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 .
Track One Status
Applicant’s Track One Request, filed 3 September 2025, has been received. Applicant’s Track One Request has been granted on 18 November 2025.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No.17/613,172, filed on 22 November 2021.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in FIGs. 7 and 14 are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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.
Claim(s) 34-42 is/are rejected under 35 U.S.C. 102(a)(1) and 10(a)(2) as being anticipated by Liu (PG Pub No. WO 2018/165629 A1, published 13 September 2018, effectively filed 9 March 2018) as evidenced by Krusong (Journal of Biological Chemistry 281.8 (2006): 4983-4992).
Regarding claim 34, Liu is drawn to a methods of using a fusion protein system that is capable of inducing a cytosine into a guanine change in a target nucleic acid (Abstract). Liu teaches that the fusion protein system comprises a napDNAbp selected from a Cas9 nucleic acid programmable DNA binding protein (i.e., a CRISPR-Cas effector enzyme comprising a Cas9 polypeptide), a cytidine deaminase, and a uracil binding protein (i.e., termed “UBP) ([0005]). Liu teaches that the UBP may be a uracil DNA glycosylase ([0063]). Liu teaches the use of a guide RNA that is capable of guiding the Cas9 to a specific DNA sequence that is complementary to the guide RNA ([0071]). Liu teaches that the fusion protein may comprise the structure NH2-[UBP]-[cytidine deaminase]-[napDNAbp]-COOH ([00222]). Liu teaches that the guide RNA may be 15-25 nucleotides in length ([00239]). Liu teaches that the fusion protein can modify a cytosine of a target nucleic acid into a guanine via the excision of uracil from the target nucleic acid molecule mediated by the UDG ([0002], [0006]; see Figure 1 for schematic illustration of C to G base editing).
As evidenced by Krusong (Journal of Biological Chemistry 281.8 (2006): 4983-4992), a comparative study concerned with the study of uracil DNA glycosylases, uracil DNA glycosylase is the primary enzyme responsible for the removal of uracil from DNA that functions via the cleavage of an N-glycosidic bond between the uracil and a deoxyribose backbone, leaving an apyrimidinic (AP) site (pg. 4983).
Thus, as evidenced by Krusong, the uracil DNA glycosylase of Liu inherently catalyzes the cleavage of an N-glycosidic bond of uracil.
Regarding claim 35, Liu teaches that the fusion protein may comprise an NLS ([00235]).
Regarding claim 36, Liu teaches that the CRISPR enzyme may be a Streptococcus pyogenes Cas9 ([0093]).
Reading claim 37, Liu teaches that the CRISPR enzyme may be an inactivated Cpf1 that has a mutation in the RuvC domain ([00100]).
Regarding claim 38, Liu teaches that the CRISPR enzyme may be a Cas9 nickase ([0064]).
Regarding claims 39-40, Liu teaches that the cytidine deaminase may be an APOBEC1 ([00176]).
Regarding claim 41, Liu teaches the use of nucleotide sequences encoding the fusion protein and guide RNA that can be present within a kit and delivered to a target cell of interest [00267], [00269]).
Regarding claim 42, Liu teaches that the fusion protein may comprise the structure NH2-[UBP]-[cytidine deaminase]-[napDNAbp]-COOH ([00222]). Liu teaches that the UBP, cytidine deaminase, and napDNAbp may be fused via the use of linkers between each element ([00223]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636