UNITED STATES PATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`PO. Box I450
`Aleundm. Virginia 22313-1450
`www.usp1o.gnv
`
`APPLICATION NO.
`
`90/007,542
`
`FILING DATE
`
`05/I 3/2005
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`6331415
`
`l0244P00l0US
`
`7585
`
`09/M005
`
`759°
`Wendy M. Lee
`Genentech, Inc. ’
`IDNA Way
`South San Francisco, CA 94080-4990
`
`DATE MAILED: 09/I 3/2005
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`PTO-90C (Rev. l0/03)
`
`Genzyme Ex. 1011, pg 394
`
`Genzyme Ex. 1011, pg 394
`
`

`
`Control No.
`90/007,542
`
`Examiner
`David J. Blanchard
`
`Patent Under Reexamination
`6331415
`
`Art Unit
`1643
`
`
`
`Office Action in Ex Parte Reexamination
`
`-- The MAILING DA TE of this communication appears on the cover sheet with the correspondence address --
`
`bl:] This action is made FINAL.
`aX Responsive to the communication(s) filed on 13 May 2005.
`cg 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.
`
`Part I
`
`THE FOLLOWING ATTACHMENT(S) ARE PART OF THIS ACTION:
`
`
`
`
`
`
`
`1.
`
`IX Notice of References Cited by Examiner, PTO-892.
`
`3. El
`
`Interview Summary, PTO-474.
`
`2. E]
`
`
`Information Disclosure Statement, PTO-1449.
`4. E]
`
`.
`
`
`
` Part ll SUMMARY OF ACTION
`1a.
`
`Claims 1 are subject to reexamination.
`
`.
`
`Dl:|E|DDDlZ|
`
`2.
`
`3 4 5 6
`
`.
`
`1b.
`
`
`
`
`
`
`
`
`
`Claims _ are not subject to reexamination.
`
`Claims ? have been canceled in the present reexamination proceeding.
`
`Claims __ are patentable and/or confirmed.
`
`Claims h3§_ are rejected.
`
`Claims
`
`are objected to.
`
`The drawings, filed on _ are acceptable.
`
`
`
`
`
`
`
`
`7. E] The proposed drawing correction, filed on ? has been (7a)I:I approved (7b)E] disapproved.
`
`8. 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
`
`1:] been received.
`
`2:] not been received.
`
`3[:I been filed in Application No. j
`
`4[:] been filed in reexamination Control No.
`
`5:} 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.
`
`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 CD.
`11, 453 O.G. 213.
`
`10. C] Other:
`
`
`
`uester if third
`
`US. Patent and Trademark Office
`
`PTOL-466 (Rev. 04-01)
`
`Office Action in Ex Parte Reexamination
`
`Part of Paper No. 20050906
`Genzyme Ex. 1011, pg 395
`
`Genzyme Ex. 1011, pg 395
`
`

`
`Application/Control Number: 90/007,542
`
`Page 2
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`Art Unit: 1643
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`DETAILED ACTION
`
`1.
`
`Claims 1-36 are pending and are considered in this re—examination.
`
`2.
`
`The patent owner is reminded of the continuing responsibility under 37
`
`CFR 1.565(a) to apprise the Office of any litigation activity, or other prior or
`
`concurrent proceeding, involving Patent No. 6,331,415 throughout the course of
`
`‘ this reexamination proceeding. The third party requester is also reminded of the
`
`ability to similarly apprise the Office of any such activity or proceeding throughout
`
`the course of this reexamination proceeding. See MPEP §§ 2207, 2282 and
`
`2286.
`
`Double Patenting
`
`The nonstatutory double patenting rejection is based on a judicially
`3.
`created doctrine grounded in public policy (a policy reflected in the statute) so as
`to prevent the unjustified or improper timewise extension of the "right to exclude"
`granted by a patent and to prevent possible harassment by multiple assignees.
`See In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re
`Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686
`F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164
`USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644
`(CCPA 1969).
`A timely filed terminal disclaimer in compliance with 37 CFR 1.321(0) may
`be used to overcome an actual or provisional rejection based on a nonstatutory
`double patenting ground provided the conflicting application or patent is shown to
`be commonly owned with this application. See 37 CFR 1.130(b).
`Effective January 1, 1994, a registered attorney or agent of record may
`sign a terminal disclaimer. A terminal disclaimer signed by the assignee must
`fully comply with 37 CFR 3.73(b).
`
`4.
`
`Claims 1-36 are rejected under the judicially created doctrine of
`
`obviousness-type double patenting as being unpatentable over claims 1-7 of US
`
`Genzyme Ex. 1011, pg 396
`
`Genzyme Ex. 1011, pg 396
`
`

`
`Application/Control Number: 90/007,542
`
`Page 3
`
`Art Unit: 1643
`
`Patent No. 4,816,567 in view of Axel et al (US Patent 4,399,216, issued
`8/16/1983, Ids filed 5/13/05) and Rice et al (Proc. Natl. Acad. Sci. USA 7917862-
`
`7865, December 1982, lds filed 5/13/05) and Kaplan et al (EP 0 044 722,
`
`published 1/27/1982, Ids filed 5/13/05) and Accolia et al (Proc. Natl. Acad. Sci.
`
`USA 77(1):563-566, January 1980, Ids filed 5/13/05) and Builder et al (US Patent
`
`4,511,502, issued 4/16/85).
`
`The instant claims (US Patent 6,331,415 B1; the ‘415 patent) are drawn to
`
`‘
`
`recombinant processes, vectors and host cells for producing immunoglobulins
`
`comprising transforming a 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 a the variable domain of the immunoglobulin light
`
`chain and independently expressing said first and second DNA sequences so
`
`that immunoglobulin heavy and light chains are so produced as separate
`
`_ molecules in the transformed host cells wherein the DNA sequences can be
`
`present in different vectors or in a single vector that is the plasmid pBR322 and
`
`the host cell can be E. coli strain X1776 or S. cerevisiaeand wherein the
`
`immunoglobulin heavy and light chains are expressed in the host cells and
`
`secreted therefrom as a functional immunoglobulin or is produced in insoluble
`
`form and subsequently solubilized and refolded in solution to form a functional
`
`immunoglobulin. Further, the claimed method for_producing an immunoglobulin
`
`wherein the first and second DNA sequences further encode at least one
`
`constant domain derived form the same source or derived from a species or
`
`class different from that which the variable domains are derived and wherein the
`
`Genzyme Ex. 1011, pg 397
`
`Genzyme Ex. 1011, pg 397
`
`

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`Application/Control Number: 90/007,542
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`Page 4
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`Art Unit: 1643
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`variable domains are derived from one or more hybridomas. The claims are also
`
`drawn to vectors comprising said first and second DNA sequences encoding at
`
`least the heavy and light chain immunoglobulin variable domains and host cells,
`
`including mammalian host cells transformed with said first and second DNA
`
`sequences as well as insoluble particles of heavy and light chains or Fab region
`
`produced in E.coli or yeast cells (i.e., inclusion bodies). Additionally, the claims
`
`recite wherein the heavy and light chains are the heavy and light chains of an
`
`anti—CEA antibody and wherein the heavy chain is of the gamma family and the _
`
`light chain is of the kappa family and wherein the method further comprises
`
`attaching the immunoglobulin to a label or drug.
`
`Claims 1-7 of US Patent 4,816,567 (the ‘567 patent) are also drawn to
`
`recombinant processes, vectors and host cells for producing immunoglobulins,
`
`comprising preparing a DNA sequence encoding a chimeric immunoglobulin
`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 is derived from a
`
`second different mammalian species, inserting the sequence into a replicable
`
`expression" vector operablyy linked to a suitable promoter compatible with a host
`
`cell, transforming the host cell with said vector, culturing the host cell and
`
`recovering the chimeric heavy or light chain from the host cell culture, wherein
`
`the first mammalian species is human. Further, the claims are drawn to a
`
`composition comprising said chimeric immunoglobulin heavy or light chain having
`
`specificity for a particular known antigen as well as a replicable vector comprising
`
`Genzyme Ex. 1011, pg 398
`
`Genzyme Ex. 1011, pg 398
`
`

`
`Application/Control Number: 90/007,542
`
`Page 5
`
`Art Unit: 1643
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`DNA encoding said chimeric immunoglobulin heavy or light chain operably linked
`
`to a promoter compatible with a suitable host cell and a recombinant host cell
`
`transformed with said vector. The claims in US Patent,4,816,567 do not
`
`specifically teach immunoglobulin expression on different .vectors or on the same
`
`vector wherein the plasmid vector is pBR322 or obtaining the heavy and light
`
`chain immunoglobulin variable domains from at least one hybridoma or
`
`immunoglobulin expression in mammalian, bacterial (i.e., E. coli strain X1776)
`
`and yeast host cells or recovering the immunoglobulin produced in insoluble form
`
`(i.e., inclusion bodies) and subsequent solubilization and refolding in solution to
`
`form functional immunoglobulin molecules or an anti-CEA antibody or gamma
`
`heavy chains and kappa light chains or insoluble particles of heavy and light
`chains produced in E. coli or yeast or the attachment of a label or drug to the
`
`produced immunoglobulin. These deficiencies are made up for in the teachings
`
`of Axel et al and Rice et al and Kaplan et al and Accolla et al.
`
`Axel et al teaches a process for inserting foreign DNA into eukaryotic cells
`
`by co-transforming the cells with this foreign DNA and an unlinked DNA that
`
`codes for a selectable phenotype not otherwise expressed by the cell (see
`
`column 3, lines 21-27). Axel describes the process as particularly suited for the
`
`transformation of DNA into eukaryotic cells for making immunoglobulins (see
`
`column 3, lines 31-36). Axel thus demonstrates the predictability of expression of
`
`multiple heterologous proteins in a single host cell. Axel also suggests the
`
`desirability of expressing immunoglobulins in mammalian host cells, and as intact
`
`(assembled) proteins.
`
`Genzyme Ex. 1011, pg 399
`
`Genzyme Ex. 1011, pg 399
`
`

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`Application/Control Number: 90/007,542
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`Page 6
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`Art Unit: 1643
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`Rice et al successfully introduced a recombinant rearranged murine kappa
`
`light chain gene construct into an Abelson murine leukemia virus (A—MuLV)-
`
`transformed lymphoid cell line, which is a cell line that already synthesized y2b
`
`heavy chain protein (see page 7862). Rice inserted the light chain gene into a
`
`plasmid, used this plasmidnto transfect the cells, and then examined the
`
`polypeptides as well as the RNA produced by the cells (see pages 7863-7864,
`
`and Figures 2 and 3). Lastly, since the cells were producing both
`
`immunoglobulin chains, the cells were examined for the ability to assemble the
`
`chains into lgG molecules, leading to the observation that “[e]ssentially all of the
`
`K chain produced in the K-2 cells appears to be assembled into lgG2b." (see
`
`page 7864). Thus, at the time of filing the application for the ‘576 and ‘415 patent
`
`it was known in the art that host cells could express “heavy or light chains,” and
`
`that expression of both chains was routine, resulting in assembly into
`
`immunoglobulins.
`
`Kaplan teaches that human hybridomas can serve as a useful source of
`
`mRNA encoding the antibody heavy and light chains to specific antigens. By
`
`using known molecular biology techniques, the mRNAs can be used for the
`
`generation of genes which, when inserted into the appropriate vector, can serve
`
`as a coding source for the production of proteins (see page 3, lines 4-9).
`
`In
`
`addition, Kaplan teaches that a variety of host cells, such as bacteria and yeast,
`
`may be used to express such recombinant immunoglobulin heavy and light
`
`chains (see page 10, lines 1-33).
`
`Genzyme Ex. 1011, pg 400
`
`Genzyme Ex. 1011, pg 400
`
`

`
`Application/Control Number: 90/007,542
`
`Page 7
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`Art Unit: 1643
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`‘
`
`Accolla et al teach CEA as an important tumor marker of human
`
`carcinomas and methods of making anti-CEA antibodies and anti-CEA antibodies
`
`as a standard reagent for CEA detection in human tissues and body fluids (see
`
`entire document, particularly the abstract).
`
`Builder et al teach that the expression of exogenous or foreign proteins in
`
`bacteria or other host cells are frequently expressed as clumps of insoluble
`
`protein (i.e., refractile bodies) and Builder teaches a procedure for recovering, I
`
`solubilizing and refolding such insoluble proteins (see entire document,
`
`particularly col. 2-6 and schemes 1 and 2).
`
`a. The ‘567 patent claims a species of the genus claimed in the later ‘415
`
`patent, causing obviousness-type double patenting.
`
`Instant claims 1, 21 and 33 (‘415 patent) are drawn methods for producing
`
`a genus of immunoglobulins and claim 1 of the ‘567 is directed to methods for
`
`producing “chimeric” immunoglobulin chains, which is a species of the
`
`immunoglobulin genus claimed in the |aterl‘415 patent. A second application
`
`containing a broader claim, more generic in character that the specific claim in
`
`the prior patent, typically cannot support a valid, independent patent.
`(i.e.,
`species anticipates the genus). The same applies for the vector (claim 5) and
`
`host cell (claim 7) claims of the ‘567 patent and the corresponding claims 15-16
`
`(vector) and 17-18 (host cell) of the ‘415 patent. Further, claim 1 of the ‘567
`
`patent recites a chimeric immunoglobulin species of the sub-genus defined by
`
`claim 13 of the ‘41 5 patent and claims 2 and 6 of the ‘567 patent are directed to a
`
`Genzyme Ex. 1011, pg 401
`
`Genzyme Ex. 1011, pg 401
`
`

`
`Application/Control Number: 90/007,542
`
`Page 8
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`Art Unit: 1643
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`human constant region of the chimericimmunoglobulin, which is another
`
`example of a species within the genus claimed in the ‘415 patent. Applicant is
`
`reminded that the term “comprising” recited in claim 1 of the earlier ‘567 patent is
`
`inclusive or open-ended and does not exclude additional, unrecited elements or
`
`method steps (MPEP 2111.03). Thus, while the claims of the ‘567 patent
`
`embrace embodiments in which separate host cell cultures express either a
`
`chimeric heavy or a chimeric light immunoglobulin chain, the claims also ‘read on
`
`embodiments in which one host cell culture expresses both the heavy and light
`
`chains, at least one of which is chimeric. Thus, claims 1-2 and 5-7 of the ‘567
`
`patent read upon claims 1, 13, 15-18, 21 and 33 in the later ‘415 patent.
`
`b. The ‘567 claims, alone or together with the prior art references, render
`
`the ‘415 claims obvious.
`
`Claim 2 of the ‘415 patent recites that the heavy and light chain DNA
`
`sequences, including sequences encoding chimeric heavy or light chains, are on
`
`different vectors. Claims 3 and 25 of the '41 5 patent, which depend from claims
`
`1 and 21, respectively, recite that the DNA sequences are present in a single
`
`vector. Claim 1 of the ‘567 patent reads on the process involving each of
`
`different vectors, or both DNAs on the same vector, since the process includes
`
`preparing each DNA sequence and inserting it in an expression vector for
`
`expression of each of the heavy and light chains before they are assembled into
`
`an immunoglobulin. Axel teaches transformed mammalian cells that produce
`
`multiple heterologous proteins on different vectors or on the same vector. Axel,
`
`Genzyme Ex. 1011, pg 402
`
`Genzyme Ex. 1011, pg 402
`
`

`
`Application/Control Number: 90/007,542
`Art Unit: 1643
`
`Page 9.
`
`col. 6, lines 44-66 and col. 7, lines 3-9. Thus, ‘415 claims 2, 3, and 25 are
`
`obvious variants of ‘567 claim 1
`
`in view of Axel.
`
`Claim 4 of the ‘415 patent recites that the vector is a plasmid, and claim 5
`
`recites that the plasmid is pBR322. A plasmid, particularly pBR322, is a type of
`
`vector within the scope of claim 1 of the 1567 patent. Axel and Kaplan both
`
`teach the use of plasmids, particularly pBR322, for expressing heterologous
`
`proteins. Axel, col. 8, lines 7-35; Kaplan, p. 10. Thus, ‘415 claims 4 and 5 are
`
`obvious variants of ‘567 claim 1 in view of Axel or Kaplan.
`
`Claim 6 of the ‘41 5 patent recites that the host cell is a bacterium or yeast.
`
`Claim 7 recites that the host cell is E. coli (a bacterium) or S. cerevisiae (a yeast),
`
`and claim 8 recites that the bacterial host cell is E. coli strain X1776. Claim 19
`
`recites that the host cell of claim 1 is a mammalian host cell. Claim 26 recites
`
`that the host cell is E. coli or yeast. Each of these host cells is a host cell within
`
`the scope of claim 1 of the ‘567 patent. Axel teaches mammalian host cells for
`
`expressing proteins, expressly including antibodies. Axel, col. 5, lines 3-7 and
`
`24-28. Rice demonstrates expression of a recombinant immunoglobulin light
`
`chain in a mammalian host cell. Rice, p. 7863. Kaplan teaches bacterial and
`
`yeast host cells for expressing recombinant immunoglobulin chains. Kaplan, p.
`
`10, lines 1-33. Thus, ‘415 claims 6-8, 19, and 26 are obvious variants of ‘567
`
`claim 1 in view of Axel, Rice, and/or Kaplan.
`
`Claims 9 and 29 of the ‘415 patent read on expression and secretion of an
`
`immunologically functional immunoglobulin. Axel teaches mammalian host cells
`
`for expressing proteins, expressly including antibodies. Axel, col. 5, lines 3-7 and.
`
`Genzyme Ex. 1011, pg 403
`
`Genzyme Ex. 1011, pg 403
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`

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`Application/Control Number: 90/007,542
`
`Page 10
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`Art Unit: 1643
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`24-28. Rice demonstrates expression of a recombinant immunoglobulin light
`
`chain in a mammalian host cell. Rice, p. 7863. Thus, ‘415 claims 9 and 29 are
`
`obvious variants of ‘567 claim 1 in view of Axel and/or Rice.
`
`Claim 10 of the ‘415 patent reads on solubilization of the insoluble heavy
`
`and light chains, followed by refolding, to form an immunologically functional
`
`immunoglobulin or fragment.
`
`‘415 claims 27 and 28 read on deposition of
`
`insoluble heavy and light chain proteins and recovery of the insoluble proteins
`
`followed by solubilization in denaturant, respectively.
`
`‘415 claim 31 recites
`
`recovering both the heavy and light chain and reconstituting the two chains to
`
`form an immunoglobulin.
`
`In each case, priorto formation of the immunoglobulin,
`
`one produces each of the heavy and light chains as separate molecules. Kaplan
`
`teaches bacterial and yeast host cells for expressing recombinant
`
`immunoglobulin chains (p. 10, lines 1-27) and Kaplan also describes rupturing
`
`the host cells, e.g., bacteria and yeast, isolating the heavy and light chains, and
`
`combining them under mildly oxidative conditions to promote refolding and
`
`disulfide bond formation (p. 10, lines 27-33). Builder et al teach that the
`
`expression of exogenous or foreign proteins in bacteria or other host cells are
`
`frequently expressed as clumps of insoluble protein (i.e., refractile bodies) and
`
`Builder teaches a procedure for recovering, solubilizing and refolding such
`
`insoluble proteins (see entire document, particularly col. 2-6 and schemes 1 and
`
`2) and the ‘41 5 patentee also admits that reconstitution of immunoglobulins by
`
`refolding was known in the art (col. 13, lines 1-52). The separate chains are
`
`recovered separately for subsequent assembly. Thus, ‘415 claims 10, 27, 28,
`
`Genzyme Ex. 1011, pg 404
`
`Genzyme Ex. 1011, pg 404
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`

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`Application/Control Number: 90/007,542
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`Page 11
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`Art Unit: 1643
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`and 31 are obvious variants of ‘567 claim 1 in view of Kaplan, Builder and the
`
`admitted prior art.
`
`Claim 15 of the ‘415 patent recites that the vector comprises DNA
`
`sequences encoding at least the variable region of both the heavy and the light
`
`chain. Claim 16 specifies that the vector of claim 15 is a plasmid. Claim 5 of the
`
`‘567 patent is directed to a vector, such as a plasmid vector, which encodes a
`
`chimeric immunoglobulin heavy or light chain. As discussed above, it includes a
`
`vector that includes DNA encoding both a heavy chain and a light chain. Axel
`
`and Kaplan teach the use of plasmids, particularly pBR322, for expressing
`
`’heterologous proteins (Axel, col. .8, lines 7-35); (Kaplan, p. 10). Thus, ‘415
`
`claims 15 and 16 are obvious variants of ‘567 claim 5 in view of Axel or Kaplan.
`
`Claim 18 of the '41 5 patent is directed to host cells transformed with two
`
`vectors, one for the heavy chain and one for the light chain. Claim 20 specifies
`
`that the host cell of claim 18 is a mammalian host cell. Claim 7 of the 1567
`
`patent is directed to host cells transformed with a vector encoding a chimeric
`
`heavy or light chain. A host cell of the ‘567 patent can be a mammalian host cell.
`
`As discussed above, the claim embraces host cells with two vectors, one for
`
`each chain, or one vector separately encoding both the heavy and light chains,
`
`so long as one or both are chimeric. Axel teaches mammalian host cells for
`
`expressing proteins, ‘expressly including antibodies (col. 5, lines 3-7 and 24-28).
`
`Rice demonstrates expression of a recombinant immunoglobulin light chain in a
`
`mammalian host cell (pp. 7863). Kaplan teaches bacterial and yeast host cells
`
`for expressing recombinant immunoglobulin chains (p. 10, lines 1-33). Thus,
`
`Genzyme Ex. 1011, pg 405
`
`Genzyme Ex. 1011, pg 405
`
`

`
`Application/Control Number: 90/007,542
`
`‘
`
`Art Unit: 1643
`
`Page 12
`
`‘
`
`‘415 claims 18 and 20 are obvious variants of ‘567 claim 7 in view of Axel and
`
`Rice, and claim 18 is further an obvious variant of ‘567 claim 7 in view of Kaplan.
`
`Claim 22 of the ‘41 5 patent limits the method of claim 21 to making an
`
`anti-CEA antibody. CEA is a specific antigen within the general scope of a
`
`“particular known antigen” of claim 1 of the ‘567 patent. Accolla et al (Proc. Natl.
`
`Acad. Sci. USA, 77(1):563-566, January 1980) describes making anti-CEA
`
`monoclonal antibodies. The ‘41 5 patentee admits that anti-CEA antibodies are
`
`useful for the detection and potentially for use in treatment of tumors that have
`
`CEA at their surface.
`
`‘415 patent, col. 16, lines 31-38, citing Gold et al, Journal
`
`of Experimental Medicine, 122:467, 1965 and van Nagell et al, Cancer Research,
`
`402502-506, March 1980. Thus, ‘415 claim 22 is an obvious variant of ‘567 claim
`
`1 in view of Accolla or the admitted prior art.
`
`0 Claim 23 of the ‘415 patent limits the method of claim 21 to that in which
`
`the heavy chain is of the gamma family, and claim 24 limits the method of claim
`
`21 to that in which the light chain is of the kappa family. The terms “heavy chain”
`
`and “light chain” of claim 1 of the ‘567 patent read on gamma heavy chain and
`
`kappa light chain, respectively. Rice teaches expressing a recombinant kappa
`
`chain with an endogenous gamma chain in a host cell to produce an
`
`immunoglobulin molecule. Rice, pp. 7862 and 7864. Thus, ‘415 claims 23 and
`
`24 are obvious variants of ‘567 claim 1 taken with Rice.
`
`Claim 30 of the ‘41 5 patent recites that (1) the host cell is a gram negative
`
`bacterium and (2) the heavy and light chains are secreted into the periplasmic
`
`space of the host cell. A gram negative bacterium, such as E. coli, is a host’ cell
`
`Genzyme Ex. 1011, pg 406
`
`Genzyme Ex. 1011, pg 406
`
`

`
`Application/Control Number: 90/007,542
`
`Page 13
`
`Art Unit: 1643
`
`within the scope of claim 1 of the ‘567 patent. As pointed out above, claim 1 of
`
`the ‘567 patent also reads on secretion of the heavy or light chain, or both,
`
`including into the periplasmic space of a bacterium. Kaplan teaches bacterial
`
`and yeast host cells for expressing recombinant immunoglobulin chains (p. 10,
`
`lines 1-33). Thus, ‘415 claim 30 is an obvious variant of ‘567 claim 1 in view of
`Kaplan.
`.
`
`Claim 32 of the ‘41 5 patent is directed to an insoluble particle of heavy
`
`and light chains produced by the method of claim 27. Thus, claim 32 is directed '
`
`to a composition of matter comprising immunoglobulin proteins. Claim 3 of the
`
`‘567 patent is directed to a composition comprising a chimeric immunoglobulin
`
`heavy or light chain, whether it is soluble or insoluble. Kapian teaches bacterial
`
`and yeast host cells for expressing recombinant immunoglobulin chains (p. 10,
`
`lines 1-33). ) and Builder et al demonstrate that expression of exogenous or
`
`foreign proteins in bacteria or other host cells are frequently expressed as
`
`clumps of insoluble protein (i.e., refractile bodies) (see entire document).
`
`‘41 5
`
`patent, col. 12, lines 39-41. Thus, ‘415 claim 32 is an obvious variant of ‘567
`
`claim 3 for insoluble chimeric heavy and/or light chain compositions in view of
`
`Kaplan and Builder.
`
`Claims 34, 35, and 36 of the ‘415 patent recite that the processes of
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`claims 9, 10, and 33 further include attaching the immunoglobulin to a label or
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`drug. For the reasons provideduabove, claims 9, 10, and 33 are obvious variants
`
`of the ‘567 claims. Kaplan teaches the use of antibodies for site directed therapy
`
`wherein the antibody is attached to a drug or other therapeutic means as well as
`
`Genzyme Ex. 1011, pg 407
`
`Genzyme Ex. 1011, pg 407
`
`

`
`Application/Control Number: 90/007,542
`
`Page 14
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`Art Unit: 1643
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`the attachment of a radiolabel for localization (see page 8, lines 7-21). Thus,
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`‘415 claims 34, 35, and 36 are obvious variants of ‘567 claim 1,
`
`if necessary in
`
`view of Axel, Rice, Kaplan and Builder.
`
`Therefore, the invention as a whole was prima facie obvious to one of
`
`ordinary skill in the art at the time the invention was made, as evidenced by the
`
`references.
`
`Consequently, the ‘415 patent claims are obvious variants of the ‘567
`
`claims. They could have been (and had been) examined together and could
`
`have issued in the same patent. The delay in issuing the ‘415 claims significantly
`
`and inappropriately extends, by more than twelve years, the right to exclude
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`others from practicing technology for recombinant expression of chimeric
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`immunoglobulins. Filing a terminal disclaimer for the ‘415 patent so that it would
`
`expire at the same time as the first ‘567 patent would prevent the timewise
`extension of the patent right and, hence, cure the obviousness type-double
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`patenting. In re Vogel, 422 F.2d 438, 164 U.S.P.Q. 619 (CCPA 1970); see MPEP
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`804.02.
`
`This rejection of claims 1-36 was proposed by the third party requestor in
`
`the request for reexamination, and is being adopted essentially as proposed in
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`the request in addition to the prior art of Builder et al.
`
`5.
`
`Then third part request also proposes Schnel/er-type double patenting,
`
`however, this is not being adopted because Schnel/er, 397 F.2d 350, 158
`
`Genzyme Ex. 1011, pg 408
`
`Genzyme Ex. 1011, pg 408
`
`

`
`Application/Control Number: 90/007,542
`
`Page 15
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`Art Unit: 1643
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`U.S.P.Q. 210 is limited to a specific fact pattern that does not match the situation
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`in the current reexam (MPEP 804).
`
`6.
`
`No claim is allowed.
`
`Conclusion
`
`All correspondence relating to this Ex parte reexamination proceeding should be
`directed:
`
`By Mail to: Mail Stop Ex Parte Reexam
`Central Reexamination Unit
`
`Office of Patent Legal Administration
`United States Patent & Trademark Office
`
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`
`By FAX to:
`
`(571) 273-0100
`Central Reexamination Unit
`
`By hand:
`
`Customer Service Window
`Randolph Building
`401 Dulany Street
`Alexandria, VA 22314
`
`Any inquiry concerning this communication or earlier communications from the
`examiner, or as to the to the status of this proceeding, should be directed to the
`Central Reexamination Unit at telephone number (703) 308-9692.
`
`David Blanchard
`gm/gflgj
`
`Art Unit 1643
`
`LARRY Ft. HELMS. mo.
`
`3'-""E3V'S0RYPATENT EXAMINER
`
`Genzyme Ex. 1011, pg 409
`
`Genzyme Ex. 1011, pg 409