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 .
Applicant’s election without traverse of Group I claims 1-2, 10, 32, 34, 40-42, 89-97, and 100-101 drawn to a CRISPR/Cas system in the reply filed on 04/14/2026 is acknowledged.
Claims 43, 103, 108, and 118 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/14/2026.
Priority
Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional Applications 63113785 and 63136953, filed on 11/13/2020 and 01/13/2021.
This application claims the benefit of priority to Patent Application PCT/US2021/059270. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/US2021/059270, filed on 11/12/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 06/20/2023, 09/25/2023, 11/20/2023, 03/07/2024, 05/08/2024, 07/18/2024, 09/19/2024, 12/10/2024, 02/26/2025, 05/06/2025, 07/03/2025, 09/29/2025, 11/18/2025, 02/20/2026, 04/16/2026, 06/02/2026, and 07/28/2026 have been considered by the Examiner.
Status of Claims
Claims 1-2, 10, 32, 34, 40-42, 89-97, and 100-101 are under examination.
Claims 43, 103, 108, and 118 are withdrawn.
Claims 3-9, 11-31, 33, 35-39, 44-88, 98-99, 102, 104-107, 109-117, and 119-127 are cancelled.
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.
Claims 1-2, 10, 32, 34, 40-42, 89-97, and 100-101 are rejected under 35 U.S.C. 103 as being unpatentable over Busser et al. (US 2020/0407694) in view of Ding et al. (The CRISPR Journal, 2019).
Regarding claim 1, Busser et al. teach improved cell immunotherapy utilizing cells engineered via CRISPR/Cas (cover page & page 7, abstract & paragraph 0094). Busser et al. teaches a guide RNA (gRNA) (page 7, paragraph 0090) targeting a gene or a regulatory element thereof in an immune cell (page 16, paragraph 0274).
Busser et al. does not teach a CRISPR/Cas fusion.
Ding et al. teach CRISPR-Cas9 fusion with chromatin modulating peptides. Ding et al. teach that modification of Streptococcus pyogenes Cas9 by fusion with chromatin-modulating peptides (CMPs), derived from high mobility group proteins HMGN1 and HMGB1, histone H1, and chromatin remodeling complexes, improves its activity by up to several fold (page 1, abstract).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the teachings of Busser et al. for improved cell immunotherapy utilizing cells engineered via CRISPR/Cas with the teachings of Ding et al. for a CRISPR-Cas9 fusion with chromatin modulating peptides. Ding et al. provide motivation by teaching that the fusion increases genome editing efficiency. One of skill in the art would have had a reasonable expectation of success at combining Busser et al. and Ding et al. because both teach genome editing with CRISPR/Cas.
Regarding claim 2, Busser et al. and Ding et al. make obvious a CRISPR/Cas system comprising a fusion protein. Busser et al. teach the gRNA is targeting B2M (cover page, Figure 1A).
Regarding claim 10, Busser et al. teach SEQ ID NO: 75 which includes targeting insertion at the B2M locus. Nucleotides 2099-2079 of SEQ ID NO:75 are the same as SEQ ID NO: 57.
Regarding claim 32, Busser et al. teach the gRNA is targeting B2M (cover page, Figure 1A). Ding et al. teach Cas9 by fusion with chromatin-modulating peptides (CMPs) and chromatin remodeling complexes. Therefore, the chromatin-modulating peptides can repress transcription activity.
Regarding claim 34, Busser et al. and Ding et al. make obvious a CRISPR/Cas system comprising a fusion protein. Busser et al. teach a preferred endogenous gene loci Tnfrsf21 transcription factor 3 pogo transposable element with KRAB (page 75, table 6).
Regarding claim 40, Busser et al. and Ding et al. make obvious an isolated polynucleotide encoding a CRISPR/Cas system.
Regarding claim 41, Busser et al. teach a vector (page 1, paragraph 0003). Busser et al. and Ding et al. make obvious a vector comprising an isolated polynucleotide encoding a CRISPR/Cas system.
Regarding claim 42, Busser et al teach engineered primary immune cells for their efficient use in cell therapy (page 1, paragraph 0003). Busser et al. and Ding et al. make obvious a vector comprising an isolated polynucleotide encoding a CRISPR/Cas system.
Regarding claim 89-90, 92, and 94-97, Busser et al. and Ding et al. make obvious delivery of CRISPR/Cas to cells to produce engineered cells for immunotherapy. Busser et al. teach improving the therapeutic potential of a nucleic acid able to direct or repress expression of other genes (page 8, paragraph 0116). Furthermore, the “a method of increasing or decreasing expression in a cell” recited in the preamble is an intended use. The claims do not recite limitations or active steps that reflect that intended use.
Regarding claim 91, Busser et al. teach improved cell immunotherapy utilizing cells engineered via CRISPR/Cas (cover page & page 7, abstract & paragraph 0094).
Regarding claim 93, Busser et al. teach a method of increasing an immune cell’s ability to kill cancer (page 3, paragraph 0020).
Regarding claim 100, Busser et al. teach improved cell immunotherapy utilizing cells engineered via CRISPR/Cas (cover page & page 7, abstract & paragraph 0094). Busser et al. and Ding et al. make obvious a cell modified by CRISPR/Cas.
Regarding claim 101, Busser et al. teach a method for preventing cytokine release syndrome (CRS) in immune cell therapy comprising administering engineered immune cells to a patient (page 195, claim 76). Busser et al. teach introduction of CRISPR/Cas to primary cells originating from patients as part of autologous treatment strategies (page 2, paragraph 0017). Therefore Busser et al. and Ding et al. make obvious a method of treating a subject having a disease by administering CRISPR/Cas to the subject.
Conclusion
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635
Prosecution Insights