DETAILED ACTION
This action is in response to the amendment filed 07 January 2026.
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 status
In the reply filed on 07 January 2026, claims 6-8 are amended, claims 1-5, 9 are canceled. Therefore, claims 6-8 and 10-18 are herein pending.
Election/Restrictions
Applicant previously elected of Group I: Claims 6, 8, 11-14, 17, and 18 drawn to a method of treating cancer in a mammal in the reply filed on 25 June 2025. The dependent claim 10 was not listed in group I in the Requirement for Restriction/Election mailed on 05/13/2025, and examiner is acknowledging this typographical error. Therefore, in the office actioned mailed on 09/08/2025, examiner disclosed for the compact prosecution, examiner has included claims 6, 8, 10-14, 17, and 18 in Group I.
Claims 7, 15-16 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
In the Response to Election, the Applicant did not distinctly point out the supposed errors in the restriction requirement with an election that mailed on 05/13/2025. Therefore, the election response filed on 25 June 2025 will be treated without traverse (MPEP § 818.01(a)).
The Examiner rejoins Group II, claims 7, 15-16 because these claims are embraced by the method step of administering reprogrammed T Cells. In view of the withdrawal of the restriction requirement, applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 6-8, and 10-18 is under current examination.
Priority
This application was filed 08/03/2022, Continuation of 16095791, filed 10/23/2018, now abandoned and is a 371 application of PCT/US2017/030062 filed on 04/28/2017, which claims benefit to the Provisional Application 62328780, filed 04/28/2016. Thus, the earliest possible priority for the instant application is 04/28/2016.
Withdrawn Objections
The Abstract is objected to for its length as set forth MPEP §608.01(b) to comply with the requirements. In this reply, Applicant has amended the abstract filed on 01/07/2026. The amended abstract is 72 words in length, therefore, the prior objection to abstract is hereby withdrawn.
Applicants have amended claim 1 to replace the term "iDP" with the full term "induced dopaminergic precursor cell" and therefore, prior objection to the claim is hereby withdrawn.
Withdrawn Rejections
Applicant has amended the claims 6 and 8 to replace "the cell" with "the T cell," for which sufficient antecedent basis is present. Furthermore, in an effort to advance prosecution, Applicants amend claims 6 and 7 to recite "a reprogrammed T cell that exhibits higher expression of cell surface thiols compared to a non-reprogrammed T cell," thus clarifying that the recited higher expression is compared to a non-reprogrammed T cell. Therefore, the prior rejection of claims 6-8 under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention is hereby withdrawn.
Applicant has amended the claims 6-8 to recite "wherein the one or more pharmacological modulator is selected from the group consisting of IL-4, recombinant thioredoxin (rTrx), thioredoxin-reductase, glutathione, a-ketoglutarate, praline, and a combination thereof." Therefore, the subject matter of claims 6-8 is sufficiently described in the Specification as-filed. Accordingly, the prior rejection of claims 6-8 under 35 U.S.C. 112(a) (Written description) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is hereby withdrawn.
Applicant has amended the claims 6-8 to recite "wherein the one or more pharmacological modulator is selected from the group consisting ofIL-4, recombinant thioredoxin (rTrx), thioredoxin-reductase, glutathione, a-ketoglutarate, praline, and a combination thereof." Therefore, the subject matter of claims 6-8 is sufficiently enabled by the Specification as-filed. Accordingly, the prior rejection of Claims 6-8 under 35 U.S.C. 112(a) (Scope of Enablement) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while enabling the scope for reprograming the T cell with a specific pharmacological modulator requirement is hereby withdrawn.
Applicant has amended the claims 6-8 and exclusively included “a method of treating cancer in a mammal, the method comprising administering an effective amount of a reprogrammed T cell to a mammal with cancer in need thereof, wherein the reprogrammed T cell exhibits a higher expression of cell surface thiols compared to a non-reprogrammed T cell, wherein the T cell is reprogrammed by culturing the I cell with one or more pharmacological modulators, wherein the one or more pharmacological modulator is selected from the group consisting of IL-4, recombinant thioredoxin (rTrx), thioredoxin-reductase, glutathione, a-ketoglutarate, praline, and a combination thereof.” In the prior art Balaji does not anticipate claims 6-8, 11, and 13-18 at least because Balaji does not describe the pathology of cancer whatsoever, let alone teach a method comprising the step of administering an effective amount of a reprogrammed T cell to a mammal with cancer, wherein the reprogrammed T cell exhibits a higher expression of cell surface thiols, wherein the T cell is reprogrammed by culturing the cell with one or more pharmacological modulators as recited in amended claims 6-8. Therefore, the prior rejection of claims 6-8, 11, and 13-18 under 35 U.S.C. 102(a)(1) as being anticipated by Balaji et al., (Journal of allergy and clinical immunology, 2011, 128(1), pp.92-99; cited in IDS filed 06/04/2025; hereinafter “Balaji”) and evidentiary reference Powis et al. (Oncol Res. 1994;6(10-11):539-44; cited in PTO892; hereinafter “Powis”) is hereby withdrawn.
Accordingly, the prior rejection of claims 6-8, and 10-18 under 35 U.S.C. 103 as being unpatentable over Balaji et al., in view of Powis et al. and further in view of Watanabe et al., (Pharmacology & Therapeutics 127 (2010) 261–270; cited in PTO892; hereinafter “Watanabe”) is hereby withdrawn.
New 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 6-8, 10, 13, 15, and 17 are newly rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kesarwani et al., (Cancer research, 74(21), pp.6036-6047; 2014; cited in IDS filed on 06/04/2025; hereinafter “Kesarwani”). This rejection is maintained for reasons of record and current applicant’s amendments.
Regarding claims 6, 10, 13, 15, and 17, Kesarwani teaches a method of treating cancer in a mammal, the method comprising administering an effective amount of a reprogrammed T cell to a mammal with cancer (i.e., melanoma (Fig. 3)) (Abstract, p. 6037, col 1 2nd ¶), wherein the reprogrammed T cell exhibits a higher expression of cell surface thiols (p. 6040, col 2 1st ¶). Furthermore, as compared with untreated control cells, rapamycin-induced c-SH provided an optimal reductive environment to withstand the H2O2-induced oxidant injury and rescued both CD62Llo and CD62Lhi subsets from H2O2-induced apoptosis (Supplementary Fig.S3C). Additionally, Kesarwani suggests that higher levels of reduced cell surface thiols are a key characteristic of T cells that can control tumor growth and that profiling this biomarker may have benefits to adoptive T-cell immunotherapy protocols for the treatment of cancer (abstract, p. 6037 col 1 2nd ¶, p. 6040 col 1 1st ¶). The T cell is reprogrammed by culturing the T cell with pharmacological modulators (e.g., glutathione, Thioredoxin reductase (Table 1, p. 6039 col 1 2nd ¶). Furthermore, expression of the thiol-regulating thioredoxin proteins, TRX-1 and TRX-2, which act as antioxidants by facilitating the reduction of other proteins through cysteine thiol-disulfide exchange (20), was reduced in higher proliferating T cells (Supplementary Fig. S2C). Moreover, the GSH/GSSG ratio (Supplementary Fig. S2D) indicated that the reduced glutathione was increased in sorted CD62Lhi T cells.
Regarding claim 7, Kesarwani teaches a method for stimulating an immune response to a target cell population or tissue in a mammal, comprising administering to a mammal an effective amount of a reprogrammed T cell that exhibits higher expression of cell surface thiols, thereby stimulating a response to a target cell population or tissue in the mammal tumor growth (p. 6045 Col 1 2nd ¶, Col 2 5th ¶).
Furthermore, Kesarwani discloses a comparison of antitumor CD8+ T-cell populations on the basis of surface thiol expression showed that thiol-high cells persisted longer in vivo and exerted superior tumor control (abstract, p. 6040 col 1 2nd ¶, Fig. 3). Therefore, this disclosure is anticipated instant claim 8.
Accordingly, Kesarwani anticipates instant claims 6-8, 10, 13, 15, and 17.
New 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 6-8, and 10-18 are newly rejected under 35 U.S.C. 103 as being unpatentable over Kesarwani et al., (Cancer research, 74(21), pp.6036-6047; 2014; cited in IDS filed on 06/04/2025; hereinafter “Kesarwani”), in view of Watanabe et al., (Pharmacology & Therapeutics 127 (2010) 261–270; cited in PTO892 (see the “List of references cited by examiner” filed on 09/08/2025); hereinafter “Watanabe”) and further in view of Kesarwani et al., (The Journal of Immunology, Volume 194, Issue 1_Supplement, 2015, Page 143.9; cited in IDS filed on 06/04/2025; hereinafter “Kesarwani-2015”). The new rejection is necessitated by applicant’s claim amendments.
As stated above, regarding claims 6-8, 10, 13, 15, and 17, Kesarwani teaches a method of treating cancer in a mammal, the method comprising administering an effective amount of a reprogrammed T cell to a mammal with cancer in need thereof, wherein the reprogrammed T cell exhibits a higher expression of cell surface thiols compared to a non-reprogrammed T cell.
Regarding claim 11, Kesarwani discloses that the maintenance of the redox molecules as thiols may play an important role not only in boosting antigen presentation but also overcoming immunosuppression and increasing survival of T cells (p. 6045 col 2 2nd ¶, p. 6046 col 1 1st ¶). Therefore, as depicted in Supplementary Fig. S4, Kesarwani conclude that promoting the reductive cellular environment could affect metabolic function and result in the long-term maintenance of CD8+ T cells, with implications for adoptive immunotherapy approaches. According, ordinary skill in the art could recognize that the reprogrammed T cell persists in vivo for at least four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, two years, or three years after administration.
However, regarding claim 12, Kesarwani is silent to a second anti-tumor agent, an antiproliferative agent, and a chemotherapeutic agent. However, such was known in the prior art.
With respect to claim 12, Watanabe teaches Thioredoxin 1 (Trx1) and anti-tumor agent thioredoxin-binding protein-2 (TBP-2) play crucial roles in pathophysiological mechanisms in metabolic disorders, cancer and inflammation. Further, Watanabe discloses the pharmacological aspects of Trx1 and TBP-2 in these diseases and propose potential therapeutic approaches for intractable oxidative stress-related disorders.
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice reprogram T cells with pharmacological modulator of Kesarwani and include an anti-tumor agent as taught by Watanabe with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Watanabe because Trx1 and TBP-2 combination is a potential targets for therapeutic approaches to cancer (p. 267 right col. 2nd ¶ of Watanabe) through linking pathways of various cell functions and is a regulator in metabolic disorders, cancer and inflammation (p. 266 left col. 2nd ¶ of Watanabe). The POSITA would have had a reasonable expectation of success in combining the teachings of Kesarwani and Watanabe because each of these teachings both successfully generated cancer treating method in combination with thioredoxin and anti-tumor agent. Therefore, the method as taught by Kesarwani et al. in view of Watanabe et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include the anti-tumor agent of Watanabe had a reasonable expectation of success since the steps thereof required no more than injecting the appropriate concentration TBP-2 in the medium.
However, regarding claim 14, Kesarwani is silent to pharmacological modulator is recombinant thioredoxin (rTrx). However, such was known in the prior art.
With respect to claims 14, 16, and 18, Kesarwani-2015 teaches that increased level of thioredoxin (Trx1), an anti-oxidant molecule that facilitates reduction of proteins by cysteine thiol-disulfide exchange, in T cells will result in sustained anti-tumor function. Resulted that adoptive transfer of Pmel cells mixed with Pmel/Trx1 cells in 1:1ratio markedly improved tumor control as compared to the mice that were transferred Pmel or Pmel/Trx T cells alone. Thus, strategies to increase anti-oxidant capacity of anti-tumor T cells could have immunotherapeutic implications (abstract).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice reprogram T cells with pharmacological modulator of Kesarwani and include an anti-oxidant pharmacological modulator Trx1 as taught by Kesarwani-2015 with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Kesarwani-2015 because Trx1 and TBP-2 combination is a potential targets for therapeutic approaches to cancer (p. 267 right col. 2nd ¶ of Watanabe) through linking pathways of various cell functions and is a regulator in metabolic disorders, cancer and inflammation (p. 266 left col. 2nd ¶ of Watanabe). Therefore, Trx1 increases anti-oxidant capacity of anti-tumor T cells that could have immunotherapeutic implications (abstract of Kesarwani-2015). The POSITA would have had a reasonable expectation of success in combining the teachings of Kesarwani and Kesarwani-2015 because each of these teachings both successfully generated cancer treating method in combination with thioredoxin. Therefore, method as taught by Kesarwani et al. in view of Kesarwani-2015 et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include the Trx1 of Kesarwani-2015 had a reasonable expectation of success since the steps thereof required no more than injecting the appropriate concentration Trx1 in the medium.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 07 January 2026 are acknowledged.
Applicant's arguments on “Rejection of Claims 6-8, 11, and 13-18 under 35 U.S.C. §102(a)(l)” and “Rejection of Claims 6-8, 10-18 under 35 U.S.C. §103” (see remark pp. 8-13) have been fully considered but are moot because the new ground of rejection relies on amendment claims and references applied in the prior rejection of record for any teaching or matter challenged explicitly in the argument. In the new rejection under 35 U.S.C. 102 and 103, Kesarwani et al., in view of Watanabe et al., and Kesarwani et al., addressed the method of treating, and stimulating an immune response with providing an anti-tumor immunity in a mammal, wherein the method comprising administering an effective amount of a reprogrammed T cell to a mammal with cancer wherein the T cell is reprogrammed by culturing the I cell with pharmacological modulators (i.e., Trx1).
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684