DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority Claim
2. The instant application, filed on 24 August, 2023 claims domestic benefit to US provisional application no. 63/373,629 filed on 26 August 2022.
Status of Application, Amendments, and/or Claims
3. The response filed on 30 November, 2023 has been entered in full. These are the amended claims of the original claim set received on 03 October, 2023. In the amendment, claims 1-20 are cancelled. Therefore, claims 21-30 are pending and are the subject of this Office Action.
Information Disclosure Statement
4. The information disclosure statement (IDS) submitted on 13 December, 2023 has been considered by the examiner.
Specification
5. The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
Claim Rejections - 35 USC § 103
6. 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.
7. Claims 21 - 26, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (2018) CAR-T cells targeting CLL-1 as an approach to treat acute myeloid leukemia Journal of Hematology & Oncology (11) 7 (hereafter Wang) in view of Aftab et al. (2020) Toward “off-the-shelf” allogenic CAR T cells Adv Cell Gene Ther. (3) e86 (hereafter Aftab) and Morgan et al. (2020) Use of Cell and Genome Modification Technologies to Generate Improved “Off-the-Shelf” CAR-T and CAR-NK Cells Front. Immunol. (11) 1965 (hereafter Morgan).
In regards to claim 21 and 30 Wang teaches a CLL-1 targeting CAR-T cell which showed strong anti-leukemic activity in vivo (abstract).
In regards to claim 24 Wang teaches the use of healthy donor cells (pg.10 col 2, lines 29-30).
Wang fails to teach the in vivo expansion of the CLL-1 targeting CAR-T by contact with an IL-15 agent of claim 21, the knockout of the expression of the genes TRAC and β-2microglobulin (β2m) with CRISPR/Cas9 of claims 22 and 23, the use of allogeneic immune cells of claim 25, and the administration of IL-15 sequentially after CAR administration of claim 26. Aftab, however, teaches that clinical efficacy of allogenic CAR T cells is associated with their initial expansion and further discusses report of post infusion CAR-T cell expansion as a major factor for clinical response in the case of autologous CD19 CAR T cells in B-ALL (pg.7 col 2, lines 8-11). Aftab also teaches expansion is enhanced by homeostatic cytokines such as IL-7 and IL-15 (pg.7 col 2, lines 12-13).
Aftab fails to teach the knockout of expression of the genes TRAC and β2m with CRISPR/Cas9 of claims 22 and 23, however, Morgan teaches the knockout of TRAC and β2m with CRISPR/Cas9 in combination with lentiviral delivery of an anti-CD19 CAR into allogeneic T cells resulted in a universal CAR T cells (pg.7 col 2 lines 45-48).
Thus, Wang discloses a CAR-T cell which targets CLL-1 derived from health donors and Aftab teaches the importance of post infusion CAR-T expansion and the efficacy of IL-15, as well as the use of allogeneic cells, and Morgan teaches the knockout of TRAC and β2m with CRISPR/Cas9 for the development of universal CAR-T cells. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Wang, Aftab, and Morgan with a reasonable expectation of success to develop a method for expanding CAR-T cells in vivo with IL-15 to improve their clinical efficacy, and wherein the CAR-T cells are allogenic and/or from a healthy donor, target CLL-1, and have knocked out TRAC and β2m expression to create a universal CAR-T cell.
8. Claims 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Wang in view of Aftab and Morgan as applied to claim 21 above, and further in view of Robinson and Schluns (2017) The potential and promise of IL-15 in immune-oncogenic therapies Immunology Letters (190) 159-168 (hereafter Robinson and Schluns) and Miyazaki et al. (2021) NKTR-255, a novel polymer conjugated rhIL-15 with potent antitumor efficacy Journal for ImmunoTherapy for Cancer (9) e002024 (hereafter Miyazaki).
Wang in view of Aftab and Morgan fails to teach the IL-15 as an agonist and further fails to teach the IL-15 agent being selected from a group consisting of a pegylated IL-15, an IL-15 fusion protein, and an IL-15 heterodimeric complex.
Robinson and Schluns, however, in regards to claims 27 and 28 teach the delivery of IL-15 by an IL-15 agonist including a fusion protein (pg.163 col 2, lines 51-52), and a heterodimeric complex (pg.163 col 2, lines 8-12) to increase IL-15 availability (pg.163 col 2, lines 4-6).
Robinson and Schluns fail to teach a pegylated IL-15 agent of claim 28 and 29, however Miyazaki teaches a pegylated IL-15 agent which retains receptor affinity, signaling, and leukocyte degranulation and had a longer half-life and reduced clearance (abstract).
Thus, Wang in view of Aftab and Morgan discloses a method to expand CAR cells targeting CLL-1 in vivo by administering IL-15, Robinson and Schluns teach the common IL-15 agonist administration methods of fusion proteins or heterodimeric complexes to increase IL-15 availability, and Miyazaki teaches the delivery of a pegylated IL-15 for enhanced half-life and decreased clearance. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Wang in view of Aftab and Morgan, with the teachings of Robinson and Schluns, and Miyazaki with a reasonable expectation of success to develop a method to expand CAR immune cells in vivo with IL-15 using known delivery methods, for increased availability, and/or increased half-life and decreased clearance.
Conclusion
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday - Thursday from 7am to 4pm and Fridays 7am to 11am.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647