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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 2, 2026 has been entered.
Election/Restrictions
Claims 53-55 and 57-63 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. After further consideration, the species elections for cancer type and retinoid type are withdrawn.
Claims 44 and 56 are under consideration in this office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(a)-(d) or (f), 365(a) or (b), or 386(a) is acknowledged. The application is the national stage entry of PCT/EP2021/059657, which claims benefit to EP20169313.2, filed April 14, 2020.
Withdrawn Objections/Rejections
Any objection or rejection of record pertaining to cancelled claims 45 and 47-50 is rendered moot by applicant’s cancellation of said claims.
The objection of claim 44 is withdrawn in view of applicant’s amendment.
The rejection of claims 44 and 56 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of applicant’s amendment of claim 44.
Applicant’s arguments filed July 2, 2026 (pg 5) regarding the rejection of claims 44 and 56 under 35 U.S.C. 112(a) as failing to meet the written description requirement are persuasive and the rejection is withdrawn.
The rejection of claim 44 under 35 U.S.C. 102(a)(1) and 102 (a)(2) as being anticipated by US 20150344583 is withdrawn in view of applicant’s amendment of claim 44 to limit the immunotherapeutic anticancer agent to a CAR comprising the binding domain of an antibody that binds to BCMA.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (two on pg 4, two on pg 39). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
New Rejections/Objections Necessitated by Amendment
Claim Objections
Claim 44 is objected to because there appears to be a drafting error in line 3. The phrase “wherein the agent is a chimeric antigen receptor (CAR)” indicates that the therapy is the CAR itself, wherein the CAR alone is administered. Based on the specification, however, the claim should clearly be directed toward a CAR-T cell expressing the CAR. To overcome this objection, the claim may be amended to recite “wherein the agent comprises chimeric antigen receptor (CAR) T cells comprising a CAR that comprises a binding domain…”.
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 44 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over by US 2019/0359727, published November 28, 2019 (“Riddell”; PTO-892 from 9/22/2025) in view of Lieberman et al, published 2009 (IDS from 9/23/2022) and Yoshida et al published 2016 (see instant PTO-892).
Riddell teaches a method of treating multiple myeloma [0180] by administering an anti-BCMA CAR T cell (see abstract, [0088], [0180], [0197]), as in claim 44. The method of Riddell further comprises administration of a gamma secretase inhibitor (abstract, [0088], [0182]), as in instant claim 56. Addition of gamma secretase inhibitor myeloma cells is associated with upregulated BCMA expression on the cell surface ([0209]-[0210]), allowing for improved recognition of BCMA positive myeloma cells by T cells [0215].
Although Riddell does not disclose coadministration of the anti-BCMA CAR T cell with ATRA for the treatment of multiple myeloma, the claimed method is not nonobvious when considered in view of Lieberman and Yoshida et al. Lieberman et al teaches that treatment of isolated B cells from PBMC of healthy adults with ATRA increases expression of BCMA of B cells (see entire document), demonstrating that ATRA, like gamma secretase inhibitor, was known in the art to increase BCMA expression in B cells. Furthermore, Yoshida et al teaches that ATRA increases expression of CD38, and that co-administration of ATRA with an anti-CD38 CAR T cell is associated with enhanced cytotoxicity (abstract). Yoshida et al find that ATRA administration increased CD38 expression, thereby allowing for more efficient anti-CD38 CAR T cell activity (abstract).
Given that Riddell teaches a method of treating multiple myeloma by administering an anti-BCMA CAR-T cell and alpha gamma secretase to increase BCMA expression, and further given that Lieberman teaches that ATRA increases BCMA expression and Yoshida et al teach improved cancer cell targeting by co-administering a B cell targeting CAR T cell and ATRA, it would have been obvious to one of ordinary skill in the art to administering both anti-BCMA CAR T cell and ATRA (as well as alpha gamma secretase, as in claim 56) in the treatment of myeloma. The motivation to do so comes from Yoshida et al, which teaches the utility of ATRA in inducible immunotherapies, especially for cancers where the intensity of the protein expression must be raised for clinical application (pg 1, column 2, para 1).
Therefore, a method of treating a patient with myeloma comprised of an anti-BCMA CAR T cell and ATRA would have been obvious and predictable given the prior art teachings of the Riddell, Lieberman et al, and Yoshida et al. One would have a reasonable expectation of successfully using this method to treat myeloma, because the artisan has good reason to pursue known options within their technical grasp to obtain predictable results. Such would amount to the combining of prior art elements according to known methods to achieve predictable outcomes and the use of a known technique (i.e. administration of ATRA with a CAR T cell therapy in cancer) to improve a similar method (i.e. the method of Riddell) in the same way, see MPEP 2143.I.
Response to Arguments
Applicant's arguments filed July 2, 2026 have been fully considered.
Applicant’s arguments filed July 2, 2026 related to the rejections under 35 U.S.C. 102 and 103 and the Armitage reference have been considered but are moot because the new grounds of rejection under 35 U.S.C. 102(a)(1) and 103 does not rely on Armitage as applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
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