DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to an amendment filed 7/7/2026.
Claims 128, 130-138, 141, 143-145, 148 and 151-153 are pending.
The instant application is a 371 filing of PCT/US2019/028858 filed 4/24/2019 which claims priority to provisional application 62/663,485 filed 4/27/2018. It is noted that SEQ ID NO:28 is the complement of the sequence provided in SEQ ID NO:12. Claims 138 and 145, drawn to introducing an HDM2 protein, lacks support in the provisional document and therefore have a priority date of 4/24/2019.
Response to Amendments
Applicants amendments are sufficient to overcome the previous rejections under 35 USC 112, second and fourth.
The amendments have not been sufficient to overcome the rejection under 35 USC 112, first as explained below.
Claims 139 and 142 indicated as free of the art have been incorporated into claim 128 and therefore have overcome the art.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 128, 130-138, 141, 143-145, 148 and 151-153 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This rejection is maintained for reasons below.
Claim 128 recites “culturing a cell to obtain a pre-stimulated cell”. The disclosure provides a single example of this in which CD34+ cells were grown in cell growth media comprising cytokines for 48 hours. The cytokines were limited to those in Table 1.
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As a second issue, the claims in part b are drawn to introducing Cas or a nucleic acid encoding thereof into a cell and a gRNA and a template polynucleotide comprising CD40LG cDNA. At issue is the recitation wherein Cas is capable of “cleaving a target locus in order to promoter insertion of a template polynucleotide within a first exon of a CD40LG gene in the cell genome” and “wherein the template polynucleotide is configured such that the cDNA is inserted downstream and operably linked to an endogenous CD40LG promoter”. These steps are specifically the result of a gRNA that has a sequence that specifically delivers the Cas to a target locus within a first exon of the CD40LG gene and for directional insertion, the template has homologous arms corresponding to the 5’ and the 3’ end of the nicked site such that the sequence is inserted i.e. downstream and linked to the endogenous CD40LG promoter. Claim 139 refers to the gRNA required and claim 142 to the homology arm that would make the claim fully described. Claim 148 indicates the gRNA necessary to direct Cas to the CD40LG gene but does not provide the requisite components for integration as required. However, claim 151 suffers from the same deficiencies noted for claim 128 part b.
Response to arguments
There are the following issues not resolved by the claims. First, claim 128 part a) recites that a cell is cultured to obtain a pre-stimulated cell. This is a goal without steps. Secondly, claim 128 part b) the claim similarly recites that the nuclease “is capable of cleaving a target locus in order to promote insertion”. Cleavage does not promote insertion. It promotes repair. Hence, this statement is a goal without a means of accomplishing it. It is noted that this is complicated by the lack of introduction of a template polynucleotide. The claim indicates that the template can be inserted but does not require one. If the claim were to be amended to require a template polynucleotide in the step of introducing, it states that the template is configured such that the cDNA is inserted downstream and linked to the CD40LG. This appears to be the consequence of “an arm of homology” wherein two arms are shown by the disclosure.
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Claim 148 also recites this “configuration” that is incomplete as does claim 151 which also requires the action of cleavage to insert the template.
The rejection can be overcome by inserting steps instead of recitation that the cells are pre-stimulated. This is a generic non-descriptive term with no recited outcome and no steps. Either of a goal or step would be sufficient to overcome this portion of the rejection. Secondly, the cleavage of the target locus does not lead to insertion but homology directed repair. This is particularly acute in claim 128 which does not require the template polynucleotide to be introduced. Hence, cleavage will not lead to promotion of the template. It is, even with the template, improperly recited. The nuclease introduces a double stranded break which promotes homology d4riven repair. In the presence of a donor template, insertion follows. But, the cleavage does not promote insertion. Finally, using the term configured in the claims means it is formulated so that cDNA is inserted downstream and linked to the CD40LG promoter. However, the claim only includes 1 arm. This can be corrected by indicated that there are a 5’ and a 3’ arm.
Conclusion
The instant claims vary from the art by requiring a gRNA with SEQ I DNO:28 or one related by 95% and an arm of homology with the sequence of SEQ ID NO:18 or 19 or a TALEN with the sequence of SEQ ID NO:11.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached 8 am - 5 pm.
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/MARIA MARVICH/Primary Examiner, Art Unit 1631
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