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 .
Applicant's response to the previous Office action, dated December 4, 2025, has been received. By way of this submission, Applicant has amended claim 1, and introduced new claims 29-32.
Claims 1-10 and 16-32 are pending in the application. Claims 7-10 and 16-28 remain withdrawn from consideration, pursuant to the Restriction Requirement mailed January 10, 2025.
Claims 1-6 and 29-32 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated June 18, 2025.
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 1-6 and 29-32 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. This is a new grounds of rejection, necessitated by Applicant’s amendments to the claims.
Claim 1 as amended recites a step of obtaining a cancerous tissue sample from the subject before and after combination therapy. It is not clear how the practitioner would obtain "a sample" both before and after treatment. It is assumed that two samples would have to be taken. The claim also recites a step of "fragmenting the cancerous tissue sample..." It is not apparent which cancer sample is meant to be fragmented, either the sample taken before or after the combination therapy. Appropriate clarification is required.
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.
Claim Rejections - 35 USC § 102
(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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 6, 29, and 31 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Tran (US20170218042A1). This is a new grounds of rejection.
Tran teaches a method of generating a pool of tumor infiltrating lymphocytes (TILs), comprising resecting and fragmenting a tumor, followed by culturing and expanding the TILs (para. 0082).
Tran further teaches generating TILs by the same method as above, after administration of T cells and cyclophosphamide and fludarabine (i.e., a combination therapy comprising T cell immunotherapy) (para. 0082-0083).
Tran further teaches performing sequencing and bioinformatics of another cancer tissue sample (i.e., a second portion) to identify neoantigens by whole exome sequencing (para. 0084).
Tran further teaches contacting neoantigens with TILs to determine whether any of the processed and presented mutated antigens were recognized by TIL (para. 0109).
Tran further teaches that cell reactivity is determined using ELISpot (para. 0111), which is pertinent to claim 6.
Tran further teaches culturing peripheral blood T cells with cancer neoantigens, and selecting T cells that have antigenic specificity for said neoantigen (para. 0039-0040).
Tran further teaches that the cancer sample may be taken from a primary tumor (para. 0030), which is pertinent to claim 29.
Tran further teaches that the patient has lung cancer (para. 0076 and 0106), which is pertinent to claim 31.
Tran also teaches that such TILs are useful in treating cancer (e.g., para. 0145).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1-3 and 6 were previously rejected under 35 U.S.C. 103 as being unpatentable over Liu (J Immunother Cancer. 2019 Jun 20;7(1):156, cited in IDS) in view of Moriarity (WO2018075664A1).
Claims 4 and 5 were previously rejected under 35 U.S.C. 103 as being unpatentable over Liu in view of Moriarity as applied to claim 1 above, and further in view of Stanciu (Methods Mol Biol. 2000:134:133-41).
Applicant argues that the use of a T cell infusion immunotherapy unexpectantly increases neoantigen-specific TCR clonotypes to provide improved personalized treatment for the subject, and neither Liu nor Moriarity teach screening for neoantigens in a subject using tissue before and after a combination therapy comprising T cell immunotherapy. Applicant further argues that there is no rationale for one of ordinary skill to combine the teachings of Liu and Moriarity.
Applicant's arguments in view of the amendments to the claims have not addressed this issue fully. In the interest of compacting prosecution, the above rejections are withdrawn, and the following new grounds of rejection are issued, necessitated by Applicant's amendment to the claims:
Claims 1-6, 29, and 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Tran (US20170218042A1) in view of Yelensky (WO2019050994A1).
Tran teaches a method of generating a pool of tumor infiltrating lymphocytes (TILs), comprising resecting and fragmenting a tumor, followed by culturing and expanding the TILs (para. 0082).
Tran further teaches generating TILs by the same method as above, after administration of T cells and cyclophosphamide and fludarabine (i.e., a combination therapy comprising T cell immunotherapy) (para. 0082-0083).
Tran further teaches performing sequencing and bioinformatics of another cancer tissue sample to identify neoantigens by whole exome sequencing (para. 0084).
Tran further teaches contacting neoantigens with TILs to determine whether any of the processed and presented mutated antigens were recognized by TIL (para. 0109).
Tran further teaches that cell reactivity is determined using ELISpot (para. 0111), which is pertinent to claim 6.
Tran further teaches culturing peripheral blood T cells with cancer neoantigens, and selecting T cells that have antigenic specificity for said neoantigen (para. 0039-0040).
Tran further teaches that the cancer sample may be taken from a primary tumor (para. 0030), which is pertinent to claim 29.
Tran further teaches that the patient has lung cancer (para. 0076 and 0106), which is pertinent to claim 31.
Tran also teaches that such TILs are useful in treating cancer (e.g., para. 0145).
However, Tran does not teach non-small cell lung cancer.
Yelensky teaches a method of identifying T cells that can bind neoantigens by co-culturing the T-cells with one or more of the neoantigens in the subset under conditions that expand the T-cells (para. 00154).
Yelensky further teaches culturing peripheral blood mononuclear cells (PBMCs) with cancer neoantigens to expand neoantigen-reactive T-cells (para. 00475).
Yelensky further teaches selecting (i.e., isolating) T cells from a sample with magnetic-activated cell sorting (MACS) (para. 00557) or FACS sorting (para. 00563-00564), which is pertinent to claim 4.
Yelensky further teaches that cancers with a high mutational burden, such as non-small cell lung cancer (NSCLC), are particularly attractive targets of T-cell therapy based on tumor-specific neoantigens given the relatively greater likelihood of neoantigen generation (para. 0001), which is pertinent to claim 32.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Tran and Yelensky to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Tran and Yelensky are both concerned with TIL therapies that target neoantigens. Methods of expanding neoantigen-specific TILs were known in the art, according to Tran. Yelensky teaches that PBMCs are also useful in the generation of neoantigen-specific TILs, especially for the treatment of non-small cell lung cancer due to the abundance of neoantigens. One of ordinary skill would be readily able to combine the PBMCs of Yelensky with the methods of Tran, with each component of the combination performing its known, usual function, and the combination would have yielded nothing more than predictable results.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Tran (US20170218042A1) in view of Slanetz (WO2018005712A1).
The teachings of Tran have been described supra. However, Tran does not teach a recurring tumor.
Slanetz teaches a method of making a composition useful in adoptive cell therapy enriched for T cells that are reactive to one or more target antigens, comprising obtaining an initial cell population comprising T-cells, stimulating the T-cells by exposing the cell population to one or more target antigens, and testing the cell population for antigen-specific reactivity (para. 0007). Slanetz further teaches that the antigen used may be a cancer neoantigen (para. 0014).
Slanetz further teaches that this method may be useful to generate neoantigens from primary and recurrent tumors (para. 0248).
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Tran and Slanetz to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Tran and Slanetz are both concerned with TIL therapies that target neoantigens. Methods of expanding neoantigen-specific TILs were known in the art, according to Tran. Slanetz teaches that it is useful to use either primary or recurring tumors for the purpose of generating neoantigens that can be used to culture TILs. One of ordinary skill would be readily able to combine the recurrent tumors of Slanetz with the methods of Tran, with each component of the combination performing its known, usual function, and the combination would have yielded nothing more than predictable results.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/PETER JOHANSEN/Examiner, Art Unit 1644