EFFICACY AND DURABLE RESPONSE OF IMMUNOTHERAPY

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 . DETAILED ACTION Restriction/Election Applicant’s election without traverse of Group I (claims 70, 72-82, and 84) in the reply filed on 06/23/2026 is acknowledged. 2. Claims 70, 72-82, 84, and 87 are pending. Claims 70, 72-82, and 84 are currently under consideration. Claim 87 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Information Disclosure Statement 3. The information disclosure statement filed on 06/23/2026 has been considered by the Examiner and an initialed copy of the form PTO-1449 is attached to this communication. Drawings 4. The drawings filed on 10/26/2023 are accepted by the examiner. Claim Rejections[Symbol font/0xBE]35 USC § 112 (a) 5. The following is a quotation of the first paragraph of 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention. 6. Claims 70, 72-82, and 84 are rejected under 35 U.S.C. 112(a), as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention. The factors that are considered when determining whether a disclosure satisfies enablement requirement include: (i) the quantity of experimentation necessary; (ii) the amount of direction or guidance presented; (iii) the existence of working examples; (iv) the nature of the invention; (v) the state of the prior art; (vi) the relative skill of those in the art; (vii) the predictability or unpredictability of the art; and (viii) the breadth of the claims. Ex Parte Forman, 230 USPQ 546 (Bd Pat. App. & Int. 1986); In re Wands, 858 F. 2d 731, 8 USPQ 2d 1400 (Fed. Cir. 1988). Claim 70 is drawn to a method for treating a cancer in a subject in need thereof wherein the subject has previously been administered a first T cell product comprising autologous T cells expressing an anti-CD19 chimeric antigen receptor (CAR), further wherein a peripheral blood sample has been taken from the subject after administration of the first T cell product, comprising (a) measuring the level of CD8+CD27-CD28+T-cells in the blood sample, and (b) if the level of CD8+CD27-CD28+T-cells in the blood sample is elevated, administering to the subject a second T cell product. Claims 72-82, 84, and 87 depend from claim 70, The claims are broad because they are drawn to a method of treating a broad genus of cancer comprising administering a second T cell product. There is no structural limitation for the second T cell product. The specification does not provide sufficient guidance/direction or working examples on how to make and use the instantly claimed invention. The specification discloses an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, Brexucabtagene autoleucel (brexu-cel or KTE-X19), for relapsed/refractory mantle cell lymphoma (R/R MCL). The specification discloses association of the phenotypes of peripheral blood T-cells (CD8+CD27-CD28+T-cells) with relapse and/or nonresponse (page 129, Table 12). However, except the brexu-cel, the specification does not disclose any other anti-CD19 chimeric antigen receptor (CAR) T-cells. The specification does not provide sufficient guidance or working example on how to treat the broad genus of cancer. There is no evidence on the record showing that administering a second T cell product can treat patients with the phenotypes of peripheral blood T-cells, CD8+CD27-CD28+T-cells (i.e., patients with relapsed responders and/or non-responders to the first T cell product, brexu-cel). The prior art teaches Brexucabtagene autoleucel for the treatment of relapsed/refractory mantle cell lymphoma (Mian et al., Expert Opinion on Biological Therapy, 21 (4):435-441, 2021). The state of the art is such that chimeric antigen receptor (CAR) T-cell therapy is a relatively recent approach to treating patients with hematologic malignancies and that factors associated with response may be specific to a given CAR T cell product and/or malignancy (page 131, paragraph [0315]). It is unpredictable whether administering any given second T cell products can treat patients with any types of cancer or with relapsed responders and/or non-responders to the first T cell product, brexu-cel. The courts have stated that patent protection is granted in return for an enabling disclosure. Reasonable detail must be provided in order to enable members of the public to understand and carry out the invention. See Genetech v. Novo Nordick A/S (CAFC) 42 USPQ2d 1001 (1997). Similarly, as stated in Rasmusson v SmithKline Beecham Corp., 75 USPQ2d 1297-1303 (CAFC 2005), “if mere plausibility were the test for enablement under section 112, Applicants could obtain patent rights to ‘inventions’ consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the 'inventor’ would be rewarded the spoils instead of the party who demonstrated that the method actually worked. The scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis. In the instant case, the evidence on the record supports that the specification does not enable the claimed invention. Undue experimentation would be required for the skilled artisan to make and use the claimed invention. Conclusion 7. No claims are allowed. Advisory Information Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, please contact the Electronic Business Center (EBC) at the toll-free phone number 866-217-9197. /RUIXIANG LI/Primary Examiner, Art Unit 1674 August 20, 2026