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 .
Claim status
In the reply filed on 12 February 2026, claims 1, 3-4, 6, 8-11, 14-16, 18-19, 21, 23, and 50 are previously presented, and cancelled claims 2,5, 7, 12-13, 17, 20, 22, 24-49 and 51. However, Applicant added new claims 52-68.
Therefore, claims, 1, 3-4, 6, 8-11, 14-16, 18-19, 21, 23, 50 and 52-68 are herein pending.
Election/Restrictions
Applicant previously elected without traverse Group I, directed to claims 1, 3-4, 6, 8-11, 14-16, 18-19, 21, 23, and 50 drawn to an ex vivo method of preparing SARS-CoV-2-specific T Cells in the reply filed on 06 August 2025. The new claims 52-68 are within the scope of the elected invention.
Applicant has cancelled non-elected claims 24-26 and 27, 34-35 of Groups 2-3 on 06 August 2025.
Claims 1, 3-4, 6, 8-11, 14-16, 18-19, 21, 23, 50 and 52-68 are under current examination.
Priority
This application was filed 10/26/2022 and is a national phase application under 35 U.S.C. § 371 of International Application No. PCT/US2021/070532, filed May 11, 2021, which claims priority to U.S. Provisional Patent Application Serial No. 63/022,896, filed May 11, 2020, and also claims priority to U.S. Provisional Patent Application Serial No. 63/076,842, filed September 10, 2020. Thus, the earliest possible priority for the instant application is 05/11/2020.
Maintained Claim Objections
Claim 1 is objected to because of the following informalities: abbreviations such as “SARS-CoV-2” should be spelled out in full at the first encounter in the claims. Appropriate correction is required.
Maintained and Modified 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 3-4, 6, 8-11, 14-16, 18-19, 21, 23, 50 and 52-68 are stand rejected in modified form under 35 U.S.C. 103 as being unpatentable over Rezvani et al., (US20180333435A1; cited in IDS filed 10/21/2024; hereinafter “Rezvani”), in view of Liu et al., (Antiviral research, 137, pp.82-92, 2017; cited in PTO892; hereinafter “Liu”) and Yang et al., (The lancet respiratory medicine, 8(5), pp.475-481, 2020; cited in IDS filed 11/08/2022; hereinafter “Yang”). This rejection is maintained for reasons of record and current applicant’s amendments.
With respect to claims 1, 50, 52, 53, and 68, Rezvani teaches an ex vivo method for generating BK virus (BKV)-specific T cells comprising the step of obtaining a starting population of T cells; and culturing the starting population of T cells in the presence of IL-2 ([0153], [0194]) IL-4 [0085], IL-7, IL-15, and a mixture of peptides, wherein the mixture of peptides comprises overlapping peptides spanning at least 3 immunodominant proteins selected from the group consisting of small T antigen, large T antigen, VP1, VP2, and VP3, thereby generating BKV-specific T cells. ([0006], claim 1 of Rezvani)
Although, Rezvani does not disclose the virus is SARS-CoV-2. However, such was known in the prior art.
Liu discloses a T-cell immunological study of SARS-CoV and the potential cross-reactivity of the SARS-CoV-specific immunity, provides and useful recommendations for the development of broad-spectrum vaccines against coronavirus infections (abstract). Further, Liu discloses that Laboratory investigation of clinical patients demonstrated that SARS-CoV-specific T-cells are important for the recognition and clearance of infected cells, particularly in the lungs of infected individuals (p. 85 “4.2. T-cell immunity to SARS-CoV” ¶ of Liu). However, Liu does not disclose that SARS-CoV is SARS-CoV-2 variant.
Yang discloses that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a dangerous virus (abstract of Yang).
MPEP 2143 (B) states that simple substitution of one known element for another to obtain predictable results. The rationale to support a conclusion that the claim would have been obvious is that the substitution of one known element for another yields predictable results to one of ordinary skill in the art. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). Accordingly, it would have been obvious to practice the ex vivo method for generating BK virus (BKV)-specific T cells of Rezvani and substitute SARS-CoV-2 virus peptide as taught by Liu and Yang with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Liu and Yang SARS-CoV-2-specific T-cells are important for the recognition and clearance of infected cells, particularly in the lungs of infected individuals (p. 85 “4.2. T-cell immunity to SARS-CoV” ¶ of Liu). It would have been obvious to POSITA at the time of filing the invention to modify the BKV invention with SARS-CoV-2, as taught by Yang, in order to provide a vaccine for the SARS-CoV-2 (abstract of Yang). In regard to the reasonable expectation of success doing so, substitute the SARS-CoV-2 virus of Yang, and Liu to produce the SARS-CoV-2 -specific T cells had a reasonable expectation of success since the substitute steps thereof required no more than recombinant DNA and cell culture technology.
With respect to claims 3-4, 54, and 55, Rezvani teaches that the starting population of cells comprises peripheral blood mononuclear cells (PBMCs) or lymphocytes ([0007], [0081], claim 3 of Rezvani) and derived from healthy donor ([0027] of Rezvani).
With respect to claims 6, and 56, Rezvani teaches that the culturing is for 10-14 days ([0027], claim 4 of Rezvani).
With respect to claims 8, and 57, Rezvani teaches that the culturing does not comprise a second population of cells pre-stimulated with the mixture of peptides ([0088], claim 6 of Rezvani).
With respect to claims 9-10, and 58-59, Rezvani teaches that the second population of cells may comprise pre-stimulated cells are may further comprises antigen presenting cells (APCs), wherein the APCs are dendritic cells, monocytes, and/or B lymphocytes ([0088], claims 7-8 of Rezvani).
With respect to claims 11, and 60, Rezvani teaches that the peptides are at least 10 amino acids long (e.g., 10-30 amino acids, 12-18 amino acids, 15-25 amino acids long) ([0082], claim 9 of Rezvani).
With respect to claims 14-16, and 61-63, Rezvani and in view of Liu and Yang, teaches that the peptides in the mixture of peptides overlap by 10-15 or 11 contiguous amino acids or comprises peptides that span part or all of the entire length of corresponding protein in interest ([0082] of Rezvani). It would have been obvious to POSITA at the time of filing the invention to substitute the BKV with SARS-CoV-2, as taught by Yang, in order to provide a vaccine for the SARS-CoV-2 (abstract of Yang).
With respect to claims 18-19, 21, 23, 64-67 Rezvani and in view of Liu and Yang teaches that the genetically engineering SARS-CoV-2-specific T cells to
a) disrupt expression of one or more endogenous genes in the cells such as TGF[Symbol font/0x62] receptor (e.g., TGF[Symbol font/0x62]-RII, reads on claims 19, 65) ([0130] of Rezvani); and
b) to express antigen receptors such as engineered TCRs and/or chimeric antigen receptors (CARs), ([0029], [0094-0095]) wherein the CAR or TCR targets one or more SARS-CoV-2 antigens [0028]. It would have been obvious to POSITA at the time of filing the invention to substitute the BKV with SARS-CoV-2, as taught by Yang, in order to provide a vaccine for the SARS-CoV-2 (abstract of Yang).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant filed Remarks and Declaration Under 37 C.F.R. § 1.132 on 12 February 2026 are acknowledged.
Applicant argues that the methods disclosed in Rezvani were tailored to work for BKV, not SARS-CoV-2, and there is not even a mention in Rezvani of SARS-CoV-2 or how BKV may be remotely related to SARS-CoV-2 or the broader family of coronaviruses. Similarly, Yang and Liu never mention BKV or a possible relationship with coronaviruses. In the Declaration, skilled artisan Dr. Katy Rezvani further details how BKV and SARS-CoV-2 would not be equivalent and substitutable (see remark p. 7 “BKV and SARS-CoV-2 are not substitutable equivalents” ¶ and Declaration, section 3)
Applicant's arguments have been fully considered but they are not persuasive.
MPEP 2145 States that the 35 U.S.C. § 103(a) based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In here Rezvani teaching every steps to culturing specific T cell in the presence of a mixture of peptides and one or more ofIL-2, IL-4, IL-7, IL-15, and IL-21. In a prior art, Pia et al. (Pia, L. SARS-CoV-2-reactive T cells in patients and healthy donors. Nat Rev Immunol 20, 353 (2020); Published 30 April 2020; cited in PTO892) discloses a peripheral blood mononuclear cells from 18 patients with COVID-19 and 68 seronegative healthy donors (HDs) were stimulated with peptide pools derived from the SARS-CoV-2 spike (S) protein suggest that S protein-specific T cells in HDs may be cross-reactive clones developed following a previous exposure to human endemic coronaviruses that cause common cold. Therefore, Pia discloses the potentiality of SARS-CoV-2-specific T cells and has important implications for the design and analysis of COVID-19 vaccines (see the abstract of Pia). Accordingly, it would have been obvious to practice the ex vivo method for generating BK virus (BKV)-specific T cells of Rezvani and substitute SARS-CoV-2 virus peptide as taught by Liu and Yang with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Liu and Yang SARS-CoV-2-specific T-cells are important for the recognition and clearance of infected cells, particularly in the lungs of infected individuals (p. 85 “4.2. T-cell immunity to SARS-CoV” ¶ of Liu). It would have been obvious to POSITA at the time of filing the invention to modify the BKV invention with SARS-CoV-2, as taught by Yang, in order to provide a vaccine for the SARS-CoV-2 (abstract of Yang).
Applicant argues that the Rezvani states that the combination of IL-2, IL-7, and IL-15 led to a surprisingly high percentage of BKV-specific T cells (Rezvani; ii [195] and Figure 3C) compared to other cytokine combinations that may include IL-1, IL-4, and IL-21 (Rezvani; ii [0085][195]. The specification of this application shows that the specific cytokine combinations of IL-2/4/7 or IL-2/7/15 (but not other cytokine combinations) are unexpectedly advantageous for producing SARS-Co V-2-specific T cells because they lead to rapid expansion (ii [158], Figure 7A-B), polyfunctionality (ii [160], Fig. 7D-E), low exhaustion markers (ii [160], Fig 7F-G), a cytotoxic Th1 phenotype indicative of direct antiviral killing capacity (ii [160], Fig 7F), and preferential targeting of the S protein of SARS-CoV-2 (ii [162], Figure 8A). Furthermore, it is expressed that these beneficial properties can be "driven both by the immunodominance of the protein and by the culture conditions" ii [168], further highlighting how the distinct properties of SARS-CoV-2, which are not shared with BKV, lead to the unexpected success in generating SARS-Co V-2-specific T cells via the method of claim 1 in this application (See remark p. 7 2nd ¶ and Declaration p. 3 1st ¶).
In response to applicant's argument that the Rezvani et al. fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the specific cytokine combinations of IL-2/4/7 or IL-2/7/15 (but not other cytokine combinations)) are not recited in the claim 1 and new claim 53. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). In hereinafter, Rezvani teaches an ex vivo method for generating BK virus (BKV)-specific T cells comprising the step of obtaining a starting population of T cells; and culturing the starting population of T cells in the presence of IL-2, IL-4, IL-7, IL-15, and a mixture of peptides.
Applicant argues that the specification of Rezvani identifies prior attempts using IL-4 with IL-7 (Gerdemann et al.) and explicitly faults the approach as "very low" in efficiency, reporting "less than 1%" CD8+ IFNy+ cells and concludes that a "high number of robust BKV-specific T cells is needed" for therapy, thereby framing a need for different, more efficient methods. See [0005]¶ of Rezvani. Rezvani teaches that IL-4 and IL-7 failed to produce therapeutic levels of functional BKV-specific T cells ([0195]¶). Thus, the teachings of Rezvani would lead a POSITA to avoid use ofIL-4 and IL-7 in the expansion of SARS-CoV-2-specific T cells. Thus, Rezvani teaches away from using IL-4 and IL-7 for expansion of SARS-Co V2- specific T cells (see remark p. 4 1-3rd ¶ and Declaration section 3 last ¶).
Applicant's arguments have been fully considered but they are not persuasive. In response to applicant's argument, MPEP 2145 X(D1) states that "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Clearly, Rezvani teaches culturing the starting population of T cells in the presence of IL-2 ([0153], [0194]) IL-4 [0085], IL-7, IL-15, and a mixture of peptides (see [0085] ¶ of Rezvani). Further, Rezvani teaches that additional cytokines may include, but are not limited to, IL-1, IL-4, IL-6, and IL-21 in the culture mixture (see [0085] ¶ of Rezvani).
Pertinent References
The art made of record and not relied upon is considered pertinent to applicant's disclosure is the following:
Le Bert et al. (SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls. Nature 584, 457–462 (2020); Published online: 15 July 2020) provides methods for generating T cell lines as follows: 20% of PBMCs were pulsed with 10 μg/ml of the overlapping SARS-CoV-2 peptides (all pools combined) or single peptides for 1 h at 37 °C, washed and cocultured with the remaining cells in AIM-V medium (Gibco; Thermo Fisher Scientific) supplemented with 2% AB human serum (Gibco; Thermo Fisher Sci entific). T cell lines were cultured for 10 days in the presence of 20 U/ ml of recombinant IL-2 (R&D Systems). See the Methods “Expanded T cell lines” ¶.
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684