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 1,17-23,25-28,33-35,37 and 39-40 in the reply filed on 02/12/2026 is acknowledged.
Claims 15 and 16 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.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 02/12/2026.
Priority
Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional Application 63071993, filed on 08/28/2020.
This application claims the benefit of priority to Patent Application PCT/US2021/047964. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/US2021/047964, filed on 08/27/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 09/29/2023 have been considered by the Examiner.
Status of Claims
Claims 1,17-23,25-28,33-35,37 and 39-40 are under examination.
Claims 15 and 16 are withdrawn.
Claim 2-14, 24, 29-32, 36, 38, and 41 are cancelled.
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.
Claims 1,17-23,25-28,33-35,37 and 39-40 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bolen et al. (US 11,389,485 B2) as evidenced by Cotta-Ramusino (US 2019/0136210 A1)
Regarding claim 1, Bolen et al. teach the guide RNAs (gRNAs) direct binding of the Cas enzyme-gRNA complexes to a pre-determined target site in a genome (column 60, lines 35-44). Bolen et al. teach the target gene is CD123 where gRNA19 is utilized, which is represented by SEQ ID NO:135 (column 141, lines 40-50). SEQ ID NO: 135 of Bolen et al. is the same as SEQ ID NO: 27 of the present application.
Regarding claim 17, Bolen et al. teach the gRNA is an sgRNA (column 123, lines 36-40). A single guide RNA contains a first complementarity domain, a linking domain, a second complementarity domain and a proximal domain as evidenced by Cotta-Ramusino (page 18, paragraphs 0216-0221).
Regarding claim 18, Bolen et al. teach the gRNA is an sgRNA (column 123, lines 36-40).
Regarding claim 19, Bolen et al. teach modified nucleotides contained 2'-O-methyl-3' phosphorothioate nucleotides (column 123, lines 46-47).
Regarding claim 20, Bolen et al. teach phosphorothioate backbone modification, 2'-O-Me-modified sugars at one or both of the 3' and 5' termini, 2'F-modified sugar, replacement of the ribose sugar with the bicyclic nucleotide-cEt, 3'thioPACE, or any combination thereof (column 72, lines 50-55).
Regarding claim 21, Bolen et al. teach a population of genetically engineered hematopoietic cells, wherein the hematopoietic cells are hematopoietic stem cells (HSCs) (column 22, lines 40-42). (ii) Bolen et al. teach introducing gRNA and a Cas molecule into the cell (column 59, lines 25-34). Bolen et al. teach the cell is a hematopoietic stem or progenitor cell (column 20, lines 1-3).
Regarding claim 22, Bolen et al. teach the Cas molecule comprises an SpCas9 endonuclease, a SaCas9 endonuclease, or a Cpf1 endonuclease (column 62, lines 10-15 and 62-65).
Regarding claim 23, Bolen et al. teach the gRNA and Cas molecule are introduced as complexes (column 70, lines 35-39). Bolen et al. teach the complexes are introduced via electroporation (column 71, lines 60-60).
Regarding claim 25, Bolen et al. teach a population of genetically engineered hematopoietic cells (column 17, lines 54-55).
Regarding claim 26, Bolen et al. teach a population of genetically engineered hematopoietic cells, wherein the hematopoietic cells are hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPSCs) (column 20, lines 1-3).
Regarding claim 27, Bolen et al. teach administration of the engineered donor bone marrow to a patient and allowing for successful engraftment (column 138, lines 9-10). Bolen et al. teach the primary endpoint is percent engraftment, which can be assessed by genotyping and flow cytometric analysis (column 129, lines 46-49). Bolen et al. further teach characterization of HSC differentiation (cell lineages) of engrafted engineered HSCs (column 129, lines 10-12). Bolen et al. teach the edited HSCs showed efficient engraftment in the NSG mice at week 4, 9 and 12 at levels substantially the same as the control HSC cells (column 129, lines 54-57)
Regarding claim 28, Bolen et al. teach the primary endpoint is percent engraftment within of the recipient (column 129, lines 44-46). Bolen et al. teach the edited HSCs expressing showed efficient engraftment in the NSG mice at week 4, 9 and 12 at levels substantially the same as the control HSC cells (column 129, lines 54-57). Bolen et al. do not report the efficiency of the bone marrow engraftment; however the engraftment of the peripheral blood is at or above controls it can be expected that the bone marrow would also be efficiently replaced.
Regarding claim 33, Bolen et al. teach the hematopoietic cells comprising a deletion or mutation of a non-essential epitope of a lineage-specific cell-surface antigen. Bolen et al. teach the hematopoietic cells are able to proliferate and/or undergo erythropoietic differentiation to a similar level as hematopoietic cells that express a wild-type lineage-specific cell-surface antigen (column 55, lines 32-37).
Regarding claim 34, Bolen et al. teach various engineered hematopoietic cells two examples which contain non-engineered CD123 genes have modified cell surface antigens which are CD19 and CD33 or CD33 and CLL-1 (column 233, claim 1).
Regarding claim 35, Bolen et al. teach the cell that is "negative" for a given lineage-specific cell-surface antigen has reduced expression level of the lineage-specific antigen as compared with its naturally-occurring counterpart. Bolen et al. teach a cell that is negative for the lineage-specific cell-surface antigen has a level of less than 10%, 5%, 2%, or 1 % of as compared with its naturally-occurring counterpart (column 54, lines 27-36), which reads on expresses less than 20% of the CD123 expressed by a wild-type counterpart cell population.
Regarding claim 37, Bolen et al. teach to reduce or avoid relapse of a hematopoietic malignancy they target more than one antigen (column 120, lines 50-53). Bolen et al. teach the genetically engineered hematopoietic cells ( e.g., HSCs) have one or more genes of antigens for expression of the proteins in mutated forms (column 39, lines 30-33). Bolen et al. teach In some embodiments, one or both of the lineage-specific cell surface proteins are chosen from CD33, CD123, and CLLl (column 43, lines 17-18).
Regarding claim 39, Bolen et al. teach administering to the subject a population of genetically engineered hematopoietic cells (column 119, lines 49-52).
Regarding claim 40, Bolen et al. teach the HSCs are obtained from a human patient, such as a human patient with a hematopoietic malignancy (column 56, lines 31-33).
Conclusion
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635
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