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 .
Election/Restrictions
Claims 1-3, 16-17, 21-23, 26-27, 34-35, 58, 61, 81-84, and 88-89 are pending.
Applicant's election with traverse of Group I, drawn to claims 1-3, 16-17, 21-22, 26-27, and 61, in the reply filed on 07/06/2026 is acknowledged. The traversal is on the ground(s) that the shared technical feature among Groups I, II, and V is the method of claim 1, and that Nakauchi (US 2013/078226 A1) fails to disclose all of the features of claim 1. This is not found persuasive because a new art has been made of record, and therefore the argument directed solely toward Nakauchi is moot. As set forth in the claim rejections under 35 USC 103 below, Dijkstra (Cell, 2018, 174(6): 1586-1598), in view of Nakauchi, teaches all the limitations of claim 1. Therefore, the shared technical feature among Groups I, II, and V is not a special technical feature.
The requirement is still deemed proper and is therefore made FINAL.
Claims 23, 34-35, 58, 81-84, and 88-89 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 07/06/2026.
Claims 1-3, 16-17, 21-22, 26-27, and 61 are examined on the merits herein.
Priority
The instant application is a 371 of PCT/US2021/046969 filed 08/20/2021, which claims benefit of 63/068,458 filed 08/21/2020.
Claim Objections
Claim 17 is objected to because of the following informalities: There is an extra closing parenthetical following the abbreviation “c-Myc” in line 4. Appropriate correction is required.
Claim Interpretation
Claims 26-27 are product-by-process claims. Product-by-process claims are not limited to the
manipulations of the recited steps, only the structure implied by the steps. See MPEP 2113. Therefore, claim 26 is interpreted as “A composition comprising tumor antigen-specific iPSCs and a pharmaceutically acceptable carrier.” Claim 27 is interpreted as “A composition comprising tumor antigen-specific T lineage cells and a pharmaceutically acceptable carrier.”
Claim 61 recites the preamble “A method of generating a polyclonal population of tumor antigen specific iPSC derived T cells.” It is noted that the steps enumerated in claim 61, which are identical to the steps enumerated in claims 1 and 21, necessarily results in a polyclonal, as opposed to monoclonal, population of tumor antigen specific iPSC derived T cells.
Duplicate Claim Warning
Applicant is advised that should claim 21 be found allowable, claim 61 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(b)
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.
Claim 61 is 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.
Claim 61 recites the limitation "the subject" in line 3. There is insufficient antecedent basis for this limitation in the claim.
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.
Claim(s) 1-2, 16-17, 21-22, 27, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Dijkstra (Cell, 2018, 174(6): 1586-1598; cited in IDS 01/07/2026), in view of Nakauchi (US 2013/078226 A1; cited in IDS 02/10/2023).
Regarding claims 1-2 and 16: Dijkstra teaches a method for generating tumor-reactive T cells by co-culturing peripheral blood lymphocytes and tumor organoids (Abstract). Dijkstra teaches obtaining peripheral blood (reads on a first sample from a subject of step (a) of claim 1) and tumor tissue from human patients with a confirmed diagnosis of colorectal or non-small cell lung cancer (p e3, para 2). Dijkstra teaches processing the tumor tissues for organoid culture (p e3, para 3), isolating peripheral blood mononuclear cell (PBMC) fractions from the peripheral blood (p e4, para 1) (claim 2), then co-culturing the PBMCs and tumor organoids (p e4, para 4-5).
To specifically expand tumor-reactive sublines, T cells from three patients were co-cultured for two weeks with autologous tumor organoids (steps (a) and (b) of claim 1), then sorted on the basis of CD137 (reads on 4-1BB of claim 16) expression 24 hours after stimulation with tumor organoids (step (c) of claim 1), then expanded for two weeks in the presence of irradiated pooled PBMC from three healthy donors (p e5, para 1).
Dijkstra teaches that the method taught therein provides a clinically feasible strategy for the generation of patient-specific T cell products for adoptive T cell transfer (p 1594, col 2, para 2 – p 1596, col 1, para 1).
Dijkstra does not teach step (d) of claim 1: contacting the isolated T-cells of (c) with one or more reprogramming factors under conditions sufficient to reprogram the cells into T-iPSCs.
Nakauchi teaches a method for inducing an iPSC from a human T cell, and subsequently differentiating the iPSC into a T cell (Abstract, para 11-34). Nakauchi teaches contacting T cells having antigen specificity with cell reprogramming factors to induce reprogramming into iPSCs (para 110-113).
Nakauchi teaches that pluripotent stem cells are the most useful source of cells for regenerative medicine because they are capable of differentiation into almost all of the organs by appropriate induction of their differentiation, with retaining their ability of actively dividing while maintaining their pluripotency (para 7). Nakauchi teaches that iPSCs, which are self-derived cells, allow for the avoidance of rejection reactions, which are the biggest obstacle to regenerative medicine or transplantation therapy (para 7).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Dijkstra by contacting the isolated T cells therein with one or more reprogramming factors under conditions sufficient to reprogram the cells into T-iPSC, as taught by Nakauchi. One of ordinary skill in the art would have been motivated to make this modification because Nakauchi teaches that iPSCs are a useful source of cells for regenerative medicine. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Nakauchi teaches that T cells having antigen specificity can be contacted with cell reprogramming factors to reprogram the cells into iPSCs.
Thus, Dijkstra, in view of Nakauchi, renders obvious the method of claim 1.
Regarding claim 17: Nakauchi teaches that the reprogramming factors for reprogramming T cells into iPSCs include Oct3/4, c-Myc, Sox2, Klf4, and SV40 (para 68, 111, 261).
Regarding claims 21-22 and 27: Nakauchi teaches subsequently differentiating the iPSC taught therein into a functional T cell, which retains the T-cell receptor (TCR) gene rearrangement pattern exhibited by the originating human T lymphocyte of the iPS cell (Abstract, para 10-34) (claims 21-22).
Nakauchi teaches that the differentiated T cells can be formulated into pharmaceutical compositions and can be utilized for cell-based immunotherapy (para 10, 160-169) (claim 22). Nakauchi teaches that the differentiated T cells can be combined with pharmaceutically acceptable carriers (para 165) (claim 27).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Dijkstra, in view of Nakauchi, by further differentiating the iPSCs into functional T cells, as taught by Nakauchi. One of ordinary skill in the art would have been motivated to make this modification because Nakauchi teaches that T cells produced from iPSCs can be formulated into pharmaceutical compositions and for cell-based immunotherapy. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Nakauchi teaches that iPSCs derived from T cells can be differentiated into functional T cells.
Regarding claim 61: As noted in Claim Interpretation above, the steps of claim 61 are identical to the steps of claims 1 and 21. Therefore, following the discussion of claims 1 and 21 above, claim 61 is rendered obvious over Dijkstra, in view of Nakauchi.
Claim(s) 1 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Dijkstra (Cell, 2018, 174(6): 1586-1598), in view of Nakauchi (US 2013/078226 A1), and Hall (Journal for ImmunoTherapy of Cancer, 2016, 4: 61).
The teachings of Dijkstra and Nakauchi are set forth above.
Dijkstra, in view of Nakauchi, renders obvious claim 1.
Regarding claim 3: Dijkstra, in view of Nakauchi, does not teach the method of claim 1, wherein the isolated T cells of step (a) are tumor infiltrating lymphocytes.
Hall teaches that tumor infiltrating lymphocytes (TILs), which are expanded from surgically resected tumors from pancreatic cancer patients, react to tumor antigen stimulation (Abstract; p 9, col 1, para 2). Hall teaches that TILs expanded in vitro to large numbers have the potential to be reprogrammed as effectors of a productive anti-tumor response (p 2, col 1, para 2).
Nakauchi teaches that a T cell which is to be induced into an iPSC can be a cytotoxic T cell (para 108), and can be isolated from a variety of tissues including peripheral blood and a lesion site (para 109).
Given the teachings of Nakauchi and Hall, there was a reasonable expectation that T cells from peripheral blood and tumor infiltrating lymphocytes, which are cytotoxic T cells, would work equivalently as T cells to be contacted with tumor antigens, which are subsequently induced into iPSCs. Therefore, it would have been prima facie obvious for someone of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the peripheral blood cells taught in Dijkstra with the tumor infiltrating lymphocytes taught in Hall with predictable results. Substitution of one element for another known in the field, wherein the result of the substitution would have been predictable, is considered to be obvious. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Claim(s) 1 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Dijkstra (Cell, 2018, 174(6): 1586-1598), in view of Nakauchi (US 2013/078226 A1), and Xiang (Theranostics, 2019, 9(1): 290-310).
The teachings of Dijkstra and Nakauchi are set forth above.
Dijkstra, in view of Nakauchi, renders obvious claim 1.
Regarding claim 26: Dijkstra, in view of Nakauchi, does not teach a composition comprising T-iPSCs and a pharmaceutically acceptable carrier.
Xiang teaches a composition comprising iPSCs and PBS (reads on pharmaceutically acceptable carrier), which are injected into immunodeficient mice (Abstract; Table 1; p 293, col 2, para 3). Xiang teaches that teratoma generation is not a natural characteristic of iPSCs in vivo, and that iPSCs can be administered in vivo (Abstract, Conclusion).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the T-iPSCs taught in Dijkstra, in view of Nakauchi, by suspending the T-iPSCs in a pharmaceutically acceptable carrier, as taught in Xiang. One of ordinary skill in the art would have been motivated to make this modification to administer iPSCs in vivo, as taught in Xiang. One of ordinary skill in the art would have had a reasonable expectation of successfully making this modification because Xiang teaches that iPSCs can be combined with a pharmaceutically acceptable carrier.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Risa Takenaka whose telephone number is (571)272-0149. The examiner can normally be reached M-F, 12-7 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, Peter Paras can be reached at (571) 272-4517. 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.
/RISA TAKENAKA/Examiner, Art Unit 1632
/KARA D JOHNSON/Primary Examiner, Art Unit 1632
Prosecution Insights