P'lb-103X
`(Rev. 7-931
`
`FILING RECBPT
`
`~e'o'i
`/J.l' 1\IN
`.-2 ?
`'1094
`
`.• J.
`
`•
`
`UNITED STATES DEPARTMENT OF COMMERCE
`Patent and Trademark Office
`ASSISTANT SECRETARY AND COMMISSIONER
`OF PATENTS AND TRADEMARKS
`Washington, D.C. 20231
`I GRP ART UNIT I FIL FEE REC'D jATTORNEY DOCKET NO.j DRWGS I TOT Clj IND CL
`1804
`$1,592 . 00 709Pl
`18
`
`APPLICATION NUMBERj FILING DATE
`
`08/ 146,206 11/17/93
`
`9
`
`9
`
`JANET E. HASAK
`GENENTECH, INC.
`460 POINT SAN BRUNO BOULEVARD
`SOUTH SAN FRANCISCO, CA 94080-4990
`
`RECEIVED
`
`MAY 131994
`
`GENENTECH, INC. LEGAL DEPT.
`
`Receipt Is acknow1edged of this patent application.
`It will' be consldor11d 111 Its order anrl yoll will be nollflo•I as to tho Msulto of
`tho axamlnallon, 6<J sure to provldo tho u.S. APPLICATION NUM6ER, FILING DATE. NAME OF APPLICANT, and TITLE OF INVENTIOll
`when Inquiring about !his appllcatlon. Fae!! transmitted by check or draft are subfecl to colloctlon. Please verify the accuracy ol the
`data presented on this receipt.
`If a n arror is noted on thl• Allng Recelpr, plHte write to the Applicetlon Procenlllg Olvielon'e Cu1tomer
`Corr.cllon Branch within 10 day• of receipt. PIHH provide a c:opy of the Fifing Receipt with th• changes noted thereon.
`Appllc:ant(s)
`PAUL J. CARTER, SAN FRANCISCO , CA; LEONARD G. PRESTA,
`SAN FRANCISCO , CA.
`
`CONTINUING DATA AS CLAIMED BY APPLICANT-
`THI S APPLN IS A 371 OF
`/US92/05126 06/15/92
`
`FOREIGN/PCT APPLICATIONS-PCT
`
`PCT/US92/05126 06/15/92
`
`TITLE
`IMMUNOGLOBULIN VARIANTS
`
`PRELIMINARY CLASS : 435
`
`231 of 1033
`
`BI Exhibit 1002
`
`

`

`WORLD INTELLECTUAL PROPERTY OR.ATION
`International Bureau
`
`INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCl)
`WO 921226521
`
`(11) International Publication Number:
`
`(51) International Patent aasslfication 5 :
`CllN lS/13, C12P 21108
`C07K 13/00, Cl2N S/10
`G06F 15/00
`
`At
`
`(43) lnternational Publication Date:
`
`23 December 1992 (23.12.92)
`
`(21) International Application Number:
`
`PCT/ US92/05126
`
`(22) International Flliog Date:
`
`15 June 1992 (15.06.92}
`
`(JO) Priority data:
`715,272
`
`14June 1991 (14.06.91)
`
`US
`
`(60) Parent Applle1tion or Grant
`(63} Related by Continuation
`us
`Filed on
`
`715,272 (CIP)
`14 June 1991 (14.06.91)
`
`(71) Applicant (for oil designated States except US): GENEN(cid:173)
`TECH, INC. (US/US); 460 Point San Bruno Boulevard,
`South San Francisco. CA 94080 (US).
`
`(72) lnveafors: and
`(75) Inventors/Applicants (for US only) : CARTER, Paul, l .
`(GB/US]; 2074 18th Avenue, San Francisco, CA 941161
`(US). PRESTA, Leonard, G. (US/USJ; 1900 Goughi
`Street, 111206, San Francisco, CA 94109 (US}.
`
`(74) Agents: ADLER, Carolyn, R. et al.; Genentech, Inc., 4601
`Point San Bruno Boulevard, South San Francisco, CA
`94080 (US).
`
`(81) Deslgoaled States : AT (European paten!), AU, BE (Euro··
`pean patent), CA, CH (European patent), DE (Euro.
`pean patent), DK (European patent}, ES (European pa(cid:173)
`tent}, fh (European patent}, GB (European patent), GR
`(European patent), IT (European patent), JP, LU (Euro·
`pean patent), MC (European patent), NL (European pa(cid:173)
`tent), SE (European patent), US.
`
`Published
`With inremational seardi repon.
`Before the expira1ion of the time limit for amending the
`claims and to be republished in 1he event of the receipt of
`amendments.
`
`(S4)Title: METHOD FOR MAKING HUMANIZED ANTIBODIES
`
`(57) Abstract
`
`Variant immunoglobulins, particularly humanized
`antibody polypeptides are provided, along with methods
`for 1heir preparation and use. Consensus immunoglobulin
`sequences and structural models are also provided.
`
`Annal b11Vi. ortmVH alilOIDfll IDpAXI u:mplm
`J '.....A..-~ -A.--A.-.....A...-._., * s·
`
`1.Upit
`1. balia ...... Ned olilOIDfll
`3. Amal ID pAKI lallplla (Xliol-, SnJ•)
`' · Emzid and lipze
`
`J. Tnmfarm E. all
`2. bolall Jlbqcmid pool
`3. &deb far lni\. llld bDVff(r.\o r , SQ&/.,
`'· Seqamc:e ..nty
`
`232 of 1033
`
`BI Exhibit 1002
`
`

`

`r:__..;i~ UNITED sv!L DEPARTMENT OF COMMERCE
`_ · 1&i' · Pam.nt and Trademark Office
`\ t!!'J:i/ Address: COMMISSIONER OF PATENTS ANO TIWJEMARKS
`----
`FIRST NAMED APPLICANT
`
`~" --......
`
`Washington, O.C. 20231
`
`SERIAL NUMBER
`
`FILING DATE
`
`ATTORNEY DOCKETT NO.
`
`EXAMINER
`
`ART UNIT
`
`PAPER NUMBER
`
`All participants (applicant, applicant's representative, PTO personnel):
`
`DATE MAILED:
`EXAMINER INTERVIEW SUMMARY RECORD
`
`(1) ~~ ~\)~ (_\)To)
`L,~ - '-
`( (>To)
`\-Wf~
`a3 Au,qq
`
`(2)
`
`w~ry ~e.
`
`(3)
`
`(4)
`
`Data of Interview
`Type: D Telephonic ~Personal (copy Is given to D applicant ~ applicant's representative).
`Exhibit shown or demonstration conducted: 0 Yes 0 No. 1f yes, brief description: _ __./..)L..=.oO-.....cl..."""'"- - - - - - - - - - - - - - - - -
`
`Agreement D was reached with respect to some or all of the clalms In question. Olwas not reached.
`
`Clalmsdiscussed:---'t\{'+"t_.\_-1~......, .... &.c_.,.,,.,...'")-..--------------------------- -(cid:173)
`~~fi~~~~M~d~~s~--~~-~~-·h~~~~~~~----------------------------
`
`DescnpUon of the general nature of what was agreed to If an agreement was reached, or any other commenls: A.pf) ,'cp. k
`lfr &a..:,.,,,_
`f\,9\i~ w-\e.Jl
`.l. ~ \""i>
`\IL
`
`I
`
`t :l-K .
`
`(A fuller description, H necessary, and a copy of the amendments, II available. which the e)(amlner agreed would mnder the claims allowable must be
`attached. Also, where no copy of the amendments which would render the claims allowable Is available, a summary thereof must be attached.)
`
`0 1. It is not necessary for applicant to provide a separate record of the substance of the Interview.
`
`Unless the paragraph below 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 (e.g., Items 1·7 on the reverse side of this form). If a response to the last Office
`action has already been filed, then applicant Is given one month from this Interview dale to provide a statement of the substance of the Interview.
`
`0 2. Since the examiner's Interview summary above (Including any attachments) reflects a complete response to each of the objections, rejections and
`requl(ements that may be present In the last Office action, and since the claims are now allowable, this completed form Is considered to fulfill the
`a separate record of the substance of the interview unless
`response requirements of the last Office action. Applicant Is not relieved from provl
`box 1 above is also checked.
`
`PTOL-413 (REV. 2 -93)
`
`233 of 1033
`
`BI Exhibit 1002
`
`

`

`rrt\
`~
`.__ ______ ....._ ____ __._______ --- -------
`I Sf RIAL NUMBER
`
`FIUNG OAT~----F,-RS-T-NA-ME_O_IN_V_E-NTO_R ____ _ _
`
`_,},....A_T_TO~t-.IEY OOC~El.NO
`
`UNITED STATES DEPARTMENT OF COMMERCf
`P•C.11& end Tredem•ril Office
`AddreH : COMMISSIONER OF PATENTS ANO TRADEMARKS
`Wutftngton. O.C. 20231
`
`08114€-,206
`
`11 /17/93
`
`CARTER
`
`J ANET E. HASAK
`GENENTECH.
`I NC .
`460 POI NT SAN BRUNO BOl.ILEV ARD
`SOUTH SAN FRANCI SCO, CA
`94 030 -499 0
`
`18 M2/0826
`
`t h" ;, a cc:n111un•c..:11.on llOOl lhe ou mrnrr ·n e'larg<i ol your •pp!Dlio~.
`COMMISSIONEn Of Pl\ TENTS ANO TAADEMARKS
`
`p
`
`.
`~l:>AM9-;- £:r-
`
`709F' \
`EXAMINE- A-- - - - - ,
`- -\ .--·- -
`· -
`-
`
`r -PAPEk~MBER · 1
`
`L ART UNIT
`-----~----~------'
`1806
`
`OATE MAILED:
`
`0 8 / 2 6/ 9 4
`
`0 TNll~,_._,._....
`0 Allpoilllwto~llled on ___ __ _ 0 Thia~ 11!1 m.O. fulal.
`<Zf' inontll(el.
`.3 fJ' days from the dale ol lhls letter.
`A lhaRs.s ltallOfJ !*bl tor,..._ to lllllJ Slbt la 981 to GPif'A
`35 u.s.c. 133
`
`Flllkn to .....-CS ..... 0. l*tod flDr .....,_ . . -
`
`0. IPClllcdcln to i.-na abendOOed.
`
`l(a) Ml f'MT fW 11M AC1lOll:
`TIE "GU.
`,_,I
`'· 0 NoOlle Of IMwwwww ai.s Dr es.m.-. PTD-192.
`2. 0 Notice .. Patent Drawing, PT0-943.
`I. 0 NollceOf Matetlbr~ PT0-1449.
`&. 0 Nob of Informal Plllenl AppOcatlon, Form PT0-152.
`I. 0 • dlwmallOn on Hlllr ID Blllcll Dnllllno Ow1gell. PT0-1474 .
`I. 0 - - - -- - -- - - -- - - -
`
`-/~
`rr:i
`1. ~ Clalnm ___ _._-'----- - -- --
`
`-
`
`-
`
`- - - - - --
`
`-
`
`- - --
`
`ate pending In Iha &Pflllcatlon.
`
`- -- - - - - - -- - -- - - -- - - - are wltr.drewn trom conaldwatlon.
`a. 0 a.rm _ ___ ______ ______ _______ _ ___ _ 11a .. been cancallacl.
`~ 0 Qllnw ________ ____ _______
`
`_ _______
`
`_
`
`.,.lllJOwad.
`
`4. 0 Cllllnm- - -- -- -- - -- -- -- -- -- - - -- -- -- - .,.,.jacled.
`
`I. 0 Cllllm- - -- -- - -- -- -- - -- -- - -- -- - - -- - 319o bjKtecllo •
`.. 21 amrns _ _ l ... -_1.-"'8 _ _ _ _ _ ____ _________ -
`.. bjacl to r98l1tcllon or elactlon raqulramenl.
`
`1. 0 Tllla •8'31111117 _ .. , llm ._., llmll llllti llllarnlll dr8Wlnga undw 37 C. F.R. 1.85 wtllC:h -
`
`accmptable for examination pu~.
`
`. Under :rr C. F.R 1.84 ! ' - Orewlnga
`I. 0 The CDn'8Cl9d or......,.. 4'-*'0I '-....,,.,..._,on
`••ff• 0 - _.....,... . . wqMllalb1 or NollDI re Patent OrawlllO. ~844).
`-
`0
`1IL 0 The prupoa9ll ~Of .-1111111......iOf dnlWlnga. filed on - - - ---ha (r-) been 0 llj)p(O....cl by Iha
`....... 0 ............. 1119_._C-~).
`
`recettad 0 not been receMld
`'D ........... d Iha dllm . . prbtly ........ u.s.c. 119. The cerllllad QCIPY lla8 0 -
`12.. 0 Aclkl
`0 - . . i tn...-i ........... . . -.... _
`_ ____ __ ; llledon ___ ______ _ _ _ _ _ _
`
`1
`
`U. 0 ~ 11111......-. ........ to be In CDldlllen tor~ 4DQ1!P1 !or eonnai maltW'8. prosecution as to Iha marlte la doeed In
`- -. . wlDI DJesnc;OaUlllW &'*'9~ 1935 c.o. tt; '53 0 .G. 2 13.
`
`---
`
`-----·- - -
`
`PTOl.-3211 (Aow. NII
`
`- -· - -- -
`
`EXAMINER'S ACTION
`
`234 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`Serial No. 08/146,206
`
`Art Unit 1806
`
`•
`
`2
`
`I.
`
`II.
`
`III.
`
`15. Restriction to one of the following inventions is required
`under 35 U.S.C. § 121:
`Claims 1-12'~and 1~,) drawn to a method of making a
`humanized a:'n tibody, ' classified in Class 4 3 5, subclasses
`69.6 , 69.7 , 70.21, 91, 172 . 2, 240 . 1, 240 . 27, 252 . 3,
`320.1 and Class 536, subcl ass 23.53
`Claim 13J drawn to a polypeptide, classified in Class
`530, subclass 325.
`Claim 14{ drawn' to a polypeptide, classified in Class
`530, subclass 325.
`Claim 16). drawn to a computer, classified in Class 364,
`subclass 413.
`Claim 17! drawn to a computer representation,
`classifi~d in Class 36, su~class 223.3, 223.4, 224.1,
`224.91, 225.9 and 226.l
`Claim 18,\ drawn to a method of storing a computer
`representation, classified in Class 369, subclass 13+
`
`IV.
`v .
`
`VI.
`
`16. The inventions are distinct, each from the other because of
`the following reasons:
`
`17. The inventions of Groups I-III are not related . The method
`of making a humanized antibody of Group I is distinct from the
`polypeptides of either Groups II or III. The polypeptides are
`not ·humanized antibodies. Thus the method of Group I is not
`expected to produce the polypeptides of Groups II or III. The
`Groups therefore have different issues regarding patentability
`and enablement and represent patentably distinct subject matter .
`
`18. The inventions of Group I and Group VI are distinct methods.
`They differ with respect to ingredients and method steps. They
`have different issues regarding patentability and enablement and
`represent patentably distinct subject matter.
`
`19. The products of Groups II- V are distinct and unrelated. The
`peptides of Groups II and III differ chemica l ly and physically
`from a computer and computer representation. Additionally, the
`peptides have different sequences and thus differed structures
`and pharmacokinetic properties. The Groups therefore have
`different issues regarding patentability and enablement and
`represent patentably distinct subject m?tter.
`
`20. The method of Group I is distinct from the products of
`Groups [IV and VJ. The method of Group I can in no manner
`produce a computer or computer representation as claimed in
`Groups IV and V. The Groups therefore have different issue s
`regartiing patentability and enablement and represent patentably
`distinct subject matter.
`
`5
`
`] 0
`
`15
`
`2 0
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`235 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`08/146,206
`
`Serial No.
`
`Art Unit 1806
`
`•
`
`3
`
`21. The products of Groups II and III can not be produced by the
`method of Group VI. They therefore have different issues
`regarding patentability and enablement and represent patentably
`distinct subject matter.
`
`22. The computer of Group IV is distinct from both a method of
`storing a computer representation of Group VI and a computer
`representation Group V. The program required for (1) storing or
`(2) providing a representation (i.e. word processing text) are
`distinct components from the architecture of a computer system.
`Thus the Groups are separate and patentably distinct from each
`other. They have different issues regarding patentability and
`enablement.
`
`23 . The computer representation of Group V is distinct from a
`method of storing a computer representation. The logic required
`for these two applications are distinct and unrelated. The Groups
`have different issues regarding patentability and enablement and
`represent patentably distinct subject matter.
`
`24. Because these inventions are distinct for the reasons given
`above and have acquired a separate status in the art shown by
`their different classification, in addition to their recognized
`divergent subject matter, they represent an undue burden on the
`examiner and restriction for examination purposes as indicated is
`proper.
`
`25. Applicant is advised that the response to this requirement
`to be complete must include an election of the invention to be
`examined even though the requirement be traversed.
`
`26. Applicant is reminded that upon the cancellation of claims
`to a non-elected invention, the inventorship must be amended in
`compliance with 37 C . F . R. § l.48(b) if one or more of the
`currently named inventors is no longer an inventor of at least
`one claim remaining in the application. Any amendment of
`inventorship must be accompanied by a diligently-filed petition
`under 37 C.F.R. §
`l.48(b) and by the fee required under 37 C.F.R.
`§l.17(h).
`
`27. A telephone call was made to Ms. Hasak on August 24, 1994 to
`request an oral election to the above restriction requirement,
`but did not result in an election being made.
`
`28. Papers related to this application may be submitted to Group
`180 by facsimile transmission. Papers should be faxed to Group
`180 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 CMl Fax
`Center telephone number is (703) 308-4227.
`
`5
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`236 of 1033
`
`BI Exhibit 1002
`
`

`

`•
`
`Serial No . 08/146,206
`
`Art Unit 1806
`
`•
`
`4
`
`29. Any inquiry concerning this communication or earlier
`communicat ions from the examiner should be directed to Donald E.
`Adams whose telephone number is (703) 308-0570. The e:.~aminer can
`normally be reached Monday through Thursday from 7:30 am to 6:00
`pm . A message may be left on the examiners voice mail service.
`If attempts to reach the examiner by telephone are unsuccessful,
`the examiner's supervisor , Mr. David Lacey can be reached on
`(703) 308-3535. The fax phone number for Group 180 is (703) 305-
`3014 or (703) 308-4227. Any inquiry of a general nature or
`relating to the status of this application should be directed to
`the Group 180 receptionist whose telephone number is (703) 308 -
`0196.
`
`5
`
`10
`
`is;:;)1J2~
`
`Donald E. Adams, Ph.D.
`Patent Examiner
`Group 1800
`
`237 of 1033
`
`BI Exhibit 1002
`
`

`

`-PATENT DOCKET 709P1~ ~
`
`IN THE UNITED STATES PATENT AND TRADEMAR
`
`FFICE
`
`n re Application of
`'~aul J. Carter et al.
`
`Serial No. 08/146,206
`
`Filed: 17 November 1993
`
`For: METHOD FOR MAKING HUMANIZED
`ANTIBODIES
`
`Group Art Unit: 1806
`
`Examiner: D. Adams
`
`RE1CEIVED
`SEP 3 0 1994
`GROUP 1800
`
`TRANSMITTAL LETTER
`
`Honorable Commissioner of Patent!;
`and Trademarks
`Washington, D.C. 20231
`
`Sir:
`
`Transmitted herewith is a Response to Restriction Requirement in the above-identified application.
`
`The fee has been calculated a:s shown below.
`
`Total
`
`lndep.
`
`20
`
`7
`
`Minus
`
`Minus
`
`23
`
`10
`
`::: 0
`
`0
`
`_
`
`First Presentation of Multiple! Dependent Claim
`
`x 22:::
`
`x 74 =
`
`+ 230 =
`
`TOTAL
`
`$0
`
`$0
`
`$0
`
`$0
`
`_x_ No additional fee is rnquired.
`The Commissioner is hereby authorized to charge Deposit Account No. 07-0630 in the amount
`of $. A duplicate copy of this transmittal is enclosed.
`Petition for Extension of Time is enclosed.
`
`The Commissioner is hereby a1uthorized to charge any additional fees required under 37 CFR 1.16 and
`1 .17, or credit overpayment to Deposi1t Account No. 07-0630. A duplicate copy of this sheet is enclosed.
`A copy of a document pursuant to 37 C.F.R. § 10.9(b) is attached as proof of the authorization of the
`undersigned to prosecute the above-mentioned application. The original of this document is on file in the Office
`of Enrollment and Discipline.
`
`Respectfully submitted,
`
`By:G~
`
`Wendy M . Lee
`
`Date: September 22, 1994
`
`460 Pt. San Bruno Blvd.
`So. San Francisco, CA 94080-4990
`Phone: (415) 225-1994
`Fax: (415) 952-9881
`
`238 of 1033
`
`BI Exhibit 1002
`
`

`

`ti
`
`UNITEC STATES DEPARTMENT OF COMMERCE.
`P;,tent and Troidemark Office
`ASSISTANT SE0£TAAY AND CDll'MISSIOl'll:R
`CE PA 1[N'TS Af\CJ TAAO::fv\AAKS
`WasM!Jl.On. O.C. 20231
`
`LIMITED AECOGNl'TION UNDER 37 CFR § 10.9(b)
`
`Wendy M. Lee is hereby given limited recognition under 37 CFR § 10.9(b) as an
`employee of Genentech, Inc. to pn~pare and prosecute patent applications and to
`represent patent applicants wherein Genentech, Inc. is the assignee of record of the
`entire interest. This limited recognition shall expire on the date appearing below, or when
`whichever of the following events first occurs prior to December 9, 1994: (i) Wendy M.
`Lee ceases to lawfully reside in the United States. (ii) Wendy M. Lee's employment with
`Genentech, Inc. ceases or is terminat~~d. or (iii) Wendy M. Lee ceases to remain or reside
`in the United States on an H-1 visa.
`
`This docurr.er:t cons~it utes proof of SLJCh recognition. The original of this docum':3nt is on
`file in the Oi!ice of Enrollment and Discipline of the U.S. Patent and Trademark Office.
`
`E ':<.p ires : December 9, 1994
`
`Office of Enrollment and Discipline
`
`239 of 1033
`
`BI Exhibit 1002
`
`

`

`i
`
`,--
`
`~~t4 ~
`
`•
`
`~
`:9.:
`PATE~~T DOCKET 709P1
`Dt ~~
`·I
`IN THE\ UN1feo STATES PATENT AND ·rnADEMARK OFF1cflECE/VED
`·Sfp 0
`Group Art Unit : 1 a·os 3 1994
`Examiner: o. Ada~~OUP 1 Boq
`
`f/1 1
`~
`
`1
`
`In re Apphcation of
`
`Paul J. Carter et al.
`
`Serial No. 08/146,206
`
`Filed:
`
`For:
`
`17 November 1993
`
`METHOD FOR MAKING HUMANIZED
`ANTIBODIES
`
`)
`
`:
`)
`)
`)
`I
`)
`)
`)
`)
`)
`)
`)
`)
`)
`)
`
`RESPONSE TO RESTRICTION REQUIREMENT
`
`Honorable Commissioner of Patents
`and Trademarks
`Washington, D.C. 20231
`
`Sir:
`
`This is responsive to the restriction requirement maile1d 8/26/94. The period for response has
`
`been set for 30 days making this response due on or beforn 9/25/94. This response is timely filed.
`
`Please amend the application as follows:
`
`IN THE CLAIMS:
`Please cancel claims 17d!Prejudice.
`
`-
`
`The Examiner required restriction to one of the following inventions under 35 USC § 1 21 :
`
`I. Claims 1-12 and 1 5, drawn to a metho~I of making a humanized antibody.
`
`REMARKS
`
`II. Claim 13 drawn to a polypeptide.
`
`Ill. Claim 14 drawn to a polypeptide.
`
`IV. Claim 16 drawn to a computer.
`
`V. Claim 17 drawn to a computer representation.
`
`VI. Claim 18 drawn to a method of storing a computer representation.
`
`240 of 1033
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`BI Exhibit 1002
`
`

`

`•
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`08/146,206
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`•
`
`Page 2
`
`The Examiner urges that the inventions of Groups 1-111 are not related insofar as the polypeptides
`
`of either Groups II or Ill are "not humanized antibodies" and are therefore distinct from the method of
`
`making a humanized antibody recited in claim 1. The Examiner has also taken the position that the
`
`method of Group I is not expected to produce the polypeptides of Groups II or Ill .
`
`Applicants hereby elect Group I, with traverse. The restriction requirement is submitted to be
`
`improper as regards the separate treatment of Groups I, II, and Ill. The claims in the remaining Groups
`
`IV, V, and Vt have been canceled from this application, without prejudice to file a continuing application
`
`directed thereto.
`
`It is submitted that the inventions of Groups I, II, and Ill as hereinabove defined are not distinct.
`
`These inventions are all respectively related as method of making a humanized antibody (Group I) and
`
`the humanized antibody made using the method of claim 1. Applicants submit that the assumption
`
`made that the polypeptides of claims 13 and 14 are not humanized antibodies is clearly in error. In
`
`particular, claims 13 and 14 encompass the light chain and heavy chain variable domain, respectively,
`
`of humanized MAb405 made using the method of claim 1 (see page 7, lines 13-2 1 and Example 1
`which describes humanization of muMAb405). Surely, the Examiner will agree that the claim
`
`encompassing the light chain variable domain of the humanized MAb405 (claim 13) and the claim to
`
`the heavy chain variable domain of this humanized antibody (claim 14) should be examined together,
`
`since both a heavy chain and a tight chain are required to form the antibody variable domain. Hence,
`
`the separate treatment of Groups II and Ill is clearly erroneous. Furthermore, since the humanized
`
`antibody variable domains of claims 13 and 14 are made using the humanization technique of claim 1,
`
`these claims should be examined together.
`
`With respect to the search required to determine the patentability of the inventions defined by
`
`the claims of Groups I, II, and Ill, applicants represent that it is impossible to conduct an exhaustive
`
`search for a method of making a hun:ianized antibody without searching for humanized antibodies made
`
`using the method. Similarly, the search for the claimed humanized antibody is bound to reveal
`
`information concerning the technique for humanizing it. In the same token, a search of the amino acid
`
`sequence encoding the humanized heavy chain variable domain of the antibody would lead to the
`
`discovery of information concerning the humanized light chain variable domain. Accordingly,
`
`performing the entire search covering the method and products made by the method is less burdensome
`
`on the Examiner than the separate search. which necessarily involves duplication of searching efforts.
`
`In view of the foregoing arguments, the Examiner is requested to reconsider and withdraw the
`
`restriction requirement.
`
`241 of 1033
`
`BI Exhibit 1002
`
`

`

`~ · -
`
`08/146,206
`
`•
`
`•
`
`Page 3
`
`A copy of a document pursuant to 37 C.F.R. § 10.9(b) is attached as proof of the authorization
`
`of the undersigned to prosecute the above-mentioned application. The original of this document is on
`
`file in the Office. of Enrollment and Discipline.
`
`Respectfully submitted,
`~::H, INC.
`
`By: lml~
`
`Wendy M . Lee
`
`Date: ~ 94 ~q~
`
`460 Pt. San Bruno Blvd.
`So. San Francisco, CA 94080-4990
`Phone: (415) 225-1994
`Fax: (415) 952-9881
`
`242 of 1033
`
`BI Exhibit 1002
`
`

`

`Gly Ser Leu Arg Leu Ser cys Ala A.la Ser Gly Phe Thr Phe Ser
`25
`20
`30
`
`Ser Tyr Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
`35
`40
`45
`
`Glu Trp Val Ser Val Ile Se:r Gly Asp Gly Gly Ser Thr Tyr Tyr
`50
`55
`60
`
`A.la Asp Ser Val Lys Gly Arq Phe Thr Ile Ser Arg Asp Asn Ser
`65
`70
`75
`
`Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg A.la Glu Asp
`80
`85
`90
`
`Thr Ala Val Tyr Tyr Cys A.la Arg Gly Arg Val Gly Tyr Ser Leu
`95
`100
`105
`
`Ser Gly Leu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Tlu: Val
`110
`115
`120
`
`Ser Ser
`122
`
`(2) INFORMATION FOR SEQ ID N0:22:
`
`( i) SEQUENCE CHARACTERIS'.rICS:
`(A) LENGTH: 454 am.in<:> acids
`(B) TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:22:
`
`f 1
`
`Gln Val Gln Leu Gln Gln Ser Gly Pro Glu Leu Val Lys Pro Gly
`l
`5
`10
`15
`
`Ala Ser Val Lys Ile Ser Cy:~ Lys Thr Ser Gly Tyr Thr Phe Thr
`20
`25
`30
`
`Glu Tyr Thr Met His Trp Met Lys Gln Ser His Gly Lys Ser Leu
`35
`40
`45
`
`Glu Trp Ile Gly Gly Phe Asn Pro Lys Asn Gly Gly Ser Ser His
`50
`55
`60
`
`Asn Gln Arg Phe Met Asp Lys Ala Thr Leu Ala Val Asp Lys Ser
`65
`70
`75
`
`Thr Ser Thr Ala Tyr Met Glu Leu Arg Ser Leu Thr Ser Glu Asp
`80
`85
`90
`
`Ser Gly Ile Tyr Tyr Cys Ala Arg Trp Arg Gly Leu Asn Tyr Gly
`95
`100
`105
`
`Phe Asp Val Arg Tyr Phe Asp Val Trp Gly Ala Gly Thr Thr Val
`110
`115
`120
`
`Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu
`125
`130
`135
`
`243 of 1033
`
`BI Exhibit 1002
`
`

`

`Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
`HO
`150
`145
`
`Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
`160
`155
`165
`
`Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
`170
`175
`180
`
`Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
`185
`190
`195
`
`Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
`200
`205
`210
`
`His Lys Pro Ser Asn ~hr Lys Val Asp Lys Lys Val Glu Pro Lys
`220
`215
`225
`
`Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
`230
`235
`240
`
`Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
`245
`250
`255
`
`Asp Thr Leu Met Ile Ser A.rg Thr Pro Glu Val Th.r cys Val Val
`260
`265
`270
`
`Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
`275
`280
`285
`
`Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys t>ro Arg Glu
`290
`295
`300
`
`305
`
`310
`
`315
`
`ft Glu Gln Ty.r Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
`
`Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
`320
`325
`330
`
`Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
`335
`340
`345
`
`Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
`350
`355
`360
`
`Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
`365
`370
`375
`
`Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
`380
`385
`390
`
`Asn Gly Gln Pro Glu Asn .Asn Tyr Lys Tbr Thr Pro Pro Val Leu
`395
`400
`405
`
`Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
`410
`415
`420
`
`Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
`425
`430
`435
`
`244 of 1033
`
`BI Exhibit 1002
`
`

`

`His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
`440
`445
`450
`
`Ser Pro Gly Lys
`4.54
`
`(2) INFORMATION FOR SEQ ID N0:23;
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 469 amino acids
`(B) TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:23:
`
`Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Th.r Ala Thr
`l
`5
`10
`15
`
`Gly Val His Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
`20
`25
`30
`
`Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Thr Ser Gly
`35
`40
`45
`
`Tyr Thr Phe Thr Glu Tyr Thr Met His Trp Met Arg Gln Ala Pro
`50
`55
`60
`
`Gly Lys Gly Leu Glu Trp Val Ala Gly Ile Asn Pro Lys Asn Gly
`65
`70
`75
`
`Gly Thr Ser His Asn Gln Arg Phe Met Asp Arg Phe Thr Ile Ser
`80
`85
`90
`
`ff
`
`Val Asp Lys Ser Thr Ser Thr Ala Tyr Met Gln Met Asn Ser Leu
`95
`100
`105
`
`Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Trp Arg Gly
`110
`115
`120
`
`Leu Asn Tyr Gly Phe Asp Val Arg Tyr Phe Asp Val Trp Gly Gln
`125
`130
`135
`
`Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
`140
`145
`150
`
`Val Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr
`155
`160
`165
`
`Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val
`170
`175
`180
`
`Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
`185
`130
`195
`
`Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser
`200
`205
`210
`
`Val Val Thr Val Thr Ser Ser Asn Phe Gly Thr Gln Thr Tyr Thr
`215
`220
`225
`
`245 of 1033
`
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`
`

`

`Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys Thr
`230
`235
`240
`
`Val Glu Arg Lys Cys Cys Val Glu Cys Pro Pro Cys Pro Ala Pro
`245
`250
`255
`
`Pro Val Ala Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
`260
`265
`270
`
`Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
`275
`280
`285
`
`Val Asp Val Ser His Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr
`290
`295
`300
`
`Val Asp Gly Met Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
`305
`310
`315
`
`Glu Gln Phe Asn Ser Thr Phe Arg Val Val Ser Val Leu Thr Val
`320
`325
`330
`
`Val His Gln Asp Trp Leu As:n Gly Lys Glu Tyr Lys Cys Lys Val
`335
`340
`345
`
`Ser Asn Lys Gly Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
`350
`355
`360
`
`Thr Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro
`365
`370
`375
`
`f'
`
`Ser Arg Glu Glu Met Thr Ly,s Asn Gln Val Ser Leu Thr Cys Leu
`380
`385
`390
`
`Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
`395
`400
`405
`
`Asn Gly Gln Pro Glu Asn Asin Tyr Lys Thr Thr Pro Pro Met Leu
`410
`415
`420
`
`Asp Ser Asp Gly Ser Phe Ph•e Leu Tyr Ser Lys Leu Thr Val Asp
`425
`430
`435
`
`Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
`440
`450
`445
`
`His Glu Ala Leu His Asn Hi:s Tyr Thr Gln Lys Ser Leu Ser Leu
`455
`460
`465
`
`Ser Pro Gly Lys
`469
`
`(2) INFORMATION FOR SEQ ID N0:24:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 214 amino acids
`(B) TYPE: Amino Acid
`(0) TOPOLOGY: Linear
`
`(Ki) SEQUENCE DESCRIPTION: SEQ ID N0:24:
`
`246 of 1033
`
`BI Exhibit 1002
`
`

`

`l .
`
`Asp Val Gln Met Thr Gln Thr Thr Ser Ser Leu SE!r Ala Ser Leu
`l
`5
`10
`15
`
`Gly Asp Arg Val Thr Ile Asn Cys Arg Ala Ser Gl n Asp Ile Asn
`20
`25
`30
`
`Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asn GJLy Thr Val Lys
`35
`40
`45
`
`Leu Leu Ile Tyr Tyr Thr Ser Thr Leu His Ser Gly Val Pro Ser
`50
`55
`60
`
`Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile
`65
`70
`75
`
`Ser Asn Leu Asp Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gin Gln
`80
`85
`90
`
`Gly Asn Thr Leu Pro Pro Thr Phe Gly Gly Gly Thr Lys Val Glu
`95
`100
`105
`
`Ile Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro
`110
`115
`120
`
`Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser Vcll Val Cys Leu
`125
`130
`135
`
`Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val
`140
`145
`150
`
`Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu SE~r Val Tlu:.: Glu
`155
`160
`165
`
`Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr
`170
`180
`17~
`
`Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val T}rr Ala Cys Glu
`185
`190
`195
`
`Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe Asn
`200
`205
`210
`
`Arg Gly Glu Cys
`214
`
`(2) INFORMATION FOR SEQ ID N0 : 25:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 233 amino acids
`(B) TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:25:
`
`Met Gly T.rp Ser cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr
`1
`5
`10
`15
`
`Gly Val His Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu
`20
`25
`30
`
`247 of 1033
`
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`
`

`

`Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr cys Arg Ala Ser
`35
`40
`45
`
`Gln Asp Ile Asn Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly
`50
`55
`60
`
`Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Thr Leu His Ser
`65
`70
`75
`
`Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr
`90
`BO
`BS
`
`Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr
`95
`100
`105
`
`Tyr Cys Gln Gln Gly Asn Th.r Leu Pro Pro Thr Phe Gly Gln Gly
`110
`115
`120
`
`Thr Lys Val Glu Ile Lys Ar9 Thr Val Ala Ala Pro Ser Val Phe
`125
`130
`135
`
`Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr Ala Ser
`140
`145
`150
`
`Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys Val
`155
`160
`165
`
`Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
`170
`175
`180
`
`~I
`
`Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
`185
`190
`195
`
`Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val
`200
`205
`210
`
`Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr
`225
`215
`220
`
`Lys Ser Phe Asn Arg Gly Glu Cys
`230
`233
`
`(2) INFORMATION FOR SEQ ID N0:26:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 122 amino acids
`(B) TYPE: Amino Acid
`(D) TOPOLOGY: Linear
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:26:
`
`Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
`1
`5
`10
`15
`
`Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Tyr Ser Phe Thr
`25
`20
`30
`
`Gly Tyr Thr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
`35
`40
`45
`
`248 of 1033
`
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`
`

`

`\
`
`Glu Trp Val Ala Leu Ile Asn Pro Tyr Lys Gly Val Thr Thr Tyr
`50
`55
`60
`
`Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Val Asp Lys 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 Ala Arg Ser Gly Tyr Tyr Gly Asp Ser
`95
`100
`105
`
`Asp Trp Tyr Phe Asp Val Trp Gly Gln Gly Thr Leu Val Thr Val
`1 10
`115
`120
`
`Ser Ser
`122
`
`---
`
`249 of 1033
`
`BI Exhibit 1002
`
`

`

`~
`~
`
`UNITED STATES DEPARTMENT OF COMMERCIE
`Pacent an" Tra .. emark Office
`
`AddreH : COMMISSIONEA OF PATENTS ANO TR~MARKS
`WHhington, O.C. 20231
`
`013/146. 206
`
`11117/93
`
`CARTER
`
`,TANET E. HASAK
`•3ENENTECH,
`INC.
`4 60 POINT SAN BRUNO BOLILEVAR[)
`SOUTH SAN FRANCISC