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
This application is in response to the papers filed on January 26, 2026. Claims 1-26 are currently pending as per claims filed on October 28, 2022. Claims 1, 3-5, 8-9, 11-15, 17, 20-26 have been amended, and claims 27-36 have been cancelled in Applicant’s amendment filed October 28, 2022.
Applicant’s election without traverse of the invention of Group III, claims 16-23, drawn to an isolated engineered cell population derived from a population of CD45RA+/CD62L+/CD95- T cells and CD45RA+/CD62L+/CD95+ T cells, in the reply filed on January 26, 2026 in response to the restriction requirement filed on October 27, 2025 is acknowledged.
Claims 1-15, and 24-26 are withdrawn from further consideration by the Examiner, pursuant to 37 CFR 1.142(b), as being drawn to non-elected inventions, there being no allowable generic or linking claim. Reinstatement of claims drawn to non-elected inventions will be withdrawn during prosecution. The requirement for restriction between Groups I-III is maintained for reasons of record, and hereby made FINAL. Applicant timely responded to the restriction requirement on January 26, 2026.
Therefore, claims 16-23 are currently under examination to which the following grounds of rejection are applicable.
Priority
The instant application claims foreign priority 35 U.S.C. 119(a)-(d) to European Patent No. EP 20171909.3 filed on April 28, 2020 and PCT Application No. PCT/EP2021/061198 filed on April 28, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Thus, the earliest possible priority for the instant application is April 28, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 28, 2022 was filed. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or an official IDS, they have not been considered.
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.
Claims 16-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim 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 terms/phrases “reduces at least one symptom”, and “has high expansion rate” in claim 16 in lines 3, 4, and 5 are relative terms which renders the claim indefinite. The terms of “reduces” and “high” are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 17-23 are rejected by dependency to claim 16.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 16-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sabatino et al. (Blood 2016; 128 (4): 519–528; of record IDS filed on October 28, 2022; hereinafter ‘Sabatino’) as evidenced by Kochenderfer et al. (Journal of immunotherapy 32.7 (2009): 689-702).
Claim 16 is directed an isolated engineered cell population derived from a population of CD45RA+/CD62L+/CD95- T cells and CD45RA+/CD62L+/CD95+ T cells and engineered to comprise a nucleic acid sequence encoding an exogenous gene wherein said population reduces at least one symptom of cytokine release syndrome (CRS) or reduces at least one symptom of neurotoxicity in a subject or wherein said population has high expansion rate.
Sabatino teaches the generation of CD19 CAR TSCM cells for the treatment of human B-cell malignancies (abstract). PBMCs were enriched for naive CD8+ CD62L+ CD45RA+ cells (TN) by serial-positive magnetic bead enrichment using Fab-streptamer technology as depicted in Fig. 1, which further shows cell yields with a median value of about 40%. To generate CD19-CAR–modified TSCM -enriched cells, naive CD8+T cells were thawed and activated with anti-CD3/CD28 beads in the presence of cytokines, transduced on days 2/3 with γ-retroviral vector encoding the CD19-CAR (FMC63-28-z), then expanded for 5 days in TSCM culture conditions characterized by the presence of IL-7 and IL-21 and the GSK313 inhibitor TWS119 known to stimulate TN cells (p. 520, par 2; p. 522, Figure 2).
It was observed that CD19-CAR+ T cells was high, averaging 73.3% + 6.8% in TSCM cultures (Fig. 2C), wherein the final products were primarily enriched with TSCM (52.2% + 12.52%). “Another large component of the final cell preparation (20.1% + 4.7%) consisted of naive-like T cells (CCR7+CD45RO-), which did not express the full phenotypic traits of TSCM. Despite the TSCM culture restraining T-cell expansion and reducing the transduction efficiency compared to the standard expansion with CD3-specific antibody and IL-2, the TSCM culture conditions generated >10-fold higher numbers of CD19-CAR+ TSCM (Figure 2E). Furthermore, Sabatino describes the generation of equivalent numbers of TSCM using the standard culture would be far more expensive (p 522, col 1-2). The CD19-CAR modified TSCM exhibited enhanced poly-functionality (Fig. 3), enhanced metabolic fitness (Fig. 5) and mediated robust, long-lasting anti-tumor responses in vivo upon adoptive transfer in NSG mice (p. 525, second full paragraph; Fig. 6). Lastly, Sabatino states in relation to cytokine release syndrome (CRS) “However, it should be noted that IL-6, a cytokine implicated as a central mediator of toxicity in CRS,66,67 was poorly released by CD19-CAR–modified TSCM-enriched cells after recognition of leukemic cells.”, and therefore is expected to not increase severity of CRS, which is prominent in hosts receiving TSCM. (p. 525, col 2- p. 626, col 1). The instant Specification describes serum samples of patients with CAR-T associated CRS and neurotoxicity have elevated levels select cytokines, that include IL-6 (p 10, line 26-27).
Regarding claim 17, dependent on claim 16, and claim 19, dependent on claim 17, Sabatino teaches the exogenous gene as a chimeric antigen receptor in reference to an antigen-recognizing receptor wherein CD19-CAR–modified TSCM-enriched cells are generated (p. 520, col 1).
Regarding claim 18, dependent on claim 16, Sabatino teaches T cells can be engineered with CAR or TCR (p. 519, col 1-2; p. 525, col 2, last par.).
Regarding claim 20, dependent on claim 17, Sabatino teaches the CAR as FMC63-28-z (p. 520, col 1, par 1), which as evidenced by Kochenderfer et al. describes the vector as having an anti-CD19 scFv that was derived from the FMC63 mouse hybridoma, a portion of the human CD28 molecule, and the intracellular component of the human TCR-ζ molecule. Further describing in Fig. 1 that the anti-CD19 scFv with a portion of the human CD28 molecule comprising the extracellular region of the CAR. Therefore, the CAR used by Sabatino is exogenous, particularly in that is has an extracellular binding domain.
Regarding claim 21, dependent on claim 17, Sabatino teaches wherein said nucleic acid sequence is introduced by a vector, particularly with a retrovirus (p. 520, col 1, par 1).
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 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.
Claim 16, 17, and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Sabatino et al. (Blood 2016; 128 (4): 519–528; of record IDS filed on October 28, 2022; hereinafter ‘Sabatino’) as evidenced by Kochenderfer et al. (Journal of immunotherapy 32.7 (2009): 689-702) as applied to claims 16 and 17 above, and further in view of Sadelain et al. (WO 2019/133969 A2; filing date of December 31, 2018; designated the US; hereinafter ‘Sadelain’).
Regarding claims 16 and 17, the disclosure of Sabatino is applied as in the 102(a)(1) rejections above, the content of which is incorporated above, in its entirety.
Regarding claims 22 and 23, both dependent on claim 17, Sabatino teaches using retrovirus vector to deliver CAR to T cells, however, the reference does not teach the insertion site of the deliver CAR.
Sadelain teaches the expression and delivery of a CAR with a vector in which “It is placed at an endogenous gene locus of the immunoresponsive cell. The endogenous gene locus is TRAC locus, TRBC locus or TRGC locus. Placement of the CAR disrupts or abolishes the endogenous expression of a TCR.” (p. 6, lines 11-18).; “In certain embodiments, the cell is selected from the group consisting of a T cell” (p. 8, line 15).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the isolated engineered T cell population taught by Sabatino to have inserted the employed CAR at an endogenous gene locus of the T cell, wherein the insertion disrupts or abolishes the endogenous expression of a TCR, based on Sadelain teaching this method with respective outcome using similar CARs delivered by a vector. Therefore, a skilled artisan would have had a reasonable expectation of success employing this taught method with the isolated cell population taught by Sabatino to obtain a population with CAR inserted at endogenous TCR sites as this was known in the art before the effective filing date of the claimed invention.
Conclusion
Claims 16-23 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL A RIGA whose telephone number is (571)270-0984. The examiner can normally be reached Monday-Friday (8AM-6PM).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (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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/MICHAEL ANGELO RIGA/Examiner, Art Unit 1634
/TERESA E KNIGHT/Primary Examiner, Art Unit 1634