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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 4/17/2026 is acknowledged.
Accordingly, claims 32, 34-41 are withdrawn from consideration for being directed to non-elected subject matter. Claims 1-31, 33 and 42 are currently under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/28/2023 and 11/11/2024 have been considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 23, 25 and 33 are objected to because of the following informalities:
Regarding claim 23, the recitation in b) and c), and e) and f) are redundant because “first” and “second” are arbitrarily assigned. As such, b and c, and e and f are same in scope.
Regarding claim 25, it is suggested to delete “a” in front of the “costimulatory ligand.”
Regarding claim 33, the claim is objected to for depending on a non-elected claim. It would be remedial to rewrite the claim to incorporate all limitation of claim 32 to this claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-31, 33 and 42 are rejected under 35 USC §101 because the claimed invention is directed to non-statutory subject matter. The term “cell” as defined by the specification at page 97 line 2-3 and 9-15 states that the cell is present or intended to be present in a human being, said cell becoming integrated into the human being and therefore being an inseparable part of the human itself. The scope of the claim, therefore, encompasses a human being, which is non-statutory subject matter. As such, the recitation of the limitation “non-human” would be remedial. See 1077 O.G. 24, April 21, 1987.
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 1-31,33 and 42 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.
Claim 1 recites the limitation "said T cell" in line 2. There is insufficient antecedent basis for this limitation in the claim because there is no prior recitation for a T cell. It is unclear whether it is the cell that comprises said antigen recognizing receptor, or another T cell that is being targeted. As such, the metes and bounds of the claim cannot be established.
Dependent claims 2-31, 33 and 42 are rejected for same reason because they depend on claim 1 but not remedy the infiniteness.
Claim 8 recites the limitation "the locus" in line 1. It is unclear whether the locus is referring to the antigen integrated locus or the CD70 locus.
Regarding claim 10, the phrase "e.g." in parenthesis renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
(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.
Claim(s) 1-8, 11, 18, 20, 28, 29, 30, 31, 33 and 42 is/are rejected under 35 U.S.C. 102(a1)(a2) as being anticipated by Terrett (WO2019/215500).
Claim 1 is interpreted as a T cell that comprises a first antigen recognizing receptor that targets a first antigen and wherein said receptor is integrated at a locus within the genome of said T cell; and a gene disruption of a CD70 locus in said cell.
Terrett teaches an engineered immune cells, e.g. a T cell, comprising a disruption in the CD70 gene, and a nucleic acid encoding a chimeric antigen receptor (CAR) (page 1, lines 22-24). Terrett teaches that the nucleic acid encoding the CAR is integrated at TRAC gene disruption site (page 1, line 29-30). The teaching from Terrett anticipates the claimed cell of claims 1, 4-6, 8, 18, 20 and 33.
Regarding claims 2-6, Terrett teaches that the gene disruption encompasses gene modification through gene editing to insert or delete one or more nucleotides, does not encode functional protein, a CD70 knockout cell (page 21, lines 29-35).
Regarding claim 7, Terrett teaches the T cell is CD3+, CD4+, CD8+ T cells (page 67, line 20).
Regarding claim 11, Terrett teaches the engineered T cell comprises a CD19 targeting CAR (page 59, lines 2-6), or CD70 targeting CAR (page 62, lines 15-19).
Regarding claim 28, Terrett teaches the engineered T cell further comprises a disruption of a B2M locus (page 95, line 11).
Regarding claim 29, Terrett teaches knockout of CD70 results in greater cell proliferation (page 101, lines 20-24).
Regarding claim 30, Terrett teaches the cell is allogeneic (page 101, line 20).
Regarding claim 31 and 42, “composition” and “kit” does not further limit the cell of claim 1 to any particular structure and/or function. As such, the teaching from Terrett anticipates both claim 31 and 42 for same reason as applied to claim 1.
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 (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 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.
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(s) 9, 10, 12-14, 17, 21, 22 and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Terrett, in view of Ahmed (US 2018/0085399).
The teaching from Terrett has been discussed above.
However, Terrett does not teach the CART cell comprises a second antigen-recognizing receptor that targets a second antigen.
Ahmed teaches immune cells such as cytotoxic T lymphocytes, natural killer cells, or natural killer T cells, comprises multiple chimeric antigen receptor (paragraph [0018], and paragraph [0013]). Ahmed teaches expressing at least two tumor specific antigen receptor in immune cells improves specificity of said immune cells, wherein cancer can recur upon targeting a single tumor antigen because of the emergence of an antigen-escape tumor cell population (paragraph [0044]).
It would have been obvious to an ordinary skilled in the art to modified the engineered CART cells taught by Terrett to further include a second antigen-targeting receptor to improve specificity of said cells based on the teaching from Ahmed. The ordinary skilled in the art would be motivated to include a second antigen targeting receptor because Ahmed teaches immune cells that comprises at least two (or more) antigen targeting receptor can prevent tumor escape cell population and improve targeting specificity. The ordinary skilled in the art would have reasonable expectation of success to make immune cells that comprises multiple CAR with CD70 knockout following combined teaching from Terrett and Ahmed. Therefore, the claimed invention of claims 9 and 21 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claims 10, 15 and 17, Terrett teaches the engineered T cell comprises a CD19 targeting CAR (page 59, lines 2-6), or CD70 targeting CAR (page 62, lines 15-19).
Regarding claims 12-14, it is known in prior art that CD70 is expressed AML, wherein AML cells are CD34+, and CD70 does not express in normal hematopoietic stem cell.
Regarding claim 22, Terrett teaches CARs comprises extracellular antigen binding domain and intracellular signaling domain (page 43, lines 11-22).
Regarding claim 23, Ahmed teaches that CARs may be expressed in a single vector, wherein an expression vector encodes one, two, three or more tumor antigen specific CARs (paragraph [0014]-[0015]). It would have been obvious to an ordinary skilled in the art that a vector that expresses both antigen recognizing receptors as taught by Ahmed may be integrated into TRAC site as taught by Terrett.
Claim(s) 9, 10, 12-17, 18, 19, 21 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Terrett, in view of Garrison (US 2021/0299177).
The teaching from Terrett has been discussed above.
However, Terrett does not teach the CART cell comprises a second antigen-recognizing receptor that targets a second antigen.
Garrison teaches isolated immunoresponsive cells comprising (1) a first chimeric receptor comprising an extracellular antigen binding domain that binds to first antigen: and (2) a second chimeric antigen receptor comprising an extracellular antigen-binding domain that binds to a second antigen, wherein each antigen is selected from FLT3, CD33…IL1RAP…and CD70, and wherein the first antigen is different from second antigen (paragraph [0005]). Garrison teaches that both IL1RAP and CD70 are AML antigen (paragraph [0336]). Garrison teaches that using AML antigens and combination of AML antigens suitable for use in chimeric receptors, including both chimeric TCRs or CARs increases efficacy and reduce off-tumor toxicity in the treatment of AML (paragraph [0334]).
It would have been obvious to an ordinary skilled in the art to modified the engineered CART cells taught by Terrett to further include a second antigen-targeting receptor based on the teaching from Garrison. The ordinary skilled in the art would be motivated to include a second antigen targeting receptor because Garrison teaches immune cells that comprises two (or more) antigen targeting receptors can prevent tumor increase efficacy and reduce off-tumor toxicity in treatment of AML. The ordinary skilled in the art would have reasonable expectation of success to make immune cells that comprises two CAR or TCR like fusion molecules with CD70 knockout following combined teaching from Terrett and Garrison. Therefore, the claimed invention of claims 9, 18, 19 and 21 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
Regarding claims 10, 15 and 17, Terrett teaches the engineered T cell comprises a CD19 targeting CAR (page 59, lines 2-6), or CD70 targeting CAR (page 62, lines 15-19).
Regarding claims 12-14, it is known in prior art that CD70 is expressed AML, wherein AML cells are CD34+, and CD70 does not express in normal hematopoietic stem cell.
Regarding claim 16, Garrison teaches both IL1RAP and CD70 are both AML antigen, wherein the first and second antigens may be this combination (paragraph [0336], and Table 1).
Regarding claim 22, Terrett teaches CARs comprises extracellular antigen binding domain and intracellular signaling domain (page 43, lines 11-22).
Claim(s) 24-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Terrett, in view of Sadelain (WO2021/016174).
The teaching from Terrett has been discussed above.
However, Terrett does not teach the engineered cell further comprises one exogenous costimulatory ligand or a fusion polypeptide comprising an extracellular domain and a transmembrane domain of a costimulatory ligand and an intracellular domain of a first costimulatory molecule.
Sadelain teaches compositions for enhancing immune responses toward tumor and pathogen antigens, which is a fusion polypeptide that can be expressed in CAR or TCR expressing cells, wherein the fusion polypeptide comprises extracellular domain of a transmembrane fusion of a co-stimulatory ligand, and an intracellular domain of a costimulatory molecule (abstract and Figure 1). Sadelain teaches that the costimulatory ligand is CD80 and the first costimulatory molecule is 4-1BB (page 3, lines 10-11). Sadelain teaches the fusion polypeptide is capable of stimulating a cell comprising an antigen recognizing receptor, enhancing the activity of said cell including cytotoxicity, cell proliferation, cell persistence, and combination thereof (page 3, lines 16-20).
It would have been obvious to an ordinary skilled in the art to further modified the cell taught by Terrett to include at least one exogenous costimulatory ligand comprises CD80/4-1BB fusion polypeptide based on teaching from Sadelain. The ordinary skilled in the art would be motivated to do so because Sadelain teaches such fusion polypeptide is capable of stimulating CAR-T cell proliferation and cell toxicity, which will make such cells more effective for immunotherapy. The ordinary skilled in the art would have reasonable expectation of success to generate an immune cell that comprises CAR-T and CD70 knockout and further include a fusion polypeptide encoding costimulatory molecule following combined teaching from Terrett and Sadelain. Therefore, the claimed invention of claims 24-27 would have been prima facie obvious to an ordinary skilled in the art at the time the application was filed.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/Primary Examiner, Art Unit 1637
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