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 .
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-13, 15-17, 19-25, 27, 28, 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lamb et al (2013, of record), Spencer et al (US 20120258532 A1, of record) and Krebs et al (2013, of record).
Lamb et al teaches administration of gamma-delta T-cells with a receptor for stress-induced antigen NKG2D that also expressed survival factor MGMT as treatment for glioblastoma, a brain cancer (abstract). The cells may be administered more than one time along with a chemotherapeutic agent (TMZ) which increases expression of NKG2D ligands (abstract). The glioblastoma can be sensitive or resistant to TMZ (abstract, page 2 first column, 4th ¶). TMZ can induce the tumor antigens MIC-A and MIC-B (MICA/B, page 1, second column) and the methods can be used for treatment of neuroblastoma (p. 2, first column, first ¶) The NKG2D receptor is considered to be present on the gamma-delta T cells as they specifically bound NKG2D ligand.
Spencer et al teach much the same as Lamb et al, but include multiple administrations of T cells (Fig. 8, 9 ) and the chemotherapeutic agent over the time periods that render instant claims 4 and 5 obvious (Figs. 15-17). Administration of chemotherapy and immunotherapy may be concurrent (¶[0098]). MGMT-modified, TMZ resistant NK cells or T cells for immunotherapy are taught in ¶’s [0088], [0094]- [0097]. Such T cells inherently comprise a majority alpha-beta T cells (Krebs et al, instant specification). The examiner concludes that a skilled artisan could combine these therapeutic cells in a ratio as recited by instant claim 17 based upon a design choice. Likewise, the skilled artisan could arrive at the time periods of claims 4 and 5. Additionally, MPEP 2144.05 (IFA) indicates that differences in concentration generally are not patentable:
"Generally, differences in concentration or temperature will not support the patentability
of subject matter encompassed by the prior art unless there is evidence indicating such
concentration or temperature is critical. “[W]here the general conditions of a claim are
disclosed in the prior art, it is not inventive to discover the optimum or workable ranges
by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA
1955)."
Therefore, the recited ranges of claims 4, 5 and 17 are obvious. The self-inactivating SIV vectors (Example 2) are considered a “suicide gene” as they inactivate themselves. The T cells are obtained from a subject (Figs 1 and 10, ¶[0128]).
The Lamb and Spencer et al references do not teach that the gamma-delta T cells express a chimeric antigen receptor (CAR) directed against a tumor antigen.
Krebs et al teaches T-cells expressing a chimeric antigen receptor (CAR) directed against a tumor antigen on glioblastoma cells (GBMs, pg. 3 col 1 para 2), which may have a single stimulatory endodomain, such as CD3zeta (Fig. 1, p. 2, second col.). The CAR can be directed to EGFRvIII or IL-13Ralpha (pg. 1, second col). Krebs et al teach “genetic safety switches”, which are considered suicide genes for T cell immunotherapy (pgs. 4-5). The specification does not provide a limiting definition of a "signaling domain", but rather describes common features of such in CAR molecules, i.e. they may comprise a CD3zeta domain with ITAM motifs. It is apparent from the cited art (Krebs, Bridgeman, Park et al) that secondary or tertiary CAR endodomains (i.e. those added in addition to the classical, first-generation CD3zeta signaling domain, such as CD28) are considered to be "co-stimulatory domains" and thus can be considered distinct from the signaling domain (e.g. CD3zeta). Thus, the instant claims are interpreted to encompass said "second-generation" and "first-generation" CAR molecules because such molecules comprise one signaling domain (CD3zeta) and one costimulatory domain (CD28) or only one signaling domain (CD3zeta).
It would have been obvious for one of ordinary skill in the art to transfect the gamma-delta T-cells with specificity for stress-induced antigen NKG2D and also expressed survival factor MGMT taught by Lamb and Spencer et al with a nucleic acid construct for expression of a chimeric antigen receptor specific for GBMs as taught by Krebs et al, using methods well-known in the art, to enable gamma-delta T cells expressing at least a chimeric antigen receptor (CAR) directed to a tumor antigen, and a survival factor that allows the immune system cell to survive in a treatment environment created by an additional therapeutic treatment and further expressing a receptor for a stress-induced antigen. It would have been obvious for the skilled artisan to do this because of the known benefit of generating CAR-modified T cells for administration in the treatment of cancer or glioblastoma as taught by Krebs, Spencer and Lamb et al. Given the teachings of the cited references and the level of skill of the ordinary skilled artisan at the time of applicants' invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Claim(s) 1-17, 19-25, 27, 28, 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lamb et al (2013), Spencer et al (US 20120258532 ) and Krebs et al (2013) as applied to claims 1-13, 15-17, 19-25, 27, 28, 30 above, and further in view of Brenner et al (US 20140004132 A1, 1/2/2014).
The teachings of Lamb, Spencer and Krebs et al are as above and applied as before. The references do not teach wherein the tumor antigen is GD2.
Brenner et al teach T cells expressing a GD2-specific CAR to target neuroblastomas expressing the GD2 tumor antigen. See the abstract, ¶’s [0004]-[0005], claims 1 and 6 in particular.
It would have been obvious for one of ordinary skill in the art to transfect the gamma-delta T-cells with specificity for stress-induced antigen NKG2D and also expressed survival factor MGMT taught by Lamb and Spencer et al with a nucleic acid construct for expression of a chimeric antigen receptor specific for GBMs as taught by Krebs et al, using methods well-known in the art, to enable gamma-delta T cells expressing at least a chimeric antigen receptor (CAR) directed to a tumor antigen, and a survival factor that allows the immune system cell to survive in a treatment environment created by an additional therapeutic treatment and further expressing a receptor for a stress-induced antigen. It would have been obvious for the skilled artisan to do this because of the known benefit of generating CAR-modified T cells for administration in the treatment of cancer or glioblastoma as taught by Krebs, Spencer and Lamb et al. Given the teachings of the cited references and the level of skill of the ordinary skilled artisan at the time of applicants' invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
The claimed methods are essentially disclosed by Lamb, Spencer and Krebs et al with the exception of the GD2 tumor antigen limitation. The ordinary skilled artisan, seeking a method to treat neuroblastoma, would have been motivated to use the CAR-GD2 T cells of Brenner et al with the methods of Lamb, Spencer and Krebs et al because Brenner et al teaches CAR-GD2 T cells to be a well-known type of immunotherapy having utility for specifically treating neuroblastoma. It would have been obvious for the skilled artisan to do this because of the known benefit of CAR T cells for administration in the treatment of such tumors as taught by Lamb, Spencer and Krebs et al. Given the teachings of the cited references and the level of skill of the ordinary skilled artisan at the time of applicants' invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6-9, 11-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 6-9, 11-14 recite the limitation "the cancer" in line 1. There is insufficient antecedent basis for this limitation in the claim.
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 1-17, 19-25, 27, 28, 30 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 12,005,078. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘078 claims anticipate the instant genus claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Michael Burkhart whose telephone number is (571)272-2915. The examiner can normally be reached M-F 8-5.
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/MICHAEL D BURKHART/Primary Examiner, Art Unit 1638
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