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 cancellation of claims 6-9, in the paper of 4/8/2025, is acknowledged. Claims 1-23 are still at issue and are present for examination.
Election/Restrictions
Applicant's election without traverse of the invention of Group 1, claims 1-4, 11, 13, and 23, drawn to a CRISPR-dCas protein and species (ii) i.e. ncRNA, in the paper of 1/26/2026, is acknowledged.
Claims 5-10, 12, 14-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper."
Applicants filing of information disclosure statements on 7/5/2023 and 11/27/2024 are acknowledged and have been considered.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: CRISPR-dCas/Cas protein derivative
Claim Objections
Claim 3 is objected to because of the following informalities:
Claim 3 is awkward in the recitation “wherein the N domain comprises 164 amino acids in a part of an amino acid sequence on the N-terminal side of the helix region of Cas13a”. It is suggested this be made clearer such as “wherein the N domain comprises 164 amino acids of a part of an amino acid sequence on the N-terminal side of the helix region of Cas13a”.
Claim 3 is awkward in the recitation “the C domain comprises 1003 amino acids in a part of an amino acid sequence on the C-terminal side of the helix region of Cas13a”. It is suggested this be made clearer such as “the C domain comprises 1003 amino acids of a part of an amino acid sequence on the C-terminal side of the helix region of Cas13a”.
Appropriate correction and/or comment is required.
Specification
The disclosure is objected to because of the following informalities:
Applicants specification is objected to because applicants specification comprises Nucleotide and/or Amino Acids Disclosures Requiring a "Sequence Listing".
Applicants attention is directed to 37 CFR 1.821(a) which presents a definition for "nucleotide and/or amino acid sequences." This definition sets forth limits, in terms of numbers of amino acids and/or numbers of nucleotides, at or above which compliance with the sequence rules is required. Nucleotide and/or amino acid sequences as used in 37 CFR 1.821 through 37 CFR 1.825 are interpreted to mean an unbranched sequence of four or more amino acids or an unbranched sequence of ten or more nucleotides.
Specifically applicants specification at Figure 27B, 28B, 28C, 28D, 29B, 29C, 30, 32 lists nucleotide sequences which require a sequence identifier and are to be included in applicants sequence listing as per 37 CFR 1.821 through 37 CFR 1.825.
Further applicants are required to include a sequence identifier in any figure which comprises a Nucleotide and/or amino acid sequences or in the description of said figure.
Appropriate correction is required.
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.
Claim 1-4, 11, 13, and 23 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 1 (claims 2-4, 11, 13, and 23 dependent on) is indefinite in the recitation “the CRISPR-dCas/Cas protein derivative or CRISPR-dCas/Cas protein derivative set comprising an N domain…” in the reference to “or” and thus the derivative “or” the derivative set comprise an N domain, not necessarily both. As such the recitation “an N domain containing the N-terminal side of the helix region …. and the C domain being linked to the second factor,” applies to the derivative or the derivative set in the alternative (i.e. not both the derivative and the derivative set). In the interest of advancing prosecution the claim is given its broadest reasonable interpretation and interpreted in the alternative that either the derivative or the derivative set comprises “an N domain containing the N-terminal side of the helix region …. and the C domain being linked to the second factor,”
Claim 3 is indefinite in the recitation “the helix region of Cas13a derived from Leptotrichia wadei (Sequence ID: WP_21746774.1)” in the reference to “(Sequence ID: WP_21746774.1)”. It is unclear as to applicants intent in the recitation. Is it applicants intent to reference an amino acid sequence? If so, it is unclear as to what amino acid sequence applicants are attempting to reference. Further it is noted that if it is applicants intent to reference an amino acid sequence, this would be considered “essential material” (see MPEP § 608.01(p)) and treated as such.
Claim 4 is indefinite in the recitation “nMAG or pMAG” as it is unclear as to what “nMAG” and “pMAG” are and what is encompassed by the terms. Applicants specification does not define or reference nMAG or pMAG beyond their mere recitation. In the interest of advancing prosecution the examiner is interpreting nMAG and pMAG as the photoswitchable proteins nMag and pMag taught by Chen and Wegner (Bioprotocol, Vol 8, Iss. 12, June 20, 2018, DOI:10.21769/BioProtoc.2893).
Appropriate correction and/or comment is required.
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.
Claim(s) 1, 2, 11, 13 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by The Broad Institute Inc (WO 2017/219027).
The Broad Institute Inc (WO 2017/219027) discloses "a non-naturally occurring or engineered composition comprising a C2c2 effector protein fused to one or more nuclear localization signals (NLS) or nuclear export signals (NES), wherein at least the one or more nucleic acid components is engineered, and the aforementioned one or more nucleic acid components directs the complex to a mammalian target of interest, and the aforementioned effector protein forms a complex with the aforementioned one or more nucleic acid components, and the complex binds to a target locus of interest (including noncoding RNAs)," and the Broad Institute Inc (WO 2017/219027) further states that C2c2 may be the C2c2 from Leptotrichia wadei strain F0279. Moreover, the Broad Institute Inc (WO 2017/219027) states the following: that the effector protein may be a split version of the RNA targeting effector protein, and the split should always be so that one or a plurality of catalytic domains are unaffected; that the RNA binding protein may be a dead-C2c2, which is essentially an RNA-binding protein with very little or no catalytic activity, due to one or a plurality of mutations in the catalytic domain thereof; that each half of the split C2c2 may be fused to a dimerization partner, and the use of a rapamycin-sensitive dimerization domain, for example, allows the generation of a chemically inducible split of C2c2 for temporal control of C2c2 activity; and that in such a case, the C-terminus of the N' terminal part of the split C2c2 is fused to one of the dimer halves, while the N' terminus of the C terminal part is fused to the other dimer half.
In this case, because the C2c2 described in the Broad Institute Inc (WO 2017/219027) is a protein corresponding to Cas 13a set forth in the description of the present application, it is clear that the Broad Institute Inc (WO 2017/219027) describes a CRISPR-Cas protein that has the "helix domain" set forth in the invention of the present application.
While the Broad Institute Inc (WO 2017/219027) does not state that the CRISPR-Cas protein is split into an N domain and a C domain within the "helix domain”, this is not a required limitation of the claimed CRISPR-dCas/Cas protein derivative by virtue of the specific language used by applicants (see also above rejection under 112(b)). The Broad Institute Inc (WO 2017/219027) disclose that the split Cas effector protein comprise an N domain containing the N-terminal side of the helix region of the CRISPR-dCas (dead Cas) protein or the CRISPR-Cas protein, a C domain containing the C-terminal side of the helix region of the CRISPR-dCas (dead Cas) protein or the CRISPR-Cas protein, and first and second factors capable of binding in response to stimulation, the N domain being linked to the first factor, and the C domain being linked to the second factor.
Thus, claim(s) 1, 2, 11, 13 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by The Broad Institute Inc (WO 2017/219027).
Claim(s) 1, 2, 4, 11, 13 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nihongaki et al. (Nature Biotechnology, Vol 33, No 7, pp 755-762, 2015).
Nihongaki et al. disclose the design, creation and use of a photoactivatable CRISPR-Cas9 for optogenetic genome editing. Nihongaki et al. disclose an engineered photoactivatable Cas9 (paCas9) that consists of split Cas9 fragments and photoinducible dimerization domains named magnets (page 756, Figure 1 and supporting text and page 761 Inducible Cas9 constructions.). Thus Nihongaki et al. teach CRISPR-dCas/Cas protein derivative derived from a CRISPR-Cas protein, the CRISPR-Cas protein having a helix region, being capable of forming a complex with a guide RNA and a target RNA, and having a nuclease activity, the CRISPR-dCas/Cas protein derivative having the first and second factors being bound via a linker containing a protease recognition sequence or via a linker containing a self-cleaving peptide, or being non-covalently bound, the CRISPR-dCas/Cas protein derivative having a structure of (N domain)-(first factor)-(non-covalent bond)-(second factor)-(C domain). Nihongaki et al. further disclose the above split Cas9 constructs wherein the first factor contains nMAG or pMAG and the second factor contains pMAG or nMAG. (page 756, Figure 1 and supporting text and page 761 Inducible Cas9 constructions.).
Thus claim(s) 1, 2, 4, 11, 13 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nihongaki et al. (Nature Biotechnology, Vol 33, No 7, pp 755-762, 2015).
Claim(s) 1, 2, 11, 13 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zetsche et al. (Nature Biotechnology, Vol 33, No 2, pp139-141, 2015).
Zetsche et al. (Nature Biotechnology, Vol 33, No 2, pp139-141, 2015).discloses a split-Cas9 architecture for inducible genome editing and transcription modulation. Zetsche et al. demonstrate that Cas9 can be split into two fragments and rendered chemically inducible by rapamycin binding dimerization domains for controlled reassembly to mediate genome editing and modulation. Zetsche et al. identified 11 potential split sites based on a crystal structure of Cas9 in complex with a single guide RNA and complementary target DNA. The resulting C-terminal Cas9 fragment and N-terminal Cas9 fragment were fused to FK506 binding protein 12 (FKBP) and FKBP rapamycin binding )FRB) domains of the mammalian target of rapamycin m(TOR) to make 11 split-Cas9 sets (Figure 1a and Supplementary Fig. 1a).
While Zetsche et al. does not state that the CRISPR-Cas protein is split into an N domain and a C domain within the "helix domain”, this is not a required limitation of the claimed CRISPR-dCas/Cas protein derivative by virtue of the specific language used by applicants (see also above rejection under 112(b)). Zetsche et al.disclose that the split Cas effector protein comprise an N domain containing the N-terminal side of the helix region of the CRISPR-dCas (dead Cas) protein or the CRISPR-Cas protein, a C domain containing the C-terminal side of the helix region of the CRISPR-dCas (dead Cas) protein or the CRISPR-Cas protein, and first and second factors capable of binding in response to stimulation, the N domain being linked to the first factor, and the C domain being linked to the second factor.
Thus, claim(s) 1, 2, 11, 13 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zetsche et al. (Nature Biotechnology, Vol 33, No 2, pp139-141, 2015).
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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rgh
6/3/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652
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