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
1. Claims 1, 12 are amended. Claims 2, 4, 6, 7, 9, 11, 13, 14, 16, 23-42, 45-49 are canceled. Claims 50-53 are withdrawn. Claims 1, 3, 5, 8, 10, 12, 15, 17-22, 43, 44 are under consideration.
2. Due to the new rejections below, this Action is a Non-Final Action.
Sequences
3. The submission of the updated Drawings containing SEQ ID NOs: is noted.
Specification
4. (previous objection, withdrawn) The disclosure was objected to because of informalities.
Applicant contends: amendments to the specification have been made.
In view of applicant’s amendments, the objection is withdrawn.
Claim Rejections - 35 USC § 112
5. (previous rejection, withdrawn) Claims 1, 3,5, 8, 10, 12, 14, 15, 17-22, 43, 44 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for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.
Applicant contends: claim 1 has been amended.
In view of applicant’s amendments, the rejection is withdrawn.
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.
6. (new, necessitated by amendment) Claim 8 is 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.
See claim 8 as submitted 9/17/2025.
Claim 8 recites “wherein the modification is obtained by administering antisense RNA” (elected species). It is not clear if the modification is obtained by “further” administering antisense RNA or if “antisense RNA” is intended to read upon the sgRNA already recited in amended claim 1 on which the claim already depends or what the relationship is.
Claim Rejections - 35 USC § 102/103
7. (previous rejection, withdrawn) Claims 1, 3, 5, 8, 10, 15, 17, 19, 20, 43, 44 were rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Conway et al. (US20180362926; previously cited).
Applicant contends: Conway et al. does not disclose sgRNA targeting exon of said TRAC as recited in claim 1.
In view of applicant’s amendments, the rejection is withdrawn.
8. (previous rejection, withdrawn) Claim 14 was rejected under 35 U.S.C. 103 as being unpatentable over Conway et al. as applied to claims 1, 3, 5, 8, 10, 15, 17, 19, 20, 43, 44 above, and further in view of Sather et al. (WO2017193107A2; previously cited).
In view of the withdrawal of the rejection over Conway et al. on which the instant rejection depends, the instant rejection is also withdrawn.
9. (previous rejection, withdrawn) Claims 21, 22 were rejected under 35 U.S.C. 103 as being unpatentable over Conway et al. as applied to claims 1, 3, 5, 8, 10, 15, 17, 19, 20, 43, 44 above, and further in view of Kim et al. (WO2015095410)(See PTO-892: Notice of References Cited).
In view of the withdrawal of the rejection over Conway et al. on which the instant rejection depends, the instant rejection is also withdrawn.
Claim Rejections - 35 USC § 103
10. (previous rejection, withdrawn) Claim 12 was rejected under 35 U.S.C. 103 as being unpatentable over Conway et al. as applied to claims 1, 3, 5, 8, 10, 15, 17, 19, 20, 43, 44 above, and further in view of Yuan et al. (WO2019052577; previously cited)(See also the WIPO English translation of WO2019052577; previously cited) and Hotta et al. (WO2019160077; previously cited)(See also the WIPO English translation of WO2019160077; previously cited).
Applicant contends: SEQ ID NO: 118 in Yuan is not an sgRNA; not any sgRNA is capable of successfully knocking out the target gene.
In view of the withdrawal of the rejection over Conway et al. on which the instant rejection depends, the instant rejection is also withdrawn.
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.
11. (new rejection) Claims 1, 3, 5, 8, 10, 15, 17-20, 43, 44 are rejected under 35 U.S.C. 103 as being unpatentable over (US20180362926; previously cited) in view of Welstead et al. (WO2015161276A2)(See PTO-892: Notice of References Cited).
See claims 1, 3, 5, 8, 10, 15, 17-20, 43, 44 as submitted 9/17/2025.
See also the 35 U.S.C. 112(b) rejection above.
Conway et al. teaches: cells for use in adoptive T cell therapy [0016]; cells in which expression of a TCR gene is modulated by modification of exonic sequences of the TCR gene [0018]; cleaving or downregulating endogenous TCR and/or B2M gene in an isolated cell [0028]; wherein inactivation is achieved via targeted cleavage of the TRAC [0028 ](as recited in claims 1, 3); in some embodiments B2M gene is cleaved [0028](implying in other embodiments, presence of B2M gene; wherein B2M gene is not cleaved/inactivated)(as recited in claims 1, 3); modification of an HLA-A gene (indicating presence of HLA-A gene; possible modifications include deletions [0017]; modifications include insertions, deletions [0017])(as recited in claims 1, 3)(wherein such modifications read on down-regulation); modification of CIITA (indicating presence of CIITA gene, including not down-regulated )[0023](as recited in claims 1, 3).
Conway et al. also teaches: T cell [0027](as recited in claim 5); sgRNA [0210](as recited in claims 8 (wherein sgRNA is interpreted as reading on antisense RNA), 10); CRISPR/Cas system including sgRNA [0118](as recited in claim 15); CAR molecules [0179]; including chimeric antigen receptors [0050](as recited in claim 17); wherein T cells can be manipulated to increase avidity for tumor antigens [0190](as recited in claim 18); targeting CD19 [0012](as recited in claim 19); wherein TCR comprises antibody [0034](interpreted as reading upon including antigen binding fragment as recited in claim 20); composition [0015](as recited in claim 43); T cell populations [0007](as recited in claim 44).
Conway et al. does not teach wherein said sgRNA targeting the exon of said TRAC is shown in SEQ ID NO:1.
Welstead et al. teaches guide RNA molecule comprising targeting domain; wherein targeting domain is complementary with a target domain of T-cell expressed gene (TRAC); nucleotide sequence of targeting domain which is used for knocking out TRAC gene; SEQ ID NO: 49364, which has 100% identity with instant SEQ ID NO: 1 (See Result 5 of STIC Sequence Search Result 20251215_143317_us-17-563-804b-1.szlim22.rng in Supplemental Content Tab).
One of ordinary skill in the art would have been motivated to use sgRNA as taught by Welstead et al. as sgRNA as taught by Conway et al. Conway et al. already teaches targeted cleavage of TRAC, and Welstead et al., which also teaches targeting and knocking out TRAC, teaches such a sgRNA used for targeting and knocking out TRAC (See MPEP 2144.06: Substituting equivalents known for the same purpose).
One of ordinary skill in the art would have had a reasonable expectation of success for
using sgRNA as taught by Welstead et al. as the sgRNA as taught by Conway et al. There would have been a reasonable expectation of success given the underlying materials (sgRNA for targeting TRAC as taught by Conway et al. and Welstead et al.) and methods (gene knockout as taught by Conway et al. and Welstead et al.) are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
12. (new rejection) Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Conway et al. in view of Welstead et al. as applied to claims 1, 3, 5, 8, 10, 15, 17-20, 43, 44 above, and further in view of Hotta et al. (WO2019160077; previously cited)(See also the WIPO English translation of WO2019160077; previously cited).
See claim 12 as submitted 9/17/2025.
Conway et al. in view of Welstead et al. does not teach: wherein the sgRNA targeting the exon of the HLA-A gene comprises a nucleotide sequence shown in any one of SEQ ID No. 17-18 and 91-92.
Hotta et al. teaches: known HLA alleles and cell therapy; sgRNA sequence SEQ ID NO: 3180, which comprises fragment with 100% identity with instant SEQ ID NO: 17
(See Result 11 in STIC Sequence Search Result 20250604_183635_us-17-563-804-17.rng in Supplemental Content Tab); as well as sgRNA sequence SEQ ID NO: 2131, which comprises
fragment with 100% identity with instant SEQ ID NO: 18 (See Result 9 in STIC
Sequence Search Result 20250604_183635_us-17-563-804-18.rng in Supplemental
Content Tab).
One of ordinary skill in the art would have been motivated to use sgRNAs as taught by Hotta et al. with the cell as taught by Conway et al. in view of Welstead et al. Conway et al. in view of Welstead et al. teaches use of sgRNA and modification of HLA-A sequences, and Hotta et al. teaches such sgRNA sequences already known and used in the art (See MPEP 2144.06: Substituting equivalents known for the same purpose).
One of ordinary skill in the art would have had a reasonable expectation of success for using sgRNAs as taught by Hotta et al. with the cell as taught by Conway et al. in view of Welstead et al. There would have been a reasonable expectation of success given the underlying materials (HLA genes as taught by Conway et al. in view of Welstead et al. and Hotta et al.) and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
13. (new rejection) Claims 21, 22 are rejected under 35 U.S.C. 103 as being unpatentable over Conway et al. in view of Welstead et al. as applied to claims 1, 3, 5, 8, 10, 15, 17-20, 43, 44 above, and further in view of Kim et al. (WO2015095410; previously cited).
See claims 21, 22 as submitted 12/28/2021.
See the teachings of Conway et al. in view of Welstead et al. above. It is noted that Conway et al. teaches adoptive cell therapy for treatment and/or prevention of a cancer [0190].
Conway et al. in view of Welstead et al. does not teach: B cell lymphoma; nonsolid tumor.
Kim et al. teaches: cancers already known in the art, including B-cell lymphoma [0018]; non-solid tumor [0018].
One of ordinary skill in the art would have been motivated to target tumor as taught by Kim et al. with the cell as taught by Conway et al. in view of Welstead et al. Conway et al. in view of Welstead et al. teaches targeting tumors, and Kim et al. teaches such tumors known in the art (See MPEP 2144.06: Substituting equivalents known for the same purpose)
One of ordinary skill in the art would have had a reasonable expectation of success for targeting tumor as taught by Kim et al. with the cell as taught by Conway et al. in view of Welstead et al. There would have been a reasonable expectation of success given the underlying materials and methods (cancer treatment as taught by Kim et al. and Conway et al. in view of Welstead et al.) are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
14. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to M FRANCO G SALVOZA whose telephone number is (571)272-4468. The examiner can normally be reached M-F 8:00 to 5:00.
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/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672