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 .
Application Status
Claims 1-10 and 13 are pending and examined on the merits herein.
Claim Rejections - 35 USC § 102
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 1-7, 10, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Valamehr (WO 2021/071962 A1; published April 15, 2021; PTO-892).
Regarding claim 1, Valamehr teaches a chimeric antigen receptor comprising: an ectodomain comprising at least one antigen recognition domain; a transmembrane domain; and an endodomain comprising at least one signaling domain; wherein the chimeric antigen receptor, when comprised in an induced pluripotent stem cell (iPSC), promotes differentiation of the iPSC directed to a desired derivative effector cell, and wherein the iPSC-derived effector cell differentiated from the iPSC has at least one of the following characteristics comprising: (i) improved persistency and/or survival; (ii) improved cell expansion; (iii) increased cytotoxicity; (iv) increased resistance to allo-rejection; (v) improved tumor penetration; (vi) enhanced ability in migrating, and/or activating or recruiting bystander immune cells, to tumor sites; and (vii) enhanced ability to reduce tumor immunosuppression (claim 1), wherein the antigen recognition domain is specific to: NKG2D ligands (claim 14), wherein the chimeric antigen receptor is comprised in a bi-cistronic construct co-expressing a partial or full length peptide of a cell surface expressed exogenous cytokine or a receptor thereof, wherein the exogenous cytokine or receptor thereof comprises: IL18 (claim 16), a cell or a population thereof, wherein: (i) the cell is an immune cell, an induced pluripotent cell (iPSC), a clonal iPSC, or an iPS cell line cell; or the cell is a derivative effector cell obtained from differentiating the iPSC; and (ii) the cell comprises at least one chimeric antigen receptor (CAR) of any one of claims 1-18 (claim 19).
Regarding claims 2-3, Valamehr teaches wherein the derivative effector cell from iPSC differentiation comprises one or more of: a derivative CD34 cell, a derivative hematopoietic stem and progenitor cell, a derivative hematopoietic multipotent progenitor cell, a derivative T cell progenitor, a derivative NK cell progenitor, a derivative T cell, a derivative NKT cell, a derivative NK cell, a derivative B cell, or a derivative immune effector cell (claim 17).
Regarding claims 4 and 10, Valamehr teaches in some embodiments, the plasmid vectors are used for delivering and/or expressing the exogenous polynucleotides to target cells (para 000233).
Regarding claim 5, Valamehr teaches that to achieve lymphocyte autonomy without the need to additionally administer soluble cytokines, a partial or full peptide of IL18 is introduced to the cell to enable cytokine signaling with or without the expression of the cytokine itself, thereby maintaining or improving cell growth, proliferation, expansion, and/or effector function with reduced risk of cytokine toxicities (para 000169).
Regarding claims 6-7, Valamehr teaches wherein the cell further comprises one or more of: (viii) deletion or reduced expression of TCR (claim 21), wherein the CAR has been (viii) inserted at one of the following gene loci (claim 20).
Regarding claim 13, Valamehr teaches a method of treating a disease or a condition comprising administering to a subject in need thereof cells comprising the CAR of any one of claims 1-18 (claim 47), wherein administration of the cells results in one or more of: (i) reducing tumor cell surface shedding of MICA/B antigen; (ii) increasing tumor cell surface MICA/B density; (iii) preventing tumor antigen escape; (iv) overcoming tumor microenvironment suppression; (v) enhancing effector cell activation and killing function; and (vi) in vivo tumor progression control, tumor cell burden reduction, tumor clearance, and/or improving rate of survival; as compared to treatment using effector cells without the CAR of claim 1 (claim 49).
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.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Valamehr (WO 2021/071962 A1; published April 15, 2021; PTO-892) as applied to claims 1-7, 10, and 13 above, and further in view of Okamoto (Cancer Res. 2009 Dec 1;69(23):9003-11; PTO-892).
The teachings of Valamehr regarding claims 1-7 and 13 are detailed above.
Valamehr does not teach TCR signaling reduction through RNA interference.
Valamehr teaches the cell population further comprises an antigen specific TCR (claim 21), and that in some embodiments the antigen specific iPSC derivative hematopoietic effector cells are capable of rescuing tumor antigen escape (para 000262).
Okamoto teaches that adoptive T-cell therapy using lymphocytes genetically engineered to express tumor antigen-specific TCRs is an attractive strategy for treating patients with malignancies with drawbacks of TCR alpha/ beta mismatch with the endogenous TCR, or competition between endogenous and introduced TCR can result in impaired cell surface expression (abstract). Okamoto further teaches the development of retroviral vectors encoding small interfering RNA constructs that specifically down regulate the endogenous TCR and a codon optimized RNAi resistant TCR specific for a particular tumor antigen that after transduction resulted in high cell surface expression of the tumor specific TCR and reduced expression of endogenous TCRs (abstract). Okamoto further teaches the transduced cells demonstrated enhanced cytotoxicity against antigen expressing tumor cells (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application to knockdown expression of the TCR using RNAi while adding an antigen specific TCR as taught by Okamoto to the immune cells expressing a NKG2D-CAR with IL-18 as taught by Valamehr. The ordinary artisan would have been motivated to do so because Valamehr teaches the cell population further comprises an antigen specific TCR and that this can overcome tumor antigen escape. Okamoto teaches retroviral vectors encoding small interfering RNA constructs that specifically down regulate the endogenous TCR and a codon optimized RNAi resistant TCR specific for a particular tumor antigen that after transduction resulted in high cell surface expression of the tumor specific TCR and reduced expression of endogenous TCRs and enhanced cytotoxicity. The ordinary artisan has a reasonable expectation of success to use a lentiviral vector to use RNAi to knockdown the endogenous TCR and add an antigen specific TCR to overcome tumor antigen escape in combination with the NKG2D-CAR with IL-18 immune cells used to treat cancer.
The rationale to apply a technique taught by the prior art as improving the therapeutic and production characteristics of a similar construct is to predictably obtain an improvement to the second construct and is consistent with the exemplary rationales provided by the Supreme Court in KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1395-97 (2007) and discussed in M.P.E.P. § 2143. For these reasons, the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
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/AMBER K FAUST/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
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