DETAILED ACTIONNotice 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 .
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 04/21/2026. Claims 1, 44-45, 50-51, 53-55, 58, 60-62, 64, 78, 84-85, 95, 97, 141, and 143 are currently pending. Claims 44 and 141 have been amended and claims 48-49 and 142 have been cancelled by Applicant’s amendment filed on 04/21/2026. Claims 2-43 were previously cancelled by amendment filed 04/11/2025. Claims 1, 58, 60-62, 64, 85, 95, and 97 remain withdrawn from consideration pursuant to 37 CPR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claims.
The examiner acknowledges receiving an executed Declaration under 37 C.F.R. § 1.132 executed by Dr. Hongbo Chi on April 17, 2026 (“Declaration”),
Therefore, claim 44-45, 50-51, 53-55, 78, 84, 141, and 143 are currently under examination to which the following grounds of rejection are applicable. Claims 1 and 141 are independent claims.
Priority
The instant application is a national stage entry under 35 USC 371 of PCT/US2020/029533
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed on 10/22/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/21/2026, was filed before the mailing date of the Non-final office action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112(a)
The rejection of claims 44, 45, 48-51, 53-55, 78, 84, and 141-143 under 35 USC § 112(a) is withdrawn in view of the amendments in the response filed on 04/21/2026. Applicant amended claims 44 and 141 to remove the recitation “a T cell specific for a tumor antigen”. The specification provides support for the T cell expressing a CAR that targets a tumor antigen.
Applicants’ arguments with regard to a withdrawn rejection are moot.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 44, 45, 48-51, 53-55, 78, 84, and 141-143 under 35 USC § 112(b) is withdrawn in view of the amendments in the response filed on 04/21/2026. Applicant amended claims 44 and 141 to remove the recitation “a T cell specific for a tumor antigen”. The specification provides support for the T cell expressing a CAR that targets a tumor antigen.
Applicants’ arguments with regard to a withdrawn rejection are moot.
Claim Rejections - 35 USC § 102
The rejection of claims 44-45,48-51,53-55, 78, 84 and 141-143 under 35 USC § 102 as being anticipated by Xin et al. as evidenced by Gale et al. and Blohm et al. is withdrawn in view of the amendments in the response filed on 04/21/2026. Applicant has amended the independent claims to require that the recited T cell expresses a chimeric antigen receptor (CAR) and the CAR targets a tumor antigen.
A response to Applicant’s arguments with regard to a withdrawn rejection is moot. A response to any argument pertaining to a new or maintained rejection can be found below.
New rejections/objections in response to Applicants’ arguments or amendmentsClaim Rejections - 35 USC § 103
Claims 44-45, 50-51, 53-55, 78, 84, 141, and 143 are newly rejected under 35 U.S.C. 103 as being unpatentable over Thokala et al. (US20190055299 A1, priority date 10/27/2016) in view of Xin et al. (Xin, G et al., Cell Rep., 2015, of record).
This rejection has been necessitated in response to the claim amendments filed 04/21/2026.
Regarding Claims 44-45, 78, Thokala et al. teaches use of CAR T cells targeting tumor antigens and describes CARs derived by fusing scFv of mAbs specific TAAs to T cell signaling domains CD28 or CD137 and CD3s. CARs re-direct the specificity of T cells to recognize tumor antigens independent of MHC (Pg. 16, Paragraph [0162]). Moreover, Thokala et al. use of cells that are immune effector cell having high mitochondrial SRC, such as CD8+ T cells as recited in instant claim 45 (Pg. 10, Paragraphs 0115-0116). Cells having high mitochondrial SRC are utilized because “Immune effector cells, such as CD8+ T cells, with high mitochondrial SRC may exhibit enhanced survival relative to cells with lower SRC during stress conditions, such as high tumor burden, hypoxia, lack of nutrients for glycolysis, or a suppressive cytokine milieu. Moreover, immune effector cells selected for high mitochondrial SRC may retain cytotoxic activity, even under stress conditions. Accordingly, by selecting immune effector cells with high mitochondrial SRC improved cell composition for both therapy and for testing of CAR constructs can be produced.” (Pg. 10, Paragraph 0116).
Although Thokala et al. does teach selection of Tcells to produce CAR T cells based on characteristics such as enhance survival, Thokala et al does not specifically teach increasing expression of BATF or enhancing function of a BATF protein.
Xin et al. teaches a method resulting in the enhanced expansion of T-cells. Specifically, Xin et al. teaches that BATF-overexpressing CD8 T cells (BATF-Thy1.1+) contained a significantly higher proportion of proliferating cells (as measured by Ki67+) and had increased survival (as measured by Annexin-V−7-AAD− [7-amino-actinomycin D]) compared with empty MIT-transduced cells (control-Thy1.1+) (page 3, last paragraph; Figures 3B and 3C).
It would have been obvious to a person of ordinary skill in the art at the time of the instant application to modify the CD8+ CAR T cell targeting tumor antigens as taught by Thokala et al. by increasing expression of BATF using the methods taught by Xin et al. who demonstrates the enhancement of CD8+ T cells by inducing BATF overexpression. One of ordinary skill in the art would have been motivated to combine these teachings as the use of a genetic modification that enhances CD8+ T cell proliferation/expansion would reasonably enhance the therapeutic fitness of a CD8+ CAR T cell. Further, the production of said CAR Tcell from these combined method would read on the cell recited in instant claim 78.
There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
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Regarding Claim 50-51 and 53-55, the combined teachings of Thokala and Xin above render obvious the method of claim 44. Moreover, Xin et al. teaches their method to utilize a BATF gene containing vector to overexpress BATF using the spin transfection method (Pg. 8, Experimental Procedures, Retrovirus-Mediated BATF Overexpression). The vector used by Xin et al. contains a vector with the sequence encoding for BATF, which reads on the instant application claim 51 for the polynucleotide encoding a BATF protein comprising nucleotide sequence of SEQ ID NO:27 (the full sequence of mRNA encoding for BATF, see alignment below). Further, the BATF vector taught by Xin et al. is incorporated into a retrovirus (for claims 54-55) and is a recombinant vector (for claim 53) (Pg. 8, Experimental Procedures, Retrovirus-Mediated BATF Overexpression).
Regarding Claim 84, the combined teachings of Thokala and Xin above render obvious the method of claim 44 and 78. Moreover, Thokala et al. teaches a pharmaceutical composition in which the engineered CAR T cells are included (Pg. 12, Paragraph 0132).
Regarding Claims 141 and 143, as discussed above the combined teachings of Thokala and Xin render obvious a method of enhancing expansion of a Tcell comprising an engineered T cell expressing a CAR targeting tumor antigen and the introduction of BATF gene to overexpress BATF in T cells and the resulting T cell produced by the method.
Response to Applicants’ Arguments as they apply to the new rejection of claims 44-45, 50-51, 53-55, 78, 84, 141, and 143 under 35 U.S.C. 103
At pages 7-8 of the remarks filed on 04/21/2026, Applicants essentially argue the Xin reference does not teach or suggest engineering a T cell to express a CAR, much less a CAR that targets a tumor antigen as recited in the newly amended claims 44 and 141.
Examiner agrees with the applicant that Xin does not teach a CAR T cell, however as the amendments to the claims have changed the scope of the claims, a new 103 rejection of claims 44-45, 50-51, 53-55, 78, 84, 141, and 143 as being unpatentable over Thokala et al. and Xin et al., has been necessitated.
The primary reference, Thokala et al. does teach an engineered CAR T cell targeting a tumor antigen. Moreover, as discussed in the 103 rejection above, it would have been obvious for a person of ordinary skill seeking to produce a pharmaceutically useful CD8+ CAR T cell with the capacity to target tumor antigens to also contemplate genetic engineering strategies shown to provide enhanced expansion/proliferation such as BATF overexpression as taught by Xin.
Applicant further states, “the claimed anti-tumor T cell is patentably distinct from the anti-viral T cell disclosed in Xin. To address the Examiner's assertion to the contrary, Applicant submits herewith the Declaration of Dr. Hongbo Chi under 37 CFR § 1.132 ("Declaration"), which provides ample evidence that a transcription factor such as BATF can have markedly different effects on T cell expansion, persistence, and/or function in anti-tumor versus anti-viral responses.”
While the declaration has been considered it is not persuasive to overcome the prima facie case because it establishes at most that BATF biology may be context-dependent depending on the setting. Moreover, the applicant’s distinction is noted, but it is not commensurate with the breadth of the claims. The claims are not limited to a particular tumor microenvironment, tumor type, CAR construct, antigen, cytokine condition, exhaustion state, or in vivo therapeutic result.
The claims broadly require enhancing expression of an engineered CAR T cell. It would be reasonable to describe a CAR T cell as a T cell that undergoes antigen-driven activation and expansion. The declaration does not show that a person of ordinary skill in the art would have lacked reasonable expectation of that BATF overexpression would enhance expansion of CAR engineered T-cells, particularly where the claims are not limited to the specific contexts in which BATF may have a divergent effect. Thus, a person of ordinary skill in the art would have a reasonable expectation that Xin’s BATF modification would enhance the CAR T cells taught by Thokala et al.
Conclusion
Claims 44-45, 50-51, 53-55, 78, 84, 141, and 143 are 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 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 KODYE LEE ABBOTT whose telephone number is (703)756-1111. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G. 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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/KODYE LEE ABBOTT/ Examiner, Art Unit 1634 /MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
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