Application/Control Number: 08/146,206
`
`Page 6
`
`Art Unit: 1642
`
`6.
`
`Any inquiry concerning this communication or earlier communications from the examiner
`
`should be directed to Julie E. Reeves. Ph.D. whose telephone number is (703) 308-7553.
`
`Julie E. Reeves, Ph.D.
`
`691 of 1033
`
`BI Exhibit 1002
`
`

`

`"
`
`Interview Summary
`
`Application No.
`08/146,2 106
`
`Applicant{s)
`
`Carter et al
`
`Examiner
`Julie E. Heeves, Ph.D.
`
`Group Art Unit
`1642
`
`111111
`
`I
`
`All participants (applicant, applicant'-s representative, PTO personnel):
`
`(11 Julie£. Reeves, Ph.D.
`
`(2) Wend"{_ Lee
`
`Date of Interview
`
`Jan 7, 1999
`
`(3)
`
`(4)
`
`Type:
`
`IX! Telephonic 0 Personal (copy is given to 0 applicant 0 applicant's representative).
`
`Exhibit shown or demonstration conducted: 0 Yes
`
`1XJ No. If yes, brief description:
`
`Agreement 0 was reached.
`
`IX! was not reached.
`
`Clalm(s) discussed: all pending
`
`Identification of prior art discussed:
`none
`
`'
`
`Description of the general nature of what was agreed to if an agreement was reached, or any other comments:
`Applicant indicated that the"{_ intend to file a sue.11.temental amdt.
`
`-
`
`-
`
`(A fuller description, if necessary, and a copy of the amendments, if available, which the examiner agreed would render
`the claims allowable must be attached. Also, where no copy of the amendents which would render the claims allowable
`is available, a summary thereof must be attached.)
`1. o - It is not necessary for applicant to provide a separate record of the substance of the interview.
`Unless the paragraph above has been checked to indicate to the contrary, A FORMAL WRITTEN RESPONSE TO THE
`LAST OFFICE ACTION IS NOT WAIVED AND MUST INCLUDE THE SUBSTANCE OF THE INTERVIEW. (See MPEP
`Section 7 13.04). If a response to the last Office action has already been flied, APPLICANT IS GIVEN ONE MONTH
`FROM THIS INTERVIEW DATE TO FILE A STATEMENT OF THE SUBSTAINCE OF THE INTERVIEW.
`
`2. 0 Since the Examiner's interview summary above (including any attachments) reflects a complete response to
`each of the objections, rejections and requirements that may be present in the last Office action, and since the
`claims are now allowable, this completed form is considered to fulfill the response requirements of the last
`Office action. Applicant is not relieved from providing a separate: record of the interview unless box 1 above
`is also checked.
`
`Examiner Note; You rnust sign and stamp this form unless it is an attachment to a siBned Office action.
`
`:\k~~\\~
`G>\ ~v~
`~~
`'/l~
`
`'
`
`U. S. Patent and Tradema<l< Office
`PT0-413 (Rev. 10-95)
`
`Interview Summary
`
`Paper No.
`
`43
`
`692 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`Official Do&ument - GENENTECH, INC.
`
`1 DNA W~. Soi.rh San Franrucu, Ol 94080-4990 Tel: 650-225-70:19 Fta: 65U·9S2-9881
`
`FAX fRANSt...llSSION COVER SHEET
`
`Dutt:
`
`l\pril 9, l !199
`
`To:
`
`E.ruminer J. &fVa
`
`Grui.p Arr Un1r. J 642 of US PTO
`
`(703)308-+:126
`
`&:
`
`U.S. Su. No 08/146,206
`
`filtd Novmibrr J 7, 1993
`
`{Arromq D11<1n No.: PU7U9P I)
`
`W&'!Uly M . Ltt
`
`CEJtTJllC(! TlON Of FAQ?JM!LE. TBANSMl'i!\JON
`
`J fuTd7 «rrtfy LWf th!> l"'J'P I> b/l•ffllrd1rt1/1 trotnt,.,iWd UJ tire P .. tnU ,.,.J '(,Olk1110Ti OjJltt 01' flit 44rt J,.,,_ llt/0"1
`
`Mp Sll11c/ll
`
`r'OU SHOULD RECEI \IE 2 PAGES. INCLUDING THIS COVER SH££T IF YOU DO NOT R.ECEJ\IE ALL THE PAGES, PLEASE
`O\LL 650-215-lO'J~
`
`Commtnts:
`
`CONF1p5Nn , , m
`
`riQTJ
`
`Tir.: ~ ~~J"fio'~ U\u ho.,.,._.. G":M~.....on (Ql'lt.l,t.l'I tl\Ull'U........., aoa1 C~.n. Ir"( • ..4.,,i:2'1 .. UIN~w.i 0.. Pfl"°'"r4 Th • .n.i111~..,yf'I .,. . ni.a'li.IW w«.&J fo. U'lc 61'.&o.• 1o.I"""" Ck 11\ltl)"
`"""'-I.on"'"" tla1i.. 1~ .,,tlil!ltl. Lt 1-
`.111~ 1tOt tN.11111~ 1a;..~1tl ,_. .lJu. U:w.& .a.If~..-.. ~t'fl•<t. .2o.U10o.lllln. • ~""' U"IC C'41frnu Of llW ~ .. lfOf'boJ."°" u An\,'.l.I/ pron.!)o.l40
`11 ~"'
`l lia'C'1~ &l\...t...:a...tw< .. 1 ftt'Oll, f*a-f\«.I') -o, &dr,-t~ • IZ'NlliG.Ad,1 llOU'V\ . . a:a ltnl"•&". IOC W
`•4'1'711 Of\N ~oiillldtln.o-.tt:. lAua .1uO Ll.r1cl••~ .. -.qn ~"<al IO U\e ~a.ndit:Cll ~tr'""'"
`
`693 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`Porenr Docket P0709Pl
`
`r
`U~.\~ -'-:( .J. c\ 'I
`\.'- c:, \~ cp?.
`.=#:-L{1
`
`'-
`
`Group Art Unit: 1042
`
`Examiner: J . Reeves
`
`.......
`·: ., i.
`
`tn re Application of
`
`Paul J. Corter er ol.
`
`Serial No.: 08/146.206
`
`E=iled: November 17. 1993
`
`For· METHOD FOR MAKING HUMANIZED
`ANTIBODIES
`
`·-
`
`. .
`
`. '
`
`~
`
`.
`
`:· '
`
`,.
`
`..
`
`.. . .
`
`.
`
`Aosponse to Restriction Reguiramam
`
`Ass1stanr CommisSioner of Patenrs
`Washington. D .C . 2023i
`
`Sir:
`Responsive to the Otf1ee Action dated March 29. i 999 at1d pursuant to tne telephonic conversation
`oetween the undersigned and Elaminer Ree11es of toaafs oa1e, App11cams nereby elect the species
`78H ("Species AA• and ·Species JJ•), witn traverse. Claims readable on tne electea species include
`claims 72-75, 102, 104. 105. 115-118, 122 and 124· 127. Applicants rraverse me restnc1ion
`requirement to me extent that 37 CFR 1. 129(b)( 1) states that in appheations such as the present
`application (which had been pending lor at least three years as of June 8, 1995 taking Into account
`reference made in lhe application under 35 USC 120 to USSN 01n15,272 filed June 14, 1991 ). ·no
`requirement ror restri1:tton or for tne tiling of divisional applications shall oe made or maintaineo in
`1he applk:ation after June B. 1995".
`
`Date: Apnl 9. 1999
`
`1 ONAWay
`So_ San Francisco. CA 94080·4990
`Pnone: (650) 225-1994
`Fat: (650) 952-9881
`
`694 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`•
`
`. Patent Docket P0709Pl
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`.
`In re Application of
`
`Group Art Unit: 1642
`
`Examiner: Julie Burke
`
`Paul J . Carter et al.
`
`Serial No.: 08/146,206
`
`Filed: November 17, 1993
`
`For: METHOD FOR MAKING
`HUMANIZED ANTIBODIES
`
`COMMUNICATION
`
`Assistant Commissioner of Patents
`Washington, O.C. 20231
`
`Sir:
`
`JUL 1 2001
`TEGH CENTER 1600/2900
`
`0
`
`:t:::>
`
`-
`"'
`
`:---<
`Ol rrl
`w O
`C>
`........
`!'\.)
`<O
`0
`0
`
`~
`
`As requested by Examiner Julie Burke enclosed is the specification for USSN
`
`07/715,272 (now abandoned) which is the priority document for the above-identified patent
`
`application .
`
`Date: June 9, 1 999
`
`1 DNA Way
`So. San Francisco, CA 94080-4990
`Phone: (650) 225- 1994
`Fax: (650) 952-9881
`
`:~:i~'
`
`. Lee
`Wendy
`Reg . No. 40,378
`
`Revised '10/1119$1
`
`695 of 1033
`
`BI Exhibit 1002
`
`

`

`(
`-l
`---------~~----~·-------...--------..-~""i~--------------~
`Application No.
`Apµ1 ... ant(s)
`081146,206
`Carter et al
`
`Interview Summary
`
`Examiner
`J ulie E. Burke. (Reeves), Ph.D.
`
`Group Art Un it
`1642
`
`All participants (applicant, applicant's representative, PTO personnel}:
`
`(1 ) Julie E. Burke, fReevesJ, Ph.D.
`
`(2) Wendy Lee
`
`(3} ~~~~~~~~~~~~~~~~~-
`
`(4)~~~~~~~~~~~~~~~~-
`
`Date of Interview ______ 16;:_...:;.J..;;;u.;..l ..;.1.;;..9.;;..9.:::..9 _ ____ _
`
`Type:
`
`IX! Telephonic
`
`0 Personal (copy is given to 0 applicant 0 applicant' s representative).
`
`Exhibit shown or demonstration conducted : D Yes
`
`!XI No. If yes, brief description:
`
`Agreement rl was reached.
`
`i&I was not reached .
`
`Identification of prior art discussed:
`none in detail
`
`Description of the general nature of what was agreed to if an agreement was reached, or any other comments:
`Examiner phoned to say the claims 43-44, 46-73, 75- 105, 115- 127 are in condition for allowance; claims 45, 74, 7 17
`are objected to for not further limiting the independent claims; claims 111- 112 are double parenting with claims reciting
`the VH subgroup Ill heavy chain consensus region, as allowed in 08/ 437, 642, accordingly a terminal disclaimer is
`necessary for the allowance of claims 117-112; claims 106- 710, 113- 114 and 128 need further prosecution. Applicant
`elected to not procede with the allowance at this time. A supplemental amdt will be filed today and an interview has
`been scheduled 23rd August.
`
`(A fuller description, if necessary, and a copy •Of the amendments, if available, which the examiner agreed would render
`the claims allowable must be attached. Also, where no copy of the amendents which would render the claims allowable
`is available, a summary thereof must be attached.}
`
`1. i 1 It is not necessary for applicant to provide a separate record of the substance of the interview.
`
`Unless the paragraph above has been checked to indicate to the contrary, A FORMAL WRITIEN RESPONSE TO THE
`LAST OFFICE ACTION IS NOT WAIVED AND MUST INCLUDE THE SUBSTANCE OF THE INTERVIEW . (See MPEP
`Section 713.04).
`If a response to the last Ofiice action has already been filed, APPLICANT IS GIVEN ONE MONTH
`FROM THIS INTERVIEW DATE TO FILE A STATEMENT OF THE SUBSTANCE OF THE INTERVIEW.
`2. ! 1 Since the Examiner' s interview summary above (including any attachments) reflects a complete response to
`each of the objections, rejections and requirements that may be present in the last Office action, and ~ince the
`claims are now allowable, this completed form is considered to fulfill the response requirements of the last
`Office action. Applicant is not relieved from providing a separate record of the interview unless box 1 above
`is also checked .
`
`Exarniner Noto: You must sign and s tamp this form unless 1t is an attachment to a signed Offic e action .
`
`U. S. Pa10111 •od T rademArk Ofllce
`PT0 -413 (Rev. 10-95)
`
`Interview Summary
`
`696 of 1033
`
`BI Exhibit 1002
`
`

`

`1 h ~Irr Official Document • GENENTECH, INC.
`
`/DNA Way. South Sari Fru,,cisco . CA <J4080-4CJ90 T.-1: 650-225-70.::9
`
`Fox: 650-952-9881
`
`FAX T~ANSMISSlON COVER SHEET
`
`Da~ :
`
`July 16, 19'19
`
`To:
`
`Cri;>lip Art Unir : 16~ 2 of US PH
`
`Faz:
`
`(703) 30,'j-4426
`
`U.S. Ser. No 0"!1146.2015
`
`.fllerl N1.1•·entbu / 7, 1993
`
`I Atrumey T>llt:k~I No.; P0109P 11
`
`Sender:
`
`Wtndy M. Lee
`
`Q!HTIFICA.l'ION OF,UC'\IMIL.f. TltA!(SMISStON
`
`f h • r" <Ufi/.• ''''" U.t. ,...,.~, iJ '"'"II focr;,,.11, ,,,...i,,.:"•d lo lkl: PtHMI o.nJ 1"'14emark OJJi•• "" lht1 do•c '"""'" bc/.ow.
`
`71111199
`J)oi.
`
`YOU SHOULD Rt::CE/Vf; 2 PACE{S). INCLLJl)INC THIS COVER SH£€ T. IF YOU DO NOT RECf..'IV£ AU. THE PAGr:s
`PLt:/'rSE CAI.I.. 650·?'1$-7039
`
`Coaunencs:
`
`Th: di&x"1J1r,c1\1t llCC'6"'~1"1)ihi;" 1h!I tJ.:.•"llfC. a:MV11u .. ll,,'f1 c.~\"11" .nr1."li•*'"'~"' ~ GC:f\i!f'rl'\"''.(;t'4. IJ'llC', •h..:n 1:.~ ... ft~111;,.1,w ;...i•ili:,-.."lt ""'•> 111fl)'Tr'.1M1on,.. 1MC"<'<:r.ru"'a '"""'"' .......... ~
`CW' CR,ft.t ft:-1-... .. ton rn111 1r.:.rtsmJQ~~· .i\:o:'- If)~ Mt' ftV" •Ii.: ff".w:l\Ck~ l\' •q•.,:.-t, f'll: ••")f'O l~ >•')o cU-.:to:.V",..., i;."t•> .. "'I• d1ilrA!o11•ftvi vr \IM!'"('~' c"'•uC11l&('lt.f ih;. !">_,,.,, ,.,.ron1-.·,•tr-ri ·~ •t...""-O'
`,...~u..'d_ Jf ~C!l• h>""l. r\;C'CiittO rNr frai"'lil .. : .. ~llW. pl(AX. ~if) " 'fl)' r.t.:r~' 11"'1c.•1:i~1, w \hOI -~-!' ll'f"1'1;'(' '<'" ••...: ((1\fil'1' ~, ttt.: ~··.:N' t.u. V t)\.C.JUI •u,,,, •If.' U\t fl.v'.,1J•1""'1C~
`of \ l..:il\ •o d\c '"lw.:r~ l\)::'1"11.c"'' ·
`
`697 of 1033
`
`BI Exhibit 1002
`
`

`

`r
`
`.
`
`.
`
`{)'f'~~ '{
`
`Patent Oucket P0709Pl
`.
`( (lb ~l1
`IN THE UNlTED ST ATES PA TENT AND TRADEMARK OFF1CE
`~t
`
`Jn re Application of
`
`Group An Unil: 164'.?
`
`P:iul J. Carter et al.
`
`Exnmin.:!r: J . Burli;c
`
`Serial No.: 081146.206
`
`filed : No\lcmber 17, 1993
`
`For: METHOD FOR MAKJNG
`HUMANIZED ANTIBODIES
`SUEPLC:-••1-"11 I " ·N l •~~N. 1
`
`Assistant Commissioner of Patents
`Washington, 0 .C. 20231
`
`Sir:
`
`Further to the Supplemental Amendment dated January 15, 1999. please amend the
`present application as follows:
`
`IN THE CLAIMS:
`. /
`../
`In line 3 of claims 43 and 11 S. please replace "further comprising an" with ··further
`comprising a Framework Re~on (FR)- -.
`-
`In line 4 of claim 77' please replace "further comprises an· with .. further comprises a
`Framework Region (FR)- -.
`
`REMARKS
`For claim prec1s1on. claims 43 . 72 and 115 now refer to a Framework Region (FR)
`substitution. which orovi,des anticedence for Framework Region (FR) in the claims which
`depend thereon.
`
`Respectfully submitted,
`
`By,G~NC.
`
`Wel'ldy M. Lee
`Reg. No. 40,378
`
`Date : July 16. 1999
`
`1 DNA Way
`So. San Francisco CA 94080·4990
`Phone: (650) 225· 1994
`Fax : (650) 952·9881
`
`698 of 1033
`
`BI Exhibit 1002
`
`

`

`Pac~n~ Dockac P070~--<::.._
`IN THE UNITED STATES PATENT AND TRADEMARK Cf'FICE
`
`~/
`
`Paul J. Cart:ar et al.
`i
`
`No . :
`
`09/14€, 206
`
`Group Art: Unit:.: 1£44
`
`Examiner: Julie Burke
`
`November 17, lSS3
`
`METHOD FOR HAJ.:ItJG HU~NrnED
`ANTIBODIES
`
`\.
`
`Ass1s'!:ant: Com.'llissioner of E'at~ent.s
`Washingt:on, O.C . 20231
`
`SUPPLEMENTAL NCE.NDMEN'r
`
`Sir:
`Furthe~ to the S~ppl emental Junend..'llent: dated July 16, 1999, p l e3se
`amend t:he pL·esent: application as follows :
`
`IN TkE
`
`CLAIMS:/
`/
`
`/
`
`/
`
`/
`can ii
`-v .'
`~yr; clcii.m 113, line 9, afi;er "one anot:her", please
`~~ ,:~erein the humanized variant binds antigen up i;o
`;V:~mcre t:\ght:ly t:han the parent: ant1bod~ binds ~nt:1gen--.
`~~it:;r(;t . .
`'fl~'"'l'in claim 114, line: l, please delet:e "at lea.st:" .
`( v1
`)
`
`/ Please
`
`claims 106-112, without: prejudice.
`
`In claim 128, ,.11ne 7, please insert: --up t:o abou t: 3-fold- - before
`" more tightly".
`
`699 of 1033
`
`BI Exhibit 1002
`
`

`

`08/H€
`
`, L06
`
`REMARKS
`
`The undeLSigned confirms having mec with Examine rs Burke and
`fe1see in the intecview August 23, 1959, and taKes this
`opportunity to thank them for tne courcesies excended in that
`int.erview.
`
`As requested by Examiner Burke 1n the above interview, claims
`113 and 128 have been revised, for cla im precision, to refer
`to tne humanized variant wnich binds antigen up to about 3-
`iold better tha n the parent antibody. Claims 113-114 and 128
`have been revised herein xn order to facilitate allowance of
`t he present application and without a cquiescing in any
`rejection. Bas1s f or che revisions of t hese claims i s found
`on at lease page 70, lines 31-32 ana in Table 3 on page 12.
`Aside from humani~ed anti-HER2 vAriants huMAb4D5-6 and
`huMAb4DS-8 in the present application, l t is notea cha~
`humanized Ml95 nas an affinit.y which is about 3-fold better
`than the parent antibody as rec1ted in claun 128 (see i1rst
`line on page 1153 of Co er al. J. 11rl1liunol. 148:1149- 1154
`<199~1 (of .record}; and Ca ron et al. Ci-.rlcar Resea.r:ch 52:6761-
`6761 (1992) (of recocd) 1.
`
`To avoid the obviousness- type double patenting r ejection of
`claim 111 over claim 47 o f co-pending applicat~on USSN
`08/ 437,642, Applicants have cancelled claims 111-112 herein,
`~ithout pre]udice to filing a continuing appl1cat1on directed
`r.t1areto.
`In addir.ion, i n order r.o simplify prosecucion, and
`without acq~iesc1ng in a ny obJection or reJection, claims
`106-110 have been cancelled. Applicants reserve rhe !'ight ~o
`
`700 of 1033
`
`BI Exhibit 1002
`
`

`

`OS1l4G, 20b
`
`file a continuing application directed to claims 106-110.
`
`Examiner Burke suggested that claims 45, 14 and 117 ce
`cancelled as not further limiting the independent claims on
`wh1ch they depend. The unders1gned pointed out tha~, due to
`the llse of t.he "comprising" language, claims 43, 72 and 115
`clearly encompass humanized antibody ~aciable domains or
`antibodies with one or more Framework Region (fR)
`substitutions, ~herein at lea3t one of those FR substitutions
`is 3et forth in the group of sites in the claims. Hence,
`claims 4S, i4 ond 117 4re fuLtn~r limiting and need not ce
`cancelled. The Examiner then asserted that, witho~t an upper
`lilllit on the numo.?r of FR subst1t ut1ons, independent claims
`43, 72 and 115 could read on a prior art antibody with an
`intac't rm1rinc variable domain. Applicants respectfully
`submit, in this rega rd, t hat given t.hat 'these claims are
`direct.ed to a "hwna nized" antibody variable demo.in or
`ant.ihody, it is apparent. t.hac the claims cannot encompass
`anticodies with intact murine variable domains. This is
`apparent from page ~' lines 29-34 and page 10, l!.nes 27-31.
`
`Dat.e: August. ?;(:>, 1S99
`
`By: -=.-"'!._:_~~~~~~~~~~---.
`Wendy M. Lee
`Reg. No.
`40,378
`
`l DNA Way
`So. San rranci sco, CA 94080-4590
`Phone: (650 J 225-19S4
`Fax: (650) 952- 9881
`
`3
`
`701 of 1033
`
`BI Exhibit 1002
`
`

`

`UNITED ST Id DEPARTMENT OF COMMERCE
`
`Patent and Trademark Office
`Address: COMMISSIONER OF PATENTS AND TRADEMARKS
`Washington, D.C. 20231
`
`FIRST NAMED INVENTOR
`CARTER
`
`p
`
`ATTORNEY DOCKET NO.
`709F'1
`
`I°"
`(.~ENENTEC:H, I NC .
`1 DNA WAY
`SOUTH SAN FRANCISCO CA 94080 - 4990
`
`HM22/1124
`
`EXAMINER
`BURKE, .J
`
`ART UNIT
`1642
`
`PAPER NUMBER
`
`DATE MAILED:
`
`1 1 /24/99
`
`Please find below and/or attached an Office communication concerning this appllcatlon or
`proceeding.
`
`CommlBSloner of Patents and Trademarks
`
`P f 0·90C (Aev. 21951
`
`1. Fiia Coo\/
`
`702 of 1033
`
`BI Exhibit 1002
`
`

`

`O&t \~., LOb
`
`..
`
`0
`
`•
`
`UNITED STATES DEPARTMENT OF COMMERCE
`Patent and Trademark Office
`COMMISSIONER OF PATENTS AND TRADEMARKS
`Washington, O.C. 20231
`p
`
`/FCE· 1994
`
`7 09P1 \/(>
`
`SERIAL NUMBER
`
`FILING DATE
`
`FIRST NAMED APPLICANT
`HM22 / 1124
`
`ATTORNEY DOCKET NO.
`
`1 DNA WAY
`SOUTH SAN FRANCISCO CA 9 4 080-4990
`
`EXAMINER
`1642
`
`ART UNIT
`
`PAP
`
`DATE MAILED:
`
`Please find below a communication from the EXAMINER in charge of this application
`Coltlmissioner of Patents
`
`1.
`
`2.
`
`Please see attachment.
`
`Any inquiry concerning this communication should be directed to Examiner
`Julie E. Burke, n~e Reeves, Ph . D, Art Unit 1642, whose telephone number
`is (703 ) 308-7553.
`
`703 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`Page 2
`
`Application/Control Number: 08/146,206
`
`Art Unit: 1642
`
`fa+b.c~~~
`DETAILED AC't'ION
`
`l.
`
`Since this application is eligible for the transitional procedure of37 CFR l.129(a), and the
`
`fee set forth in 37 CFR l.l 7(r) has been timely paid, the finality of the previous Office action is
`
`hereby withdrawn pursuant to 3 7 CFR 1.129(a). Applicant's second submission after final filed on
`
`8/26/98 has been entered.
`
`2.
`
`The amendment to claim 113, filed 8/30/97 as Amendment L, Paper no 54 is not in
`
`compliance with 3 7 CFR 1.121 because more than five words are included in the amendment to
`
`the claim.
`
`3.
`
`The application is not in compliance with the Sequence Requirements for the reasons set
`
`forth on ·the attached raw sequence listing error report. In brief, the application contains a new
`
`paper copy of the sequence listing containing 30 sequences, which was added by amendment G
`
`filed 1017/97. The computer readable fonn of the sequences filed on the same day has only 26
`
`sequences. Therefore the statements on page 3 of Paper no 32 filed 1017197 that the paper copy
`
`and computer readable fonn are the same is not sufficient. Additionally, it is not clear which new
`
`sequences have been added to the application, whether these sequences are new matter or
`
`whether the new sequences have unique SEQ ID NO:s.
`
`4.
`
`Since the above-mentioned reply appears to be bona fide, and (1) in order to allow
`
`applicant the opportunity to amend the claims as they intend and (2) to complete the application
`
`with regards to Sequence Requirements, applicant is given a TIME PERIOD of ONE (1)
`
`MONTH or THIRTY (30) DAYS, from the mailing date of this notice, whichever is longer,
`
`704 of 1033
`
`BI Exhibit 1002
`
`

`

`,,
`
`Application/Control Number: 08/ 146,206
`
`Art Unit: 1642
`
`•
`
`Page 3
`
`within which to supply the omission or correction in order to avoid abandonment.
`
`EXTENSIONS OF THIS TIME LIMIT MAY BE GRANTED UNDER 37 CFR l .136(a).
`
`5.
`
`In an interest to complete the record of which papers have been entered in to the
`
`application, the following section is enclosed.
`
`6.
`
`Claims 1-8, 10-12, 15 and 22-42 have been canceled and claims 43-114 added by
`
`Amendment H filed 9/26/98 as paper no 39 along with the Shak Declaration under 1.132.
`
`7.
`
`Claims 43, 72, 104-106 and 112 have been amended by Amendment I, filed 11/6/98 as
`
`paper no 42.
`
`8.
`
`Claims 43-44, 72-73, 104-106, 113- 114 have been amended and claims 115-128 added by
`
`Amendment J filed Ill 5/99 as Paper no 44.
`
`9.
`
`Claims 43 and 72 have been amended By amendment K filed 7/ 16/99 as paper no 51.
`
`10.
`
`Claims 106-112 have been canceled, claims 114 and 128 amended by amendment L field
`
`8130199 as paper no 54. Please note in view of the noncompliance with 37 CFR 1.121 , the
`
`amendment to claim 11 3 has not been entered.
`
`11 .
`
`Claims 43-105, 113-128 are pending and under examination.
`
`12.
`
`It is noted that the Restriction Requirement set forth in Paper no 48 mailed 3129/99 has
`
`been withdrawn in view of the arguments set forth in Paper no 49 filed 4/9/99.
`
`13.
`
`Once the application is in compliance with the Sequence Requirements and the claims are
`
`amended as applicant's intended, the claims will be examined for their merits.
`
`705 of 1033
`
`BI Exhibit 1002
`
`

`

`. , . ,·
`
`Application/Control Number: 08/146,206
`
`Art Unit: 1642
`
`••
`
`Page4
`
`14.
`
`Any inquiry concerning this communication or earlier communications from the examiner
`
`should be directed to Julie E. Burke, nee Reeves, Ph.D, whose telephone number is (703) 308-
`
`7553. The examiner can normally be reached on Monday through Friday from 8:00 am to 5:30
`
`pm, with alternate Fridays off. ff attempts to reach the examiner by telephone are unsuccessful,
`
`the examiner's supervisor, Paula Hutzell, can be reached on (703) 308-4310. Any inquiry of a
`
`general nature or relating to the status of this application or proceeding should be directed to the
`
`Group receptionist whose telephone number is (703) 308-0196.
`
`15.
`
`Papers related to this application may be submitted to Group 1600 by facsimile
`
`transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Crystal
`
`Mall 1. The faxing of such papers must conform with the notice published in the Official Gazette,
`
`1096 OG 30 (November 15, 1989). The CM1 Fax Center telephone number is (703) 305-7401 .
`
`RespectfulJy,
`
`q~,~
`
`Julie E. Burke, nee Reeves, Ph.D.
`
`Primary Patent Examiner
`
`(703) 308-7553
`
`706 of 1033
`
`BI Exhibit 1002
`
`

`

`• .. °'~
`
`r.w
`
`V V(
`
`... , \ . /
`
`RECEHND 0--\) Iv ~ -
`vJD
`JllN 0 3 2000
`I• 0
`DEC 2 8 1999 t;
`.
`P,Cl"'f.l\lf:"Q
`,
`f
`TECH CENTER. 1600/M&lDb~k~f~~ib~~{ ·. 0 I 2 9 O o
`~&
`rRAo~t--~
`IN THE UNITED STATES PATENT AND TRADEMARK OF~1!f?J -l; p;; 12: ~ 3
`
`1
`
`"
`
`\
`"1?-4
`
`Group Art Unit: 1642
`
`Examiner: J. Burke
`
`In re Application of
`
`Paul J. Carter et al.
`
`Serial No.: 08/146,206
`
`Filed: November 17, 1993
`
`For: METHOD FOR MAKING
`HUMANIZED ANTIBODIES
`
`SUPPLEMENTAL AMENDMENT AND RESPONSE TO OFFICE COMMUNICATION
`
`Assist ant Commissioner of Patents
`Washington, D.C. 20231
`
`Sir:
`
`Responsive to the communication dated November 24, 1999, please amend the present
`
`application as follows:
`
`IN THE SPECIFICATION:
`On page 9, line 16, please replace "(I)" wit7· )--.
`
`L r/
`On page 9, line 16, please replace "(n)" wr)--.
`
`On page 9, line 17, please replace "(0" with-¥-
`
`On page 62, line 3, please replace "12301 P a r k i / -Rockville, MD" with --10801
`
`University Blvd., Manassas, VA--.
`
`On page 84, line 3, please replace "(Rockville, MD)" with --(Manassas, VA)--.
`
`/
`
`\
`
`,\A
`
`707 of 1033
`
`BI Exhibit 1002
`
`

`

`Please replace the existing sequence li~pecification with the attached sequence
`
`listing (pages 90-105).
`
`f ·
`
`IN THE CLAIMS:
`
`Please amend claim 113 as follows:
`
`113.
`
`(Twice Amended) A humanized vari nt of a non-human parent antibody which binds
`
`an antigen with better affinity than the par nt antibody and comprises ~- consensus human
`
`variable domain of a human heavy chain i munoglobulin su~group wherein amino acid
`
`residues formingComplementarity Deter
`
`·
`
`g Regions (CDRs)thereof comprise non-human
`
`antibody amino acid residues, and further co prises a Framework Region (FR) substitution
`
`where the substituted FR residue: (a) noncoval ntly binds antigen directly; (b) interacts with
`
`a CDR; (c) introduces a glycosylation s,ite whic affects the antigen binding or affinity of the
`
`antibody; or (d)participates in. the VL-VH interfa e by affecting the proximity or orientation of
`
`the VL and VH regions with respect to one ano er. wherein the humanized variant binds
`
`arent antibod binds anti en.
`
`REMARKS
`In the above communication, the Examiner states that the amendment to claim 113 filed
`
`8/30/99 (Paper# 54) was not in compliance with 37 CFR 1.121. Accordingly, claim 113 is
`
`amended herein in a manner which complies with 37 CFR 1.121. Comments in paragraph 2
`
`on page 2 of the 8/30/99 amendment with respect to the amendment of claim 113 are
`
`incorporated herein.
`
`The Examiner further states in the above communication that the substitute sequence listing
`
`filed 1017/97 is not in compliance with the sequence requirements. Applicants submit that
`
`their records indicate that the content of the CRF of the sequence listing filed 10/7/97 was
`
`indeed the same as the paper copy of that sequence listing filed 10/7/9?. Nevertheless, a
`
`replacement sequence listing (paper copy and CRF) are filed herewith. In accordance with 37
`
`CFR §§ 1.821 (f) and (g), the undersigned hereby states (a) that the content of the paper and
`
`computer readable sequence listings submitted herewith is the same; and (b) that this
`submission includes no new matter.
`
`708 of 1033
`
`BI Exhibit 1002
`
`

`

`With respect to the attached sequence listing, Applicants point out that due to the
`
`nonprejudicial cancellation of claim 41 (which referred to SEQ ID NO's 27-30) in the 8/24/98
`
`amendment, SEQ ID NO's 27-30 have been removed from the sequence listing filed herewith.
`
`For the Examiner's convenience, Applicants will summarize here the differences between the
`
`1.
`
`presently-filed sequence listing, and the originally-filed (11117/93) sequence listing:
`SEQ ID N0:4 was corrected 1017/97 to correspond to the HUV HIII sequence in Fig. lB.
`SEQ ID N0:19 was corrected 6/2/94 to correspond to the niuxCD3 sequence in Fig. 5.
`
`2.
`
`3.
`
`4.
`
`SEQ ID N0:23 was amended 6/2/94 to correspond to the pH52-8.0 sequence in Fig. 6A.
`
`SEQ ID N0:26 was added 9/'2/97 for the hu.xCD3vl sequence in Fig. 5.
`
`Corrections to the specification have been made hereinabove as follows: The symbols from Fig.
`
`3 have been corrected on page 9; and the ATCC address has been updated on pages 62 and 84.
`
`Applicants submit that no new matter is added by these amendments.
`
`Further prosecution on the merits is anxiously awaited. Should the Examiner have any
`
`questions concerning this submission, she is invited to call the undersigned at the number
`
`noted below.
`
`Respectfully submitted,
`
`GENENTECH, INC.
`
`By:~~
`
`WendyM.Lee
`Reg. No. 40,378
`
`Date: December~ 1999
`
`lDNAWay
`So. San Francisco, CA 94080-4990
`Phone: (650) 225-1994
`Fax: (650) 952-9881
`
`709 of 1033
`
`BI Exhibit 1002
`
`

`

`RECEIVE
`JAN 0 3 20C
`TECH CENTER 1 SOC
`
`v
`0
`DEC 2 8 919 ~
`~
`~
`1?-
`~
`<I TRAofN.P..~"t-'5
`
`Sequence Listing
`
`SEQUENCE LISTING
`
`(1) GENERAL INFORMATION:
`
`(i) APPLICANT: Carter; Paul J.
`Presta, Leonard G.
`
`(ii) TITLE OF INVENTION: Method for Making Humanized Antibodies
`
`(iii) NUMBER OF SEQUENCES: 26
`
`(iv) CORRESPONDENCE ADDRESS:
`(A) ADDRESSEE: Genentech, Inc.
`(B) STREET: 1 DNA Way
`(C) CITY: South San Francisco
`{D) STATE: California
`(E) COUNTRY: USA
`(F) ZIP: 94080
`
`(v) COMPUTER READABLE FORM:
`(A) MEDIUM TYPE: 3.5 inch, 1.44 Mb floppy disk
`(B) COMPUTER:
`IBM PC compatible
`(C) OPERATING SYSTEM: PC-DOS/MS-DOS
`(D) SOFTWARE: WinPatin (Genentech)
`
`(vi) CURRENT APPLICATION DATA:
`(A) APPLICATION NUMBER: 08/146206
`(B) FILING DATE: 17-Nov-1993
`(C) CLASSIFICATION:
`
`(vii) PRIOR APPLICATION DATA:
`(A) APPLICATION NUMBER: 07/715272
`(B) FILING DATE: 14-JUN-1991
`
`/fV\ I
`
`(viii) ATTORNEY/AGENT INFORMATION:
`(A) NAME: Lee, Wendy M.
`(B) REGISTRATION NUMBER: 40,378
`(C) REFERENCE/DOCKET NUMBER: P0709P1
`
`(ix) TELECOMMUNICATION INFORMATION:
`(A) TELEPHONE: 650/225-1994
`(B) TELEFAX: 650/952-9881
`(2) INFORMATION FOR SEQ ID NO:l:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 109 amino acids
`(B} TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO : l:
`
`Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
`1
`5
`10
`15
`
`Gly Asp Arg Val Thr Ile Th± Cys Arg Ala Ser Gln Asp Val Asn
`20
`25
`30
`
`90
`
`710 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`Th;r: Ala Val Ala Trp Tyr Gln Gln Lys
`35
`
`Pro
`40
`
`Gly Lys Ala Pro Lys
`45
`
`Leu Leu Ile Tyr Ser Ala Ser Phe Leu
`50
`
`Glu
`55
`
`Ser Gly Val Pro Ser
`60
`
`Arg Phe Ser Gly Ser Arg Ser Gly Thr
`65
`
`Asp
`70
`
`Phe Thr Leu Thr Ile
`75
`
`Ser Ser Leu Gln Pro Glu Asp Phe Ala
`80
`
`Thr
`85
`
`Tyr Tyr Cys Gln Gln
`90
`
`His Tyr Thr Thr Pro Pro Thr Phe Gly
`95
`
`Gln
`100
`
`Gly Thr Lys Val Glu
`105
`
`Ile Lys Arg Thr
`109
`
`(2) INFORMATION FOR SEQ ID N0~2:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH; 120 amino acids
`(B) TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi} SEQUENCE DESCRIPTION: SEQ ID N0:2:
`
`Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
`1
`10
`5
`15
`
`Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Asn Ile Lys
`20
`25
`30
`
`Asp Thr Tyr Ile His Trp Val Arg Gln .Ala Pro Gly Lys Gly Leu
`35
`40
`45
`
`Glu Trp Val Ala Arg Ile Tyr Pro Thr Asn Gly Tyr Thr Arg Tyr
`so
`55
`60
`
`Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Ala Asp Thr Ser
`65
`70
`75
`
`Lys Asn Thr Ala Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
`80
`85
`90
`
`Thr Ala Val Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr
`95
`100
`105
`
`Ala Met Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
`110
`115
`120
`
`(2) INFORMATION FOR SEQ ID N0:3:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 109 amino acids
`(B) TYPE: Amino Acid
`{D) TOPOLOGY: Linear
`
`91
`
`711 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`1
`
`•
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:3:
`
`Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val
`1
`5
`10
`15
`
`Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Val Ser
`20
`25
`30
`
`Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys
`35
`40
`45
`
`Leu Leu Ile Tyr Ala Ala Ser Ser Leu Glu Ser Gly Val Pro Ser
`50
`55
`60
`
`Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
`65
`70
`75
`
`Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln
`80
`85
`90
`
`Tyr Asn Ser Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Val Glu
`95
`100
`105
`
`Ile Lys Arg Thr
`109
`
`(2) INFORMATION FOR SEQ ID N0:4:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 120 amino acids
`(B) TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:4:
`
`Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
`5
`10
`15
`1
`
`Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
`20
`25
`30
`
`Asp Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
`35
`40
`45
`
`Glu Trp Val Ala Val Ile Ser Glu Asn Gly Ser Asp Thr Tyr Tyr
`so
`55
`60
`
`Ala Asp Ser Val Lys Gly Arg Phe Tbr Ile Ser Arg Asp Asp Ser
`70
`75
`65
`
`Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
`80
`85
`90
`
`Thr Ala Val Tyr Tyr Cys Ala Arg Asp Arg Gly Gly Ala Val Ser
`95
`100
`105
`
`Tyr Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
`110
`115
`120
`
`92
`
`J ,..,......,
`
`712 of 1033
`
`BI Exhibit 1002
`
`

`

`(2) INFORMATION FOR SEQ ID NO:S:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 109 amino acids
`(B) TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO:S:
`
`Asp Ile Val Met Thr Gln Ser His Lys Phe Met Ser Thr Ser Val
`10
`15
`l
`5
`
`Gly Asp Arg Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Asn
`20
`25
`30
`
`Thr Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly His Ser Pro Lys
`35
`40
`45
`
`Leu Leu Ile Tyr Ser Ala Ser Phe Arg Tyr Thr Gly Val Pro Asp
`SO
`SS
`60
`
`Arg Phe Thr Gly Asn Arg Ser Gly Thr Asp Phe Thr Phe Thr Ile
`65
`70
`75
`
`Ser Ser Val Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln
`90
`BO
`BS
`
`His Tyr Thr Thr Pro Pro Thr Phe Gly Gly Gly Thr Lys Leu Glu
`95
`100
`105
`
`J~ A I Ile Lys Arg ~~:
`vv l .l x (2) INFORMATION FOR SEQ ID ·N0:6 :
`(AA.
`lJVV
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 120 amino acids
`(B) TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:6:
`
`Glu Val Gln Leu Gln Gln Ser Gly Pro Glu
`5
`10
`1
`
`Leu Val Lys Pro Gly
`15
`
`Ala Ser Leu Lys Leu Ser Cys Thr Ala Ser
`20
`25
`
`Gly Phe Asn Ile Lys
`30
`
`Asp Thr Tyr Ile His Trp Val Lys Gln Arg
`35
`40
`
`Pro Glu Gln Gly Leu
`45
`
`Glu Trp Ile Gly Arg Ile Tyr Pro Thr Asn
`50
`55
`
`Gly Tyr Thr Arg Tyr
`60
`
`Asp Pro Lys Phe Gln Asp Lys Ala Thr Ile
`65
`70
`
`Thr Ala Asp Thr Ser
`75
`
`93
`
`1 . ..., </
`
`713 of 1033
`
`BI Exhibit 1002
`
`

`

`Ser Asn Thr Ala Tyr Leu Gln Val Ser Arg Leu Thr Ser Glu Asp
`80
`85
`90
`
`Thr Ala Val Tyr Tyr Cys Ser Arg Trp Gly Gly Asp Gly Phe Tyr
`95
`100
`105
`
`Ala Met Asp Tyr Trp Gly Gln Gly Ala Ser Val Thr Val Ser Ser
`110
`115
`120
`
`(2) INFORMATION FOR SEQ ID N0:7:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 27 base