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 .
Priority
The instant application, filed on 20 February, 2024 is a 371 of PCT/JP2022/031444 filed on 18 August, 2022.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) to JP 2021-135138 filed 20 August 2021. Receipt is acknowledged of certified copies of the paper required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 20 May, 2024 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 27 November, 2024 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 06 October, 2025 has been considered by the examiner.
The information disclosure statement (IDS) submitted on 25 March, 2026 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
The response filed on 20 February, 2024 has been entered in full. These are the amended claims of the original claim set received on 20 February, 2024. In the amendment, claims 3-5 and 7-13 are amended and no claims are cancelled. Therefore, claims 1-17 are pending and are the subject of this Office Action.
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.
Claims 1-17 are rejected under 35 U.S.C. 103 as being unpatentable over Turtle and Fiorenza (US 2023/0218669, priority date 03/31/2020) in view of Hasegawa and Hosen (2019) (of record IDS 03/25/2026, No. 39) and Ruella and Lee (WO 2019/165215, of record IDS 10/06/2025 No.35).
In regard to claims 1 and 2 Turtle and Fiorenza teach a combination therapy comprising an immune cell modified to express a chimeric antigen receptor (CAR) and a TNF-α signal potentiator (claim 1 of Turtle and Fiorenza) and further where the TNF-α signal potentiator comprises a small molecule selected from a list which includes ASTX660 (Tolinapant) which has the structure of the formula 1 (pg.24) of the instant application (claim 13 of Turtle and Fiorenza).
In regard to claims 3, 9, and 10 Turtle and Fiorenza teach the binding domain of the CAR being selected from a list of targets which includes NY-ESO-1 (claim 16 of Turtle and Fiorenza).
In regard to claims 5 and 10 Turtle and Fiorenza teach the modified immune cell can be T cell or natural killer cell (claim 23 of Turtle and Fiorenza) and further that the CAR comprises an extracellular component, an intracellular component which contain an effector domain (claim 1 of Turtle and Fiorenza) and the extracellular or intracellular components are linked through a transmembrane domain (claim 19 of Turtle and Fiorenza). Turtle and Fiorenza teach the effector domain can be CD3ζ (claim 20 of Turtle and Fiorenza).
In regards to claims 7 Turtle and Fiorenza teaches the transmembrane domain can be selected from a list including CD8 and CD28 (pg.17, col 1, lines 20-25).
In regards to claims 5 and 8 Turtle and Fiorenza teaches the costimulatory molecule can be selected from a list which includes CD2, CD28, CD134 (OX40) and CD 137 (4-1BB) (pg.18, col 1, line 22-30).
In regard to claims 9 and 10 Turtle and Fiorenza teach the binding domain can be a TCR derived from the CDRs of an antibody (claim 15 of Turtle and Fiorenza)
In regards to claims 11 and 15-17 Turtle and Fiorenza teach using the combination therapy to treat cancer (claim 38 of Turtle and Fiorenza).
In regard to claim 14 the kit does not add any further components which further limit the combination therapy and thus is taught by Turtle and Fiorenza as outlined above.
Turtle and Fiorenza fail to teach the CAR or TCR recognizing integrin β7 and CD19 of claims 4 and 6, and the dosing amounts of claims 12 and 13.
Hasegawa and Hosen, however, in regards to claim 4 and 6 teaches CAR T cells targeting both CD19 and integrin β7 have been seen to be very effective against B cell leukemia and multiple myeloma (MM) respectively (abstract). Anti-CD19 CARs have been clinically approved and have very high complete remission rates (pg.1, col 1, lines 14-18), and the anti-integrin β7 were highly specific to MM cells and showed significant anti-MM effects without damaging normal hematopoietic cells (pg.2, col 1, lines 19-28/ pg.2, col 2, lines 15-19).
Hasegawa and Hosen fail to teach the dosing amounts of claims 12 and 13, however, Ruella and Lee teach an effective amount of modified T cells in an invention in which a CAR-T cells and small molecule inhibitor are delivered in combination is between 104 to 109 cells/kg (pg.39, lines 12-15). Further Ruella and Lee teach an effective dose of a small molecule within a range of 1-95 mg daily and exemplary 50 mg daily (pg.41, lines 18-21).
Thus, Turtle and Fiorenza discloses a method and composition for treating cancer comprising a combination therapy comprising a modified immune cell and a small molecule drug which teaches embodiments which arrive at the therapy of the instant application, Hasegawa and Hosen teach that anti-CD19 and integrin β7 CAR-T cells are effective CAR T immune cells which have shown success in cancer models, and Ruella and Lee teach an effective dosing amount for a small molecule and modified T cell when they are delivered in combination. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Turtle and Fiorenza, with the teachings of Hasegawa and Hosen and Ruella and Lee to simply substitute the modified T cell of Turtle and Fiorenza with CAR T cells of Hasagawa and Hosen and to try the dosing scheme taught by Ruella and Lee with a reasonable expectation of success to develop a combination therapy which is effective in treating cancer wherein the CAR can be selected from molecules which have shown selectivity and/or clinical success with a dosing scheme which has been shown to be successful for treatment to improve treatment efficacy.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday – Friday from 8:30am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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