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 .
This action is in response to the amendment filed 03/20/2026, in which claims 1, 7 and 10 were amended, claims 2-6, 11, 16 and 17 were previously presented and claims 8, 12, 13 and 15 were withdrawn due to a restriction election set forth in a previous Office Action. Claims 1-7, 10, 11, 16 and 17 are currently under examination.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the
reasons that follow. Any rejection and objections not reiterated in this action have been
withdrawn. This action is FINAL.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statement filed on 12/01/2025 have been received and all references have been considered.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-7, 10, 11, 16 and 17 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1 and 10 are drawn to a genus of sequences. The rejected claims thus comprise a genus of sequences that encompass (a) “the RNA-guided DNA endonuclease comprises an amino acid sequence of SEQ ID NOs: 29, 1 or 3” and (b) “the nucleic acid sequence comprises a nucleotide sequence of SEQ ID NOs: 30, 2 or 4” in claim 1; and (i) “the nucleic acid molecule comprises a nucleotide sequence of SEQ ID NOs: 30, 2 or 4” in claim 10. The phrase “an amino acid sequence” and/or “a nucleotide sequence” means two or more consecutive amino acids/nucleotides and not the entirety of the sequence. Therefore, the claims would require a variant or truncated sequence to be capable of the same functions as the full amino acid and/or nucleotide sequences.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes the sequences disclosed such as the amino acid sequences of SEQ ID NOs: 29, 1 and 3 as the RNA-guided DNA endonuclease (Page 3, Lines 5-25) as well as the nucleic acid molecule encoding the sequences of SEQ ID NOs: 30, 2 and 4 (Page 3, Lines 5-25). No description is provided of how only fragments of the sequences would be possible to have the same function as the entirety of the sequence with 95% identity or more to the sequences of SEQ ID NOs: 1-4, 29 and/or 30 as outlined in the current limitations of the claims.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of the full length of the sequences with at least 95% identity or more to the entire length. The results are not necessarily predictive of a fragment of the sequences as the current limitations of the claims read. Thus, it is impossible for one to extrapolate from the few examples described herein those fragments of the sequences that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of variants of the sequences that would still be able to function the same as the RNA-guide DNA endonucleases claimed. For some relevant background, Chen et al (ACS Chem Biol. 2018 February 16; 13(2): Pgs. 1-21) teaches approximately 47% of analyzed bacterial genomes and 87% of analyzed archaeal genomes have at least one CRISPR system, and many contain multiple CRISPR-Cas systems in which these CRISPR-Cas systems in bacteria or archaea exhibit notable diversity and are organized according to a specific classification scheme (Page 3, 2nd Paragraph). Chen teaches that different Cas proteins with little to no sequence similarity will also comprise different nuclease domains as well as different functions (Page 6, last paragraph).
Kiernan et al (Nucleic Acids Res. 2025 Jan 7;53(1); Pgs. 1-12) teaches shortening Cas9 sequences typically leads to a loss of function because the essential catalytic domains (like HNH and RuvC in Cas9) become disrupted or misaligned (Page 9, Column 2). Kiernan teaches REC3 residues are critical for sensing distortions in the PAM-distal R-loop and have been shown to significantly reduce cleavage rate of mismatched tar- gets independent of DNA unwinding rate and in addition, structures of Cas9 in complex with consecutive mismatches in positions +15–17 show that conformational activation of Cas9 is prevented due to inefficient DNA kinking (Page 9, Column 2).
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1-7, 10, 11, 16 and 17.
Response to Amendments - Claim Rejections - 35 USC § 112
The previous rejection of claims 10 and 11 under 35 U.S.C. 112(d), 4th paragraph, has been withdrawn in view of Applicant’s amendments to the claims filed on 03/20/2026.
Claim Rejections - 35 USC § 101
The previous rejection of claims 7, 10 and 11 under 35 U.S.C. 101, has been withdrawn in view of Applicant’s amendments to the claims filed on 03/20/2026.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7, 10, 11, 16 and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12,13 and 15 of copending Application No. 18/730,505 (reference application) in view of Begemann et al (WO 2019/030695 A1) and Li et al (Cell Research, Vol 28, Pgs. 1-3; 2018).
Although the claims at issue are not identical, they are not patentably distinct from each other because claim 12 of the copending application ‘505 anticipates claim 1 of the instant application. SEQ ID NO: 1 of copending ‘505 is 100% identical to SEQ ID NO: 1 of the instant application (See Appendix I). Claim 13 of the copending application ‘505 anticipates claim 4 of the instant application. SEQ ID NO: 1 of copending ‘505 is 100% identical to SEQ ID NO: 1 of the instant application (See Appendix I). Claim 15 of the copending application ‘505 anticipates claim 11 of the instant application because claim 15 of ‘505 recites, “...one or more nucleic acid molecules, or the CRISPR nuclease and the guide RNA, or the RNP is administered to a patient to treat a disease...”. The instant specification envisions that the pharmaceutical composition relates to a composition for administration to a patient, preferably a human patient.
The claims of the “505 application do not require the nucleic acid molecule is operably linked to a promoter that is native or heterologous to the nucleic acid molecule, said nucleic acid molecule is codon-optimized for expression in a eukaryotic cell, a eukaryotic or prokaryotic host cell comprising the nucleic acid molecule, an RNA-guided DNA endonuclease encoded by the nucleic acid molecule and a diagnostic composition comprising the RNA-guided DNA endonuclease and a single-stranded DNA strand being attached to a marker, so that when the RNA-guided DNA endonuclease polypeptide cuts the single-stranded DNA, the endonuclease polypeptide activates the marker, causing the marker to fluoresce or change color. However, Begemann teaches characterization of a novel group of Type V, Class 2 nucleases termed Cms1 (CRISPR from microgenomates and Smithella), characterized the structure, independence from tracrRNA, and preference for AT-rich PAM sites (Page 4, Lines 6-23). Begemann teaches the Cms1 polypeptide or fusion protein capable of efficient genome editing in a plant host cell being operably linked to at least one promoter to control the expression of the sequence in the host cell (Page 15, Lines 25-28). Begemann teaches Cms1-encoding genes were codon optimized for plant codon usage (Page 15, Lines 21-22). Begemann teaches the RNA-guided DNA endonuclease such as Cms1 polypeptide containing a RuvC or RuvC-like nuclease domain where the dCms1 protein can bind to the desired region of DNA (Page 5 bridging Page 6). Begemann teaches the Cms1 polypeptide can also comprise at least one marker domain such as a fluorescent protein (Page 6, Lines 32-34).
Begemann do not teach a diagnostic composition comprising the RNA-guided DNA endonuclease and a single-stranded DNA strand being attached to a marker, so that when the RNA-guided DNA endonuclease polypeptide cuts the single-stranded DNA, the endonuclease polypeptide activates the marker, causing the marker to fluoresce or change color.
Li teaches Cas12a is guided by a single CRISPR RNA (crRNA) with a T-rich protospacer adjacent motif (PAM) sequence to cleave double-stranded DNA (dsDNA) targets, generating sticky ends (Page 1, Column 1). Li teaches promiscuous cleavage of collateral ssDNAs transcleavage to distinguish it from the programmable on-target cleavage of target ssDNA (namely, cis-cleavage) (Page 1, Column 2). Li teaches the RNA-guided DNA endonuclease and a single-stranded DNA strand being attached to a marker, so that when the RNA-guided DNA endonuclease polypeptide cuts the single-stranded DNA, the endonuclease polypeptide activates the marker, causing the marker to fluoresce (Page 2, Figure Id).
It would have been obvious to one of ordinary skill in the art to include the detection method to ensure the proper collateral cleavage within the system as taught by Li. One would have had the expected benefit of definitive success of the system prior to administration to a subject.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments - Double Patenting
The previous provisional nonstatuatory double patening rejection of claims 1-7, 9-11 and 16-18 of the instant application over claims 12, 13 and 15 of copending Application No. 18/730,505 in view of Begemann et al (WO 2019/030695 A1) and Li et al (Cell Research, Vol 28, Pgs. 1-3; 2018) has been maintained in view of Applicants arguments filed 03/20/2026 are not found to be persuasive.
Applicant’s arguments are not persuasive because Applicant stated that the double patenting rejection should be withdrawn in view of the claims being allowable.
The double patenting rejection cannot be withdrawn because the claims are not currently allowable.
Conclusion
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 ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JENNIFER A DUNSTON can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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