DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the claims
Claims 1-20 are pending and are examined.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 8-11 and 18-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jensen M (WO2017027291- Jensen ‘291- cited by Applicant).
The reference teaches methods of engineering a bi-specific T-cell expressing chimeric antigen receptors for promoting the in vivo expansion and activation of an effector cell and a second chimeric antigen receptor or TcR specific for a ligand on a tumor. Methods of administering to subjects in need, bi-specific chimeric antigen receptor bearing cells are also provided (abstract).
The cells are T cells transduced with nucleic acids a CAR encoding an antigen-binding fragment (e.g. glypican-2 or 3 or mesothelin); a nucleic acid encoding an extracellular lgG4 hinge region; a nucleic acid encoding a CD28 transmembrane domain; a nucleic acid encoding an intracellular 41 BB co-stimulatory domain, a nucleic acid encoding a CD3 zeta intracellular signaling domain; a nucleic acid encoding a self-cleaving 2A peptide; and a nucleic acid encoding a huEGFRt corresponding to SEQ ID NO: 14 of the present application ([0009]-[0012], [0021], [0025], [0032], [0038], [0157], [0174], Figures 1 and 2, claims 66-94). The cells are therapeutically used in pharmaceutically compositions ([0160]).
Thus, in the broadest reasonable interpretation, the claims 1-5, 8, 9, 10, 11 and 18-20 are anticipated by the reference cited.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 6 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Jensen ‘291 (cited supra) in view of Jensen M (WO2013123061- Jensen ‘061- cited by Applicant).
The claims add the limitation that the extracellular hinge region comprises a CD8α hinge region, the transmembrane domain comprises a CD8α transmembrane domain, the intracellular co-stimulatory domain comprises a 4-1BB co-stimulatory domain and the intracellular signaling domain comprises a CD3ζ signaling domain.
The Jensen ‘291 does not specifically disclose these specific sources for the specific domains claimed instantly.
Jensen ‘061 discloses such domains in the context of immunotherapies comprising T cells which co-express cancer-targeted CARs and EGFRt proteins (1-104; Fig. 2, 11; ex 8; SEQ ID NO: 9, 11, 15).
However, the mere usage of an alternative CAR construct (e.g. a CD8 alpha hinge region, a CD8 alpha transmembrane region, 4-1BB co-stimulatory domain and CD3 zeta signaling domain) are considered routine modifications.
Thus, based on the prior art, the skilled person would produce a cell comprising the nucleic acid molecule of claims 6 and 7 with a reasonable expectation of success.
Claims 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Jensen M (WO2017027291- Jensen ‘291) in view of Jensen M (WO2013123061-Jensen ‘061) and in further view of Ho et al. (WO2012145469) (all cited by Applicant)..
The claims add the limitation that the tumor antigen is GPC3 and that the antibody binding fragment comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 30 and comprises residues 25-140 of SEQ ID NO: 18.
The teachings of both Jensen references were presented supra and they were
silent about these exact sequences of the anti-GPC3.
Ho et al. discloses an anti-GPC3 antibody having an amino acid sequence (SEQ ID NO: 2 that is 100% identical to amino acids of SEQ ID NO: 30 of the instant Application and comprises residues 25-140 of SEQ ID NO: 18.
Furthermore, it discloses cytotoxic T cells with an engineered CAR expressing said antibody and its use to treat GPC3-positive tumors (p. 47-48; claims 1-52; SEQ ID NO: 2).
It would have been obvious for a person of ordinary skill in the art to have used
the teaching of Ho et al. combined with the teachings of Jensen ‘291 and Jensen ‘061
and obtain the cell claimed in the instant claims 14 and 15 with a reasonable expectation of success. It is of note that GPC3 antibodies described by Ho et al. were in fact used by the applicant to clone the anti-GPC3 CARs of the present application.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially 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. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); 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); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 16 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-17 of U.S. Patent No.11,066,479 in view of Jensen ‘291.
The claims are drawn to an isolated host cell co-expressing a chimeric antigen receptor (CAR) and a truncated human epidermal growth factor receptor (huEGFRt), wherein: the CAR comprises an GPC2-specific antibody or antigen-binding fragment thereof, an extracellular hinge region, a transmembrane domain, an intracellular co-stimulatory domain and an intracellular signaling domain; and the huEGFRt comprises a Domain III, a Domain IV and a transmembrane domain from human EGFR, but lacks an epidermal growth factor (EGF)-binding domain and a cytoplasmic domain. The amino acid sequence of the antigen-binding fragment comprises the CDR1, CDR2 and CDR3 sequences of SEQ ID NO: 32 or the amino acid sequence of the antibody-binding fragment comprises residues 25-144 of SEQ ID NO: 20.
The teaching of Jensen ’291 were presented supra and they were silent about the specific anti-GPC2 amino acid sequences.
The claims of the ‘479 Patent are drawn to a chimeric antigen receptor (CAR) comprising the VH single domain anti-GPC2 monoclonal antibody comprising the amino acid sequences of SEQ ID NO: 12. The CAR comprises a hinge region comprises a CD8α hinge region, the transmembrane domain comprises a CD8α or a CD28 transmembrane domain, the costimulatory signaling moiety comprises a 4-1BB and/or a CD28 signaling moiety, the signaling domain comprises a CD3ζ signaling domain, or any combination thereof; the CAR is expressed in an isolated cell. The SEQ ID NO: 12 of the Patent is 100% identical with the SEQ ID NO: 32 of the instant Application and comprises residues 25-144 of SEQ ID NO: 20 of the instant Application.
it would have been obvious for a person of ordinary skill in the art at the time that the invention was filed to have used the GPC2 antibody CAR of the Patent and, combined with the teachings of Jensen ‘291, obtain a cell co-expressing the CAR and the huEGFRt with a reasonable expectation of success. This is because the Jensen ‘291 indicated the feasibility of the constructs and the anti-GPC2 of the Patent (with the same amino acid sequence) was used in a CAR having the same characteristics of the CAR of the instant Application.
Allowable Subject Matter
Claims 12 and 13 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed. Claims 1-11 and 14-20 are rejected and claims 12 and 13 are objected to as being dependent upon a rejected base claim.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLY GERALD STOICA whose telephone number is (571)272-9941. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647
Prosecution Insights