Prosecution Insights
Last updated: October 02, 2026
Application No. 18/332,335

Polynucleotides, Compositions, and Methods for Genome Editing Involving Deamination

Non-Final OA §102§103§112
Filed
Jun 09, 2023
Priority
Dec 11, 2020 — provisional 63/124,060 +4 more
Examiner
REGA, KYLE THOMAS
Art Unit
1636
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Intellia Therapeutics Inc.
OA Round
1 (Non-Final)
63%
Grant Probability
Moderate
1-2
OA Rounds
2m
Est. Remaining
99%
With Interview

Examiner Intelligence

Grants 63% of resolved cases
63%
Career Allowance Rate
74 granted / 118 resolved
+2.7% vs TC avg
Strong +41% interview lift
Without
With
+41.4%
Interview Lift
resolved cases with interview
Typical timeline
3y 6m
Avg Prosecution
41 currently pending
Career history
171
Total Applications
across all art units

Statute-Specific Performance

§101
4.3%
-35.7% vs TC avg
§103
39.9%
-0.1% vs TC avg
§102
17.6%
-22.4% vs TC avg
§112
25.9%
-14.1% vs TC avg
Black line = Tech Center average estimate • Based on career data from 118 resolved cases

Office Action

§102 §103 §112
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 . Election/Restrictions Applicant’s election without traverse of Group II, claims 5, 16, 77-78, 89-90, 93, 147, 149, 152, 155, 158, 161, 164, 167, 170, 173, and 176 in the reply filed on 31 July 2026 is acknowledged. Applicant’s election without traverse of the species of SEQ ID NOs: 40, 73, 46, 63, 3, and a Spy Cas9 nickase in the reply filed on 31 July 2026 is acknowledged. Claims 1-3, 8, 11-12, 15, 17, 19, 24-25, 29, 34-35, 41-42, 44-45, 47-49, 52-53, 60-61, 68, 70-71, 73-74, 126, 128, 132, 144-145, 148, 150-151, 153-154, 156-157, 159-160, 162-163, 165-166, 168-169, 171-172, 174-175, and 177-179 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 31 July 2026. Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i). 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 FIG. 3A-3E 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 § 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 93 is 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. Regarding claim 93, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. It is unclear if the claim is to be limited to the claimed lipids or if the claims are directed towards different genera of lipids that are similar to the claimed lipids. See MPEP § 2173.05(d). 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) 5, 16, 147, and 161 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang ("Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor." Cell research 27.10 (2017): 1289-1292). Regarding claim 5, for the purposes of examination the phrase “delivering to a cell a first mRNA” is interpreted as being inclusive of delivering a DNA vector encoding an mRNA, wherein the mRNA is subsequently expressed by the cell (i.e., each claimed mRNA is delivered to the cell through the use of a different DNA vector). Wang is drawn towards a study concerned with enhancing base editing by co-expression of a free uracil DNA glycosylase inhibitor (Abstract). Wang teaches a method of editing a target gene within a cell’s genome comprising delivering a first vector encoding a BE3 (i.e., an nCas9 fused to an APOBEC cytidine deaminase (pg. 1289-1290; see Figure 1)) alongside a second vector encoding a UGI that is different from the first vector and is expressed in trans with the BE3 such that both proteins are expressed within the cell and can mediate targeted base editing through the use of separately expressed sgRNAs that are directed to different genomic sites of interest (i.e., the different vectors facilitate the delivery of mRNAs comprising open reading frames encoding the BE3, UGI, and sgRNAs to the cell) (pg. 1290-1291; see Figure 1). Regarding claim 16, Wang teaches that the cells that were co-transfected with the vectors encoding the UGI and BE3/sgRNA were 293FT cells (pg. 1291). Regarding claim 147, Wang teaches that BE fusion proteins are generated by fusing an APOBEC cytidine deaminase with the CRISPR/Cas9 system (i.e., the cytidine deaminase in the BE3 is an enzyme of APOBEC family) (pg. 1289). Regarding claim 161, Wang teaches that the cytidine deaminase is located upstream (i.e., N-terminal) to the nCas9 (pg. 1290; see Figure 1). Claim Rejections - 35 USC § 103 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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action: A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention. Claim(s) 149, 155, 158, 167, 173, and 176 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang ("Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor." Cell research 27.10 (2017): 1289-1292) as applied to claims 5, 16, 147, and 161 above, and further in view of Joung (PG Pub No. US 2022/0411777 A1, filed 31 August 2020). Regarding claim 149, Wang anticipates claims 5, 16, 147, and 161 as described above. Wang does not teach or suggest that the cytidine deaminase is an APOBEC3A deaminase, further wherein the APOBEC3A comprises an amino acid sequence with at least 87% identity to the claimed SEQ ID NO: 40 (Claim 149). Wang does not teach or suggest that the RNA-guided nickase is an S. pyogenes Cas9 nickase (Claim 155). Wang does not teach or suggest the use of an RNA-guided nickase that comprises an amino acid sequence that has at least 90% identity to the claimed SEQ ID NO: 73 (Claim 158). Wang does not teach or suggest that the RNA-guided nickase further comprises an NLS at either the C-terminus or N-terminus of the nickase (Claim 167). Wang does not teach or suggest that the polynucleotide further comprises an SV40 and nucleoplasmin NLS at its N-terminus (Claim 173). Wang does not teach or suggest that the polypeptide comprising the cytidine deaminase and RNA-guided nickase comprises an amino acid sequence having at least 80% identity to the claimed SEQ ID NO: 3 (Claim 176). Joung is drawn towards an invention concerned with fusion proteins containing cytidine deaminases (e.g. human or rat APOBECs, pmCDA1 or AID), adenosine deaminases (e.g. E. coli TadAs), or a combination thereof, catalytically impaired CRISPR-Cas proteins (e.g. Cas9, CasX or Cas12 nucleases), linkers, nuclear localization signals (NLSs) and a human or E. coli uracil-n-glycosylase (UNG) and/or REV1 protein that enable the CRISPR-guided programmable introduction of C-to-G and G-to-C transversions in DNA (Abstract). Joung teaches the use of an APOBEC3A cytidine deaminase that has 100% identity to the claimed SEQ ID NO: 40 (pg. 44; see SEQ ID NO: 89 in attached sequence alignment). Joung teaches the use of an RNA-guided nickase that comprises 100% identity to the claimed SEQ ID NO: 73 (pg. 74; see SEQ ID NO: 180 in attached sequence alignment). Joung teaches the use of a fusion protein comprising a cytidine deaminase and RNA-guided nickase that has 99.9% sequence identity to the claimed SEQ ID NO: 3 (pg. 73; see SEQ ID NO: 177 in attached sequence alignment). Joung teaches that the APOBEC3A can be present within a functional fusion protein comprising a Cas9 nickase ([0006]-[0007], [0048]; see FIG. 6). Joung teaches that the Cas9 nickase can be an S. pyogenes Cas9 ([0117]; pg. 23; see Table F). Joung teaches that NLSs can be positioned at wither the N-terminus or C-terminus of the fusion protein ([0120]). Joung teaches that the fusion protein can comprise an SV40 NLS and nucleoplasmin NLS ([0140]). Joung teaches the use of expression vectors encoding the fusion protein ([0144]). Therefore, with regard to the claimed amino acid sequences present in claims 149 (i.e., SEQ ID NO: 40), 158 (i.e., SEQ ID NO: 73), and 176 (i.e., SEQ ID NO: 3). it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the nucleic acid encoding the S. pyogenes nCas9, cytidine deaminase, or nCas9-cytidine deaminase fusion protein linked by peptide linkers of Wang for the nucleic acid encoding the nCas9 having 100% identity to the claimed SEQ ID NO: 73, the cytidine deaminase having 100% identity to the claimed SEQ ID NO: 40, or the fusion protein comprising a cytidine deaminase and RNA-guided nickase linked by a peptide linker that has 99.9% sequence identity to the claimed SEQ ID NO: 3, because it would have merely amounted to a simple substitution of one known element for another to obtain predictable results. Because both Wang and Joung teach that the claimed components can be present within a functional fusion protein comprising an nCas9 and cytidine deaminase that were known in the art to have the same function, one of ordinary skill in the art would have expected the nCas9, cytidine deaminase, and fusion protein of Joung to have predictably resulted in a functional fusion protein that could edit nucleic acids of interest when administered to the cell of Wang. Additionally, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the fusion protein of Wang to include an NLS at the N-terminus of the nickase, wherein the NLSs are an SV40 and a nucleoplasmin NLS at its N-terminus because it would have merely amounted to a combination of prior art elements according to known methods to yield predictable results. Because both Wang and Joung teach the use of nCas9-cytidine deaminase fusion proteins, alongside an explicit disclosure that the fusion proteins can function when an SV40 and a nucleoplasmin NLS are positioned at its N-terminus, one of ordinary skill in the art would have expected positioning those same NLSs at the N-terminus of the fusion protein of Wang to have performed the same function as they do in the fusion protein of Joung: localizing the fusion protein to the nucleus of a target cell. Additionally, because both Wang and Joung teach the use of the same fusion protein, the combination of Joung’s NLSs with the fusion protein of Wang would have predicably resulted in the expression of a functional fusion protein with the claimed NLSs positioned at its N-terminus. Claim(s) 77-78 and 89-90 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang ("Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor." Cell research 27.10 (2017): 1289-1292) in view of Webber ("Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors." Nature communications 10.1 (2019): 5222) and Hajj ("A potent branched-tail lipid nanoparticle enables multiplexed mRNA delivery and gene editing in vivo." Nano letters 20.7 (4 June 2020): 5167-5175). Regarding claim 77, the applicable teachings of Wang are discussed above as applied to claims 5, 16, 147, and 161. Wang does not teach or suggest the use of one or more LNPs comprising a first mRNA encoding a polypeptide comprising a cytidine deaminase and an RNA-guided nickase, a second mRNA encoding a UGI, and one or more gRNAs (Claim 77). Webber is drawn towards a study concerned with multiplexed genome engineering through the use of Cas9 base editors (Abstract). Webber teaches that codelivery of sgRNAs targeting a genomic region of interest alongside mRNA encoding a BE3 nCas9-deamianse fusion protein mediated measurable editing of target Cs at all target loci (i.e., Webber teaches that delivery of mRNA encoding an sgRNA and an nCas9 fused to a deaminase allowed for the successful editing of target nucleic acids of interest) (pg. 2). Webber teaches that free UGI expression has been shown to reduce both indel frequency and nontarget editing in the context of BE3 (pg. 7). Hajj is drawn towards a study concerned with the development of a lipid nanoparticle that can enable multiplexed mRNA delivery and gene editing in vivo (Abstract). Hajj teaches the use of an LNP, termed 306Oil0, allowed for the successful delivery and expression of different mRNAs of different lengths encoding firefly luciferase, mCherry, and erythropoietin (pg. 5168). Hajj teaches that the lipid nanoparticle was neither immunogenic nor toxic to the liver when delivered to target cells in vivo (Abstract). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the two separate vectors encoding the BE3 and UGI of Wang such that they were present within an LNP and delivered to a target gene in a cell because it would have merely amounted to a combination of prior art elements according to known methods to yield predictable results. Because Webber teaches that, when delivered to a cell, mRNA encoding the BE3 allowed for the same gene editing activity when compared to the vector of Wang, alongside a disclosure that free UGI can enhance the activity of the BE3, one would have expected that delivering the BE3 and free UGI of Wang as mRNA molecules to the target cell would have resulted in them predicably performing the same function (i.e., gene editing) as when they were delivered to the cell as DNA vectors. Additionally, because Hajj teaches that different mRNA molecules of different lengths can be present within, and expressed from, the disclosed LNP that neither elicited an immune response nor was toxic to the liver, one would have been motivated to utilize the disclosed LNP of Hajj to reduce immunogenic responses and would have expected placing the first and second mRNAs, alongside a gRNA, within the LNP to have resulted in their successful expression within the target cell of interest. Regarding claim 78, Hajj teaches that multiple different mRNA molecules can be present within the LNP (pg. 5168). Thus, the combination of Wang, Webber, and Hajj renders obvious the use of an LNP wherein parts (a), (b), and (c) are present within the same LNP. Regarding claims 89-90, Hajj teaches that the 306Oil0 LNP was formulated by combining lipidoid, DOPE, cholesterol (i.e., a helper lipid), and C14-PEG2000 at a molar ratio of 35:16:46.5:2.5 in 90% (v/v) ethanol and 10% (v/v) 10 mM sodium citrate (pg. 5168). Claim(s) 93 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang ("Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor." Cell research 27.10 (2017): 1289-1292) in view of Webber ("Highly efficient multiplex human T cell engineering without double-strand breaks using Cas9 base editors." Nature communications 10.1 (2019): 5222) and Hajj ("A potent branched-tail lipid nanoparticle enables multiplexed mRNA delivery and gene editing in vivo." Nano letters 20.7 (4 June 2020): 5167-5175) as applied to claims 77-78 and 89-90 above, and further in view of Brito (PG Pub No. WO 2015/095340 A1). Regarding claim 93, it is noted that the instant specification teaches that the term “about” encompasses variations within 10% (Instant specification; [0095]). Hajj teaches that the 306Oil0 LNP was formulated by combining lipidoid (i.e., an amine lipid), DOPE (i.e., a neutral lipid), cholesterol (i.e., a helper lipid), and C14-PEG2000 (i.e., a stealth lipid) at a molar ratio of 35 (i.e., about 35 mol-% of the amine lipid):16 (i.e., about 15 mol-% of the neutral lipid) :46.5 (i.e., the remainder of the lipid component is the helper lipid cholesterol): 2.5 (i.e., about 2.5 mol-% of the stealth lipid) in 90% (v/v) ethanol and 10% (v/v) 10 mM sodium citrate (pg. 5168). Hajj teaches that the N/P ratio of the 306Oil0 LNP is 6.3 (i.e., about 6) (see Figure S1). Wang in view of Webber and Hajj does not teach or suggest that the amine lipid is the claimed lipid A (Claim 93). Brito is drawn towards an invention concerned with lipid compositions for the delivery of active agents (Abstract). Brito teaches the use of an amine lipid that is termed “(9Z, 12Z)-3-((4,4-bis(octyloxy)butanoyl)oxy)-2-((((3-(diethylamino)propoxy)carbonyl)oxy)methyl)propyl octadeca-9, 12-dienoat” (i.e., “Lipid A” as defined in the instant specification at paragraphs [00347]-[00349]) (pg. 15). Brito teaches that the lipid may be present within a lipid nanoparticle (see Claims 8 and 11). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the amine lipid of Hajj for the claimed lipid A because it would have merely amounted to a simple substitution of one known element for another to obtain predictable results. Because both Hajj and Brito teach the use of amine lipids alongside their known structures, and that those amine lipids are functional within lipid nanoparticles, one would have expected that using the amine lipid of Brito within the LNP of Hajj to have predictably resulted in the successful delivery of the different mRNAs within the single LNP. Claim(s) 152, 164, and 170 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wang ("Enhanced base editing by co-expression of free uracil DNA glycosylase inhibitor." Cell research 27.10 (2017): 1289-1292) as applied to claims 5, 16, 147, and 161 above, and further in view of Joung (PG Pub No. US 2022/0411777 A1, filed 31 August 2020), Evans (PG Pub No. WO 2020/051562 A2, published 12 March 2020, filed 7 September 2019), and Evans sequence alignment (accessed 26 August 2026). Regarding claims 152, 164, and 170, the applicable teachings of Wang in view of Joung and the obviousness of utilizing fusion proteins comprising an nCas9 linked to a deaminase through the use of an amino acid linker, alongside the obviousness of utilizing NLSs, is discussed above as applied to claims 149, 155, 158, 167, 173, and 176. Wang in view of Joung does not teach or suggest that the UGI comprises an amino acid sequence having at least 80% identity to the claimed SEQ ID NO: 27 (Claim 152). Wang in view of Joung does not teach or suggest that the peptide linker comprises the claimed SEQ ID NO: 46 (Claim 164). Wang in view of Joung does not teach or suggest that each NLS independently comprises a sequence with at least 80% identity to the claimed SEQ ID NO: 63 (Claim 170). Evans is drawn towards an invention concerned with nucleobase editors (Abstract). Evans teaches that the nucleobase editors can comprise an nCas9 linked to a deaminase and a UGI through the use of peptide linkers (pg. 2). Evans teaches the use of a nucleobase editor comprising a UGI having 96.7% identity to the claimed SEQ ID NO: 27, wherein the UGI further comprises an NLS having 100% identity to the claimed SEQ ID NO: 63 (see SEQ ID NO: 132 in attached sequence alignment). Evans teaches the use of a linker sequence that can link the nucleobase editor to the deaminase and has 100% identity to the claimed SEQ ID NO: 46, wherein the linker can be placed between the RNA-guided nickase and the cytidine deaminase (pg. 52 line 21 to pg. 53 line 7). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the UGI, NLS, and amino acid linker of Wang in view of Joung for those disclosed in Evans having 100% identity to the claimed SEQ ID NO: 27, 63, and 46 respectively because it would have merely amounted to simple substitution of one known element for another to obtain predictable results. Because Wang in view of Joung teaches the use of an RNA-guided nickase that can be linked to a deaminase through the use of a linker and attached to an NLS, one would have expected that utilizing the deaminase, UGI, and NLS of Evans within the construct of Wang in view of Joung to have functioned identically to those disclosed in Wang in view of Joung because both substituted components perform the same function within the same base editor construct. Thus, it would have been predictable that the resulting substitution would have resulted in a functional base editor and UGI that could be utilized to edit target nucleic acids of interest within cells. 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 Mon-Fri, 9AM-5PM (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
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Prosecution Timeline

Jun 09, 2023
Application Filed
Sep 09, 2026
Non-Final Rejection mailed — §102, §103, §112 (current)

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Prosecution Projections

1-2
Expected OA Rounds
63%
Grant Probability
99%
With Interview (+41.4%)
3y 6m (~2m remaining)
Median Time to Grant
Low
PTA Risk
Based on 118 resolved cases by this examiner. Grant probability derived from career allowance rate.

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