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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/24/2026 has been entered.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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(s) 222, 235-237, 239, 240, 245, 247-250, 252, 260, 261, 269, 276-290, 294-299 is/are rejected under 35 U.S.C. 103 as being unpatentable over June et al (US 20150283178 A1, of record) in view of Thakurta et al (US 2016/0051530), Kuramitsu et al (Cancer Gene Ther., 2015, of record) and Brentjens et al (US 2018/0360880). This rejection is maintained for reasons made of record in the previous Office Actions dated 3/14/2024, 7/5/2024, 12/19/2024, 4/24/2025, 7/30/2025, 12/17/2025 and for reasons set forth below.
June et al teach the treatment of cancer by administration of T cells (e.g. CD19-specific CAR T cells) in conjunction with immunomodulatory compounds such as lenalidomide (a thalidomide analog) or thalidomide. See the abstract and ¶’s [0466]-[0469], [0593] and [0604] in particular. Immunomodulatory compounds may be administered, e.g., at 13 days after T cell infusion (Fig 59). Lenalidomide (3-(4-Amino-1-oxo 1,3-dihydro-2H-isoindol-2-yl)piperidine-2,6-dione, ¶[0611] June et al) may be administered in daily 10mg doses whereas CAR T cells may be administered at days +12-14 (¶’s [0848]-[0853]). Multiple myeloma treatment is the focus of Example 6, beginning with ¶[0814]. The amounts of additional agents administered in CAR T-cell combination therapies may be, e.g., 50% of the dose when administered individually (¶[0602]). The engineered CAR T cells of June et al comprise antigen-specific receptors (e.g. to CD19). Such CAR receptors are considered “non-TCR” as they comprise components (e.g. an scFv) that provide antigen binding that are derived from IgG, which is not a TCR (T-cell receptor). The T cells may be effector T cells, CD8+, autologous, or allogenic (¶’s [0006], [0030], [0472], June et al ). One dose of CAR T cells may be 5X107, considered to be “at least 50%” T cells (¶ [0851] June et al). The administration of melphalan (a lymphodepleting chemotherapeutic) prior to CAR T cell therapy is taught by June et al in ¶ [0849]. The CAR therapy may be administered in a staggered manner, e.g. 1-2 administrations per week (¶ [0041). June et al teach their methods suitable for relapsed or refractory cancers from prior administration of immunomodulatory drugs (¶’s [0062], [0275], [0589]-[0591]).
June et al do not teach administration of an immunomodulatory compound and CAR T cells according to one of the schedules of claim 235, or a CAR directed to the BCMA antigen.
Thakurta et al teaches the use of immunomodulatory compounds, such as lenalidomide, in the treatment of multiple myeloma. One exemplified administration cycle is 3 weeks daily (21 consecutive days) followed by 2 weeks of rest for a cycle of 35 days. See in particular ¶[0544]. Thakurta et al (¶’s [0524], [0526]) teach administration of an immunomodulatory compound after initiation of T cell therapy and rest periods of from one to two weeks (¶ [0543]).
Kuramitsu et al teach that administration of lenalidomide the next day after CAR administration enhances the function of CAR T cells (abstract, p. 489, second col., last ¶).
Brentjens et al teach CAR T cells for the treatment of multiple myeloma that are specific for the BCMA antigen. See the summary of the invention in particular.
Taken together, the prior art cited above renders the initiation of immunomodulatory compound, or lenalidomide, therapy from 7 to 42 days after initiation of T cell therapy obvious as to the skilled artisan. This is because such initiation events would be dependent upon the needs and health of the patient, a significant consideration of the skilled artisan in treating, e.g. multiple myeloma. It would be readily apparent that extension of the single day period of Kuramitsu et al to multiple days might best serve a given patient depending on their level of toxic side effects from previous regimens of lenalidomide (the reason for the rest periods of Thakurta et al) or other health reasons. This is in line with the administration of lenalidomide after CAR T cell therapy by June et al as set forth above. Furthermore, the court has found that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). That is the case here. The cited art teaches the flexibility with the initiation times of both CAR and lenalidomide therapy in order to adapt to the needs of the patient. The instant specification presents no surprising or unexpected result by delaying the initiation of lenalidomide treatment for as little as 7 days as compared to the teachings of the cited art.
Further, the claimed methods are essentially disclosed by June et al with the exception of the dosage regimen and BCMA limitations. The ordinary skilled artisan, seeking a method to treat multiple myeloma, would have been motivated to use the lenalidomide dosage cycle of Thakurta and BCMA CAR of Brentjens et al with the methods of June et al because all three references teach the effectiveness of their respective disclosures in treating multiple myeloma. It would have been obvious for the skilled artisan to do this because of the known benefit of generating combination therapies for multiple myeloma as taught by June, Brentjens and Thakurta et al.
Given the teachings of the cited references and the level of skill of the ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Response to Arguments
Applicant's arguments filed 7/24/2025 have been fully considered but they are not persuasive. Applicants essentially assert that: 1) the cited art does not teach the claims as amended; 2) the rejection relies on the rest period teachings of Thakurta et al; 3) the reliance upon the specification is misplaced; 4) the prior art does not teach or suggest the claimed regimen; 5) there is no identification of why the prior art would depart from the teachings of Kuramitsu et al; 6) the reliance upon In re Aller is incorrect; 7) Applicants do not agree with the Examiner’s characterization of Example 4 regarding unexpected results.
Regarding 1), all of the claim limitations have been addressed above, and applicants assertions do not take into account the teachings of June et al administering an immunomodulatory compound 13 days after administration of CAR T cells, a time period within the amended claims.
Regarding 2), such is not convincing. Reliance for a teaching of time point to administer the immunomodulatory compound is based on June, Thakurta and Kuramitsu et al.
Regarding 3), the instant rejection does not rely solely on the specification for an interpretation of the claimed invention, and the analysis of rest periods as pertaining to the instant claims. The prior art (e.g. June et al) clearly teaches administration of an immunomodulatory compound 13 days after initiation of T cell therapy.
Regarding 4), such is false. The prior art (e.g. June et al) clearly teaches administration of an immunomodulatory compound 13 days after initiation of T cell therapy.
Regarding 5), the reasoning for combination with the other references stands. Nothing in Kuramtisu et al definitively teaches administration of lenalidomide more than one day after CAR T cells would not have a beneficial effect. Further, this line of reasoning does not take into account the totality of the prior art teachings regarding combination therapy. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding 6), time points within applicants claimed range for administration have been pointed out, and thus fit the conditions of In re Aller for a teaching of “general conditions”.
Regarding 7), the previous analysis of this assertion stands. Example 4 begins lenalidomide treatment on day 0 of CAR T cell treatment, i.e. “with T cell administration”. See ¶[1018]. It is thus unclear how any “arm” of Example 4 can provide evidence of unexpected results for claims initiating lenalidomide administration after CAR T cell therapy when the experimental design and results do not provide any data for such a method step. In Example 18, it appears that “delayed” treatment with Compound 1 made no difference in the therapeutic outcome as compared to administration of day 0 (“concurrent”). It is therefore unclear what exactly is unexpected with these results. Further, the successful use of lenalidomide in conjunction with CAR T cell therapy in the cited art renders such assertions of unexpected results unpersuasive. Applicants compare these results with Kuramitsu et al only, and still provide nothing that is unexpected relative to the prior art results. Applicants do not explain why it is unexpected that known anti-cancer agents, e.g. lenalidomide or CAR T-cells provide an anti-cancer effect.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 Michael Burkhart whose telephone number is (571)272-2915. The examiner can normally be reached M-F 8-5.
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/MICHAEL D BURKHART/ Primary Examiner, Art Unit 1638
