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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/13/2025 has been entered.
Claims 103-104, 108-114, 128-131, 133-153 are pending.
Claims 136-153 are withdrawn
Claims 103-104, 108-114, 128-131, and 133-135 are examined.
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 103-104, 108-114, 128-131 and 133-135 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 103 recites “a new mutation”, it is unclear if the mutation is new to the organism or new to the art. In either case, the limitation of “a new mutation” would appear to be to be redundant since a mutation is defined as being different or new from that which came before.
In claim 128 in line 3 “in sequence” is indefinite because it is unclear if “in sequence” is referring to sequentially generating or it refers to the sequence of the target gene. If it is referring to “sequentially generating” then it is redundant.
In claim 128, in line 3 “generating certain editing events” would appear to fall outside of the scope of what the specification has set forth as the invention. The phrase “generating certain editing events” is followed by the phrase “after the specific site of the first target gene is sequentially cut and repaired”. It would appear that “certain editing events” are in addition to the mutation made by the “sequentially cut and repaired” and unrelated to the “sequentially cut and repaired”. In addition, it since “certain editing events” are not defined by the claim it is unclear what a certain event would be.
In claim 128 in section 3) third line “screening an editing event of the second target gene synchronously through the screening of the selectable trait generated by mutations of the first target gene” is unclear because it appears there is no defined selection for the editing events of the at least one second target gene. In addition, there is no definition in the specification or embodiement that would explain synchronicity between the first and second traits.
Claim 128 is indefinite for reciting in the optionally section in the last 5 lines of claim 128 a wherein clause, which appears to be optional. It is not clear if the wherein clause is optional or not. Appropriate correction is required.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 129 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In line 2 of claim 129 the first target gene now encodes at least one phenotypic trait, whereas in claim 128 it was just a phenotypic trait. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claims 104, 108, 109 and 131 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 104 and 131 recite that the DNA break is achieved by delivering “a nuclease with a targeting property into a cell of the organism” which is broader that the CRISPR/Cas system recited in the optionally portion of claim 128. CRISPR/Cas nucleases have art defined features and capabilities. Whereas any nuclease with targeting property would encompass nucleases or base editors that different specificities and mechanisms of activity from a CRISPR/Cas system.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 134 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. In claim 134 if the nuclease are different from each other as recited in the last line of claim 134 then claim 134 fails to further limit claim 128 because in claim 134 if they are different then the second nuclease is not a CRISPR/Cas nuclease and may have a different activity as presented supra. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 103-104, 108-109, and 111-114 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Perli, S. et al., Science (2016) Vol.353, issue 6304; pp. 1-11.
The claims are broadly drawn to a method of generating a new mutation in an organism by generating sequentially two or more breaks at a specific site in the genome of the organism wherein a later DNA break is generated based upon a new sequence generated from a previous DNA break repair; wherein each DNA break is generated by a CRISPR/Cas system comprising a target RNA, and the later DNA break is generated by the CRISPR/Cas system comprising the target RNA targeting the new sequence generated from the previous DNA break repair at the specific site; wherein no exogenous DNA repair template is introduced into the organism (claim 103); wherein the break is achieved by delivering a nuclease (e.g. Cas9) with targeting property (e.g. gRNA) into a cell of the organism (claim 104); wherein the two or more breaks are generated by sequentially delivering different targeted nucleases (interpreted as differentially targeted nucleases where the difference is found in the gRNA portion) (claim 108); wherein the targets are different (claim 109); wherein the targeted nuclease is any CRISPR/Cas nuclease (claim 111); wherein the targeted nuclease is in the form of DNA (claim 112); wherein the targeted nuclease is in the form of DNA, RNA, or protein (claim 113); and wherein the targeted nuclease is delivered into the cell by PEG transfection, liposome transfection, electroporation, microinjection, gene gun bombardment, or Agrobacterium transformation (claim 114).
Although claim 103 recites “an organism” there is no regeneration of any organism in the rejected claims and there are no method steps directing “an organism” in any of the method steps. The claims only recite manipulation of cells; and are thus interpreted as being limited to a method of generating a mutation in a cell.
Perli teaches a HEK 293 T cell line transformed with a coding sequence for a NF-kB-induced Cas9 expression cassette and transfection with lentiviral particles coding for a self-targeting gRNA coding region for Cas9-stgRNA guided DNA cleavage/NHEJ; wherein the gRNA is self-targeting; following NHEJ generation of a mutation in the original gRNA coding sequence and subsequent transcription of the mutant gRNA and targeting of the mutated gRNA nucleotide sequence by the mutant gRNA-cas9, which is iterative; and thus teaches the limitations of claims 103-104, 108-109, 111-114 (see figure 1A and on page aag0511-7 in right column first full paragraph).
All claims are rejected.
Response to Arguments
Applicant’s arguments with respect to independent claim(s) 103, 118, 123, 125, 126, and 128 have been considered but are moot because the new ground of rejection does not rely only on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. In particular, the originally examined claims were broad and failed to recite the lack of a repair template and the rejection has been modified to include the added limitations.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUSSELL KALLIS whose telephone number is (571)272-0798. The examiner can normally be reached Monday-Friday 8AM-5PM.
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/RUSSELL KALLIS/Primary Examiner, Art Unit 1663