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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/12/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group 1 drawn to method of transfecting or transducing T-cells with plurality of nucleic acid molecules in the reply filed on 11/25/2025 is acknowledged.
Claim 22 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-4, 6-9, 12-19 and 21 are pending and under exam.
WITHDRAWN REEJCTIONS AND OBJECTIONS
Claim Objections
Claim objection of claim 2 is following claim amendments
Objections of claims 3, 13, 17-18 and 20 are withdrawn following claim amendments.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5 was rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth the subject matter which the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the applicant regards as the invention.
The rejection is withdrawn following claim amendment.
Claim Rejections - 35 USC § 102
Claims 1-4, 6-9, 12-19 and 21 were rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Chen et al (WO2021101956A1; Published May 27, 2021; hereinafter “Chen;” See PTO-892).
The rejection is withdrawn following claim amendments.
Claim Rejections - 35 USC § 103
Claims 5-7, 10-12, 15-17, and 20-21 were rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (WO2021101956A1; Published May 27, 2021; hereinafter “Chen;” See PTO-892) in view of Chervin et al (Gene Ther. 2013 Jun; hereinafter "Chervin;" See PTO-892), and as evidenced by Yeung et al., (PNAS, published online August 18, 2014; hereinafter “Yeung”; See PTO-892).
The rejection is withdrawn following claim amendments. New rejections are set forth below.
NEW REJECTIONS NECESSITATED BY CLAIM AMENDMENTS
Claim Objections
Claim 1 is rejected for minor informality for missing an “is” in “wherein the amino acid substitution is in only one of the CDR1 or CDR3 of the alpha or beta chain of the TCR.” Appropriate correction is required.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-4, 6-9, 12-19 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Robbins et al (J Immunol. 2008 May 1; hereinafter “Robbins;” See PTO-892) in view of Chen et al (WO2021101956A1; Published May 27, 2021; hereinafter “Chen;” See PTO-892 of 01/09/2026) further as evidenced by Yeung et al., (PNAS, published online August 18, 2014; hereinafter “Yeung”; See PTO-892 of 01/09/2026).
Regarding claim 1, 7-9, 12, 17 and 21: Chen disclosed a method of identifying a TCR by providing a plurality of T cells expressing a plurality of TCRs, wherein each T cell of the plurality of T cells expresses a cognate pair of a TCR of the plurality of TCRs; contacting the plurality of recipient cells with one or more antigens, thereby activating a marker in a subset of the plurality of recipient cells; wherein the one or more antigens are represented on one or more antigen presenting cells (APCs), MHC tetramers, nanoparticles or any combination thereof. (See claims 1 and 11 of Chen). The method of identifying activated T-cells is interpreted to read on the method for identifying TCR reactive to peptide as the method inherently involves activating T-cells expressing the TCRs. Additionally, claim 27 of Chen disclosed “selecting the TCR identified in (i) from the TCR repertoire of the plurality of recipient cells or the TCR repertoire of the subset of the plurality of recipient cells.” It is noted that [0029] of Chen indicated that “[t]he terms “enriching,” “isolating,” “separating,” “sorting,” “purifying,” “selecting” or equivalents thereof can be used interchangeably and refer to obtaining a subsample with a given property from a sample. As such, Chen disclosed the claimed sorting for T-cells with activated TCRs However, Chen did not teach the use of a TCR comprising an amino acid substitution at CDR position, particularly, a substitution in only one of CDR1 or CDR3 regions of α or β chain to identify T-cells having enhanced antigen-specific TCR activity.
Robbins was directed to “simple TCR substitution variants that enhance T cell function” identifiable “by rapid transfection and assay techniques, providing the means for generating potent Ag complex-specific TCR genes for use in the study of T cell interactions and in T cell adoptive immunotherapy.” (See Robbins Abstract). Robbins demonstrated that single or dual AAS in the 1G4 TCR CDR2 or CDR3 regions can provide relatively modest increases in TCR affinity that nevertheless significantly enhance the ability of CD4+ T cells to recognize the NY-ES0-1/HLA-A*02 Ag complex while maintaining (and in one case enhancing) Ag-specific reactivity in CD8+ T cells. (See Robbins p.3, para 2).
Robbins taught that “[n]oncodon optimized WT 1G4 α and β constructs were generated from TRAV-21 and TRBV6-5 cDNA clones identified within bulk tumor-infiltrating lymphocytes by carrying out overlapping PCRs using primers as detailed in Table I containing sequences corresponding to the junctional regions of the WT 1G4 α- and β-chains.) This reads on the claimed “transducing a plurality of T-cells with a plurality of nucleic acid molecules encoding a T- cell receptor (TCR) specific for the target peptide.” It is noted that Robbins particularly exemplified β51:AI construct and α95:LY and WTβ constructs (CDR3 β substitution), which reads on the claimed “amino acid substitution in only one of the CDR1 or CDR3 of the alpha or beta chain of the TCR”. Robbins also disclosed that “[f]or measurement of IL-2 release, cocultures of T cells and target cells were incubated with 5 μg/ml of a blocking Ab directed against IL-2Rα that was added to inhibit the uptake of IL-2 by T cells” This reads on the claimed “co-culturing the T-cells with antigen presenting cells presenting an epitope of the target peptide.” (See Robbins p. 6, para 2). Robbins disclosed that “[t]he abilities of CD8+ and CD4+ T cells expressing the DMF4 or DMF5 WT TCRs to mediate specific tumor cell lysis were then compared with T cells that express the corresponding TCR variants.” (See Robbins p. 11, last para). Additionally, Robbins also taught evaluation of “[t]he levels of IFN-γ released by CD8+ T cells that were transfected with 1G4 TCR CDR2β chain variants” (See Robbins p. 7, last para). As Robbins taught screening and identification of T-cells expressing substituted TCRs based on antigen-specific functional activity, including cytokine-release assays, which provided a basis for selecting T-cells having activated TCRs. This read on the claimed “sorting for T-cells with activated TCRs; and comparing the activation levels of the substituted TCRs”.
It would have been obvious to a person of ordinary skill in the art to incorporate the CDR3 substituted TCR variants of Robbins into the TCR screening and selection method of Chen. Chen taught providing plurality of T cells expressing plurality of TCRs, contacting the contacting the TCR-programmed cells with antigen presented by, for example, antigen-presenting cells or MHC-containing complexes identifying a subset of cells having an activated marker, and selecting the activated TCR-programmed cells. Chen further taught that such selection maybe done by FACS. A skilled artisan would therefore have had a reasonable expectation of success in using CDR3 substituted TCR variants taught by Robbins as members of the plurality of TCRs screened according to Chen. Doing so would have been predictable application of Robbins demonstrated TCR variants with Chen’s established antigen-dependent screening and selection platform to identify T-cells expressing TCRs having enhanced antigen-specific activity.
Regarding claims 2 and 13: Chen disclosed sequencing TCR repertoire of recipient cells (See Chen claim 1h).
Regarding claim 3 and 14: Claim 29 of Chen disclosed that the polynucleotide pair encoding TCR delivered to the T-cells comprises a barcode.
Regarding claim 4: [0032] of Chen indicated that “the TCR-programmed recipient cells can be contacted with one or more antigens (e.g., one or more antigens in complexed with MHCs). Subsequent to contacting with the one or more antigens, the TCR-programmed recipient cells can be subject to selection (e.g., using fluorescence-activated cell sorting (FACS), magnetic activated cell sorting (MACS), panning or other method) to obtain post-selection TCR- programmed recipient cells.“
Regarding claims 8-9 and 18-19: Claim 26 of Chen disclosed that the antigen is upregulated in cancer cells and claim 23 disclosed that the antigen can be NY-ESO-1 antigen. It is also noted that Robbins taught NY-ESO-1 antigen.
Regarding claim 6 and 16: As indicated above, Chen taught measurement of TCR activation by FACS. It is noted that as evidenced by Yeung et al, see PTO-892 Fig. 7, the measurement of fluorescence in FACS is equivalent to comparing MFI.
Regarding claim 15: [0032] of Chen indicated that “the TCR-programmed recipient cells can be contacted with one or more antigens (e.g., one or more antigens in complexed with MHCs). Subsequent to contacting with the one or more antigens, the TCR-programmed recipient cells can be subject to selection (e.g., using fluorescence-activated cell sorting (FACS), magnetic activated cell sorting (MACS), panning or other method) to obtain post-selection TCR- programmed recipient cells.”
Conclusion
No claim is allowed.
No claim is free of art.
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 JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
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