache model s i n rel at i on t o acut e ant i mi gr ai net her apy, 375 Eur . J . Phar m. 61 ( 1999) .

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( I d. ; see al so SF 11- 13; Per out ka Tr . 536: 2- 14. ) By 1991,

t her e was a l ot of gener al i nt er est i n ser ot oni n because of i t s

numer ous bi ol ogi c ef f ect s and r esear ch i nt o serot oni n was

ext r emel y act i ve. ( DTX- 11969 at 1; Per out ka Tr . 517: 14- 25; see

al so J ohnson Tr . 938: 21- 939: 6 ( expl ai ni ng t hat Gl ennon 1987 was

a ver y si gni f i cant paper i n t he f i el d of ser ot oni n r esear ch) . )

Serot oni n i nt er act s wi t h numer ous r ecept or s t hr oughout t he

body, known as 5- HT or ser otoni n recept ors, and causes a

physi ol ogi cal r esponse. ( See Nel son Tr . 1198: 3- 7; Rocco Tr .

110: 23- 111: 9. ) A chemi cal compound t hat bi nds t o a r ecept or can

be r ef er r ed t o as a l i gand. ( Per out ka Tr . 614: 25- 615: 2. ) I f

t he l i gand bi nds t o t he r ecept or and causes a physi ol ogi cal or

bi ol ogi cal r esponse, t hen t he l i gand i s cal l ed an agoni st .

( Rocco Tr . 111: 1- 9. ) I f t he l i gand bi nds t o t he r ecept or but

does not cause a physi ol ogi cal or bi ol ogi cal r esponse, t hen i t

i s cal l ed an ant agoni st . ( Rocco Tr . 111: 10- 22. ) Ser ot oni n

t r eat s mi gr ai ne by i nt er act i ng wi t h cer t ai n 5- HT r ecept or s.

( Rocco Tr . 110: 23- 111: 9. )

9 Ri char d A. Gl ennon, Cent r al Ser ot oni n Recept or s as Tar get sf or Dr ug Resear ch, J . Med. Chem. , Vol . 30, No. 1 ( J an. 1987)( Gl ennon 1987) .

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Ser ot oni n r ecept or s ar e cat egor i zed i nt o gener al f ami l i es,

i ndi cat ed by subscr i pt s af t er 5- HT, such as t he 5- HT1 f ami l y.

( Rocco Tr . 112: 23- 113: 4. ) Some f ami l i es ar e f ur t her subdi vi ded

as i ndi cat ed by subscr i pt l et t er s t hat f ol l ow t he numer i cal

desi gnat i on, such as 5- HT- 1B and 5- HT- 1D. ( Rocco Tr . 112: 23-

113: 4. ) As of 1991, i dent i f i cat i on of ser ot oni n r ecept or

subt ypes was ongoi ng and desi gnat i ons changed as r esear ch

r egar di ng t he subt ype st r uct ur e advanced. ( See Per out ka Tr .

546: 9- 547: 19, 545: 4- 546: 8. ) By t he begi nni ng of t he 1990s, a

per son of or di nar y ski l l i n t he ar t knew t hat mi gr ai ne dr ugs

i nt er act ed wi t h t he 5- HT1 r ecept or f ami l y. ( Per out ka Tr . 546: 9-

17; Rocco Tr . 112: 2- 4. )

D.The King Patents1.'864 Patent

On November 7, 1995, t he Uni t ed Stat es Pat ent and Tr ademarkOf f i ce ( t he PTO) i ssued t he 864 Pat ent , ent i t l ed Use of

Tet r ahydrocar bazol e Der i vat i ves As 5HT1 Recept or Agoni st s. ( PX-

0001. ) The 864 Pat ent i ssued f r om U. S. Pat ent Appl i cat i on No.

08/ 167, 846, f i l ed J une 17, 1992, and l i st s a f or ei gn appl i cat i on

pr i or i t y dat e of J une 26, 1991. ( I d. ) The named i nvent or s are

Franci s D. Ki ng, Lar ami e M. Gast er , Al ber t o J . Kaumann, and

Rodney C. Young. The 864 Patent was grant ed a Pat ent Ter m

Ext ensi on under 35 U. S. C. 156 on Febr uary 10, 2006, whi ch on

i t s f ace ext ends t he pat ent t er m t o November 7, 2015. ( SF 39. )

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At i ssue i n t hi s case ar e cl ai ms 1, 2, 3, and 6 of t he 864

Pat ent .

2.'611 PatentOn J une 10, 1997, t he Uni t ed St at es Patent and Tr ademark

Of f i ce i ssued t he 611 Pat ent , ent i t l ed Medi cament s. ( PX-

0003. ) The 611 Pat ent i ssued f r om U. S. Pat ent Appl i cat i on No.

08/ 442, 719, f i l ed May 15, 1995, and i s a cont i nuat i on of t he

appl i cat i on whi ch l ed t o t he 864 Pat ent . The 611 Pat ent

or i gi nal l y expi r ed on J une 10, 2014. ( SF 46. ) However , on

Oct ober 30, 2013, Endo f i l ed a ter mi nal di scl ai mer wi t h r espect

t o t he 611 Pat ent , whi ch ef f ect i vel y di scl ai med t hat por t i on of

i t s t er m t hat ext ends beyond t he t er m of t he 864 Pat ent . ( See

Dkt . Ent . 178. ) The PTO accept ed t he t er mi nal di scl ai mer on

November 27, 2013. ( Dkt . Ent . 188. )

The asser t ed cl ai ms ar e 1, 2, 3, 8, 9, and 10 of t he 611

pat ent .

3.'871 PatentOn Oct ober 27, 1998, t he Uni t ed St at es Pat ent and Tr ademark

Of f i ce i ssued t he 871 Pat ent , ent i t l ed Medi cament s 1, 2, 3, 4, -

Tet r ahydrocar bazol es and 5- HT1 Agoni st Use Ther eof . ( PX- 0002. )

The 871 pat ent i ssued f r om U. S. Pat ent Appl i cat i on No.

08/ 442, 720, f i l ed May 15, 1995, and i s a cont i nuat i on- i n- par t of

t he appl i cat i on l eadi ng t o t he 864 Pat ent . The 871 Pat ent

or i gi nal l y expi r ed on Oct ober 27, 2015. ( SF 53. ) However , Endo

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f i l ed a t er mi nal di scl ai mer , whi ch di scl ai ms t hat por t i on of i t s

t er m t hat ext ends beyond t he ' 611 and ' 864 Pat ent s. ( See Dkt .

Ent . 178. ) The PTO accept ed t he termi nal di scl ai mer on November

27, 2013. ( Dkt . Ent . 188. )

The asser t ed cl ai ms ar e 1, 2, 3, 4, 5, 6 and 7 of t he 871

pat ent .

E.Ownership of Frova and the King PatentsThe Ki ng Pat ent s i dent i f y Smi t hKl i ne Beecham P. L. C. ( SKB)

as t he assi gnee. ( SF 56. ) SKB l i censed cer t ai n r i ght s t o Frova

t o Ver nal i s Lt d. ( f / k/ a Vanguar d Medi ca, and r ef er r ed t o her ei n

as Ver nal i s) . ( Phi l i p Gr een ( Gr een) Tr . 2011: 23- 2012: 4; see

al so SF 57. ) I n 1999, Vernal i s submi t t ed t o t he FDA NDA 21- 006

f or f r ovat r i pt an t abl et s, whi ch t he FDA appr oved on November 8,

2001. ( SF 58, 60. ) However , i n 1998, whi l e Frova was st i l l i n

devel opment , Vernal i s l i censed Nort h Amer i can sal es and

di st r i but i on r i ght s t o El an Cor por at i on P. L. C. ( El an) . ( SF

59. )

I n 2000, SKB and Gl axo Wel l come P. L. C. merged. ( PX- 0378 at

3. ) However , because t he merged ent i t y woul d have owned t hree of

t he seven t r i pt ans, t he Uni t ed St at es Federal Tr ade Commi ssi on

ent ered i nt o a Consent Agr eement wi t h t he mergi ng ent i t i es

pur suant t o whi ch SKB agr eed t o t r ansf er and sur r ender ,

absol ut el y and i n good f ai t h, al l Fr ovat r i pt an Asset s . . . t o

Ver nal i s . . . . ( I d. at 37. ) As a r esul t , SKB t r ansf er r ed al l

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of t he r i ght s t o t he Frova pr oduct and assi gned t he Ki ng Pat ent s

t o Ver nal i s. ( Gr een Tr . 2012: 4- 12. )

Pur suant t o an agr eement wi t h Ver nal i s, and i n conj unct i on

wi t h UCB Pharma I nc. , El an l aunched t he Fr ova pr oduct i n t he

Uni t ed St at es i n 2002. ( See Campbel l Tr . 30: 11- 14; Gr een Tr .

2004: 6- 15; DTX- 1153 at 9. ) Two year s l at er , Ver nal i s r eacqui r ed

f r om El an t he commer ci al i zat i on r i ght s f or t he Frova pr oduct i n

Nor t h Amer i ca. ( Gr een Tr . 2012: 13- 16. ) Ver nal i s subsequent l y

l i censed t he U. S. r i ght s t o Endo i n 2004 ( DTX- 1003; Gr een Tr .

2012: 17- 18) and ul t i mat el y assi gned the Ki ng Pat ent s t o Endo i n

2011 ( SF 61; DTX- 1059) .

F.This Court's Claim Construction OpinionOn August 7, 2013, t he Honorabl e J oseph E. I r enas i ssued a

Cl ai m Const r uct i on Opi ni on t hat addr essed t hr ee di sput ed cl ai m

t er ms of t he Ki ng Pat ent s. Fi r st , t he Cour t const r ued t he t er m

compound of ( gener al ) f or mul a ( I ) , whi ch appear s i n cl ai m 1 of

each of t he Ki ng Pat ent s. ( See Cl ai m Const r . Op. 8- 10. ) Af t er

not i ng t hat t he par t i es agr eed t hat t he compound i ncl udes al l R

[ enant i omer s] and no S t o al l S and no R, and ever y rat i o i n

bet ween, t he Cour t det er mi ned t hat t hi s t er m r ef er s t o t he

f or mul a wi t hout r egar d t o i t s st er eochemi st r y. ( I d. at 9. )

Second, t he Cour t const r ued t he t er m or a sal t , sol vat e or

hydr at e t her eof , whi ch appear s i n cl ai m 1 of t he 864 Pat ent ,

as meani ng or one or mor e of sal t , sol vat e or hydr at e t her eof .

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( I d. at 11- 14. ) The Cour t saw no basi s f or f i ndi ng t hat sal t

does not al so i ncl ude a sal t t hat i s al so a hydr at e or al so a

sol vent . ( I d. at 12. ) The par t i es agr eed t hat sal t shoul d be

si mi l ar l y const r ued i n cl ai m 6, whi ch r ef er s t o a

physi ol ogi cal l y accept abl e sal t t her eof . ( I d. at 11. ) 10

Thi r d, t he Cour t const r ued t he t er m t r eat ment of a

condi t i on wher ei n a 5- HT1- l i ke agoni st i s i ndi cat ed, whi ch

appear s i n cl ai m 2 of t he 864 Pat ent , 11 cl ai m 1 of t he 871

Pat ent , and cl ai m 10 of t he 611 Pat ent , as meani ng t r eat ment

wi t hout pr ophyl axi s. ( I d. at 20. )

LEGAL ANALYSIS

A pat ent and each of i t s cl ai ms ar e pr esumed t o be val i d,

even wher e t hose cl ai ms may be dependent upon ot her i nval i d

cl ai ms i n t he pat ent . 35 U. S. C. 282( a) . A par t y may rebut t hi s

pr esumpt i on of val i di t y wi t h cl ear and convi nci ng evi dence of

i nval i di t y. Sci el e Phar ma I nc. v. Lupi n Lt d. , 684 F. 3d 1253,

1260 ( Fed. Ci r . 2012) ( ci t i ng 35 U. S. C. 282 and Mi cr osof t

Cor p. v. i 4i Ltd. P shi p, - - U. S. - - , 131 S. Ct . 2238, 2245

( 2011) ) . The cl ear and convi nci ng st andar d of pr oof of f act s

10 The Cour t s Cl ai m Const r uct i on Opi ni on addr essed si mi l art er ms appear i ng i n ot her asser t ed cl ai ms of t he 611 and 871Pat ent s ( i d. ) , whi ch ar e no l onger r el evant i n l i ght of Endo swai ver of i t s r i ght s and t he Cour t s deci si on t o est op Endo f r ompr oceedi ng under t hese Pat ent s i n t hi s l i t i gat i on.

11 Thi s t er m al so af f ect s cl ai m 3 of t he 864 Pat ent , whi chr ef er s t o t he met hod i n cl ai m 2.

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i s an i nt ermedi at e st andard whi ch l i es somewhere bet ween beyond

a r easonabl e doubt and a pr eponder ance of t he evi dence . . .

[ and] has been descr i bed as evi dence whi ch pr oduces i n the mi nd

of t he t r i er of f act an abi di ng convi cti on t hat t he t r ut h of

[ t he] f act ual cont ent i ons ar e hi ghl y pr obabl e. Bui l dex I nc. v.

Kason I ndus. , I nc. , 849 F. 2d 1461, 1463 ( Fed. Ci r . 1988)

( ci t at i ons omi t t ed) .

Wher e an i nval i di t y chal l enge i s based upon pr i or ar t t hat

was consi dered by t he PTO dur i ng t he patent pr osecut i on, and

wher e a pat ent was i ssued not wi t hst andi ng t he pr i or ar t , a

cour t owes some def erence t o t he PTO s deci si on. Mi nnesot a

Mi ni ng & Mf g. Co. v. J ohnson & J ohnson Or t hopaedi cs, I nc. , 976

F. 2d 1559, 1572 ( Fed. Ci r . 1992) ( ci t at i ons omi t t ed) ) . Al t hough

Def endant s bur den does not change, evi dence consi dered by t he

PTO may not be gi ven t he same wei ght as new evi dence. See Sci el e

Pharma I nc. , 684 F. 3d at 1260 ( [ N] ew evi dence not consi dered by

t he PTO may carr y more wei ght . . . t han evi dence pr evi ousl y

consi dered by the PTO, and may go f ur t her t oward sust ai ni ng

t he at t acker ' s unchangi ng bur den. ( ci t i ng Mi crosof t Cor p. , 131

S. Ct . at 2251) ) .

I. Endo Abandoned Its Claims Related to the 871 and 611Patents

Dur i ng t he t r i al , Endo abandoned i t s cl ai ms r el at ed t o t he

871 and 611 Pat ent s. As a resul t , t hi s Cour t r ul ed t hat Endo

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woul d be est opped f r om r esur r ect i ng t hose cl ai ms at a l at er dat e

i n t hi s l i t i gat i on. 12 Endo s abandonment of t hose cl ai ms occur r ed

i n t he mi dst of t r i al af t er some evi dence r el at i ng t o t hose

pat ent s al r eady had been pr esent ed. Endo st at ed t hat wi t h thi s

[ t er mi nal ] di scl ai mer ever yt hi ng r i ses and f al l s on t he 864

pat ent , we can l i t i gat e t he 864 pat ent and t hat wi l l gover n

what occur s i n t he case. 13 ( Tr . 268: 22- 269: 19. ) Hence, i t was

t he Cour t s vi ew t hat any f ur t her ef f or t t o pur sue cl ai ms

agai nst Myl an r el at ed t o t he 871 and 611 pat ent s, i n t hi s

l i t i gat i on, woul d be j udi ci al l y est opped. Endo had asser t ed

cl ai ms agai nst Myl an r el at i ng t o the 871 and 611 Pat ent s i n

t he cur r ent l i t i gat i on but mi dway chose i nst ead t o abandon t hem

i n f avor of t he 864 Pat ent . Per mi t t i ng Endo to reasser t t he

abandoned cl ai ms agai nst Myl an l at er i n t hi s l i t i gat i on ( or even

12 I t i s cl ear Endo woul d al so be est opped i n subsequentl i t i gat i on.

13 On t he eve of t r i al , Endo f i l ed a t er mi nal di scl ai mer ,whi ch di scl ai ms:

( i ) t he t er mi nal par t of t he t er m of t he 871 pat entwhi ch woul d ext end beyond the expi r at i on dates of t hef ul l t er ms of t he 611 pat ent and . . . [ t he 864pat ent ] , and ( i i ) t he t er mi nal par t of t he t er m of t he

611 pat ent whi ch woul d ext end beyond t he expi r at i ondat e of t he f ul l t er m of t he 864 pat ent .

( Dkt . Ent . 178- 1. ) I n addi t i on, t he di scl ai mer pr ovi des t hat t he 871 and 611 Pat ent s shal l be enf or ceabl e onl y f or and dur i ngsuch per i od t hat t hey and t he 864 pat ent are commonl y owned. ( I d. ) The t er mi nal di scl ai mer was l at er appr oved by t he PTO.( See Dkt . Ent . 188. )

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i n t he f ut ur e) woul d be mani f est l y unj ust t o Def endant s and,

t her ef or e, j udi ci al est oppel i s an appr opr i at e r emedy. Cf . Van

Bl unk v. McAl l i st er Towi ng of Phi l a. , I nc. , No. 10- 00686, 2012

WL 832997, at *5 ( D. N. J . Mar . 12, 2012) ( j udi ci al l y est oppi ng

pl ai nt i f f f r om pr esent i ng i nconsi stent posi t i on i n or der t o

pr event mani f est i nj ust i ce and pr ej udi ce t o def endant ) ; Hai nes

& Ki bbl ehouse, I nc. v. Bal f our Beat t y Const r . , I nc. , 789 F.

Supp. 2d 622, 636 ( E. D. Pa. 2011) ( same) .

Endo now ar gues t hat t he Cour t er r ed because Endo was

per mi t t ed t o f i l e t he t er mi nal di scl ai mer at any poi nt i n t hi s

l i t i gat i on and t hat f i l i ng coul d not be deemed an admi ssi on of

t he mer i t s of t he doubl e- pat ent i ng al l egat i on. Al t hough Endo i s

cor r ect as t o t he l egal ef f ect of t he t er mi nal di scl ai mer , i t s

ar gument s mi ss t he poi nt : t he Cour t based i t s deci si on not on

t he t er mi nal di scl ai mer , but on t he unequi vocal st at ement s of

counsel si gni f yi ng Endo s i nt ent t o abandon i t s cl ai ms her e.

See, e. g. , Boehr i nger I ngel hei m I nt l GmbH v. Bar r Labs. , I nc. ,

592 F. 3d 1340, 1347 ( Fed. Ci r . 2010) ( t ermi nal di scl ai mer may be

f i l ed l awf ul l y at any t i me af t er i ssuance of t he chal l enged

pat ent or dur i ng l i t i gat i on, [ or ] even af t er a f i ndi ng t hat t he

chal l enged pat ent i s i nval i d f or obvi ousness- t ype doubl e

pat ent i ng) ( ci t at i ons omi t t ed) ; Quad Envt l . Techs. Cor p. v.

Uni on Sani t ar y Di st . , 946 F. 2d 870, 874 ( Fed. Ci r . 1991) ( I t i s

i mpr oper t o conver t t hi s si mpl e expedi ent of obvi at i on [ of a

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r ej ect i on of doubl e- pat ent i ng] i nt o an admi ssi on or acqui escence

or est oppel on t he mer i t s. ) ; ( see al so Pl . s Openi ng Post - Tr i al

Br . ( Pl . s Br . ) , Dkt . Ent . 191, at 36- 37) . When Endo advi sed

t he Cour t t hat i t had f i l ed a t er mi nal di scl ai mer wi t h r espect

t o t he 871 and 611 Pat ent s, i t st at ed t hat [ i ] n pr epar i ng f or

t r i al i t has become cl ear t hat i ssues concer ni ng Myl an s

i nf r i ngement of t he 871 and 611 Pat ent s are consi st ent wi t h

t hose f or i nf r i ngement of t he 864 Pat ent , and Endo wi shed t o

si mpl i f [ y] t he i ssues f or t he upcomi ng t r i al by moot i ng

Myl an s doubl e- pat ent i ng def ense. 14 ( Let t er , Dkt . Ent . 178 at 2. )

The Cour t underst ood f r om t hi s l et t er , t oget her wi t h t he

vol unt ar y f i l i ng of t he t er mi nal di scl ai mer , t hat , cont r ar y to

t he Fi nal Pr et r i al Or der , Endo no l onger wi shed t o pr oceed wi t h

i t s cl ai ms agai nst Myl an as t o t hese two pat ent s. Endo t r eated

t he t er mi nal di scl ai mer , i n essence, as a wi t hdr awal of Endo s

cl ai ms. ( See, e. g. , Tr . 254: 24- 255: 18 ( THE COURT: . . . ei t her

way you l ook at i t Myl an i s not t hr eat ened by t hose patent s as a

r esul t of t he f i l i ng of t he di scl ai mer . . . you no l onger have

any t hr eat of pr osecut i on. ) ; Tr . 268: 3- 7 ( MS. STAFFORD: . . .

I t hi nk Endo i s cl ai mi ng i f you al l ow t hei r t er mi nal cl ai ms t o

14 Obvi ousness- t ype doubl e pat ent i ng i s a j udi ci al l y creat eddoct r i ne i nt ended t o pr event t he extensi on of t he t er m of apat ent . . . by pr ohi bi t i ng t he i ssuance of t he cl ai ms i n asecond pat ent not pat ent l y di st i nct f r om t he cl ai ms of t he f i r stpat ent . I n r e Longi , 759 F. 2d 887, 892 ( Fed. Ci r . 1985) .

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moot our def ense t hat t hei r cl ai ms f or t hose pat ent s st i l l

cont i nue. THE COURT: But not as t o Myl an. ) . ) 15

Endo s counsel t hen r epeat edl y conf i r med i t s i nt ent i on t o

abandon t he cl ai ms r el ated t o t he 871 and 611 Pat ent s as set

f or t h i n t he Pr et r i al Or der :

THE COURT: . . . Do I have i t al l wr ong, Mr . Lewi s?Maybe I do. . . .MR. LEWI S: Unf or t unat el y, a l ot of i t wr ong, but noton that point.THE COURT: I t hought you wer e gi vi ng up your f i ghtagai nst Myl an on t he ot her t wo pat ent s by f i l i ng t hedi scl ai mer .MR. LEWI S: What Ive said, your Honor, is that withthis disclaimer everything rises and falls on the 864

patent, we can litigate the 864 patent and that will

govern what occurs in the case.THE COURT: Okay. But j ust answer my quest i on wi t h ayes or no, i f you can. Do you agr ee t hat by f i l i ng t hedi scl ai mer . . . t hat you no l onger woul d have anycl ai ms agai nst Myl an on t he remai ni ng t wo patent s?MR. LEWI S: I t i s ef f ect i ve and t he cl ai m st ops at t hedat e t hat t hose pat ent s are t er mi nal l y di scl ai med ont hose pat ent s, but t he 864 r uns l onger . And we

believe the 864 patent covers all of the issues inthe case and everything else [rises and falls] on that

in terms of the infringement.

15 See al so Tr . 275: 18- 276: 2 ( THE COURT: . . . So Iunder st and Endo s posi t i on i s t hat [ t he di scl ai mer i s] ef f ect i ve

because t hat s where Endo i s, t hey no l onger wi sh to pur sue t he 611 and 871, I get t hat , t he i ssue f or t he Cour t i s i s i t af i nal or der , so t o speak. And, as of now, i t i sn t . But i tr eal l y i s a moot poi nt at t hi s j unct ur e because I t hi nkr egar dl ess t he i ssue of goi ng f or war d i s t hi s case wi l l gof or war d on t he 864 . . . and Endo i s est opped f r om f ur t herpur sui ng any cause of act i on agai nst Myl an f or t hose t wo patent son t hi s ANDA. ) .

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( Tr . 268: 22- 269: 19 ( emphasi s added) ; see al so Tr . 271: 23-

272: 1. ) 16 I ndeed, counsel af f i r med t hat t her e i s no r i sk t o

Myl an separate t hat goes beyond t he 864 patent ( Tr . 272: 10-

11) , and of f er ed t o st i pul at e t hat t he case [ r i ses] and f al l s

wi t h t he 864 pat ent ( Tr . 277: 19- 21; Tr . 278: 3- 6) . These

st at ement s pr ovi ded t o t he Cour t a cl ear i ndi cat i on of Endo s

i nt ent t o abandon or wi t hdr aw i t s cl ai ms r egar di ng t he 871 and

611 Pat ent s, and t o pr oceed onl y wi t h t he 864 Pat ent

i nf r i ngement act i on her e.

Despi t e t hese concessi ons, Myl an r emai ned concerned t hat

Endo woul d at some l at er poi nt at t empt t o revi ve t he cl ai ms i t

had j ust wai ved. Thus, t he Cour t st at ed:

But what I asked Mr . Lewi s i s why shoul dn t [ you be]j udi ci al l y est opped f r om prosecut i ng under t he 611and 871 i f I deem t he t er mi nal di scl ai mer t o have t heef f ect you say I shoul d deem i t t o have. And Mr .

Lewi s r esponse i s t hat we shoul d be j udi ci al l yest opped and I t hi nk t hat s t he r i ght answer .

( Tr . 274: 10- 15. ) Endo, however , cl ar i f i ed onl y t hat i t bel i eved

t he t er mi nal di scl ai mer t o be ef f ect i ve. ( Tr . 275: 4- 6. ) But ,

havi ng deci ded t o l i t i gat e the 864 pat ent onl y at such l at e

j unct ur e, i . e. , t he second day of t r i al , Endo woul d not l at er be

16 Counsel s st at ement s i mpl y that t he asser t ed cl ai ms oft he 871 and 611 Pat ent s may not be pat ent abl y di st i nct f r omt he asser t ed cl ai ms of t he 864 Pat ent and, t her ef or e, seemi ngl ybol st er Def endant s doubl e- patent i ng argument . However , nopr oof s wer e submi t t ed on t hi s i ssue, and t he Cour t does notdeci de i t her e.

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per mi t t ed t o resur r ect cl ai ms agai nst Myl an on t he ot her t wo

pat ent s. 17 ( See Tr . 269: 4- 7. )

Endo al so now ar gues t hat t he r equi r ement s f or j udi ci al

est oppel ar e not met as t her e i s no evi dence of bad f ai t h.

Though t her e i s no r i gi d t est f or j udi ci al est oppel , t hr ee

f actor s i nf or m a f eder al cour t s deci si on whet her t o appl y i t :

t her e must be ( 1) i r r econci l abl y i nconsi st ent posi t i ons; ( 2)

adopt ed . . . i n bad f ai t h; and ( 3) a showi ng t hat . . .

est oppel . . . addr ess[ es] t he har m and . . . no l esser sanct i on

[ i s] suf f i ci ent . Si nger Mgmt . Consul t ant s, I nc. v. Mi l gr am,

650 F. 3d 223, 239 ( 3d Ci r . 2011) ( quot i ng GI Hol di ngs, I nc. v.

17 Cf . J ohnson v. Zer bst , 304 U. S. 458, 464 ( 1938) ( Awai ver i s or di nar i l y an i nt ent i onal r el i nqui shment orabandonment of a known r i ght or pr i vi l ege. ) , over r ul ed on ot hergr ounds by Edwards v. Ar i zona, 451 U. S. 477 ( 1981) ; BoroConst r . , I nc. v. Lenape Reg l Hi gh Sch. Di st . Bd. Of Educ. , No.05- 4689, 2010 WL 5419035, at *6 ( D. N. J . Dec. 23, 2010) ( not i ngwai ver of cont r actual r i ght s may be suppor t ed by such conductas t o st op t he wai vi ng par t y f r om denyi ng t he i nt ent t o wai ve) ;Si nger Mgmt . Consul t ant s, I nc. v. Mi l gr am, 650 F. 3d 223, 239 ( 3dCi r . 2011) ( I f t he St at e wer e t o asser t agai n t hat t he Tr ut h i nMusi c Act does not r ecogni ze val i d common l aw t r ademarks, i twoul d be asser t i ng an i nconsi st ent posi t i on i n pr esumpt i ve badf ai t h af t er al r eady havi ng conceded t he wr ongf ul ness of such an

asser t i on. J udi ci al est oppel , t her ef or e, woul d appl y to pr eventt he St at e f r om per pet uat i ng a f r aud on t he cour t . ) ; see al soHol st ei n v. Ci t y of Chi . , 803 F. Supp. 205, 211 ( N. D. I l l . 1992)( I f an i ndi vi dual i nt ent i onal l y r el i nqui shes a known r i ght ,ei t her expr essl y or by conduct i nconsi st ent wi t h an i nt ent t oenf or ce t hat r i ght , he has wai ved i t . ( ci t i ng J . H. Cohn & Co. v.Am. Appr ai sal Assocs. , I nc. , 628 F. 2d 994, 1000 ( 7t h Ci r .1980) ) ) .

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Rel i ance I ns. Co. , 586 F. 3d 247, 262 ( 3d Ci r . 2009) ) . 18 Endo i s

cor r ect . I t s change i n posi t i on bef or e t hi s Cour t , i . e. , t hat i t

woul d pur sue t he 864 Pat ent onl y, di d not evi nce bad f ai t h at

t he t i me. But , Endo s cur r ent posi t i on - t hat i t s i nf r i ngement

cl ai ms agai nst Myl an on t he 611 and 871 Pat ent s shoul d have

r emai ned a par t of t hi s case i s di r ect l y cont r adi ct ed by t he

argument s made bef ore t hi s Cour t dur i ng t r i al ( and summar i zed

above) . ( Pl . s Br . at 37. ) Mor eover , i t s cur r ent asser t i on t hat

i t has somehow mai nt ai ned a consi st ent posi t i on al l al ong

t r oubl es t he Cour t . Nonet hel ess, f or t he r easons st at ed, Endo

abandoned i t s cl ai ms, and i s t hus est opped f r om f ur t her pur sui ng

cl ai ms agai nst Myl an r el ated t o t he 871 and 611 Pat ent s i n

t hi s mat t er .

II. Invalidity of the '864 PatentTurni ng t o t he 864 Pat ent , Endo asser t s t hat Myl an s ANDA

pr oduct wi l l i nf r i nge cl ai ms 1, 2, 3, and 6. Cl ai m 1, t he onl y

i ndependent cl ai m, st at es: A compound of f or mul a( I ) whi ch i s 3-

met hyl ami no- 6- car boxami do- 1, 2, 3, 4- t et r ahydr ocar bazol e, or a

sal t , sol vat e or hydr at e t her eof . ( PX- 0001 col . 20 l l . 44- 46. ) 19

18 I n a pat ent acti on, j udi ci al est oppel i s appl i ed i naccor dance wi t h t he l aw of t he regi onal ci r cui t as opposed toFeder al Ci r cui t l aw. Novo Nor di sk A/ S v. Bi o- Tech. Gen. Cor p. ,Lt d. , No. 02- 332, 2003 WL 21383717, at *2 ( D. Del . J une 9, 2003)( ci t at i ons omi t t ed) .

19 Cl ai m 2 cl ai ms A met hod of t r eat ment of a condi t i onwher ei n a 5- HT1- l i ke agoni st i s i ndi cat ed, whi ch compr i sesadmi ni st er i ng t o a subj ect i n need t her eof an ef f ect i ve amount

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Al t hough Myl an di sput es t he Cour t s cl ai m const r uct i on, Myl an

f i l ed a Not i ce of Concessi on of I nf r i ngement pr i or t o t he

commencement of t r i al whereby i t conceded t hat , under t he cl ai m

const r uct i on, t he manuf act ur e, use, sal e, of f er f or sal e, or

i mpor t at i on of Myl an s ANDA Pr oduct i nf r i nges and/ or wi l l

const i t ut e cont r i but or y i nf r i ngement or i nduce i nf r i ngement of

each cl ai m at i ssue. ( Dkt . Ent . 182; see al so Pr et r i al Or der ,

Dkt . Ent . 171, at 19. )

Myl an cont ends, however , t hat t he 864 Pat ent i s i nval i d on

f our separ at e gr ounds: ant i ci pat i on, obvi ousness, l ack of

wr i t t en descri pt i on, and f ai l ur e t o enabl e. Bef or e t ur ni ng t o

t he mer i t s of t hese ar gument s, t he Cour t not es t wo thi ngs.

Fi r st , t he par t i es agr ee t hat t he di f f er ence i n how t hey def i ne

a per son of or di nar y ski l l i n t he ar t ( POSA) wi t h r espect t o

t he pat ent s i s i mmat er i al t o t he i nval i di t y anal ysi s. ( See Tr .

of Oct . 24, 2013 H r g 45: 10- 25 ( acknowl edgi ng t hat expert s woul d

r ender t he same opi ni ons r egar dl ess of whi ch def i ni t i on i s

ut i l i zed) ; see al so J ohnson Tr . 658: 24- 659: 3; Rocco Tr . 1700: 25-

1701: 4. ) Ther ef or e, t he Cour t adopt s Endo s def i ni t i on:

A per son of or di nar y ski l l i n t he ar t of t he Ki ng

Pat ent s as of t he J une 26, 1991 pr i or i t y dat e woul d be

of a compound of cl ai m 1. Cl ai m 3 cl ai ms The method accor di ngt o cl ai m [ 2] wher ei n t he condi t i on i s mi gr ai ne. Cl ai m 6 cl ai msA pharmaceut i cal composi t i on compr i si ng t he compound accor di ngt o cl ai m 1, or a physi ol ogi cal l y accept abl e sal t t her eof and aphysi ol ogi cal l y accept abl e car r i er . ( PX- 0001 col . 20 l l . 47- 52,57- 59. )

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a medi ci nal chemi st wi t h a Ph. D. or i t s equi val ent and2- 5 year s of exper i ence i n t he phar maceut i cali ndust r y, wor ki ng i n conj unct i on wi t h bot h aphar macol ogi st wi t h a Ph. D. or i t s equi val ent wi t hexper i ence i n the phar maceut i cal i ndust r y and a

medi cal pr of essi onal wi t h exper i ence i n t he t r eat mentof condi t i ons f or whi ch a 5- HT1- l i ke agoni st i si ndi cat ed and/ or dr ug devel opment . ( See Tr . 1608: 1- 9( Rocco) . )

Second, t he Cour t not es t hat t he par t i es have st i pul at ed

t hat t he pr i or i t y dat e appl i cabl e t o al l cl ai ms at i ssue i n t hi s

case i s J une 26, 1991. ( SF 34. )

A.AnticipationMyl an argues t hat U. S. Pat ent No. 4, 257, 952 ( Moor adi an

952) , ent i t l ed 3- Ami no- Tet r ahydr ocar bazol es, ant i ci pat es t he

assert ed cl ai ms i n t he 864 Pat ent . The Cour t di sagr ees.

[ T] he di sposi t i ve quest i on r egar di ng ant i ci pat i on i s

whet her one ski l l ed i n t he ar t woul d r easonabl y under st and or

i nf er f r om a pr i or ar t r ef er ence t hat ever y cl ai m el ement i sdi scl osed i n t hat r ef er ence. Ast r aZeneca v. Apot ex, 633 F. 3d

1042, 1055 ( Fed. Ci r . 2010) ( quot i ng I n r e Baxt er Tr avenol

Labs. , 952 F. 2d 388, 390 ( Fed. Ci r . 1991) ) ( i nt er nal quot at i ons

and br acket s omi t t ed) . I n ot her wor ds,

Cl ai med subj ect mat t er i s ant i ci pat ed when i t i s not

new; t hat i s, when i t was previ ousl y known.I nval i dat i on on t hi s gr ound r equi r es t hat ever yel ement and l i mi t at i on of t he cl ai m was pr evi ousl ydescri bed i n a si ngl e pr i or ar t r ef er ence, ei t herexpr essl y or i nher ent l y, so as t o pl ace a [ POSA] i npossessi on of t he i nvent i on. See Scher i ng Cor p. v.Geneva Phar ms. , I nc. , 339 F. 3d 1373, 1379 ( Fed. Ci r .

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2003) ; Cont i nent al Can Co. USA v. Monsant o Co. , 948F. 2d 1264, 1267- 69 ( Fed. Ci r . 1991) .

Sanof i Synt hel abo v. Apot ex, I nc. , 550 F. 3d 1075, 1082 ( Fed.

Ci r . 2008) , cer t . den d, 130 S. Ct . 493 ( 2009) . Ant i ci pat i on i s

a quest i on of f act , and t he par t y i nvoki ng t hi s def ense must

est abl i sh i t at t r i al by cl ear and convi nci ng evi dence.

Ast r aZeneca, 633 F. 3d at 1055 ( ci t i ng Sanof i Synt hel abo, 550

F. 3d at 1082, and Pur due Phar ma L. P. v. Boehr i nger I ngel hei m

GmbH, 237 F. 3d 1359, 1365 ( Fed. Ci r . 2001) ) .

Ant i ci pat i on r equi r es t hat al l l i mi t at i ons of t he cl ai med

i nvent i on ar e descr i bed i n a si ngl e r ef er ence, r at her t han a

si ngl e exampl e i n t he r ef er ence. Net MoneyI N, I nc. v. Ver i Si gn,

I nc. , 545 F. 3d 1359, 1369 n. 5 ( Fed. Ci r . 2008) . The cour t must

l ook at t he r ef erence as a whol e and det ermi ne whether i t

di scl oses al l el ement s of t he cl ai med i nvent i on as ar r anged i n

t he cl ai m. I d. ; see al so Cel l ect i s S. A. v. Pr eci s i on Bi osci s. ,

I nc. , 937 F. Supp. 2d 474, 487 ( D. Del . 2013) ( As not ed above, a

pr i or ar t r ef er ence must di scl ose al l of t he l i mi t at i ons of t he

cl ai m, ar r anged or combi ned i n t he same way as i n t he cl ai m,

t o ant i ci pat e a cl ai m. ( quot i ng Net MoneyI N, I nc. , 545 F. 3d at

1370) ) .Moor adi an 952 i s a pr i or ar t pat ent t hat was consi der ed by

t he PTO i n t he pr osecut i on of t he 864 Pat ent and i s i n f act

l i st ed as a r ef er ence on t he cover page of t he 864 Pat ent . ( PX-

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0001, at [ 56] ; accor d DTX- 1077 at 191. ) I t di scl oses a br oad

cl ass of compounds chemi cal l y desi gnat ed as 3- ( subst i t ut ed-

ami no) - 1, 2, 3, 4- t et r ahydr acar bazol es wi t h anal get i c and

psychot r opi c act i vi t i es as wel l as, i n some cases,

ant i hi st ami ni c act i vi t y. ( DTX- 1019, at [ 57] . ) The 1, 2, 3, 4-

t et r ahydr acar bazol e i s char act er i zed by a t r i cycl i c r i ng cor e

st r uct ur e as pi ct ur ed bel ow. ( See, e. g. , J ohnson Tr . 760: 13- 14. )

( PX- 0001, at [ 57] . )

Cl ai m 1 of Moor adi an 952 cl ai ms a 3- ( N==B) - 9- R- 1, 2, 3, 4-

t et r ahydr acar bazol e havi ng t he f or mul a

wher e N==B i s NHR , NR R or NR - Y_NR NR, wher e R and R ar e

l ower - al kyl or AR- l ower - al kyl , R i s hydr ogen and Y i s l ower -

al kyl ene; R i s hydr ogen, l ower - al kyl , Ar - l ower - al kyl or l ower -

al kenyl , or R i s Y- NR R, where Y, R and R have t he same

meani ng gi ven above. ( DTX- 1019 col . 63 l l . 4- 22. ) Cl ai m 1 per mi t s

Q1, Q2, Q3, and Q4 t o be sel ect ed f r om a var i et y of subst i t uent s

l i st ed i n t he cl ai m. Thus, Moor adi an 952 per mi t s subst i t ut i on

on t he l ef t - hand si de of t he t et r ahydr ocar bazol e r i ng syst em at

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t he 5- , 6- , 7- , or 8- posi t i on. ( J ohnson Tr . 759: 8- 12. ) A

car boxami do i s one of t he subst i t uent s. ( DTX- 1019 col . 64 l l . 1-

6 . )

I t i s undi sput ed t hat cl ai m 1 of Moor adi an ' 952

encompasses f r ovat r i pt an and t he el ement s of f r ovat r i pt an.

( Rocco Tr . 1620: 13- 25, 1795: 24- 1796: 1. ) Speci f i cal l y, Dr .

J ohnson, Myl an' s exper t , t est i f i ed t hat f r ovat r i pt an can be

envi saged wher e N==B i s NHR and R i s met hyl ; R i s hydr ogen; Q1

i s CONR2R3 at t he si x posi t i on of t he r i ng st r uct ur e, and R2 and

R3 are hydr ogen; and Q2, Q3, and Q4 ar e hydr ogen at t he f i ve,

seven, and ei ght posi t i on. ( J ohnson Tr . 762: 6- 763: 5. ) However ,

[ i ] t i s wel l est abl i shed t hat t he di scl osur e of a genus i n t he

pr i or ar t i s not necessar i l y a di scl osur e of ever y speci es t hat

i s a member of t hat genus. At of i na v. Gr eat Lakes Chem. Corp. ,

441 F. 3d 991, 999 ( Fed. Ci r . 2006) . I f a pr i or ar t r ef er ence

mer el y di scl oses a genus and t he cl ai m at i ssue r eci t es a

speci es of t hat genus, t he i ssue of ant i ci pat i on t ur ns on

whether t he genus was of such a def i ned and l i mi t ed cl ass t hat

one of or di nar y ski l l i n t he ar t coul d at once envi sage each

member of t he genus. Cel l ect i s, 937 F. Supp. 2d at 487

( quot i ng Wm. Wr i gl ey J r . Co. v. Cadbur y Adams USA LLC, 683 F. 3d

1356, 1361 ( Fed. Ci r . 2012) ) ; see al so El i Li l l y & Co. v. Zeni t h

Gol dl i ne Phar m. , I nc. , 471 F. 3d 1369, 1376 ( Fed. Ci r . 2006)

( f i ndi ng a POSA must be abl e t o at once envi sage each member

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of a cl ass of compounds) ; I n r e Gl eave, 560 F. 3d 1331, 1338

( Fed. Ci r . 2009) . The i ssue, t hen, i s whet her , t he par t i cul ar

genus di scl osed i n cl ai m 1 of Moor adi an 952 i s so def i ned and

l i mi t ed t hat a POSA can at once envi sage each speci es.

Bot h expert s agr ee t hat Moor adi an 952 di scl oses a br oad

genus of compounds wi t h a var i ety of f unct i onal gr oups t hat can

be at t ached t o the l ef t r i ng, whi ch ul t i mat el y embodi es a ver y

l arge number of compounds. ( J ohnson Tr . 895: 6- 16; Rocco Tr .

1616: 1- 18, 1617: 14- 1618: 14; see al so Dr . Fr anci s D. Ki ng

( Ki ng) Tr . 290: 20- 291: 2 ( [ G] ener i cal l y [ Moor adi an 952] does

di scl ose t he Frovat r i pt an t ype compound, but i t i s onl y one of a

pot ent i al mi l l i on pl us compounds t hat t hat gener al st r uct ur e

di scl oses. ) . Endo s exper t , Dr . Rocco, t est i f i ed t hat t hi s

genus encompasses mi l l i ons, t ens of mi l l i ons of compounds,

whi l e Dr . J ohnson, conceded t hat t hi s broad genus of compounds

consi st ed of what coul d be a l ar ge number of i ndi vi dual

compounds. ( J ohnson Tr . 895: 6- 16. ) Fur t her mor e, i t i s undi sput ed

t hat f r ovat r i pt an i s not among t he appr oxi mat el y 297 compounds

di scl osed i n t he Moor adi an 952 speci f i cat i on ( J ohnson Tr .

895: 22- 25; Rocco Tr . 1620: 3- 10) or one of t he ei ght compounds

speci f i cal l y cl ai med. ( Rocco Tr . 1619: 21- 1620: 2; see al so DTX-

1019 col . 64. )

I n l ooki ng at t he pat ent as a whol e, as t hi s Cour t must ,

see Net MoneyI N, I nc. , 545 F. 3d at 1369 n. 5, t he Cour t does not

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f i nd t hat cl ai m 1 of t he 864 Pat ent i s ant i ci pat ed by Moor adi an

952. Dr . Rocco, whom t hi s Cour t f ound per suasi ve, opi ned t hat ,

al t hough a POSA coul d tease out t he el ement s of f r ovat r i pt an

f r om t he br oad di scl osur e i n Moor adi an 952, she woul d not

i mmedi at el y envi si on t he f r ovat r i pt an mol ecul ar st r uct ur e.

( Rocco Tr . 1616: 20- 23, 1620: 24- 1621: 3. ) Dr . Rocco s opi ni on i s

suppor t ed by the pat ent s l i st of f our pr ef er r ed gr oups of

compounds whi ch pr ovi de l i mi t at i ons on t he subst i t uent s i n

cer t ai n posi t i ons on t he compounds. See Br i gham & Women s Hosp.

I nc. v. Teva Phar ms. USA, I nc. , 761 F. Supp. 2d 210, 227- 28 ( D.

Del . 2011) ( ci t i ng I n r e Pet er i ng, 301 F. 2d 676, 681 ( C. C. P. A.

1962) ) ( l ooki ng t o pr ef er r ed gr oups of compounds set f or t h i n

pr i or ar t pat ent and det ermi ni ng t hat cl ai ms wer e not

ant i ci pat ed) ; ( DTX- 1019 col . 2 l l . 19- 41; Rocco Tr . 1616: 14-

1618: 14) . Al t hough t hese pr ef err ed gr oups nar r ow t he br oader

genus of di scl osed compounds i n Moor adi an 952, t hey st i l l

encompass hundreds or t housands of compounds. ( Rocco Tr .

1616: 14- 1617: 14. ) Even so, Dr s. Rocco and J ohnson agr ee t hat

none of t hese pr ef er r ed gr oups i ncl ude t he f r ovat r i pt an

st r uct ur e. ( Rocco Tr . 1616: 14- 20, 1618: 17- 20; J ohnson Tr . 896: 1-

25. ) I n f act , t he mor e pr ef er r ed gr oup speci f i cal l y excl udes a

car boxami do gr oup si mi l ar t o t he one t hat appear s at t he si x

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posi t i on of f r ovat r i pt an. ( Rocco Tr . 1617: 10- 1618: 15. ) 20 Gi ven

t he compounds and pr ef err ed gr oups actual l y di scl osed i n

Moor adi an 952, t hi s pat ent does not pr ovi de any mot i vat i on or

r eason f or anyone t o pul l [ f r ovat r i pt an] out expl i ci t l y. ( See

Rocco Tr . 1625: 13- 21. )

Dr . J ohnson t est i f i ed, however , t hat Moor adi an 952 t eaches

a pr ef erence f or each el ement of t he f r ovat r i pt an compound - t he

1, 2, 3, 4- t et r ahydr ocar bazol e cor e, t he 3- methyl ami no, and t he 6-

car boxami do such t hat a POSA woul d at once envi sage

f r ovat r i pt an. Cl ai m 7 of Moor adi an 952, whi ch i s t he same

compound l i st ed i n Exampl e 23, speci f i cal l y cl ai ms a compound

cont ai ni ng a 3- methyl ami no. ( Rocco Tr . 1796: 7- 1797: 1; DTX- 1019

col . 64 l . 29; i d. col . 29 l l . 1- 18. ) However , t he cl ai m 7 compound

i s t he onl y cl ai med compound t hat cont ai ns a methyl ami no: f i ve

of t he seven cl ai med compounds cont ai n a 3- di met hyl ami no, whi ch

20 Dr . Rocco t est i f i ed t hat :

There i s no way t hat wi t hi n t hi s pref er r ed group youcoul d even cont empl at e t he car boxami de becausecar boxami de i sn t l ower al kyl , car boxami de i s nothal o. Carboxami de i s not an aromat i c gr oup bondedt hr ough an oxygen, or i s an aromat i c group i n and of

i t sel f . So i t seems t o be excl udi ng t hat t ype off unct i onal i t y gr oup f r om t hi s pr ef er r ed gr oup ofcompounds . . . one of ski l l i n t he ar t l ooki ng att hi s pr ef er r ed gr oup of compounds . . . coul d nott ease out f r om t hat gr oup [ car boxami do] because i t ' snot t her e . . .

( Rocco Tr . 1619: 1- 15. )

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seems t o suggest a pr ef erence f or t he di met hyl ami no subst i t uent

over t he met hyl ami no. ( See DTX- 1019 col . 64 l l . 20- 33. ) At t he

ver y l east , t he f act t hat onl y one of t hese compounds i s a

met hyl ami no undermi nes Dr . J ohnson s concl usi on t hat Moor adi an

952 t eaches a 3- met hyl ami no.

Admi t t edl y, t he onl y di f f erence between the compound i n

cl ai m 7 and f r ovat r i pt an i s t he car boxami do gr oup t hat appear s

at t he si x posi t i on of f r ovat r i pt an. ( J ohnson Tr . 753: 12- 20. )

Dr . J ohnson t est i f i ed t hat Moor adi an 952 i ndi cat es a cl ear

pr ef er ence f or pl aci ng a car boxami do gr oup at ei t her t he si x or

ei ght posi t i on ( Tr . 764: 10- 765: 17, 771: 6- 17) , and a cl ear

t eachi ng f or t he 6- car boxami do subst i t uent ( Tr . 777: 8- 12) . I n

suppor t , he poi nt s t o si x exampl es r ef l ect i ng a car boxami do-

der i vat i ve subst i t uent at t he 6- posi t i on, 21 and seven exampl es at

t he 8- posi t i on. 22 ( J ohnson Tr . 764: 10- 765: 17, 771: 6- 17. ) However ,

as Dr . Rocco poi nt ed out , most of t hese car boxami do- der i vat i ves

ar e ver y el abor at e f unct i onal gr oups t hat ar e ver y di f f er ent

subst i t ut i ons f r om t he unsubst i t ut ed car boxami do t hat i s i n

f r ovat r i pt an. ( Rocco Tr . 1628: 4- 1629: 3. ) Onl y t he car boxami do

subst i t uent i n Exampl e 250 i s t he same gr oup as t hat i n

21 The compounds t hat cont ai n 6- carboxami do der i vat i ves ar ef ound i n Exampl es 69, 71, 73, 74, 77, and 79 of DTX- 1019.

22 The compounds t hat cont ai n 8- carboxami do der i vat i ves ar ef ound i n Exampl es 68, 70, 72, 75, 76, 78, and 250 of DTX- 1019.

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f r ovat r i pt an, and t hat gr oup appear s at t he 8- posi t i on of t he

di scl osed compound. 23 ( J ohnson Tr . 765: 20- 766: 6; Rocco Tr .

1799: 2- 19. ) Thus, Moor adi an 952 does not t each any pr ef erence

f or an unsubst i t ut ed car boxami do at t he 6- posi t i on. 24 ( See Rocco

Tr . 1625: 24- 1627: 1. )

The Cour t f i nds Dr . Rocco s t est i mony t o be cr edi bl e and

per suasi ve. I t i s f ur t her i nf l uenced by t he f act t hat Moor adi an

952 was di scl osed t o t he PTO dur i ng t he pr osecut i on of t he 864

Pat ent and t he PTO i ssued the 864 Pat ent not wi t hst andi ng t hi s

r ef er ence. ( PX- 0001, at [ 56] . ) 25 See Mi nn. Mi ni ng & Mf g. Co. , 976

23 Exampl e 250 i s 3- di methyl ami no- 8- ami nocar bonyl - 1, 2, 3, 4-t et r ahydr ocar bazol e. ( DTX- 1019 col . 52 l l . 8- 24. ) Myl an f ai l ed t odemonst r at e why a POSA woul d be mot i vat ed t o change t he 3-di met hyl ami no t o a 3- met hyl ami no, and al so move the car boxami dot o t he 6- posi t i on.

24 Dr . J ohnson ci t es a st atement cont ai ned wi t hi n anot her

SKB pat ent as conf i r mi ng hi s opi ni on t hat a POSA woul d at onceenvi sage t he f r ovat r i pt an compound wi t hi n Moor adi an 952. Thatpat ent st at es:

U. S. Pat . Nos. 4, 257, 952, 4, 172, 834, 4, 062, 864 and3, 959, 309 descr i be a br oad cl ass of 3- ami no and 3-( subst i t ut ed ami no) t et r ahydr ocar bazol es havi ng avar i et y of subst i t uent s at t he 5, 6, 7 and/ or 8posi t i ons, i ncl udi ng i nt er al i a t he gr oup - - CONR2R3wher ei n R2 and R3 ar e hydr ogen, l ower al kyl or t oget herwi t h t he ni t r ogen at om f or m a het er ocycl i c r i ng.

( DTX- 1395 col . 1 l l . 9- 16; see al so J ohnson Tr . 767: 15- 769: 22,770: 16- 17. ) However , t hi s pat ent was f i l ed December 16, 1993 andcl ai ms pr i or i t y t o a f or ei gn appl i cat i on dat ed December 21, 1992( DTX- 1395, at [ 22] , [ 30] ) bot h of whi ch ar e af t er t he pr i or i t ydat e appl i cabl e her e.

25 Al t hough Myl an makes much of t he f act t hat Moor adi an 952was not subst ant i vel y di scussed dur i ng t he pr osecut i on of t he 864 Pat ent , t he f i l e wr apper shows t hat t he PTO exami ner

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F. 2d at 1572 ( Where t he PTO has consi dered a pi ece of pr i or

ar t , and i ssued a pat ent not wi t hst andi ng t hat pr i or ar t , a cour t

owes some def er ence t o t he PTO' s deci si on. ( ci t at i ons

omi t t ed) ) . Cf . Sci el e Phar ma I nc. , 684 F. 3d at 1260.

The Cour t concl udes t hat Def endant s have not est abl i shed by

cl ear and convi nci ng evi dence t hat Moor adi an 952 ant i ci pat es

t he compound cl ai med i n cl ai m 1 of t he 864 Patent because

( i ) Moor adi an 952 di scl oses a broad genus t hat encompasses

mi l l i ons of compounds, ( i i ) t hi s br oad genus i s nar r owed i nt o

pr ef er r ed groups of compounds t hat st i l l i ncl ude t housands of

compounds but do not i ncl ude f r ovat r i pt an, and ( i i i ) Moor adi an

952 does not t each a pr ef er ence f or ei t her t he 3- met hyl ami no or

an unsubst i t ut ed car boxami do gr oup at t he 6- posi t i on. See, e. g. ,

Br i gham & Women s Hosp. I nc. , 761 F. Supp. 2d at 227- 28 ( f i ndi ng

t hat a POSA woul d not at once envi sage t he cl ai med compound

f r om a pr i or ar t pat ent t hat di scl osed a br oad genus of

compounds and a nar r ower l i st of pr ef er r ed compounds t hat di d

not i ncl ude t he chal l enged compound) ; Hof f mann- La Roche I nc. v.

i ni t i al ed t he r ef er ence sheet t o i ndi cat e t hat t hi s r ef er ence

was consi dered and t he Cour t wi l l not assume ot herwi se. ( DTX-1077 at 191. ) Not abl y, t he appl i cant s speci f i cal l y di r ect ed t heExami ner t o Moor adi an 952: Appl i cant s t ake t hi s oppor t uni t y t ocal l t o t he Exami ner s at t ent i on U. S. Pat ent 4, 257, 952, i ssuedMarch 24, 1981 t o Moor adi an, whi ch i s bel i eved t o be ofpar t i cul ar r el evance t o t he subj ect mat t er of t hi s i nvent i on. ( I d. at 118. ) Yet , t he Exami ner per mi t t ed t he cl ai ms. ( I d. at99- 100. )

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Cobal t Pharms. I nc. , No. 07- 4539, 2010 WL 4687839, at *5 ( D. N. J .

Nov. 10, 2010) ( Cobal t has not per suaded thi s Cour t t hat , based

on t he st at ement s of pr ef er ence, a ski l l ed ar t i san coul d at once

envi si on t he speci es t hat i s i bandr oni c aci d. On t hi s r ecor d,

t hi s Cour t cannot concl ude t hat Cobal t i s mor e l i kel y t han not

t o be abl e to pr ove ant i ci pat i on by t he Van Duzee patent by

cl ear and convi nci ng evi dence. ) .

Because cl ai m 1 i s not ant i ci pat ed by Moor adi an 952, as a

mat t er of l aw i t s dependent cl ai ms are not ant i ci pat ed. Cor ni ng

Gl ass Works v. Sumi t omo El ec. USA, I nc. , 868 F. 2d 1251, 1256 n. 4

( Fed. Ci r . 1989) ( Because we concl ude t hat cl ai m 1 i s not

ant i ci pat ed, cl ai m 2, whi ch i s dependent on cl ai m 1, need not be

separ at el y di scussed. ) ; RCA Cor p. v. Appl i ed Di gi t al Dat a Sys. ,

I nc. , 730 F. 2d 1440, 1446 ( Fed. Ci r . 1984) ( same) ; see al so

Car negi e Mel l on Uni v. v. Mar vel l Tech. Gr p. , Lt d. , No. 09- 290,

2011 WL 4527353, at *5 ( W. D. Pa. Sept . 28, 2011) ( same) .

B.ObviousnessMyl an next cont ends t hat each asser t ed cl ai m of t he 864

Pat ent i s i nval i d as obvi ous as of t he pr i or i t y dat e. A pat ent

i s i nval i d as obvi ous i f t he di f f er ences bet ween t he cl ai med

i nvent i on and pr i or ar t ar e such t hat t he i nvent i on as a whol e

woul d have been obvi ous t o a POSA at t he t i me t he i nvent i on was

made. Sci el e Pharma I nc. , 684 F. 3d at 1259 ( quot i ng 35 U. S. C.

103( a) ) . Whet her a pat ent cl ai m i s obvi ous i s a quest i on of l aw

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based on f our under l yi ng f act s: 1) t he scope and cont ent of t he

pr i or art ; ( 2) t he l evel of or di nar y ski l l i n t he per t i nent ar t ;

( 3) t he di f f er ences bet ween t he pr i or ar t and t he cl ai ms at

i ssue; and ( 4) such secondary consi derat i ons as commerci al

success, l ong f el t but unsol ved need, and t he f ai l ur e of ot her s.

I d. ( quot i ng Gr aham v. J ohn Deer e Co. , 383 U. S. 1, 17- 18

( 1966) ) ; see al so KSR I nt l Co. v. Tel ef l ex, I nc. , 550 U. S. 398,

406 ( 2007) . Gener al l y, t hi s i nqui r y consi der s whet her a per son

ski l l ed i n t he ar t woul d have had ( 1) a reason t o combi ne t he

t eachi ngs of t he pr i or ar t r ef er ences t o achi eve t he cl ai med

i nvent i on, and ( 2) a reasonabl e expect at i on of success i n doi ng

so. 26 I n re Cycl obenzapr i ne Hydr ochl or i de Ext ended- Rel ease

Capsul e Pat ent Li t i g. , 676 F. 3d 1063, 1068- 69 ( Fed. Ci r . 2012)

( i nt er nal ci t at i ons omi t t ed) .

I n KSR, t he Supr eme Cour t caut i oned t hat t hi s i nqui r y must

be expansi ve and f l exi bl e and must account f or t he f act t hat a

POSA i s al so a per son of or di nar y cr eat i vi t y, not an

aut omat on. I d. at 415, 421. There need not be preci se

26

The Cour t not es t hat [ o] bvi ousness does not r equi r eabsol ut e pr edi ct abi l i t y of success. . . . For obvi ousness under 103, al l t hat i s r equi r ed i s a r easonabl e expect at i on ofsuccess. I n r e O Far r el l , 853 F. 2d 894, 903- 04 ( Fed. Ci r .1988) ; see al so Bayer Scher i ng Phar ma AG v. Bar r Labs. , I nc. ,575 F. 3d 1341, 1350 ( Fed. Ci r . 2009) ; Pf i zer , I nc. v. Apot ex,I nc. , 480 F. 3d 1348, 1364 ( Fed. Ci r . 2007) .

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t eachi ngs di r ect ed t o t he speci f i c subj ect mat t er of t he

chal l enged cl ai m, f or a cour t can t ake account of t he i nf er ences

and cr eat i ve st eps t hat a [ POSA] woul d empl oy. I d. at 418.

I mport ant l y, i f a t echni que has been used t o i mpr ove one

devi ce, and a [ POSA] woul d r ecogni ze t hat i t woul d i mpr ove

si mi l ar devi ces i n t he same way, usi ng t he techni que i s obvi ous

unl ess i t s actual appl i cat i on i s beyond hi s or her ski l l . I d.

at 417. Rel evant t o t hi s anal ysi s i s whet her t her e was a r eason

or mot i vat i on t o combi ne t he known el ement s i n the manner

cl ai med by t he pat ent . I d. at 418. I ndeed, [ o] ne of t he ways i n

whi ch a patent s subj ect mat t er can be pr oved obvi ous i s by

not i ng t hat t her e exi st ed at t he t i me of i nvent i on a known

pr obl em f or whi ch t here was an obvi ous sol ut i on encompassed by

t he pat ent s cl ai ms. I d. at 419- 20. [ I ] n many cases a per son

of or di nar y ski l l wi l l be abl e t o f i t t he t eachi ngs of mul t i pl e

pat ent s t oget her l i ke pi eces of a puzzl e. I d. at 420.

Fi nal l y, an i nvent i on i s obvi ous- t o- t r y and t her ef or e

i nval i d under 35 U. S. C. 103 i f i t r esul t s f r om a ski l l ed

ar t i san mer el y pur sui ng known opt i ons f r om a f i ni t e number of

i dent i f i ed, pr edi ct abl e sol ut i ons. I n r e Cycl obenzapr i ne, 676

F. 3d at 1070 ( quot i ng KSR, 550 U. S. at 421) ( i nt er nal quot at i ons

omi t t ed) .

I n conduct i ng i t s anal ysi s, t he Cour t must be cogni zant

t hat [ a] l most any i nvent i on, no mat t er how nonobvi ous at t he

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t i me, wi l l appear obvi ous when l ooki ng backwar d f r om t he

sol ut i on. I t i s f or t hat r eason t hat [ c] ar e must be t aken t o

avoi d hi ndsi ght r econst r uct i on by usi ng t he pat ent i n sui t as a

gui de t hr ough t he maze of pr i or ar t r ef er ences, combi ni ng t he

r i ght r ef er ences i n t he r i ght way so as t o achi eve t he r esul t of

t he cl ai ms i n sui t . J anssen Phar maceut i ca N. V. v. Myl an

Phar mas. , I nc. , 456 F. Supp. 2d 644, 662 ( D. N. J . 2006) ( ci t at i on

omi t t ed and emphasi s i n or i gi nal ) .

Myl an submi t s t hat t he asser t ed cl ai ms of t he 864 Pat ent

ar e ( 1) obvi ous i n l i ght of pr i or ar t r ef er ences Moor adi an 952

and/ or Moor adi an 1977, 27 when consi dered al one or i n combi nat i on

wi t h a POSA s knowl edge as of t he pr i or i t y dat e; ( 2) obvi ous i n

l i ght of 5- CT as t he appr opr i at e l ead compound; and ( 3) obvi ous

i n l i ght of pr i or ar t whi ch woul d mot i vat e a POSA t o modi f y 5- CT

t o obt ai n f r ovat r i pt an wi t h a reasonabl e expect at i on of success.

Subsumed wi t hi n t hi s l ast argument i s t he assumpt i on t hat a POSA

woul d begi n wi t h 5- CT, whi ch as set f or t h bel ow, t he Cour t

rej ect s .

1.Mooradian 952 and Mooradian 1977 Do Not Render theAsserted Claims Obvious

Myl an asser t s t hat Moor adi an 952 and Moor adi an 1977, al one

or i n combi nat i on, r ender t he cl ai ms obvi ous. The Cour t

27 Adam Moor adi an et al . , 3- Ami not et r ahydr ocar bazol es as aNew Ser i es of Cent r al Ner vous Syst em Agent s, J . Med. Chem. , Vol .20, No. 4 ( 1977) ( Moor adi an 1977) .

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di sagr ees. I ndi vi dual l y and separ at el y, t hese r ef er ences t each a

pr ef er ence f or a 3- di met hyl ami no subst i t uent , whi ch i s not f ound

wi t hi n f r ovat r i pt an, and do not suggest a pr ef er ence f or a 6-

car boxami do. They f ur t her do not suggest ut i l i t y i n t r eat ment of

a condi t i on wherei n a 5- HT1- l i ke agoni st i s i ndi cat ed ( cl ai m 2)

or mi gr ai ne ( cl ai m 3) . And, of par t i cul ar i mpor t ance t o t he

Cour t , bot h Moor adi an 952 and Moor adi an 1977 were di scl osed t o

and consi dered by the PTO dur i ng pr osecut i on of t he 864 Pat ent ,

and yet t he PTO i ssued t he 864 Pat ent not wi t hst andi ng t hese

pr i or ar t r ef er ences. ( PX- 0001, at [ 56] ; DTX- 1077 at 191. ) The

Cour t accor ds some def er ence t o t he PTO s f i ndi ngs i n t hi s

r egar d. See Sci el e Phar ma I nc. , 684 F. 3d at 1260.

As expl ai ned i n det ai l above, Moor adi an 952 di scl osed a

ver y br oad genus of 3- ( subst i t ut ed- ami no) - 1, 2, 3, 4-

t et r ahydracarbazol e compounds, and i n some ways t eaches away

f r om f r ovat r i pt an. For i nst ance, t he br oad genus of compounds

di scl osed by Moor adi an 952 i s nar r owed i nt o pr ef er r ed groups

of compounds t hat st i l l i ncl ude t housands of compounds but do

not i ncl ude f r ovat r i pt an. I ndeed, as Dr . Rocco opi ned, as l east

one of t hese pr ef er r ed gr oups expl i ci t l y excl udes and

t her ef or e t eaches away f r om i ncl usi on of a car boxami do si mi l ar

t o t hat of f r ovat r i pt an. ( See Rocco Tr . 1618: 10- 14) ; Gal der ma

Labs. , L. P. v. Tol mar , I nc. , 737 F. 3d 731, 738 ( Fed. Ci r . 2013)

( A ref erence may be sai d t o t each away when a per son of

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or di nar y ski l l , upon r eadi ng t he r ef er ence, woul d be di scour aged

f r om f ol l owi ng t he pat h set out i n t he r ef er ence, or woul d be

l ed i n a di r ect i on di ver gent f r om t he pat h t hat was t aken by the

appl i cant . ( ci t i ng DePuy Spi ne, I nc. v. Medt r oni c Sof amor

Danek, I nc. , 567 F. 3d 1314, 1327 ( Fed. Ci r . 2009) ) ) . I n

addi t i on, as set f or t h above, Moor adi an 952 t eaches a

pr ef er ence f or a 3- di met hyl ami no subst i t uent , whi ch woul d l ead a

POSA away f r om f r ovat r i pt an. ( See DTX- 1019 col . 64 l l . 24- 33. )

Fi ve of t he seven speci f i cal l y- cl ai med compounds i n Moor adi an

952 i ncl ude 3- di met hyl ami no whi l e onl y one compound i ncl udes a

3- met hyl ami no subst i t uent . ( DTX- 1019 col . 64 l l . 20- 33. ) Thus,

Myl an has f ai l ed t o demonst r ate by cl ear and convi nci ng evi dence

t hat t he 3- met hyl ami no- 6- car boxami do- 1, 2, 3, 4- t et r ahydr acar bazol e

( cl ai m 1) i s obvi ous i n l i ght of Moor adi an 952.

Li kewi se, nothi ng i n Moor adi an 1977 r enders t he

f r ovat r i pt an compound obvi ous t o a POSA. The under l yi ng pr emi se

of Moor adi an 1977 was t hat 3- ami nocar bazol es mi ght have cent r al

ner vous syst em act i vi t y par al l el i ng t he t r ypt ami ne t ypes. ( DTX-

1082 at 487. ) The aut hors prepared and st udi ed a var i ety of 3-

subst i t ut ed ami no- 1, 2, 3, 4- t et r ahydr acar bazol e compounds,

i ncl udi ng compounds wi t h 3- met hyl ami no and 3- di met hyl ami no

subst i t uent s. ( See DTX- 1082 at 487- 88. ) Thus, as wi t h Moor adi an

952, Moor adi an 1977 t eaches a pr ef erence f or a 3- di methyl ami no

subst i t uent . I n t est i ng pt osi s pr event i on, Compound 3, a

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di met hyl ami no, showed appr oxi mat el y t hr ee t i mes t he act i vi t y

l evel of Compound 2, a methyl ami no. ( DTX- 1082 at t bl . I I ; see

al so J ohnson Tr . 882: 6- 12. ) Not abl y, as t he aut hor s expl ai ned,

I t became appar ent t hat 3 ( Tabl e I I ) [ t he di met hyl ami no] was

t he most i nt erest i ng CNS compound i n t he ser i es and t hi s

compound was st udi ed i n gr eat detai l . ( DTX- 1082 at 487; J ohnson

Tr . 1138: 19- 1139: 10. ) 28 Dr . J ohnson agr eed that Moor adi an was

r eal l y hi ghl i ght i ng compound t hr ee i n t hi s par agr aph. ( J ohnson

Tr . 1138: 19- 1139: 10; see al so J ohnson Tr . 902: 14- 17 ( act i vi t y

r esul t s i n pt osi s assay showed a Moor adi an pr ef er ence f or t he

di met hyl ami no) . ) Because t he Moor adi an r ef er ences r ef l ect a

cl ear pr ef er ence f or t he di met hyl ami no subst i t uent , i t i s

uncl ear why a POSA woul d be mot i vat ed t o modi f y a 3- met hyl ami no-

t et r ahydr ocar bazol e.

Moor adi an 1977 al so does not t each or expr ess any

pr ef er ence f or a 6- car boxami do subst i t uent , whi ch Dr . J ohnson

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