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 Claims
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on 11 November 2025. Claims 1 – 2, 4 – 16, 24, 36 – 43 are currently pending. Claims 1, 4 – 6, and 10, 12 have been amended and claims 42 and 43 have been newly added in the Applicant’s amendment filed 11 November, 2025. No claims have been canceled in the Applicant’s amendment filed 11 November, 2025.
Applicant's election, in the reply filed 16 July, 2025 of Group I, without traverse, claims 1 – 2, 4 – 16, and 38 - 41, directed to a method of treating a cancer in a subject; and the following election of Species, without traverse, was previously acknowledged:
Species (A): the immunoresponsive cell is selected from the group consisting of lymphocytic cells (Claim 4);
Species (B): the one or more kinds of cells…….comprises at least one selected from the group consisting of an immunoresponsive cell, a virus, an anaerobic microorganism, a liposome, a MSC, and a nanoparticle (claim 7);
Species (C): the immunosuppression inhibitor comprises at least one selected from the group consisting of a PD-1 inhibitor…..and a Siglec-15 inhibitor (claim 13);
Species (D): the immunosuppression inhibitor comprises at least one selected from the group consisting of a PD-1 inhibitor…..and a Siglec-15 inhibitor (claim 38);
Claims 24, and 36 - 37 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claim 4, 8, 9, 14 – 15, and 39 - 40 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim. The restriction requirement was previously made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1 – 2, 5 – 7, 10 – 13, 16, 38, and 41 - 43 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed 26 May, 2022, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/JP2020/040503, filed 28 November, 2020; which claims the benefit of JP2019-195407, filed 28 November, 2019.
Therefore, the earliest priority date is 29 November, 2019.
Withdrawn Objections/Rejections
Claim Rejection - 35 USC § 112(b)
The rejection of claims 5, 6, 7, 10, 11, 38, and 41 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, is withdrawn.
The claims have been amended and the Applicant has detailed where to find the language in the as-Filed Specification.
In view of the withdrawn rejection, Applicant’s arguments are moot.
Maintained Objections/Rejections
Claim Rejection - 35 USC § 103
Claim 1 – 2, 5 – 7, 10 – 13, 16, 38, and 41 remain rejected and claim 42 is newly rejected under 35 U.S.C. 103 as being unpatentable over Adachi et al. (hereinafter referred to as “Adachi”) (Adachi K. et al. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol. 2018 Apr;36(4):346-351. doi: 10.1038/nbt.4086. Epub 2018 Mar 5. PMID: 29505028.), and further in view of Brogdon et al. (hereinafter referred to as “Brogdon”) (WO 2017/112741 A1, published 29 June, 2017). This rejection has been modified necessitated by the response filed November 11, 2025.
Regarding claim 1 and 6, Adachi teaches engineered CAR-T cells that express IL-7 and CCL19 (Abstract). Adachi teaches transfected CAR-T cells specific to human CD20 (hCD20) (page 346, col. 2) (interpreted as an immunoresponsive cell expressing IL-7, CCL19, and a cell surface molecule that recognizes a cancer antigen). Adachi teaches that following treatment of mice with the CAR-T cells, the CAR-T cells generated memory responses against tumors (Abstract).
Adachi does not specifically exemplify administering an immunosuppression inhibitor, wherein the immunosuppression inhibitor is administered twice or more (claim 1, (in part) and 6 (in part)), that the immunoresponsive cell and immunosuppression inhibitor are administered at different times (claims 2 and 11), the immunosuppression inhibitor is a polypeptide (claim 10), and that the immunosuppression inhibitors is selected from a PD-1 inhibitor….. a Siglec-15 inhibitor (claim 13 and 38), and that the cancer is a solid cancer (claim 16 and 41).
Brogdon teaches compositions for use in methods for treating diseases associated with expression of mesothelin comprising administering a cell that expresses a chimeric antigen receptor (CAR) specific to mesothelin in combination with a PD-L1 inhibitor for use in anti-cancer therapy (Title and Abstract). A disease or disorder associated with mesothelin is pancreatic cancer, including solid and pseudopapillary tumors (pg. 187, lines 29 – 31) (interpreted as the cancer is a solid cancer, claims 16 and 41). Brogdon teaches a method of treating a subject having a disease associated with mesothelin expression comprising administering to the subject a population of immune effector cells comprising a CAR and a PD-L1 inhibitor, wherein the PD-L1 inhibitor is administered prior to administering the CAR (claim 1). Brogdon teaches that the treatment comprises 1,2,3,4, or 5 or more subsequent doses of the PD-L1 inhibitor (claim 4) (interpreted as the immunosuppression inhibitor is administered twice or more). Antibodies and other inhibitors of PD-1, PD-L1, and PD-L2, such as nivolumab, can be used in combination with the CARs (pg. 220, lines 11 – 14). (Please Note: the as-Filed Specification teaches that examples of the anti-PD-1 antibody include Nivolumab (Paragraph [0321]). Brogdon teaches that treating a subject having a disease associated with mesothelin expression, e.g., a cancer described herein, with a combination therapy that includes a mesothelin CAR-expressing cell and a PD-L1 inhibitor is believed to result in improved inhibition or reduction of tumor progression in the subject, e.g., as compared to treating a subject having the disease with a mesothelin CAR-expressing cell or a PD-L1 inhibitor alone (pg. 3, lines 15 – 20).
Therefore, in view of the benefits of treating a disease associated with mesothelin expression by administration of engineered CAR T-cells targeting a tumor antigen and anti-PD-1 antibody as taught by Brogdon, it would have been prima facia obvious for one of ordinary skill in the art to administer the engineered CAR-T cells expressing IL-7 and CCL19 and targeting a tumor antigen as evidenced by Adachi, along with the anti-PD1 inhibitor (nivolumab), as evidenced by Brogdon, with a reasonable expectation of success in enhancing the efficacy of the treatment. It would have been prima facia obvious to combine the cited sources because Adachi teaches engineered CAR-T cells that express IL-7 and CCL19 that are administered to treat cancers, and Cao teaches that the CAR-expressing T cells and a PD-L1 inhibitor is believed to result in improved inhibition or reduction of tumor progression in the subject, as compared to the CAR expressing cell or PD-L1 inhibitor alone.
Regarding claim 5 and 42, the combined teachings of Adachi and Brogdon render obvious independent claims 1 and 6. Moreover, Adachi teaches that the T cells were isolated from the spleen and lymph nodes of the mouse, and transduced with the CAR-expressing retroviral vectors (pg. 352, left column, Mice and Cell Line, and Retroviral Vectors for Gene Transfection).
Regarding claim 7 and 12, the combined teachings of Adachi and Brogdon render obvious independent claims 1 and 6. Moreover, Adachi teaches engineered CAR-T cells (interpreted as an immunoresponsive cell, claim 7, and the cell surface molecule is a CAR, claim 12).
Response to Applicants’ Arguments as they apply to rejection of claims 1 – 2, 5 – 7, 10 – 13, 16, 38, and 41 under 35 USC § 103
Applicant’s arguments filed 11 November, 2025 have been fully considered but they are not persuasive. Applicant essentially asserts (a) the combination of cited references fails to teach every limitation of the claims (pg. 7, third paragraph), (b), the present claims are not rendered obvious by the unexpectedly superior anti-cancer effect, wherein the anti-cancer effect was improved (pg. 7, third paragraph); and (c) one of ordinary skill in the art would have no reasonable expectation of success in treating cancer by administering anti-PD1 antibody with these immunoreactive cells (pg. 8, first paragraph), and (d), Cao teaches the treatment of lymphomas, which is not a solid tumor (pg. 8, second paragraph).
Regarding (a) and (d), the claims are no longer rejected under Adachi and Cao as the claims have been amended, and thus, the applicants’ arguments related to the combined teachings of Adachi and Cao are moot.
Regarding (b), Applicant teaches the unexpectedly superior results pertaining to the anti-cancer effect, however, this is not found persuasive. As an initial matter, Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979) and In re Baxter TravenoILabs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991). See MPEP § 716.02 - § 716.02(g). Evidence has not been provided that the "superior results" were unknown in the prior art. Specifically, the Applicant has only written that “the synergistic effect (of a expressing Interleukin-7, CCL19, the immunosuppression inhibiting polypeptide, and the cell surface molecule that specifically recognizes a cancer antigen) is superior to a degree that cannot be predicted from the individual effects of the respective factors (Paragraph [0327]).
Furthermore, it is unclear how these results are “unexpected,” as the method is pertaining to a method of treating cancer. Thus, the anti-cancer effect as discussed in the as-Filed Specification and Remarks is very much expected.
Regarding (c), Applicant has provided references that CAR-T cells expressing IL-7 and CCL-19 have a lower rate of expression of PD-1 compared to CAR-T cells that don’t express IL-7 and CCL-19. Thus, one of ordinary skill in the art would expect that these cells that express IL-7 and CCL-19 would exhibit weaker effects when combined with an anti-PD1 antibody, and there is no reasonable expectation of success in treating cancer. However, Applicant’s argument is not persuasive. As an initial matter, the instant claims do not teach about the levels of PD-1.
Furthermore, please see the teachings of Brogdon above, wherein Brogdon teaches CARs and anti-PD1 antibodies are administered together to treat cancer. Thus, it is common in the art to see this combination of components being administered together to treat cancer.
Additionally, regarding the point that that these cells expressing IL-7 and CCL-19 have a lower rate of expression of PD-1, one of ordinary skill in the art would know how to overcome this issue. Specifically, Monteiro et al. teaches about optimizing anti-PD1 immunotherapy, including an optimized individual dose for a more favorable clinical response. (Monteiro JF. Et al. Optimizing Anti-PD1 Immunotherapy: An Overview of Pharmacokinetics, Biomarkers, and Therapeutic Drug Monitoring. Cancers (Basel). 2025 Oct 8;17(19):3262. doi: 10.3390/cancers17193262. PMID: 41097788; PMCID: PMC12524187) (pg. 16, first paragraph).
New Rejections
Claim Rejection - 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.
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.
Claim 1 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Adachi et al. (hereinafter referred to as “Adachi”) (Adachi K. et al. IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nat Biotechnol. 2018 Apr;36(4):346-351. doi: 10.1038/nbt.4086. Epub 2018 Mar 5. PMID: 29505028.), and further in view of Wagner et al. (hereinafter referred to as “Wagner”) (US 20170151281 A1, published June 1, 2017). This is a new rejection necessitated by the response filed November 11, 2025.
Regarding claim 1, Adachi teaches engineered CAR-T cells that express IL-7 and CCL19 (Abstract) ). Adachi teaches transfected CAR-T cells specific to human CD20 (hCD20) (page 346, col. 2) (interpreted as an immunoresponsive cell expressing IL-7, CCL19, and a cell surface molecule that recognizes a cancer antigen). Adachi teaches that following treatment of mice with the CAR-T cells, the CAR-T cells generated memory responses against tumors (Abstract).
Adachi does not specifically exemplify that the antigen presenting cell comprises at least one selected from the group consisting of monocytes, macrophages, and dendritic cells (instant claim 43).
Wagner teaches utilizing CAR-DC cells by directly targeting them to the tumor endothelium, which is in direct contact with blood and therefore not susceptible to intra-tumoral factors that limit the efficacy of conventional T cell therapies (Paragraph [0054]). Wagner teaches that the invention applies chimeric antigen receptor technology to dendritic cells, which are capable of antigen presentation and direct killing of tumors (Paragraph [0010]).
Therefore, in view of the benefits of applying chimeric antigen receptor technology to dendritic cells as taught by Wagner, it would have been prima facia obvious to one of ordinary skill in the art to replace the T cells as taught by Adachi, with the dendritic cells as taught by Wagner to generate CAR-DC cells, with a reasonable expectation of success in enhancing the efficacy of the cancer treatment. It would have been prima facia obvious to combine the cited sources because Adachi teaches that CAR-T cells are used to treat cancers, and Wagner teaches that CAR-DCs are more advantageous to treat cancer (as compared to conventional T cell therapies) as they are in direct contact with the blood and not susceptible to intra-tumoral factors.
Conclusion
Claims 1 – 2, 5 – 7, 10 – 13, 16, 38, and 41 - 43 remain rejected.
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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHUBHAM TIWARI whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634
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