`
`Notice of Intent to Issue
`
`Control No.
`
`Patent Under Reexamination
`
`90/007,859 3 70/00513!-2..
`, Examiner
`
`6331415
`Art Unit
`
`'
`
`Padmashri Ponnaluri
`
`3991
`
`-- The MAILING DA TE of this‘ communication appears on the cover sheet with the correspondence address --
`1. [Z Prosecution on the merits is (or remains) closed in this ex parte reexamination proceeding. This proceeding is
`subject to reopening at the initiative of the Office or upon petition. Of. 37 CFR 1.313(a). A Certificate will be
`issued in view of
`
`
`(a) [Z Patent owner's communication(s)flled: 2/12/09 2/13/09.
`(b)
`[:1 Patent owner's late response filed:
`.
`(c) E] Patent owner’s'failure to file an appropriate response to the Office action mailed:
`(d) [I Patent owner’s failure to timely file an Appeal Brief (37 CFR 41.31).
`(e) E] Other:
`.
`.
`Status of Ex Parte Reexamination:
`
`(f) Change in the Specification: D Yes [Z No
`(g) Change in the Drawing(s): D Yes E No
`(h) Status of the C|aim(s):
`(1) Patent claim(s) confinned: 1-20 and 33-36.
`(2) Patent claim(s) amended (including dependent an amended claim(s)): 21-32
`(3) Patent claim(s) cancelled:
`.
`(4) Newly presented claim(s) patentable:
`(5) Newly presented cancelled claims:
`
`.
`
`2. IX Note the attached statement of reasons for patentability and/or confirmation. Any comments considered
`necessary by patent owner regarding reasons for patentability and/or confirmation must be submitted promptly
`to avoid processing delays. Such submission(s) should be labeled: “Comments On Statement of Reasons for
`Patentabilily and/or Confinnation."
`
`3. CI _Note attached NOTICE OF REFERENCES CITED (PTO-892).
`4. l2 Note attached LIST OF REFERENCES CITED (PTO/SB/08). ll P35!
`5. D The drawing correction request filed on
`is: El approved
`I:l disapproved.
`6. D Acknowledgment is made of the priority claim under 35 U.S.C. § '119(a)-(d) or (f).
`a)I:] All b)D Some‘
`c)I:] None
`of the certified copies have
`El been received.
`l:I'not been received.
`.
`El been filed in Application No.
`.
`I] been filed in reexamination Control No.
`[:| been received by the international Bureau in PCT Application No.
`* Certified copies not received:
`
`7.tl:i Note attached Examiner's Amendment.
`
`8. IX Note attached interview Summary (PTO-474).
`9. I] Other:
`
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`DEBORAH D. JONES
`
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`PRIMARY EXAlVilNEF:
`CRU SPE-AU 3991
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`Notice of Intent to Issue Ex Parte Reexamination Certificate
`
`Part of Paper No 20090211
`
`Sanofi/Regeneron Ex. 1025, pg 802
`
`Mylan Ex. 1025, pg 802
`
`
`
`Application/Control Number: 90/007,859 9: ‘/6’/0.07.l54'2
`Art Unit: 3991
`
`I
`
`Page 2
`
`Reexamination
`
`Procedural Posture
`
`This is the merged Ex parte reexamination proceedings of 90/007,542 and 90/007,859.
`
`This is merged reexamination of US Patent 6,331,415 (Cabilly II), issued on December 18, 2001.
`
`_ Decision merging reexamination ‘proceedings 90/007,542 and 90/007,859 was mailed on 6/6/06.
`
`_
`
`A First Office Action in this merged proceedings was mailed on 8/ 16/06.
`
`Patent Owner filed a response on 10/3 0/06.
`
`Final Rejection was mailed on 2/16/07.
`
`A Request for Continued Reexamination was filed on 5/21/07. The Request for
`
`Continued Reexamination was granted on 6/10/07.
`
`Final Rejection was mailed on 2/25/08.
`
`Afier Final response was mailed on 6/6/08.
`
`Advisory action was mailed on 7/19/08.
`
`Notice of Appeal was filed on 8/22/08.
`
`Appeal Brief was filed on 12/9/08.
`
`A supplemental response and amendment are filed on 2/12/09. The amendment to claim
`
`21 does not comply with Rule 1.530. A second supplemental amendment is filed on 2/13/09.
`
`Amendment
`
`Claims 21, 27 and 32 are amended by the amendment filed on 2/13/09.
`
`Information Disclosure Statement
`
`Sanofi/Regeneron Ex. 1025, pg 803
`
`Mylan Ex. 1025, pg 803
`
`
`
`Application/Control Number: 90/007,859 3; 7r9/37072542
`Art Unit: 3991
`
`'
`
`Page3
`
`The Information disclosure statements (PTO/SB/O8) filed on 2/11/09 and 6/6/08 have
`
`been considered. The documents L11 to L30 related to the litigation (cited in the 6/6/08’ IDs) are
`
`considered, however a line is drawn through the citations because these documents are not
`
`appropriate for printing on the face of the reexamination certificate.
`
`The Cabilly 6,331,415 Invention (Cabilly II Patent)
`
`The invention is drawn to a method for producing an immunologically functional
`
`immunoglobulin molecule or an immunologically functional immunoglobulin fragment by
`
`transforming a single host cell with a first DNA sequence encoding immunoglobulin heavy chain ‘
`
`and a second DNA sequence encoding immunoglobulin light chain and independently expressing
`
`the first DNA sequence and second DNA sequence so that said immunoglobulin heavy chain and
`
`light chain are produced as separate molecules in said transformed single host cell.
`
`Claims 1, 21 and 33 are representative of the invention.
`
`Based on the prosecution history of the patent at issue, and the interference record from
`
`Interference No. 102,572, the term “immunoglobulin molecule” in claims 1 and 33 is considered
`
`to be immunologically functional molecule and capable of binding to a known antigen.
`
`Withdrawn Rejections
`
`The lobviousness-type double patenting rejection of claims 1-36 of U.S. Pat. No.
`
`6,331,415 (Cabilly 2) over claims 1-7 ofU.S. Patent No. 4,816,567 (Cabilly 1) in view of Axel et
`
`al. U.S. Pat. No, 4,399,216 (8/83), Rice and Baltimore, PNAS USA 79 (12/82);7862-7865,
`
`Kaplan et al, EP 0044722 (1/82), Builder et al U.S.'Pat. No. 4,511,502 (issued 4/85), Accolla et
`
`Sanofi/Regeneron Ex. 1025, pg 804
`
`Mylan Ex. 1025, pg 804
`
`
`
`Application/Control Number: 90/007,859 3 Q6/0077,3712‘
`Art Unit: 3991
`
`Page 4
`
`al PNAS USA 77(1): 563,566 (1980), Dallas (WO 82/03088), Deacon (Biochemical. Society
`
`Transactions, 4 (1976):818-820), 1981 Valle (Nature, 291 (May '81) pages 338-340; Ochi
`
`(Nature, 302(3/24/83) pages 340-342 alone, or fiarther in view of Moore et al.'U.S. Pat. No.
`
`5,840,545 (Nov. 24, 1998: effectively filed March 15, 1982) is withdrawn upon reconsideration
`
`.and in view of Patent Owner’s response and Declarations presented in this reexamination
`
`proceedings.
`
`Cabilly I Patent (the ‘567 patent) claims are drawn to a method for preparing chimeric
`
`immunoglobulin heavy chain or immunoglobulin light chain molecules separately from
`
`transformed host cells. The host cell in the Cabilly I patent claims is transformed with either
`
`'
`
`immunoglobulin heavy chain or immunoglobulin light chain. Cabilly I patent claims do not
`
`recite a single host cell transformed with DNA sequences encoding both immunoglobulin heavy
`
`chain and immunoglobulin light chain independently as required in the present Cabilly II claims.
`
`Axel et al taught a process for inserting foreign DNA into eukaryotic cell by
`
`cotransformation with the disclosed foreign DNA I and DNA II that encodes‘ a selectable marker.
`
`Axel et al did not teach asingle host cell transformed with immunoglobulin heavy chain and
`
`immunoglobulin light chain independently. Axel et al did not teach co—expression of two foreign
`
`DNA sequences (see I-Iarris declaration, McKnight declaration, Botchan declaration, Rice
`
`declaration, and Colman declaration).
`
`Rice exogenously introduced a recombinant murine kappa light chain gene into a mutant
`
`lymphoid cell line (8lA-2 cell line) that contains heavy chain (endogenous). Rice taught the co-
`
`expression of immunoglobulin heavy and light chain in the mutant cells. However, Rice did not
`
`teach that a single host cell is transformed with both immunoglobulin heavy chain and light
`
`Sanofi/Regeneron Ex. 1025, pg 805
`
`Mylan Ex. 1025, pg 805
`
`
`
`Application/Control Number: 90/007,859 3 79/0073 542.
`Art Unit: 3991
`
`’
`
`Page 5
`'
`
`chain (see Rice Declarations, Colman declaration, Harris declaration, Botchan declaration, and
`
`McKnight declaration). Rice taught the successfiil expression of immunoglobulin light chain
`
`' genes is linked to the ongoing ability of the cell to express its endogenous heavy chain gene (see
`
`Harris declaration, and Rice declaration).
`
`Kaplan taught a method for producing an immunoglobulin multimer, wherein the
`
`individual immunoglobulin heavy chain and light chain are produced in separate cell culture.
`Kaplan did not teach producing immunoglobulin heavy chain and light chain in a single host cell
`
`(see Harris declaration, McKnight declaration, Botchan declaration, Colman declaration, and
`
`Rice declaration).
`
`K
`
`Dallas taught a method of making an E.coli vaccine by inserting into one E.coli cell
`
`genes obtained from another strain of E.coli. Dallas did not teach a method for producing
`
`multiple eukaryotic proteins from a single host cell (see Harris declaration, McKnight
`
`declaration, Rice declaration, and Botchan declaration).
`
`Moore patent disclosed a method for producing “rFv” binding molecule comprising
`
`variable regions of immunoglobulin heavy chain and light chain. Moore patent taught producing
`
`immunoglobulin heavy chain and light chain in separate host cells. Moore patent taught the
`
`immunoglobulin heavy chain and light chain are inserted into two separate single-marker pGM1
`
`based ‘plasmids, resulting in pGMlH and pGM1iL. Since both pGMlH and pGM1L plasmids
`
`contain the same selectable marker, two separate host cell cultures are transformed with each
`
`plasmid (see Scott declaration, McKnight declaration, Altman declaration). Thus, the Moore
`
`patent taught producing immunoglobulin heavy chain and light chain inseparate host cells.
`
`Sanofi/Regeneron Ex. 1025, pg 806
`
`Mylan Ex. 1025, pg 806
`
`
`
`Application/Control Number: 90/007,859 g 70/670% 54-7-
`Art Unit: 3991
`
`Page 6
`A
`
`Deacon and Valle introduced and expressed exogenous immunoglobulin heavy chain and
`
`light chain in xenopus oocyte cells. Valle 1982 is cumulative in its teachings to Deacon and
`
`Valle reference. The Deacon and Valle reference did not describe any experiment where a
`
`eukaryotic host cell is transfected with DNA (see Rice Declarations, Colman declaration, Harris
`
`declaration, ‘McKnight declaration and Botchan declaration).
`
`_ Ochi taught a method of producing antibody by cloning an immunoglobulin light chain
`
`into a cell line endogenously producing an immunoglobulin heavy chain. Ochi did not teach that
`
`a single host cell is transformed with both immunoglobulin heavy chain and light chain (see Rice
`Declarations", Harris declaration, McKnight declaration and Botchan declaration).
`
`Builder taught reconstitution techniques for recovering expressed polypeptides from
`
`bacterial host cells. Builder did not teach assembly of immunoglobulin tetramer (see Harris
`
`declaration).
`
`Accolla described methods for making anti-CEA monoclonal antibodies. Accolla did not
`
`teach a method for producing monoclonal antibodies that bind to the CEA antigen through
`
`recombinant DNA techniques (see Harris declaration).
`
`Upon reconsideration of the declarations by Harris, McKnight, Botchan, Colman, and
`
`‘Rice, a person of ordinary skill in the art at the time the invention was made would not have had
`
`a reasonable expectation of success modifying the Cabilly I Patent claims in accordance to the
`
`teachings of Axel, Rice, Kaplan, Builder, Accolla, Dallas, Moore patent, Deacon and Valle, and
`
`Ochi references of record to produce an immunologically fiinctional immunoglobulin molecule
`
`by independently expressing immunoglobulin heavy chain and light chain in a single
`
`transformed host cell.
`
`Sanofi/Regeneron Ex. 1025, pg 807
`
`Mylan Ex. 1025, pg 807
`
`
`
`Application/Control Number: 90/007,859 5 70/007, 542
`Art Unit: 3991
`
`Page‘7
`
`STATEMENT OF REASONS FOR PATENTABILITY AND/OR CONFIRMATION
`
`The following is an examiner's statement of reasons for patentability and/or confirmationof the
`
`claims found patentable in this reexamination proceeding:
`
`The combination of the Cabilly I patent claims and the teachings of Axel, Rice, Kaplan,
`
`Builder, Accolla, Dallas, Moore patent, Deacon and Valle and Ochi references do not suggest or
`
`contain an enabling disclosure of a method to produce an immunologically fimctional
`
`. immunoglobulin molecule by independently expressing immunoglobulin heavy chain and light
`
`chain in a single transformed host cell.
`
`Any comments considered necessary by PATENT OWNER regarding the above
`
`statement must be submitted promptly to avoid processing delays. Such submission by the
`
`patent ownershould be labeled: "Comments on Statement of Reasons for Patentability and/or
`
`Confirmation" and will be placed in the reexamination file.
`
`Conclusion
`
`Claims 1-20, 33-36 are confirmed and amended claims 21-32 are allowed.
`
`Future Correspondences
`
`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to Padmashri Ponnaluri whose telephone number is 571-272-0809.
`
`The examiner can normally be reached on Monday through Friday between 7 AM and 3.30 PM.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
`
`supervisor Deborah Jones can be reached on 571-272-1535. The fax phone number for the -
`
`organization where this application or proceeding is assigned is 571-273-9900.
`
`Sanofi/Regeneron Ex. 1025, pg 808
`
`Mylan Ex. 1025, pg 808
`
`
`
`Application/ControlNumber: 90/007,859 S 70/002540.
`Art Unit: 3991
`
`. Page 8 _
`
`Information regarding the status of an application may be obtained from the Patent
`Application Information Retrieval (PAIR) system. Status information for published
`applications may be obtained from either Private PAIR or Public PAIR. Status information
`for unpublished applications is available through Private PAIR only. For more information
`about the PAIR system, see http://pair-direct.uspto. gov. Should you have questions on access
`to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197
`(toll-free).
`
`All correspondence relating to this Ex parte Reexamination proceeding should be directed to:
`
`By EFS:
`
`Registered users may submit via the electronic filing system EFS-Web at
`
`ht_tps 2//sportaluspto. gov/authenticate/authenticateuserlocalepf. html
`
`By Mail to:
`
`Attn: Mail Stop “Ex Parte Reexam”
`Central Reexamination Unit
`Commissioner for Patents
`P. O. Box 1450
`
`Alexandria VA 22313-1450
`
`‘
`By FAX to:
`(571)273-9900
`Central Reexamination Unit
`
`Hand-Deliver any communications to:
`Customer Service Window
`Attn: Central Reexamination Unit
`
`Randolph Building, Lobby Level
`401 Dulany Street
`Alexandria, VA 22314
`
`Conferee:
`
`AH [1 JONES
`DE 1
`CRU SPE-AU 399‘
`
`
`iiiQ‘=" N i‘vo.
`'3-lUifi;i'\.lt'3;
`_
`5M/RFEY EXAlVlil\!EFr
`*;'.‘.fRl,.i
`-. AH 399:
`
`P mashri Ponnaluri
`Primary Examiner
`Unit 3991
`
`13 February 2009
`
`Sanofi/Regeneron Ex. 1025, pg 809
`
`Mylan Ex. 1025, pg 809