DETAILED ACTION
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 .
Status of Application/Restriction/Claims
Applicant’s election without traverse of Group I (claims 1-7, 9-10, 15, 19-20, 22, 24 and 27) in the reply filed on 10/1/2025 is acknowledged.
Claims 33, 41, 49 and 50 have been canceled. Claims 1-7, 9-10, 15, 19-20, 22, 24 and 27 are pending and are the subject of the present Official action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 63/014,382 and 371 of PCT/US2021/028437 filed on 4/23/2020 and 4/21/2021, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 4/23/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/20/2022 and 4/29/2024 were received. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement was considered by the examiner.
Claim Interpretation
Claims 6 describes one or more costimulatory domains and “optionally” CD3zeta. It is emphasized that claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure, see MPEP 2111.04.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 6-7, 9-10, 15, 19, 22, 24 and 27 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zhang Hongling et al. CN 109957020, Machine Translation, published 7/2/2019 (hereinafter Zhang, cited in applicants IDS).
Claim 1: Zhang describes an engineered CAR T cell that specifically targets and kills malignant tumor cells that express TRAIL-R2, also known as Death Receptor 5 (DR5), on their surface while minimizing harm to normal cells which express low levels of DR5 (Zhang, para 4, 36). Zhang discloses a single-chain antibody (scFv) that binds to DR5 which is incorporated into the extracellular region of the CAR protein which is expressed on the surface of the T cell (Zhang, para 11-15). Zhang discloses an intracellular signaling region that is not from DR5 but includes a CD28 signaling region to provide a co-stimulatory signal and a CD3 zeta signal region to provide the primary T cell activation signal (Zhang, para 25-30).
Claims 2-3: Zhang discloses a single-chain monoclonal antibody (scFv) that binds to DR5 which is incorporated into the extracellular region of the CAR protein which is expressed on the surface of the T cell (Zhang, para 11-15).
Claims 6-7 and 9-10: Zhang discloses an intracellular signaling region that includes a CD28 signaling region to provide a co-stimulatory signal and a CD3 zeta signal region to provide the primary T cell activation signal (Zhang, para 25-30). Zhang describes a CD8 transmembrane domain (Zhang, para 83). Zhang describes a scFv that binds to DR5 and a intracellular region that comprises a costimulatory domain from 4-1BB (Zhang, para 11, 25).
Claims 15, 19, 22, 24 and 27: Zhang discloses an engineered CAR T cell that expresses the CAR targeting DR5. As explained by Zhang, DR5 is widely expressed in various solid tumor cells such as liver cancer but is expressed as a weak cell surface antigen in ordinary cells (Zhang, para 4).
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 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.
Claims 1-7, 9-10, 15, 19-20, 22, 24 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. CN 109957020, Machine Translation, published 7/2/2019 (hereinafter Zhang, cited in applicants IDS) in view of Murad et al. "Advances in the use of natural receptor-or ligand-based chimeric antigen receptors (CARs) in haematologic malignancies." Best Practice & Research Clinical Haematology 31.2 (2018): 176-183 (hereinafter Murad).
A description of Zhang can be found above with respect to 1-3, 6-7, 9-10, 15, 19, 22, 24 and 27.
Claims 4-5: Zhang does not describe the TRAIL-R2 (DR5) binding agent as a ligand or TRAIL ligand. Instead of using the TRAIL ligand as the targeting mechanism, Zhang focuses on using a scFc as the DR5 binding component to achieve specificity. However, Zhang mentions that TRAIL is the naturally occurring ligand that binds to DR5 (Zhang, para 4).
Claim 20: Zhang describes isolating antigen-specific T lymphocytes by immunomagnetic bead method, wherein CD3-possitive T lymphocytes were isolated and transfected with the DR5 specific CAR. Although it is admitted that Zhang does not expressly state that the cells are 𝛼𝛽 T cells, the vast majority of CD3 positive T cells would be 𝛼𝛽 T cells which express the 𝛼𝛽 T cell receptor (TCR) along with the CD3 complex. Furthermore, the genus of T cell subtypes is sufficiently small that 𝛼𝛽 T cells
Would be considered immediately envisagable. A generic disclosure will anticipate a claimed species covered by that disclosure when the species can be “at once envisaged” from the disclosure, such is the case presently, see MPEP § 2131.02.
Claims 4-5: Murad describes the use of ligand-based CARs as an alternative to scFv derived CAR T cell therapy (Murad, abstract and Fig 1). Murad offers several advantages that ligand-based CARs have over scFv derived CAR T cells including reduced immunogenicity, structural stability and broad targeting (Murad, pg 177). Murad also discloses predictable methods for generating ligand-based CARs (Murad, pg 179).
It would have been prima facie obvious to one of ordinary skill in the art to use a TRAIL ligand-based CAR as described by Murad rather than the scFv derived CAR in the extracellular region of the chimeric protein. It would have been a matter of simple substitution of one known extracellular targeting domain for another with predictable results given the methods disclosed by Murad. One would have been motivated to make this substitution given that ligand-based CARs often exhibit reduced immunogenicity, structural stability and broad targeting when compared to scFv derived CAR T cells (Murad, pg 177). One would have a reasonable expectation of success given that Zhang discloses that TRAIL is the naturally occurring ligand that binds to DR5 (Zhang, para 4) and that there are predictable methods for generating ligand-based CARs (Murad, pg 179). Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the invention to have been prima facie obvious to at the time the invention was made.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dr. ALEXANDER NICOL whose telephone number is (571)272-6383. The examiner can normally be reached on M-F 8-5 EST.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634