UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.0. Box 1450
`Alexandria, Virginia 21313-1450
`www.usplo.gov
`
`90/007,542
`
`05/13/2005
`
`6331415
`
`l0244P00l OUS
`
`7585
`
`2, .-I
`
`05/15/2005
`
`759°
`47554
`SIDLEY AUSTIN LLP
`ATTN: Dc PATENT DOCKETING
`1501 K STREET, Nw
`WASHINGTON, DC 20005
`
`.
`
`3e"”e” Ce/‘SQ’
`
`399,
`DATE MAILED: 08/ 16/2006
`
`ZFW
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`mmc (Rem W03)
`
`'
`
`Genzyme Ex. 1016, pg 460
`
`Genzyme Ex. 1016, pg 460
`
`

`
` e"““
`
`WV.‘ UNITED STATES PATENT AND TRADEMARK OFFICE
`i’
`
`
`DO NOT USE IN PALM PRINTER
`
`THIRD PARTY REQUE$fER'S CORRESPONDENCE ADDRESS
`
`LISA v. MUELLER
`WOOD PHILLIPS KATZ CLARK & MORTIMER
`
`3800 WEST MADISON STREET, SUITE 3800
`
`CHICAGO, IL 60661
`
`Commissioner for Patens
`United States Patent and Trademark Office
`P.0. Box14so
`Alexandria, VA 223111450
`\~wwu:pwo.oov
`
`8/ 16/06
`
`j
`
`
`
`EX PARTE REEXAMINATION COMMUNICATION TRANSMITTAL FORM
`
`REEXAMINATION CONTROL NO 90/007542
`
`PATENT NO.
`
`6,331,415
`
`ART UNI
`
`3991
`
`Enclosed is a copy of the latest communication from the United States Patent
`and Trademark Office in the above identified ex parte reexamination
`proceeding (37 CFR 1.550(f)).
`-
`
`Where this copy is supplied after the reply by requester, 37 CFR 1.535, or the
`time for filing a replly has passed, no submission on behalf of the ex parte
`reexamination requester will be acknowledged or considered (37 CFR 1.550(9)).
`
`
`
`Genzyme Ex. 1016, pg 461
`
`Genzyme Ex. 1016, pg 461
`
`

`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`Commissionerfor Patens
`United States Patent and Trademark Ofllce
`P.0. Box1450
`Alexandria. VA 2231 3.1450
`wwauspwogov
`
`DO NOT USE IN PALM PRINTER
`THIRD PARTY REQUESTER'S CORRESPONDENCE ADDRESS
`
`8/16/06
`
`ALAN J. GRANT
`
`CARELLA BYRNE BAIN GILFILLAN ET AL
`
`5 BECKER FARM ROAD, 2ND FLOOR
`
`ROSELAND, NJ 07068
`
`: ©
`
`
`
`EX PARTE REEXAMINATION COMMUNICATION TRANSMITTAL FORM
`
`REEXAMINATION CONTROL NO 90/007859
`
`PATENT NO.
`
`6,331,415
`
`ART UNI
`
`3992
`
`Enclosed is a copy of the latest communication from the United States Patent
`and Trademark Office in the above identified ex parte reexamination
`proceeding (37 CFR 1.550(f)).
`
`Where this copy is supplied after the reply by requester, 37 CFR 1.535, or the
`time for filing a replly has passed, no submission on behalf of the ex parte
`reexamination requester will be acknowledged or considered (37 CFR 1.550(g)).
`
`Genzyme Ex. 1016, pg 462
`
`Genzyme Ex. 1016, pg 462
`
`

`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`PO. Box I450
`Alexandria. Virginia 22313-1450
`www.uspto.gov
`
`12/23/2005
`°W°°6
`
`90/007,859
`759°
`47554
`SIDLEY AUSTIN LLP
`ATTN: DC PATENT DOCKETING
`1501 K STREET, Nw
`WASHINGTON, DC 20005
`
`“RS7 “AME” WW0“
`6331415
`
`469201-587
`
`°°"“’W“°" "°-
`6447
`
`27d
`
`.
`
`5°” "3 '5‘ 03/3“)
`
`399,
`DATE MAILED: 08/16/2006
`
`IFW
`
`CQY
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`PTO-90C (Rev. I0/03)
`
`Genzyme EX. 1016, pg 463
`
`Genzyme Ex. 1016, pg 463
`
`

`
`
`
`
`
`
`
`Control No.
`90/007,542
`
`Patent Under Reexamination
`6331415
`
`Examiner
`Bennett Celsa
`
`Art Unit
`3991
`
`
`
`
`
` Office Action in Ex Parte Reexamination
`
`
`
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address -
`
`
`
`
`
`bI:] This action is made FINAL.
`a Responsive to the communication(s) filed on 25 January 2005 .
`cl: A statement under 37 CFR 1.530 has not been received from the patent owner.
`
`
`
`A shortened statutory period for response to this action is set to expire g month(s) from the mailing date of this letter.
`Failure to respond within the period for response will result in termination of the proceeding and issuance of an ex parte reexamination
`certificate in accordance with this action. 37 CFR 1.550(d). EXTENSIONS OF TIME ARE GOVERNED BY 37 CFR 1.550(c).
`If the period for response specified above is less than thirty (30) days, a response within the statutory minimum of thirty (30) days
`will be considered timely.
`
`
`
`
`
`THE FOLLOWING ATTACHMENT(S) ARE PART OF THIS ACTION:
`
`2. X lnforrnation Disclosure Statement, PTO-1449.
`
`4.
`
`[:1
`
`.
`
`1b. D Claims j are not subject to reexamination.
`
`2. E] Claimsj have been canceled in the present reexamination proceeding.
`
`3. CI Claims __ are patentable and/or confirmed.
`
`4. X Claims 1;?6 are rejected.
`
`5. D Claims j are objected to.
`
`6. E] The drawings, filed on j are acceptable.
`
`7. CI The proposed drawing correction, filed on __ has been (7a)I:] approved (7b)[:] disapproved.
`
`8. E] Acknowledgment is made of the priority claim under 35 U.S.C. § 119(a)-(d) or (f).
`
`a)CI All b)[] Some’ c)E] None
`
`of the certified copies have
`
`
`
`Part I
` 1.’ E] Notice of References Cited by Examiner, PTO-892.
`
`
`3. E]
`Interview Summary, PTO-474.
` Part II
`SUMMARY OF ACTION
`
`
`
`1a.
`IX Claims _1;3_6_ are subject to reexamination.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`1I:] been received.
`
`2E] not been received.
`
`3l:I been filed in Application No.
`
`43 been filed in reexamination Control No.
`
`SD been received by the International Bureau in PCT application No.
`
`* See the attached detailed Office action for a list of the certified copies not received.
`
`
`
`
`
`
`11,453 O.G. 213.
`
`9. I] Since the proceeding appears to be in condition for issuance of an ex parte reexamination certificate except for formal
`matters, prosecution as to the merits is closed in accordance with the practice under Ex parte Quayle, 1935 C.D.
`
`10. C] Other:
`
`
`
` uester if third .
`
`U.S. Patent and Tradenark Office
`
`PTOL-466 (Rev. 04-01)
`
`Office Action In Ex Parte Reexamination
`
`Genzyme E§art|fili’a)ebl§).4?82_60619
`
`Genzyme Ex. 1016, pg 464
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`
`Page 2
`
`Art Unit: 3991
`
`/
`
`Reexamination: NON-Fina/ Office Action
`
`Reexamination of US Patent No. 6,331,415 (Cabilly 2 patent).
`/
`Merger of 3"‘ Partly Requests 90/007,542 and 90/007,859
`
`Procedural Posture:
`
`i. 90/O07542(‘7542 Proceeding):
`
`ii. 90/007859 (‘7859 Proceeding)
`
`Reexamination request filed:
`
`5/13/05
`
`12/23/05
`
`Reexamination ordered:
`
`7/7/05.
`
`1/23/06
`
`Patent Owner Statement:
`
`none
`
`none
`
`First Office Action mailed:
`
`9/13/05
`
`Patent Owner Response dated
`
`1/25/05.
`
`N/A
`
`N/A
`
`‘7542 AND ‘7859 merged:
`
`6/6/06
`
`Status of the Claims
`
`Claims 1-36 are pending and under reexamination. The text of those sections of
`
`Title 35, U.S. Code not included in this action can be found in a prior Office action.
`
`OFFICE ACTION
`
`The First Office Action (mailed 9/13/05) in the 90/007,542 proceeding is hereby
`
`withdrawn in lieu of the instant office action. The Patentee arguments and declarations
`
`presented in response to the First Office Action will be considered in this office action to
`
`the extent it is pertinent to the new ground(s) of rejection stated herein.
`
`Information Disclosure Statement (IDS)
`
`The Nov. 28, 2005 IDS has been Examiner initialed. It is noted that:
`
`Once the minimum requirements of 37 CFR 1.97 and 37 CFR 1.98 are met, the examiner has an obligation to consider
`
`the information. It is to be noted, however, that consideration by the examiner of information submitted in an IDS is
`
`conducted in the same manner as other documents in Office search files are considered by the examiner while conducting
`
`a search of the prior art in a proper field of search. See MPEP 609, at page 600-125, Revision 2, May 2004. The initials of
`
`Genzyme Ex. 1016, pg 465
`
`Genzyme Ex. 1016, pg 465
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`
`Page 3
`
`Art Unit: 3991
`
`the examiner placed adjacent to the citations on the PTO-1449 or PTO/SB/08A and 08B or its equivalent mean that the
`
`information has been considered by the examiner to the extent noted above. If there is a reference of particular relevance, the
`
`patentee is required to point out the document and its relevance to the Examiner.
`
`Priority
`
`The 6,331,425 Cabilly 2 patent issued on December 18, 2001 from application
`
`07/20541 (filed 6/10/88) which was a continuation of 06/483,457 (filed 4/8/83) now
`
`4,816,567 (Cabilly 1 patent).
`
`The 6,331,415 (Cabi/Iy 2) Invention.
`
`The instant patent claims methods and compositions are representative.
`
`i. METHODS:i
`
`1. A process for producing an immunoglobulin molecule or an immunologically
`functional immunoglobulin fragment comprising at least the variable domains of the
`immunoglobulin heavy and light chains, in a single host cell comprising:
`(i) transforming said single host cell with a first DNA sequence encoding at least the
`variable domain of the immunoglobulin heavy chain and a second DNA sequence
`encoding at least the variable domain of the immunoglobulin light chain, and
`(ii) independently expressing said first DNA sequence and said second DNA sequence
`so that said immunoglobulin heavy and light chains are produced as separate
`molecules in said transformed single host cell. See Claim 1.
`
`33. A process for producing an immunoglobulin molecule or an immunologically
`functional immunoglobulin fragment comprising at least the variable domains of the
`immunoglobulin heavy and light chains, in a single host cell comprising:
`independently expressing a first DNA sequence encoding at least the variable
`domain of the immunoglobulin heavy chain and a. second DNA sequence encoding at
`least the variable domain of the immunoglobulin light chain so that said immunoglobulin
`heavy and light chains are produced as separate molecules in said single host cell
`transformed with said first and second DNA sequences.
`
`21. A method comprising:
`a) preparing a DNA sequence consisting essentially of DNA encoding an
`immunoglobulin consisting of an immunoglobulin heavy chain and light chain or Fab
`region, said immunoglobulin having specificity for a particular known antigen;
`b) inserting the DNA sequence of step a) into a replicable expression vector operably
`linked to a suitable promoter;
`
`Genzyme Ex. 1016, pg 466
`
`Genzyme Ex. 1016, pg 466
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`
`Page 4
`
`Art Unit: 3991
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`c) transforming a prokaryotic or eukaryotic microbial host cell culture with the vector of
`step b);
`d) culturing the host cell; and
`e) recovering the immunoglobulin from the host cell culture, said immunoglobulin being
`capable of binding to a known antigen.
`ii. COMPOSITIONS:
`
`15. A vector comprising a DNA encoding at least a (first) variable immunoglobulin heavy
`chain domain and a second DNA sequence encoding at least a variable immunoglobulin
`light chain domain wherein the 15' and 2"” DNA sequences are located at different
`insertion sites in the vector.
`
`18. A transformed host cell comprising at least two vectors in which one vector
`comprises a variable immunoglobulin heavy chain domain and a second vector
`comprises a variable immunoglobulin light chain domain.
`
`32. The insoluble particles of heavy and light chains or Fab region produced by the
`method of claim 21 in which the heavy and light chains or Fab regions are deposited
`within the cells (e.g. claim 27).
`
`Art Used In SNQ’s Regarding Obviousness Double Patenting
`
`‘7542 3”’ Party cited references:
`
`1. US Pat. No. 4,816,567 (Cabilly 1): claims 1-7;
`
`2. US Pat. No. 4,399,216 (Axel et aI): (issued 3-16-83);
`
`3. EP 0 044722 (Kaplan et al.) (published 01-27-82)
`
`4. Accolla et al., PNAS USA 77:563 (1980);
`
`5. Rice and Baltimore, PNAS USA 79 :7862 (1982).
`
`‘7542 examiner-cited reference:
`
`6. US Pat. No. 4, 511, 502 (Builder et al.) (issued April 1985).
`
`‘7859 3"’ Party additionally cited references:
`
`Genzyme Ex. 1016, pg 467
`
`Genzyme Ex. 1016, pg 467
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`
`Page 5
`
`Art Unit: 3991
`
`7. Deacon, Biochemical Society Transactions, 4:818-20 (1976).
`
`8. 1982 Valle, Nature, Vol. 300, pp. 71-74 (4 Nov.1982).
`
`9. 1981 Valle, Nature, Vol. 291, pp. 338-340 (28 May 1981).
`
`10. Dallas WO 82l03088.
`
`11. Ochi, Nature, Vol. 302, pp. 340-342 (24 March 1983).
`
`12. Oi PNAS USA, Vol. 80, pages 825-829 (Feb.1983).
`
`Cumulative Prior Art :
`
`The 1982 Valle and Deacon references are cumulative in their teaching of
`
`microinjection of mRNA encoding light and heavy immunoglobulin chains into Xenopus
`
`oocyte cells to produce secreted active antibody. Accordingly, only the Deacon
`
`reference will be utilized in the obviousness double patenting rejection(s) recited below.
`
`Additionally, the Oi and Ochi references are cumulative in their teaching of
`
`restoring hybridoma cell antibody expression by vector transformation with a light chain
`
`gene. Accordingly, only the Ochi reference will be utilized in the obviousness double
`
`patenting rejection(s) recited below.
`
`35 U.S.C. 121 Does Not Preclude Obviousness Double Patenting
`
`The third sentence of 35 U.S.C. 121 prohibits the use of a patent issuing on an
`
`application with respect to which a requirement for restriction has been made, or on an
`
`application filed as a result of such a requirement, as a reference against any divisional
`
`application, if the divisional application is filed before the issuance of the patent. The
`
`35 U.S.C.121 prohibition applies only where the Office has made a requirement for
`
`restriction. The prohibition does not apply where the divisional application was
`
`Genzyme Ex. 1016, pg 468
`
`Genzyme Ex. 1016, pg 468
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`
`Page 6
`
`Art Unit: 3991
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`voluntarily filed by the applicant and not in response to an Office requirement for
`
`restriction. See MPEP 804.01. Accordingly, 35 U.S.C. 121 requires claims of a
`
`divisional application to have been formally entered, restricted, and removed from an
`
`earlier application in order for a patentee to obtain the benefit of 35 U.S.C. 121.
`
`Geneva Pharmaceuticals. Inc. v. GlaxoSmithKIine PLC, 349 F.3d 1373, 1379, 68
`
`USPQ2d 1865, 1870 (Fed. Cir. 2003).
`
`Both 3”’ party requesters argue the absence of a 35 U.S.C. 121 bar to double
`
`patenting under the instant facts regarding the parent 06/483,457 and sibling
`
`07/205,419 applications which issued as the 4,816,567 (Cabilly I) and 6,331,415
`
`(Cabilly ll) patents, respectively. See: ‘7542 request at pages 10-21; ‘7859 request at
`
`pages 9-11. The requesters argue that 35 USC 121 isn’t presently applicable since the
`
`Examiner did not make a restriction in the parent 06/483,457 application; and a
`
`subsequent Examiner restriction in the 07/205,419 continuation application cannot raise
`
`a 121 bar to obviousness double patenting rejection.
`
`The 3"’ parties position regarding the absence of a 121 bar to a double patenting
`
`rejection in the instant case is consistent with 35 USC 121 and related case law; and
`
`the patentee has failed to provide a rebuttal argument to the contrary.
`
`The US Pat. No. 4,816,567 Cabi||y1 Patent Claims:
`
`Construing the Cabilly 1 Patent Claims
`
`a. The '567 Claims
`
`Independent claims 1, 3, 5, and 7 of the ‘567 patent read as follows;
`
`1. A method comprising
`
`Genzyme Ex. 1016, pg 469
`
`Genzyme Ex. 1016, pg 469
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`
`Page 7
`
`Art Unit: 3991
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`a) preparing a DNA sequence encoding a chimeric immununoglobulin heavy or light
`
`chain having specificity for a particular known antigen wherein a constant region is
`
`homologous to the corresponding constant region of an antibody of a first
`
`mnmmalian species and a variable region thereof is homologous to the variable region
`
`of an antibody derived from a second, different mammalian species;
`
`b) inserting the sequence into a replicable expression vector operably linked to a
`
`suitable promoter compatible with a host cell;
`
`c) transforming the host cell with the vector of (b);
`
`d) culturing the host cell; and
`
`e) recovering the chimeric heavy or light chain from the host cell culture.
`
`3. A composition comprising a chimeric immunoglobulin heavy or light chain having
`
`specificity for a particular known antigen having a constant region homologous to a
`
`corresponding constant region of an antibody of a first mammalian species and a
`
`variable region homologous to a variable region of an antibody derived from a
`
`second, different mammalian species.
`
`5. A replicable expression vector comprising DNA operably linked to a promoter
`
`compatible with a suitable host cell, said DNA encoding a chimeric immunoglobulin
`
`heavy or light chain having specificity for a particular known antigen and having a
`
`constant region homologous to a corresponding region of an antibody of a first
`
`mammalian species and a variable region homologous to a variable region of an
`
`antibody derived from a second, different mammalian species.
`
`7. Recombinant host cells transformed with the vector of claim 5.
`
`Claims 2, 4 and 6 (dependent on claims 1, 3 and 5, respectively) recite that the first
`
`mammalian species (i.e. the source of the constant region) is human.
`
`Genzyme Ex. 1016, pg 470
`
`Genzyme Ex. 1016, pg 470
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`
`Page 8
`
`Art Unit: 3991
`
`b. ‘567 Claim Interpretation
`
`During reexamination, claims are given the broadest reasonable interpretation
`
`consistent with the specification and limitations in the specification are not read into the
`
`claims. In re Yamamoto, 740 F.2d 1569, 222 USPQ 934 (Fed. Cir. 1984)).
`
`The words of a claim are given their ordinary meaning to one skilled in the art
`
`unless it appears from the patent and prosecution history that the words were used
`
`differently by the inventors. Brookhi/I-Wilk 1, LLC v. Intuitive Surgical, Inc., 334 F.3d
`
`1294, 1298, 67 U.S.P.Q.2d 1132, 1136 (Fed. Cir. 2003),.Vitronics Corp. v.
`
`Conceptronic, Inc., 90 F.3d 1576, 1582, 39 U.S.PQ.2d 1573, 1577 (Fed Cir. 1996); Tom
`
`Co. v. White Consol. Indus, Inc., 199 F.3d 1295, 1299, 53 U.S.P.Q.2d 1065, 1067 (Fed.
`
`Cir. 1999). The ordinary and customary meaning attributed to claim terms may be
`
`determined by reviewing various sources, including “the claims themselves; dictionaries
`
`and treatises; and the written description, the drawings, and the prosecution history."
`
`Brookhi/I-Wilk 1, LLC, 334 F.3d at 1298, 67 U.S.P.Q.2d at 1136 (citations omitted).
`
`Common words, unless the context suggests otherwise, should be accorded their
`
`ordinary meaning. Desper Products, Inc. v. Qsound Labs, Inc., 157 F.3d 1325, 1336, 48
`
`U.S.P.Q.2d 1088, 1096 (Fed. Cir. 1998).
`
`Antibodies are proteins which generally refer to tetramers or aggregates thereof
`
`having specific immunoreactive activity comprising light and heavy chains in a “Y"
`
`configuration (having variable branch and constant stem regions), with or without
`
`covalent linkage. ‘567 patent col. 6, lines 14-18.
`
`Genzyme Ex. 1016, pg 471
`
`Genzyme Ex. 1016, pg 471
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`
`Page 9
`
`Art Unit: 3991
`
`Similarly, an "immunog|obu|in" generally comprises two heavy and two light
`
`chains “but may have specific immunoreactive activity (i.e. an "antibody”) or lack such
`
`specific immunoreactive activity (i.e. “non-specific immunog|obu|in” or “NS|"). See
`
`Cabilly I patent col. 6, lines 18-20; and Cabilly 2 patent Fig. 1.
`
`The phrase “chimeric immunoglobulin heavy or light chain" refers to a species of
`
`immunoglobulin heavy or light chain in which the constant region is homologous to the
`
`constant region of an antibody of a first mammalian species and the variable region is
`
`homologous to the variable region of an antibody derived from a second, different
`
`mammalian species. See claim 1 and 3 definition;‘567 patent col. 6, lines 48-59.
`
`The phrase “replicable expression vector (comprising DNA) operably linked to a
`
`suitable promoter compatible with a host cell" of Cabilly 1 claims 1 and 5 is discussed in
`
`the ‘567 patent specification. An “expression vector" includes:
`
`vectors which are capable of expressing DNA sequences
`contained therein, i.e., the coding sequences are operably linked to
`other sequences capable of effecting their expression. It is implied,
`although not always explicitly stated, that these expression vectors
`must be replicable in the host organisms .
`.
`.
`.
`
`‘567 patent, col. 8, 11. 21-27.
`
`“Host cells," as recited in Cabilly 1 claims 1 and 7, include prokaryotic or
`
`eukaryotic cells, including eukaryotic microbes, and cells derived from multicellular
`
`organisms, such as mammalian cells. See ‘567 patent, col. 8, line 46 to col. 10, 1ines
`
`13-30, 57
`
`The final step of the Cabilly 1 claim 1 process calls for “recovering the chimeric
`
`heavy or light chain from the host cell culture": "[t]he protein thus produced is then
`
`Genzyme Ex. 1016, pg 472
`
`Genzyme Ex. 1016, pg 472
`
`

`
`Application/Control Number: 90/007,542; 90/007,859
`Art Unit: 3991
`
`Page 10
`
`recovered from the cell culture by methods known in the art, but the choice of which is
`
`necessarily dependent on the form in which the protein is expressed. “ ‘567 patent, col.
`
`13, lines 3-6.
`
`The recombinant procedures used to obtain the DNA sequences, prepare
`
`vectors, transform cells, culture cells, and recover the immunoglobulins are the same,
`
`whether for recombinant immunoglobulins that mimic naturally occurring ones or for
`
`altered recombinant immunoglobulins, such as chimeric antibodies. See e.g., ‘567
`
`patent, col. 15, lines 59 to col. 16, line 15; and col. 28, lines 44-47.
`
`c. The Cabilly 1 Claims Read on Expressing Bl!) Heavy and Light Chains
`
`Together, and Each Separately.
`
`The 4,816,567 Cabilly 1 patent claims use the conjunction “or’ when referring to
`
`the "heavy or light chain”.
`
`Although, normally the conjunctive term “or” is interpreted to mean that the items
`
`in a sequence are alternatives to each other (e.g. Brown v. 3M, 265 F.3d 1349,1352, 60
`
`U.S.P.Q. 2d 1375,1377 (Fed. Cir. 2001) the patentee can be hislher own
`
`lexicographer and impart a different meaning. Kustom Signal Inc. v. Applied
`
`Concepts Inc., 264 F.3d 1326,1331, 60 U.S.P.Q. 2d 1135,1138 (Fed. Cir. 2001)
`
`(emphasis provided). See also Vitronics Corp. v. Conceptronic, Inc., 90 F. 3d
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`1576,1582, 39 U.S.P.Q.2d 1573,1576 (Fed. Cir. 1996)(“[A] patentee may choose to be
`
`his own lexicographer and use terms in a manner other than their ordinary meaning, as
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`long as the special definition of the term is clearly stated in the patent specification or
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`file history. ”).
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`Genzyme Ex. 1016, pg 473
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`Genzyme Ex. 1016, pg 473
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`

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`Application/Control Number: 90/007,542; 90/007,859
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`Page 11
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`Art Unit: 3991
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`Both the reference Cabilly I (4,816,567) patent specification and the its file
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`history support construing "of’ to be “and/or.
`
`During the prosecution of the reference Cabilly 1 patent application, applicant
`
`in
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`an amendment dated October 28, 1985, cancelled original claims 1-52 and added the
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`following new claims 53, 57, 65 and 68 (among others):
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`53. A method comprising
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`a) preparing a DNA sequence encoding an immunoglobulin heavy or light chain, or an
`immunoglobulin Fab region, of known specificity;
`b) inserting the sequence into a replicable expression vector operably linked to a
`suitable promoter;
`c) transforminga prokaryotic or eukaryotic microbial host cell culture with the vector of
`b); and
`d) recovering mature heavy chain, light chain or Fab from the host cell culture unfused
`to a portion of the amino acid sequence of a host cell-homologous polypeptide.
`
`57. The method of claim 53 wherein the vector contains DNA encoding both a heavy
`chain and a light chain.
`
`65. The method of claim 53 wherein the heavy and light chain
`are co-expressed in the same host.
`
`68. A method comprising
`
`a) preparing a DNA sequence encoding a chimeric immunoglobulin heavy or light chain
`of known specificity wherein the constant regions are homologous to the corresponding
`constant regions of an antibody of a first mammalian species and the variable regions
`are homologous to the variable regions of an antibody derived from a second, different
`mammalian species;
`b) inserting the sequence into a replicable expression vector operably linked to a
`suitable promoter;
`c) transforming a prokaryotic or eukaryotic microbial host cell culture with the vector of
`b); and
`d) recovering the chimeric heavy chain or light chain from the host cell culture.
`
`(emphasis provided).
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`Genzyme Ex. 1016, pg 474
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`Genzyme Ex. 1016, pg 474
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`

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`Application/Control Number: 90/007,542; 90/007,859
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`Page 12
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`Art Unit: 3991
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`Claim 68 above is essentially identical to issued claim 1.
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`The amendment provide support for new claims 53, 57 and 65 in tabular form as
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`follows:
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`NEW CLAIM NO.
`
`(specification page/line or original claim)
`
`53
`
`57
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`65
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`51; 52; 10/30; 12/4;7/25-31
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`22/29-33
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`23/29
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`Original claim 51 was drawn to preparing heavy chain or light chain comprising:
`
`a) preparing a DNA sequence encoding heavy or light chain,
`b) inserting said sequence into a replicable expression vector operably linked to a
`suitable promoter,
`c) transforming host cell culture with the vector of b) and
`d) recovering heavy or light chain from cell culture.
`
`The ‘567 patent specification support relevant to claims 57 and 65 are:
`
`a. page 22, lines 29-33;
`
`In the present invention, the gene coding for the light chain and that coding for
`the heavy chain are recovered separately by the procedures outlined above.Thus
`they may be inserted into separate expression plasmids, or together 'i'n the same
`p|asm'i'd,so long as each is under suitable promoter and translation control.
`
`b. page 23, lines 1-7:
`
`The expression vectors constructed above are then used to transform suitable
`cells. The light and heavy chains may be transformed into separate cell cultures,
`either of the same or of differing species; separate plasmids for light and heavy
`chain may be used to co-transform a single cell culture or, finally, a single
`expression plasmid containing both genes and capable of expressing the genes
`for both light and heavy chain may be transformed into a single cell culture.
`
`Genzyme Ex. 1016, pg 475
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`Genzyme Ex. 1016, pg 475
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`

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`Application/Control Number: 90/007,542; 90/007,859
`Art Unit: 3991
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`Page 13
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`c. page 23, lines 29-33
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`When heavy and light chain are coexpressed in the same host, the isolation
`procedure is designed so as to recover reconstituted antibody. This can be
`accomplished in vitro as described below, or might be possible in vivo in a
`microorganism which secretes the lgG chains out of the reducing environment of
`the cytopl asm. A more detailed description is given in D.2, below.
`
`Accordingly, newly presented claim 53 in the Cabilly 1 application defined “or” to be
`
`“and/or” when referring to immunoglobulin heavy and light chains and their expression
`
`in order to encompass specification embodiments where:
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`a. light chain and heavy chain encoding DNA is inserted into 2 separate vectors for
`
`individual expression in 2 different hosts (“or” embodiment);
`
`b. light chain and heavy chain encoding DNA is inserted into 2 separate vectors for
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`coexpression of both vectors into 1 host (claim 65 “and” embodiment);
`
`c. light chain and heavy chain encoding DNA are inserted into 1 vector for expression
`
`in 1 host (claim 57 “and” embodiment).
`
`Additionally, the ‘567 patent claims utilize the transitional term “comprising” which
`
`opens the claim to the inclusion of additional, unrecited elements or method steps
`
`necessary to effect the described (and claimed) “and/or” embodiments.
`
`lnvitrogen
`
`Corp. v. Biocrest Mfg., L.P., 327 F.3d 1364,1368, 66 U.S.P.Q.2d 1631, 1634 (Fed. Cir.
`
`2003) (defining “comprising”).
`
`Thus, by analogy to claim 53 introduced during the 06/483,457 application
`
`prosecution, the claim 68 (which corresponds to reference Cabilly patent claim1)
`
`phrase “heavy or light chain” means heavy and/or light since it includes embodiments
`
`where both chains are present in the same host cell, even on the same DNA
`
`Genzyme Ex. 1016, pg 476
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`Genzyme Ex. 1016, pg 476
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`

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`App|icationlControl Number: 90/007,542; 90/007,859
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`Page 14
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`Art Unit: 3991
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`construct i.e. the Cabilly I claims encompass independent expression in one host of
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`light and heavy immunoglobulin chains utilizing two separate vectors or the use of a
`
`single vector encoding both immunoglobulin heavy and light chains, as well as the
`
`resulting vector constructs.
`
`OBVIOUSNESS DOUBLE PATENTING .
`
`New Rejection(s)
`
`1.
`
`Claims 1-4, 11, 13, 15-18, 21, 23-25 and 33 of U.S. Pat. No. 6,331,415 (Cabilly
`
`2) are rejected on the ground of nonstatutory obviousness-type double patenting
`
`as being unpatentable over claims 1-7 of U.S. Patent No. 4,816,567 (3l89: Cabilly1)
`
`(wherein “or” is being interpreted as “and/or” in light of the Cabilly 1 patent
`
`prosecution history).
`
`Both the Cabilly 1 and the instant Cabilly 2 patented inventions include claims
`
`directed to the same statutory subject matter: recombinant processes, vectors and host
`
`cells for making immunoglobulins (particularly chimeric immunoglobulins), and
`
`immunoglobulin products.
`
`The Reference Cabilly 1 Patent:
`
`The reference Cabilly 1 patented invention is drawn to (claim 1) a method
`
`comprising
`
`a) preparing a DNA sequence encoding a chimeric immununoglobulin heavy or light
`
`chain having specificity for a particular known antigen wherein a constant region is
`
`homologous to the corresponding constant region of an antibody of a first
`
`mammalian species and a variable region thereof is homologous to the variable region
`
`of an antibody derived from a second, different mammalian species;
`
`Genzyme Ex. 1016, pg 477
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`Genzyme Ex. 1016, pg 477
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`

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`Application/Control Number: 90/007,542; 90/007,859
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`Page 15
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`Art Unit: 3991
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`b) inserting the sequence into a replicable expression vector operably linked to a
`
`suitable promoter compatible with a host cell;
`
`c) transforming the host cell with the vector of (b);
`
`d) culturing the host cell; and
`
`e) recovering the chimeric heavy or light chain from the host cell culture.
`
`In the reference Cabilly 1 disclosure, “immunoglobulins” are defined as being
`
`comprised of light (kappa or lambda) and heavy chains (gamma, mu, alpha, delta or
`
`epsilon), which if when assembled possess “specific immunoreactive activity” are
`
`labeled “antibodies”. See Cabilly 1 at col. 3, lines 15-42; col. 6, lines 14-24. The phrase
`
`“chimeric immunoglobulin heavy or light chain” refers to a species of immunoglobulin
`
`heavy or light chain in which the constant region is homologous to the constant region
`
`of an antibody of a first mammalian species and the variable region is homologous to
`
`the variable region of an antibody derived from a second, different mammalian species.
`
`See Cabilly 1 patent: claims 1 and 3; and col. 6, lines 48-59. The Cabilly l patent
`
`includes mammalian chimeric immunoglobulin light and heavy chains which are derived
`
`from humans (dependent claims 2 and 4). Mammalian antibody sources are derived in
`
`situ from mammalian B lymphocytes or from cell culture hybridomas. See Cabilly 1
`
`patent col. 1, lines 38-42. The claimed “(replicable ) expression vector” is defined as
`
`vectors capable of expressing DNA sequences contained therein which are frequently in
`
`the form of plasmids, thus ‘plasmid’ and ‘expression vector’ are often used
`
`interchangeably. See Cabilly1 patent col. 8, lines 21-45. “Host cells" include
`
`prokaryotic (most preferably the gram (-) bacteria E. Coli. Strains ATCC: 31446 and
`
`31537) or eukaryotic cells, including eukaryotic microbes, and cells derived from
`
`Genzyme Ex. 1016, pg 478
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`Genzyme Ex. 1016, pg 478
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`

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`Application/Control Number: 90/007,542; 90/007,859
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`Page 16
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`Art Unit: 3991
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`multicellular organisms, such as mammalian cells. See Cabilly 1 patent , col. 8, 1ine 46
`
`to col. 10, lines 13-30, 57. The means of recovery of successfully transformed chimeric
`
`heavy or light chains is determined by the type of protein and host organism but utilizes
`
`art known techniques including cell lysis of insolubilized particles present in the host
`
`followed by denaturant solubilization. See Cabilly 1 patent col. 4, lines 27-35.
`
`The Cabilly 1 reference patented invention differs from the instant patent since:
`
`_a_. reference Cabilly 1 produces a (replicable expression) vector comprising DNA
`
`encoding immunoglobulin heavy or light chain for transforming and culturing of a host
`
`cell; whereas the instant patent requires that the vector comprise DNA encoding
`
`immunoglobulin heavy and light chain for transforming and culturing of a single host
`
`cell 1 and
`
`Q reference Cabi|ly1 is directed to the production of chimeric immunoglobulins (i.e. a
`
`species); whereas the instant invention produces an immunoglobulin (i.e. is generic);
`
`Regarding item a, as discussed supra, the Cabilly I reference patent claims
`
`(using "or”) read on expressing both heavy and light chains together (“and”) as well as
`
`expressing heavy or light chains separately in different vectors (“or”) since both the
`
`Cabilly 1 patent specification and prosecution history provide support for this
`
`inter