Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

Filing 1006

MEMORANDUM in Support re #1005 MOTION in Limine to Preclude Amgen from Asserting that there Was a Restriction Requirement Separating the '008 Patent Claims From the Claims of the '868 and '698 Patents filed by F. Hoffmann-LaRoche LTD, Roche Diagnostics GmbH, Hoffmann LaRoche Inc.. (Attachments: #1 Exhibit A#2 Exhibit B#3 Exhibit C#4 Exhibit D (Part 1 of 3)#5 Exhibit D (Part 2 of 3)#6 Exhibit D (Part 3 of 3)#7 Exhibit E)(Seluga, Kimberly)

Amgen Inc. v. F. Hoffmann-LaRoche LTD et al

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Exhibit D, Part 1

UNITED STATES DISTRICT COURT

DlSTIlCT OF MASSACHUSEn'S

:\!\'lGEN INC.
)

Plaintiff
v.

)

) Civil Action No,: 05-1223ï W(;Y
) ) )

F. HOFFMANN-LA ROCHE
1.'1D" a Swi$s Company, ROCHE
DIAGNOS'I'ICS Gmbll, ¡ì German

)

Compuny and I-IOFFMANN-LA ROCl-IE

) ) )
) )

INC., a New Jersey Corporatioii,
Ddcnda1Hs,

)

REBUTTAL EX)'Elrr REPORT OF STEPHEN G. KUNIN

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(MPEP § 201.06 (8th ed. Rev. 5, Aug. 2006))
As evidenced hy the wriUcl1 record, c.ich orDr. Uils patents-in-stilt meet the definition ora

divisional arrlic¡ition: (i ~ I.Her applìc:Hions fur distinct or iriJcpcndcnl invi.ntions: (2) carved

out ora pí.iiding ;ippllc¡:tion: (3) disclosing ;ind claiming only subject matier disclosed in the

pan~ni '298 application: (4) lìcd as a result or n restriction requirement made by the Examini.r:
~Uld (5) claims the benefit of

the nonprovisional '298 parent applicution under 35 U.S.c. i 20,

XII_ ROCHE'S OBVIOUSNESSCfYPE DOUBLE PATENTING DEFENSE
137. Obviousness-type double patcntit)g is a judkially.created doctríne
designed 10 pn:vcm improper timcwisc t"tensíon of

the patent right by prohibiting claíms in a

!utcr paicni which ari. not "p::ientably distinct" from claims in a commonly-owned earlier patent

from enjoying a longer patent icrm. 1/1 re Bmal, 937 F.2d 589, 592 (Fed. eir. i 99 i). The
unde-rl)iing policy is ¡hm the public should "be able to act on the assumptíon that upon the
expiration ülthe learlíerl pi:ent it wil be- free to lIse not only the invention c!aimi.d in the patent

b\J1 ,dso l1wdi!I(atroiis or varianb which wüuld have b(:('n ohl'ioii,i' to those of úrdiiwry stdll iii

the m at ihe tìmc ¡hi; iiw\.iiiion was made." 1111'e l.m¡gi, 759 F.2d 887. ~N2-9J íh:d. ("if. j985)
(emphasis in original) (intcrnal quotation omìui.d).
¡ 38. Obviousness-type double pa.tenting is a question oriaw. In re Berg, 140

F.3d 1428, 1432 (Fed. eir, i 998). As with other affnnativc defenses ofinval¡ditv, the defcndant
bears the burden olproving obviousness-type double patenting by clear and convincing
eviJcli(.c-, Un bCílVY and uiisliifìing burden." S):libo171.'chs., Iiic. I'. Opticol7, lI1C., 935 F.2d 1569,

158ü (Fed. ('II" ì 99 ¡). Whcfe. as h.:re. the Sail1\ allegations ol\ibviousiicsHypc double
patenting wi.rc '()llsiJcf\~d and overcome during cxaniil1aiìon üfthe patcnts-iIH,uit, ¡he ddcmhint

bears an cwn heavier burden ín proving obviousness-type düuble paicming, (f. Aiigm, !n(' I'.

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/Joechsr Marioii Roussel, Inc.. 126 F .Supp.2d 69, i 05 (D, Mass. 2001) ("MOrC(lVCr, if

the Patent

Olìce considered a pnnicular prior;irt reference, then ihe challenger has the added burden of
overcoming ¡he dcíercnçe thai is due to;i qwl1ineJ govi.rnini.nt agency presumed to have

properly doni. iisjüb....i (inicl'al quoiation uiniiied).
13\). Double paicniing is ev:-iluatcd on a cÜim-by-claili basis. Thus. the

invalidity or one claim because of double patenting docs not automatically ri.quire the
invalid¡ition ofotlierc1aims in ¡he silnc p:iient. 01'1110 Pharm. Corp. v. Siiìr/i, 959 F.2d 936, 9'12

(Fed. Cir. 1992).

140.

In dctcnl1íning whether or nOllwo clniiis are "pateniably distinci," couns

(and thi. USPTO) have applied an obviousni.s$ analysis ¡hat parallels the analysis set forth in

Graham I'. John Deere Co., 383 lj,S. L. 15 (1966), and applied in thc context of35 U.S,C. ~ 103.
5,'('1, I.migi, 759 F.2d at 892 n.4: MPEP § 804(1I)(B)(1). Fonhis rc;ison, the "paicniably disiinct"

analysis is olkn fhll1ed:is a determination ofwhcthc-r:i claim in a I:tcr patent is "obvious over"
¡i cl:iiin in a commonly-owned earlier patent, or whether the differcn;:es between two siich claims

would have been "obvious" to one of ordinary skill in the ¡ir ~t th~' t¡!1i-' ilw invention claimed in

the laler r:i~~nt \\:," made. As pan o(this inquiry, couns look 10 ¡hi. f:iClors that ;In.' pcriineni
when detcrmining nOl1ob;iousl1csS undcr 35 U.s.C ~ ioi including whcther thcre was II

l1oiîv:iiionto modify ¡he prior art, S(.'t, t.~., OtrhtJ, 959 F.ld at 943; 1/1 re Baird. 348 F.2d 974,
979 (C.C.P.A. i 965), a rc¡¡sol1able expectaiion of success, see, e.g., Longi. 759 F,2d at 896~9Î,

and objcctivi. evidence ofnon-obviotlsncss, stich as long~rdt need, unexpected results, etc., see,
e.g.., Inre Hllai, 124 FJd 1458. 1462 (Fed. Cir. 1997); Longi, 759 F.2d at 896-97; III il'

CfadrOiv, 406 F.2d 1376. 1383 (c.ePA. 1(69). Onc iiiportan¡ dincrt'nt'e, however, is ihat tlw
Joubk.p¡¡!cniing ;ui:dysis involvts a comparisoii ofmo claims, and it is impermissible LÜ trcal

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the pmcnt spccHìcltion underlying one clniii(or even the Ji:,do:;ure (ound ¡ntha! claim) ~iS prior
an against the other claim. See Cell Foods, Corp, v, SllidiengesellSchafi KohlI. mb! 1,972 F.2d
1272, 128 I (Fed. Cìr. 1992) ("Our precedent makes dC3rthat thc disclosure of a patent cited in

:;upport of a double patenting rejection cannot be ust.-d as though it were prior iirt, even where thc

disdüsurc is 1()uriJ in the daims."); Longi, 759 F.2d at 892ii.4: Iii n' Kaplaii, 189 F,2d 1574,
iSSO (F~'d. Cir. 1986),7 1i b impermissible tü apply thi. i.arlicr l.ollmonly-ownd paient's

disclosure in assessing doubk p:ii¡;iiting-¡t docs not qualify under 35 USe. ~ 102 ~b prior an.
The rC,lson for this is becausc "that disclosure is the iipplicants :ind is not inllw 'prior an.'"
Gerbr.1' Garmtnt Tech.. fiic. v. Leclra S:Jls., Inc., 916 F.2d 683, 687 (Fcd, Cir. 1(90),
¡.; I, Under certain circumstances wheri. ihe USPTO has deiemiined that ¡¡

p:ikni ~¡rpliiaii()n r\)fiaÎns ci:ìms to rnuliiplc independent ilnd distinct invcntions ,md has isstJed
u rcqui,cllenl !1)l'cing the ;ipplicaliilO dividi. out :1I1J prosccllle cbims 10 ihese ¡r1V,:ntions in

separate ~ipplk:iiion$ (i.e" a "restriction requircmcni"), 35 U,S.c. § i 2 i bars ¡itiganis and the
USPTO from using the: claims in one oftlic rc:sulting applic,itions (or in ¡he patent issuing
therefrom) against the claims in another for double patenting purposes, Section 121 provides in
pertinent part:
;\ paien! issuing on an ,ipplkatioii with rcspC'ct to which a

requiremeiii rÜr restriction undi.r this seciion has bccn made. or :m application ¡i\cd as a result ofsudi:i r.:qiiireim:iil. sh,ill not
be lIsed as :i ri.lÎ:p:nçi. ciiher inihe Pilleiit and Tmdemark OITÍ-ee or in tli¡; courts against a divi:ÚolHil appliciliioii or ¡¡gainsi ¡he

Î In scvi.rnl instances in his report, Mr. SOjì1clcous: mistakenly overlooks this inipon,lli principle when he contends: ihat "the '008 fnueii(' is available as ;i doiiblc-pnteniing rçfi.rence :igainst the
clrims of

Dr. Uii's pawnts.in-suil. Sec, e.g., $olucleoiis'~ 447, 450. 457, '165, 468, 474,

'J Union Carbide Corp. \" Do\i Chem. Co., 619 L Supp. 1036, 1060 (D, Dd. 1985) ("It is almost the claims will occur iitìer restriciion is: ordered, since incvitiiblc that some reiìnement of res:triç¡ion olien comes :is a preliminary step before the examiner fe,idics ¡he mcr¡ts oîihe patent c!ai¡m.")

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origiiialapplication Qr any patent issued on eiiher of divisional applic¡nion is l1ed before the issuance of

them, ilthi. the patent

on the othcr applícation,

, I'1":.

Congress cnacicd § 121 iis a rcmedinl slntutc- to protect applic~nts aiid

paICI1!CCS froin ¡lw iinl;iir consequences or USPTO rcslriciion prattic\.. For this reason. § 12 i is
olkn (Ìi.scribeJ ,is providing a "sate harbor" lÒr ¡Xl1i.I1ICCS. Si.ciiol1 i 2 i OpCr¡iICS by "cf!ccij ingj ;1

form ol\.'sioppd thai shicldsthe applic¡:ni from having 10 pmve the corrccliiess ofihe rcstriciion
requirement in order to prescrve thc validity of

the second patc-Ill." Swdicngc.leil.lclia(i Kohle

mbll \'. N. h:irochemical Co., iS4 F.2d 351, 361 (Fed. eir, 1986) (Newman. J., concurrìng). In
so doing, * ¡ 21 ";issiires that the tcchnÎC¡iliiks of n..'sirictioii practice are not ekvaled from ihcir

purposc oÎcx:imination (onvo:nio:ii¡;e to;l PO¡Cliia winl on the validity tll thc erisuìng pai\.nis."
(!jipli"d J1a/(i"a!,\,. Ille \'. Ad\' .'Ù'iJico¡;dÚClor Maraiii!s .-IIIL, inc.. 98 F.3J 1563, 1568 (h:J. Cii".
1996), i\t its most basic level, ~ i 2 I makes sense because it would be unf,iir 10 n.'qiiire ¡j
paientee to defend against double patenting ,macks ¡fthe rC¡ì$on why he hu:\ multiple patents is

becmlsC" the Patent Oftce required him to separate one applkation into l1ultiplciipplicatíoiis
which led 10 ihe ¡miltiplc pments. Cf Applied Materials, 98 F.3d at 1568 riWjhcn ihi. existence

ofmultipk pmcnis is due 10 ¡he administrativc reqll¡rCIl\.llts imlK!Sed by the PmclH and
Tradçmark Ollkc, 35 U.S.C. § 121 provides ihat the ¡nv('ntor shall nol bl. jlri.jiidkcd by lWV¡lig

complkd with those reqiiirciicnts.").
143. In the ¡itigaiion contexi. § 121 provides paicnkes with II dd-L'nsc 10 ccrt¡iin

clr:hns ofÎlivalidity based on ùouble palCnting. Although the heavy burdi.n olpl'ving
obviousness-type double paicnting remains with 1he pany challenging the v,ilidíiy of thc palCnt

;It all times (¡,c.. it never shills 10 the pmenicc-), ihe pateiitee bears thc burden or proving. by ii
prepomkr;¡l1cc oftftc l.vjÙCllC\.'. that the safe harbor provision of § 12 i ;ipp!ies. Pjb'l" ll1c. 1',

Ti.wl PfUlfils. uS:!, Inc., No. 04-cv-754, 20Üï U.S. Disl. LEXIS 20190,:::1 "215-16 (D.N.J.1\:J¡ir.
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20, 2007). The dc-lÇnnin¡l\ion of whether § i 21 applies is:t quc-siîun or lai,'. iJri.\'(()!-,Irl('.1

Squibb CO. I'. Res. Corp. Techs.. Ine.. 361 F.3d nn, 134811.1 (h:d, (ir. 20Ü.f); App!ld
Maraiaf.i', 98 F.3d ¡ll 1567.

144. There arc tWO rund:imcl1tal elements required for proving the applicability

ol§ 12 i in u litigation context: (1) the p;iieni-iii-suit issued from an appJie-tiol1that w:is fìkd us
a ri.siilt of a n:striction requiremeni; and (2) the claims in ihe pateni uri. consoiiml with the

restriction n:quireiicni. Gerber, 916 F.2d at 6Si~S8,
145. Requirement (I) is satis!lcd iftlii. first application giving rise 10 the lXllni~
in~suit filed alter the resiríction requirement coniained claims drawn only to the lioli..lecieJ
invention or inventions (and not to the invention di.cted in rcspoiisC to the restriction

ri.quircl1ent lor examination in the parent applîcation). Gerber, 916 r .2d at 68i~S8. This
requiremcnt makes sense because it ensures ihat the protec.tions of § 121 arc nm eXltnded to
¡:pplicanis who voluntarily lìle multiple palen! applications, or who n~çi;itn ¡he invention ckclo.d
!(,r cxmninatiün in !Îìt: p¡!r;;ni applic¡lticlJ.

146. Ri.quiremciii (2),--,~ "consonanci." -- is $atislkd ,iS long;\$ the cl;iins in
thc Î$Sued patcnt fall within the same group(s) as the claims in the parent application drawn 10
the /lon-elected invention or inventions and "do not cross the line of dcmarc¡¡tion drawn around

the inveniion dccicd in the restriction requirement." ,~vl1bol Teelis.. 935 F.2d ui 15ï9. Thus.
new or amendd claims in the paicnt~in~siiii (i.e., claims that were nol originally in the
;ipr1ic:iiion filed ..as;i resu!i or' the restriction n:quircnieni) also :!no' ;;n!Ítld (0 ¡hc proicciiom; of

~ í 21. rrüvidcd they J:111 within (he scope oftht non.dccted group(s) ¡iid ari. not dniwn 10 ih::
invention elccttd in response to the re::lriction r~~q\lin..ment and prosecuted in the parent

appiic~tion. Id This requirement maKes sense: bccausi. it ,illow5 for daiiis to be ¡idded or

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¡uncndd diii"ing CX:\niinat¡ol1, whith is "almüst il1cv¡wbk,"') but at ¡he saini: iimc cnsuri:s ¡hut tlie

protections of § 12 ¡ tire nol e\\cndcd to applic¡llb who n~claim the invention ck-c\ed in ihe
parent application Juring subSi:quCllt i.X.iiiiiw.tion orihc ¡ipplìc:iion tiled as ¡l. result of

the

restriction requirement. (f Gi!rher, 9 i 6 r .2d at 688 (.'¡\ consonancc rcquirem(:l1l is col1sÍ$tel\

with the kgislativc piirpose behind Section 121, Congress could not have intended to deny all
inquiry inlO whether the resiriction requircmcni established in Section 121 had been disrcgardi.d

during prosecution of a divisional application."). When assessing whether chiinis arc consonant
with a restriction re-qiiirciicnt. the- proper point of rcference is the- actual resiriction groupings
(i.c., the substance oftlie dainis in etlch restriction group), not the examiner's written
descripilüns thereof. Texas !Jì'lr¡¡II('n!s lne, \" lTC, 988 F .2d J 165, i 179 (Fed. Cir. 1993).

A. TllEJULY 1986 RESTHICTlü:- REQtJlltEi\lF.NT

147. After an initial U5sessmcni of!)r. Un's '298 application. on July 3,1986,
Examìrwrs Thomus Wiseman and Joanne Gicsscr decided that ¡Iii '298 application included

d:i!nis lü multipk indcpcnJt:nt ¡md distinct inventions undi.r 35 U.S.c. ~ í2 I and, (()f tiiç
convcnk-ncc ofilic USPTO ¡¡nd its c;.¡i.iiinatÎon. insisted that ¡Î1I d,jinh to ¡hesi. iim.:ntiiHls b..
examined in multipk applications. Accordingly, ¡hey issued an Qflcc Action n:quiríng ¡hat

Amgen's counsel selCC! one of

six invention groups for further examination in Dr. tin's '298

npplicution and forcing Amgcils counsel to prosecute si.pnratc-y the claims to the oiher, "non.
i:b::tcd" inventions. The- text olihis "restriction require-ment" read as follows:
"Restriction to one oftlic ro!!owil1g inventions is required under

35 U.S,c. 121:
i. Claims 1-13, 16. 39-.J1. '17-54 ilnd 59, drawn 10

polype.ptide, clussltkd in Clas:, 260, subclass i 12,

II. Claims 14, 15, 17-36,58 and 61-72, drawn to DNA, classified in Class 536, subclass 27.

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Il. Claims 37-38, drawn t( plasmid, classified in Cla.'is 435,
subclass 240.

IV. Claims 42-46, drawn to cells, classified in CliiSS 435,
subclass 240,

V. Claims 55-57, drawn I\ phannai.clltic::l comp0siiio!1,

classilied in Cbss 435, subclass in.
VI Claim 60, drawn to assay. classl¡¡od In Class 435.
subclass 6.

Inventions I and II arc rclated as process of making and product made.

The inventions arc dis¡inct if either (i) the process as claimed
Ç:Hl be used tú m:,kc another ;lId materially d¡nì:ren! product. or

(2) ¡he ¡m)du~'t as cl:ím¡,d can be m;ide by another and materiai!y d¡fli:ri.n¡ process. t\WEP 806.05(1).

In this case, ¡he produC! as claimd m:iy be mude by ¡i
materially diíïCrc-iit product, siich ;is isolation from a nmmally
occurring sourcc.
Inventions II and ii arc rclated as product and process of use.

111e inventions arc distinct if either (1) the process for using the
product claimed can be practiced with ¡mother and materially

ditlì:rcnt product, or (2) the product as claimed ';lll be used in a
materially d¡lTcn:nt pl()Cc~s of using the product. \.lPEP

S06,05(h).

In this eiise, the produci as claimed may be made by a
materially different product. such as ¡solation from urine.

Inventions I and V arc rclaieJ as subcombin:niol1s disçìosc-d as

useablc together in it single combination. The subconibin:itions nri distinct from each other iltiH~)' arc shown to be sep:iritdy
use;:lblc. 111 the instant C:lSt, invention i has separate util!y such us usi. in iin ass-ay. See ivlPEP SOG.05(d).

Invl.l1tiol1S i and V¡ ari. rcl;:tcd as s\:bcombjnntiüns disclosed as

1I5cabk~ iogi.ihi.r in a singic eümbin;:lìol). The subc()llbinalÌons me dî~i¡ncl from each other ¡(they arc shown lü be s(.r¡lr:iciy iiscabk, III ihe instant casi., invention i has scpür;iic lHiliiy :iilCh ~iS Ilse as a phami:ccutkal. Sc\. MPEP 806.05(d).

Be-cause these inventions ari. distinct ror ihe rc;!.';ons given

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above ;ind h:wc acquired a scpan:lc Slatus in ihe :i1 because of

¡heir recognized divergent subject lTaltcr restrictÎon for
examination purposes as indîcmcd is propi.r,"

(Sa' '008 File History, Tab S, 7í3/86 ümcc Action (AM~ITC 00952500)),
148. 111e language of

the claims identified in the Exumincrs' restriction

rcquiri.mcnt is shown in the following chart, which I may use in connection with my testimony:

Resiction Group _ _ Claim Laguage '
Gr(iupl: l'dy¡ii:ptidc

-.

i.

,\ purified and isolated poly¡i;;piid;; h~l'il1g p"ri () iil! urihe primary struclUr.i!

c0iifur:n;ltion;:iiùoncormoicofthebiologiç::lpruperiicsofn:iim¡l!1y.üccurring
er)'thro¡xíctin and di,lr.ictciized by being the product of prok;lryc!Ì;; \.ir cubrymic exprC$sìon of:iii exogenous DNA 5c(jucm;c.

2, ,\ polypeptide according tú d:iîm 1 funhcr d\ür:\Clerizcd by hci:ig rn.::: ljf
a.~$OCi.iiiol1w¡tli;1ny 11\;i1lI1nlianrroicil\.

i\ pdypql!Ìde :icn:,idiiig to claim I "h~r~in ih~ :.'XO!;Cn¡I¡¡, DNA ,equeiic:; I' a
cl);.:\ ;:~qw:nçe.

f\ P0\:Tqiii:.k ;¡çcürding l,¡ e!"im 1 wherein ih.: ,,,,;;crW\I, D7,,,\ ",'Ilicnc" i,; ;\
ni¡!Iii!;~c!m(;d D:\II ';"l::cl1ce_

,
6.

,\ ¡i0iyp,;p1Íd~ accurding to 'lJim I wlw¡diiih'~ c.\o;;i.ni)U, DNA :,qiiel¡C;; is a gcltomicDN/isC'llicn;:(;.

II polypeptide ¡¡ccording 10 claim I wherein the c-'wgcnlll$ DNA :;cqucllcc is
carded 011 an autonomous replicniins circular DNA p!¡¡mid or viral VCCIOf.

7.

!\ polypcpiidc aCtúrding to claim 1 possessing pi\ or all of the primary slrucltr.l
cclifunnaiioii ofhuni;u¡ erythropoietin a$ set forth in Table VI öi ;\JY nal\lIl11y

(Xcurring;illcliçw:rìm\tlhcreof.
E.

cDnl(;nn;li,)I\;ifmoliJ.:c';' eryihro¡xiicti¡¡ ;bsei'foflh inl':;bk:V

¡\ po!vpc!l!Ìde acwrdiiii. to c!;iiii i p(j,scs~;jiw ¡un or ::I! oftÏii: prim¡u-\' ,iruciunil or:iny i;;l\w;diy

,xClirril\,::ilkiic v;iri;mt (h~n:u1.

'l.

A l..lypcptidc ;içcording iù claim I which h::s tl1; ill1llJIK-íügic;ll pf(j1crtíi,'S û!' n::hlr;ilIY-\'CClirringel''lhr()p\littin.
l\ pdyp;:pi¡dc ¡¡ccording to claim 1 which hn~ the iii i'i!") bìolù:;ic:il ,iCiivi1Y i;f n:itur-.illy-occurriiigc-ryihropoiciin.

lü.

II.

A polypcptide- ::ccording to claim 1 which has ih~ iii vllro biülogic.:il ;\ci¡vi¡y üf n;\!lJrnllY.,)CCining.¡:rythroli-okiili,

"

:\ püly¡wpiidc ;\(wrdir.g w d;Ü111 I ti:1!i~r eh~i':elaizd by heing c0\','lìcI1IIY

ii$$0(íaidl'i\b:idclç;;;:lik¡iibt:sIlDsi;,ncc.

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13. :\ p01ypcptidc :iccordir.g to c!;iim 12 ",he-rein s;;íd dCic\;,:,\;h,: bbd b ,; mdÎ,'bbd_
l6. :'\p..iI)'PcpiìdcpmduclOfthcc-xpit:sioliofuDN.'\$cq(jcnc.;ufcbini l-iinil

proi..i.f)'oikürcubryolichosl.
30. A polypeptide product cîihc èxim:$sioii in a prnk;ryoik () c¡¡bryolÎc ii()~t cdl ora
DNA $cqucncc;1ccarding 10

claìms 170(34.

,HI. A glycoprotein pm.:!!c: having:i primary strucim;i! confonmitìon sufficiently
duplìc:iiivc Ofih,,! da naturally-occurring erythropoietin to allow 1~')S$Css¡0n of oni~

Of mon::üfthcbioh)gic;i! propcrliCi thcrcüf;;iid h;;ving an avc-rJg;,ci\rb-ohydrJl\~

compo,itjç,\whicbdiffcr;; fWi\\k,!nfnMw:illy-úccurringcryÜimpoÌ\Ün.
,j i. A gl)'l,:0proicin pn..'-ll\;( h;¡ving:i primary sirw:lUf;i! colifor¡ii,ilÙm s\inìci¡;mly
duplicativc -ifllmt of,'( n,mir~lly-(p,:ciifing lmm;il) ei-,throp;,)íciin Ii) ¡:l1ùw
poSSlSSí() of one or nion; of

the biol(¡;:ie,,1 properties iiicrc(\î~nd h;iving ;111

;'vcrage c'1rbohydrJlc CO!lpO:;¡ÜOIl whieh dil1-crs from that of ii;Jiur:llIy.occurring

hUl1ancf)lhrüpoìciin.

4ï. A synthetic polypeptide having par oLil1 ofihe amino acid sequence:\$ $(; fonh in
Table V imd h~vii\g one or more orihe Í/I l'¡I'O or ¡¡¡vitro bioiogic:i! activities of

1131umlly.-curringmonkcycryihrop-oielin.
48. ,\ synthetic ¡xilyix:ptidc having pari ofal! ofthc, ~inin(J ncid 5equc-ncc :15 set furih in

TiJ_bk Vi, other thaii;' ,cq\tcr,çe ofrc;;Îdue$ entirely williin ¡he sequence numbcicd

¡thwugh10.anJli;ivil\g;lbiologiC¡¡lpwpcriyofliaua;¡lly-;:ccurrilighlll1:m
cryt!tftp0Îciiii.
.;(). :\synihcÜcpdypcptidch;wirig;p,;rol,llli¡fd\i:,;ecumbrycúiifor:u,:iionofp;i¡:;\f

,1)1 ,~ftÎw amino acid SCqU'.IKC set !,,;rli in T,ibk VI. m!icr tl1:'I1;¡ ';"',lill:i\Ce úi residue, l'llire);' within the: $C(jilC1\CC m¡mbcred I Üm)ii¡:h :;(¡.l:¡vin~;1 bin;ogi,:;i! prcpcny \lln~lnir;i1¡y.()çCiirr¡llg !Ulrmm ciythropoid¡n.
50. :\ process for the prodiic!Íon ür:i pOlYPt,ptidc l¡¡ving p:irt Or~\l! oethe pr¡Il~:Y

sln¡ctur;:! conformation and one or mor; orth.. bìo!ogic;:l propcriiö o(nalur~!ly.
occUfril\g cryilimr,oictìn, 5iiìd process compri,ing: growing, under suit:ib1c iiutrîcn! conditions, prokaiyotìc ,ir i:uk;:ryotic host cell, tr.n5foniicd or Ir.U1Sfcctcd with ,i
tlii.:xprcssim\

DNA vector according to daim 37, and isolating dcsircd polypeptide products of in silid vector. ofDN:\;;cquences

5!. Annniibodysuhst,:nccchnr:cicriwJbyimnHlI\Oreiiç!ivitywilhcryihwpoiciii:and

wi1h;i synthetic polypeptide b~ving ~ primary S!I\IClur¡¡ ccnforni~t¡(1n ~,ubst~nIÎnlly diiplic:itive of;: coniiniious scqucnc.: ofani¡nn acid rc,î,hics o:xt:u1l În n~\iur;illy-

¡¡ccurrìngerythropoic¡¡r.exccptforanypolypcptidcconi¡irísii\g:i,equcnccüf
amino acíd residues elltirely cmiiprcl\emkd ,v¡¡hin sC(jucncc, :\.P-P.R-L-l-C.¡).S-

I(.\f-L.I:.R- Y.L-L-E-A.\(
, ,

¡ 51. Aii ,wiibody according to claim;; i, ",,'hid: is:ì lIol\0donal :mtíbody. ,
, I , I 1

! 53. An :mlÍhody:;ccorJing \( cbim 5t, which is 1l pÜlydmi;1 .1I1ibëidy. i

.,' 5' I' h' . ,L ~ xi"y ;1~'Cm \E!,:_~~~i~~_-i '----_._.-- ,.I2..-.__.An ;l\ll ct' I'm£J~,_~c...~!C"~IIVC..'ill..,... I
65

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andasynihciicpoly¡icp¡idc-li:ivingc-lisctuCllCt-sclccICd fromihc~caucncc5: V.p.
D-T.t(- V -N-F- Y -!\- W .¡'.R-!i'¡.E. V .0; K.E.A-l.S"P.I'.!)./h\-S.:\-A; v- Y .S-l'.j'.

lAt.C.¡'.i..K.I.. y .T-(j.E-..-C.R.T.G-D.R.
59_

:\ ¡wlypi:piiJ:: prüdüci ülthe cxpn:ssi0l of ~l j)~:\ ,cqucncc- ;:êco:dinS hI d;llI\ ~8
ili¡lpWk;\t)'0tÎcürC\i).;¡I'Y0Ü;;ho,lcdL.

I

l~-~~--i Groun!!: DNA

--+-~
14.

,

,~_..,_.._-,,-,-_.--A DNA sequence fDr use in securing expresion in 3 prokaryotic Of c-ukaryolic host
cell of a polypepiide product having at IC3S1 a part ofihc primary slniclur.i

,

I.
, I I

confonnal¡oii and one or more of the biologiçal properties (If imiurally-occurring erythropoietin, $-id DNA $ctJucncc selected froin mnong: (:i) the DNA sequence
sd out in Tiblcs V ¡¡nct Vi or ihcír complementary strads; (hi DNA sequences

whìdi hybridizi: 10 the DNA ~cqucnccs Jdind in (~) or jj-agmcnts the-reoE ~nd (el DNA 5i:qucnces whîdi, btll for die degem:!;),)' ofi!ie gentiie eNe, wöulJ liybridi,.e l,) ihe DN,\ sc-qtlcncö delÎllcd in (3) \1 (hi.

))

:\ probryoiic () ¡:l)k;iryilic~ hüot cd) ir~nsformc-d Dr iml,(¡:~.te\Ì with" DN,\
sCljLl\:necaceordingioelaini ).lin;llI;\Incl'¡,!I()wingtb:ho:,icc!itucxprö.;,:lid

pciylx:ptidc¡irù,hlCL

,.~ "

:\ purified and ÎSlÍ¡~ted D1',\ Sea:Jenc~' coii;llg fer prd.;;iryütic or ,'iibr:'o!ic host

eXjlfcssionofap,-11y¡x:piidch;ivil\gpariorallofllieprirn;lr:.'slfUi:turaIC()i\fÒrin:,lion

:tndoncormoreofthebioiogicM,lctivitii:soferythropoictin.

is.
19.

.A.cDNAscqueiii:e;icordingwc!aiIl17.
A monkey species el)1hmpoictjn coding D~A sequence iiccQrdiiig to c!aìm IS.
A DNA seql!ei\CC iice-rdiiig to cliiim 19 iind including ihe prlJdn co-ding r¡;gion ,c~
fGrih íii

2ü.

Figurc5.

:;1. 2:;.
_.I.

,\ genGmic DNA sequence ¡¡ccording to ¡;aim 17.

A hU1liil1 s¡xciis erylliropoiÔn coding DNA sequence ,(ccording to claim 21,
1\ DNA scqiiCr.CC ;:;,xordíng to cbim 22 and il1cludil\g the protein ,;,,iliag rcgiür. sct

,-

Jorthjri Figurel,.
2.1.

A l1¡mu("clured DNA scquci\ce ¡iccürding 10 claim 17.

25.

A manuf"ciurcd DNA sequence accúrding to claim 24 :uitl including (lnc () more cooons prefc-md for expression in E. coli cells.
¡\ manuliicwrcd DNA ú"'liicncc iiccoriiíng 10 dilÌm 25. coding ¡,:ir expression of humiir ;;r-.;dcs ;,'ryi!¡wpoktiii
,\ miinUfiiçl\lfC'd DN,\ ,;cqiicnçc ;\ccol'din!:; h) cbini 26 inciudi:ig trl,~ pr01cin etiding

26.

27,
,

rc~',i()r; ~c! forth iii Fi.ö.l)rc 7

,.,_~,_._¡ 2~:~~~!1£~~l:!¡-'~hir;;d ¡?N,~..s(.'-,i~.~l\~;; iiCê)rJin_¡u?A~im :;.1 ;Hid im:I_¡ijín;!.2!.~S"'::r IH(j.£__,c

66

Case 1:05-cv-12237-WGY

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Page 12 of 12

Restction Group Claim Language
codcns preferred for expression m yeast Ctlls.

29,

A m;\Jiufaclurcd DNA sequence according to d:iill 28, ceing for cxprc5s¡mi of bunums¡xcicscl"'ùiropoii:iín.
,'1mimufaclurcd DNA sequence according 10 d;iim:in including the protein coding
¡cgion SCI forth iri Figure

30.

8.

.Il.

..\ D:\:\ ,cqucncc ¡;ccording III cbÎ:n 17 cilv;i!cn(!y i~swçirikd with i: dclcctahk

bbclsubst;mcc.
.'_.
"

:\ DN,\. ,cqi:i:ncc :~ccordil\¡; to .:Iaim 31 wlicr¡;;:: ibi: dclccl;ll.k Libel is ¡l raJi(ll;bd.

33.
3.1.

:\ ,in~!ç-st¡;ind DNA ~cq(jCf1CC ;)(((JlJing tt! d;iim.î ¡,
:\ puri!ìcd :md isolaied !)N:\ scqiicncc coding for ii polypeptide (¡,igmen¡ 01"

poiypcpt¡dcnnrilogofnawralìy-occllringi:ryihm¡xiciîri.
"

-,
36.

.'\. DNA scqucnçc çoding for lllhel'j,!;r'0. ¡Phc"';h":ro(~ ¡JhCI':iLci,\)' ¡1¡isiL,:,:), ¡AS:,:

des- Pro~ through Jlc~hi:a, ldcs.lliriÚ¡ through Argl"'lri'i), or f;.127-55b:ri).
A DN,\ sequence ¡¡ccNding 10 c!rim 34 which b ;, m:,m¡l~tCI¡¡rcd ,cq~¡cncc.

5S.

A ¡i\¡rilkd ;iid IsDbl(.d DNA Sequence ,is ~ct Dtlt iii Figure 5 Dr 6 Dr:l fmgm::m

¡!ici:oìüiihccornplcmenl:irysir;nJo(sidi;iscq\¡Cl1ccorfr¡);;mcli.

6f.

:\ biologic::!!y (unction;il cl¡Ci¡l:ir pla.mid or ,,;131 DN:" VCtlOr ¡¡¡cludiii&::, DNA

$cqutiicc;iecDfding:ocl;irn 1.1.
62.
A prokaJ)'oiic or eubryoiic hO$1 edl stably lr~l1sf()rnied or lfa!lsr~ctL'd with il ON,,,
"ecwrnccordirig 10

d;:iIi61,

63.

li biologically fUlKliona! c¡¡cllIM p!:ismid úr viml DNA vcc\(r including ,¡ DN,\.
seqtlcllcc;:ecmdingioc!:ijm 17,

6-.

A probryoiic DI ciik:iry"iic host ccll stub!y transfomicd or tmnsrcctd with:i DNA vccioraccordingI0c!;¡im63.

,,~ ..\ híülug:c;iily iÌ-:nÇii0il;d c'irCiil¡irpl;,,;niidür\"ir;il DN,\ vtçtor ind,¡diiig.;¡ I)~.-\

s~qtJen(~ ;lÇÇüfJíng wcl:iini 3.1_

(:5.

t\ prd;;lfYO¡i;, or ;:¡i!-MY(Jti(: Iw~\ (:cI! siab!y ir,;:bt()¡¡n~d m ir;llhl~çl~d i..ith ;) f)i'.-

VtClM ;~C(:Nd¡IlS il cbim 65.

! v.
i (,7

A biologically fwi:;lioi¡:\1 ,¡rcul;i pi:ismíd Dr viml DNA \'CClOf indmjjng ,; DX:\ scqu;;l1C;; ,¡ççorJing 10 c1;im 35.

63. A prokuyoiic Dr i:ubryotk h",;i cell Sl3b!y transformed úi Iran,fCcll. w¡ih:i DX:\ vector uccording lod~¡ni 67.

1_____._1

m. :\ pro-c,; for ilic production of¡i polypeptide having pm or all ofihc prim3f)' ¡
_'_m,,~...~!E!!£~ur¡¡1 ,£onfor:.:ition ¡¡~ £lnt ür iiort oftlic biolo¡:ic;:1 ;ictiviií,'S of lI;ltlJr;~I.~_.~l

67