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 .
Claims Status
Claims 1-11, 13-19, & 34-42 filed on 03/02/2026 are pending. Claims 12 & 20-33 are withdrawn from consideration as being drawn to a non-elected invention. Claims 1, 3, 8, 10, 12, 16, 18, & 19 are currently under examination directed to the elected species of SEQ ID NO: 11 in claims 1, 8, 10, 12, 16, & 19, of 5mC in claim 3, and of pyrrolo-dCTP in claim 18 (see response dated 09/12/2025). The species of SEQ ID NO: 33 is rejoined with SEQ ID NO: 11 in claims 1, 8, 10, 12, 16, & 19 and the species of 5mdCTP is rejoined with the species of pyrrolo-dCTP in claim 18. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant application. Response to Applicant’s argument follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Priority
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/264,513, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The provisional application, 62/264,513, does not have support for all of the limitations in claims 1-19 of the instant application. The provisional application, 62/264,513 does not provide support for a double-stranded deaminase having an amino acid sequence that is at least 80% identical to SEQ ID NOs: 2-4, 6-9, 11, 12, 14-16, 19, 24, 26-28, 40, 49, 50, 63, 95, 97, & 99. Accordingly, claims 1-19 are not entitled to the benefit of the prior applications. Therefore, claims 1-19 are given the priority date of the date of filing 11/22/2022.
Response to Arguments
The response traverses the rejection. The response asserts that support, in part, for SEQ ID NOs. 10, 33, and 96, are disclosed in the provisional application 62/264,513, as SEQ ID NO: 10 (LbsDa01), the provisional discloses SEQ ID NO: 3 as LbsDa01 in Figure 2B, SEQ ID NO: 33 (RaDa01), the provisional discloses SEQ ID NO: 5 as RaDa01 in Figure 2B, and SEQ ID NO: 96 (MGYPDa829), the provisional discloses SEQ ID NO: 1 as MGYP001104162829 in which the present specification in Table 4 discloses that the instant application name of MGYPDA829 corresponds to the provisional name MGYP001104162829. The response further asserts that, in view of this disclosure in the provisional, applicant submits that the provisional provides written description and enablement in the manner required by 35 USC 112(a) for claims reciting double-stranded DNA deaminases having an amino acid sequence at least 80% identical to SEQ ID NOs: 10 and 96 and for variants of SEQ ID NO: 33 and that for avoidance of mixed priority claims, applicant has amended claims 1 and 8 to remove SEQ ID NOs: 10 and 96 and has added claim 34 (and dependents) reciting SEQ ID NOs: 10 and 96 and therefore submits that new claims 34-42 are entitled to the Provisional filing date of 11/24/2021 as their effective filing date. This argument has been thoroughly reviewed and was found persuasive. Therefore, claims 1-19 are given the priority date of the date of filing 11/22/2022, as discussed above, and new claims 34-42 are given the priority date of the provisional filing date of 11/24/2021.
Claim Rejections - 35 USC § 112
Claims 17-19 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.
Regarding claim 17, the recitation of “(a) ligating a hairpin adapter…modified dCTP in lines 2-7 of the claim is unclear. It is unclear where the steps (a)-(c) in claim 17 take place in claim 1, from which claim 17 depends from. Do steps (a)-(c) in claim 17 take place before or after the double stranded DNA substrate is contacting with a double stranded DNA deaminase in claim 1, from which claim 17 depends from.
Claims 18 & 19 are rejected due to their dependence on claim 17.
Claim Rejections - 35 USC § 102
Claim(s) 1, 6, & 13 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Fauser (WO 2022/067122 A1, September 2021).
Regarding claim 1, Fauser teaches a method for base editing comprising a system of fusion proteins and cytidine deaminase domains that can be used to specifically alter a single base pair in a target DNA sequence comprising a cytidine deaminase domain that operates on double-stranded DNA (contacting double-stranded DNA substrate that comprises cytosines and a double-stranded DNA deaminase) in which the cytidine deaminase can be derived from a toxin and referred to as a toxin-derived deaminase (TDD) comprising the cytidine TDD of SEQ ID NO: 89, in which SEQ ID NO: 89 is 82.5% identical to SEQ ID NO: 33 of the instant application (a double-stranded DNA deaminase having an amino acid sequence that is at least 80% identical to SEQ ID NO: 33) (abstract lines 1-3; paragraph [0053] lines 1-8; paragraph [0054] lines 1-6; paragraph [0060] lines 1-4).
Regarding claim 6, Fauser teaches that any type of cell comprising eukaryotic or prokaryotic cells may be targeted for base editing with cytidine toxin-derived deaminase that operates on double-stranded DNA (the double-stranded DNA substrate is eukaryotic or bacterial DNA (paragraph [0053] lines 1-8; paragraph [0054] lines 1-6; paragraph [00112] lines 1-2).
Regarding claim 13, Fauser teaches that the double-stranded DNA is not pre-treated with either a TET methylcytosine dioxygenase or DNA beta-glucosyltransferase (abstract lines 1-3; paragraph [0053] lines 1-8; paragraph [0054] lines 1-6; paragraph [0060] lines 1-4).
Response to Arguments
The response traverses the rejection. The response asserts that SEQ ID NO: 10 has been removed from claim 1 in the present amendment and the subject matter relating to SEQ ID NO: 10 is now recited in claim 34 and therefore the applicant address the 102 rejection relating to SEQ ID NO: 10 in the discussion of claim 34 below. Further, the response asserts that Farzadfard cannot anticipate new claim 34 because the reference is not prior art for the subject matter relied upon and applicant asserts that claims reciting SEQ ID NO: 10 have an effective filing date of 11/24/2021, which predates Farzadfard’s earliest effective date of 01/12/2022 for SEQ ID NO: 50, and, accordingly, Farzadfard is not prior art to new claim 34 or its dependent claims and cannot anticipate them. This argument has been thoroughly reviewed but was found persuasive.
The response also asserts that turning to claim 1 as amended, which recites elected species SEQ ID NO: 11, the office action does not identify a double-stranded DNA deaminase having an amino acid sequence that is at least 80% identical SEQ ID NO: 11 in Farzadfard and therefore Farzadfard cannot anticipate claim 1 or any claim depending therefrom. This argument has been thoroughly reviewed but was not found persuasive as SEQ ID NO: 33 is rejoined with SEQ ID NO: 11 in claims 1, 8, 10, 12, 16, & 19 and the prior art of Fauser, as applied to amended independent claim 1 as necessitated by amendment, teaches every element of claim 1 as discussed above.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Claim Rejections - 35 USC § 103
Claim(s) 2-5, 9, & 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fauser (WO 2022/067122 A1, September 2021), in view of Farzadfard (Farzadfard (U.S. Patent Application Publication US 2024/0138159 A1, January 2022).
The teachings of Fauser with respect to claim 1 is discussed above and incorporated herein.
Regarding claims 2 & 3, Fauser does not teach the double-stranded DNA substrate further comprises a modified cytosine or that the modified cytosine is 5mC.
Farzadfard teaches a method for deaminating double-stranded (ds) DNA in which dsDNA-specific deaminases, including dsDNA-specific deaminases that deaminate cytosine nucleotides, deaminate target nucleotides in double-stranded DNA (paragraph [0008] lines 1-5; paragraph [0018] lines 1-13; paragraph [0019] lines 1-14; paragraph [0023] lines 1-8; paragraph [0143] lines 1-5; paragraph [0144] lines 1-8; paragraph [0199] lines 1-13). Farzadfard also teaches the method can be used for identifying modified nucleotides in a target nucleic acid in which the dsDNA-specific deaminase are active on methylated (modified) cytosines including mC, hmC, fC, and caC (double-stranded DNA substrate comprises a modified cytosine of 5mC) (paragraph [0059] lines 1-18; paragraph [0060] lines 1-31). Farzadfard also teaches that this method of deaminase domains that are capable of deaminating cytosine nucleotides in double-stranded DNA facilitate specific and efficient editing of targeted sites withing the genome of a cell or subject with low off-target effects (abstract lines 1-12).
Fauser and Farzadfard are considered to be analogous to the claimed invention because they are all in the same field of deaminating cytosines in target double-stranded DNA with a deaminating enzyme. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of deaminating double-stranded DNA with a cytidine toxin-derived deaminase (TDD) in Fauser to incorporate the use of dsDNA-specific deaminases that are active on methylated (modified) cytosines including mC, hmC, fC, and caC as taught in Farzadfard because Farzadfard teaches that doing so would provide a method capable of deaminating cytosine nucleotides in double-stranded DNA facilitate specific and efficient editing of targeted sites withing the genome of a cell or subject with low off-target effects.
Regarding claims 4 & 5, Fauser does not teach sequencing the deamination product and amplifying the deamination product and further analyzing the sequence reads.
Farzadfard teaches a method for deaminating double-stranded (ds) DNA in which dsDNA-specific deaminases, including dsDNA-specific deaminases that deaminate cytosine nucleotides, deaminate target nucleotides in double-stranded DNA (paragraph [0008] lines 1-5; paragraph [0018] lines 1-13; paragraph [0019] lines 1-14; paragraph [0023] lines 1-8; paragraph [0143] lines 1-5; paragraph [0144] lines 1-8; paragraph [0199] lines 1-13). Farzadfard teaches the deaminated target sequence comprising the modified cytosine can be subsequently sequenced and the methylated (modified) cytosine nucleotides in the target nucleic acid are identified (sequencing the deamination product and analyzing the sequence reads to identify modified cytosines) and that the deaminated target sequence can be PCR amplified and then sequence to determine position/frequency of edits (amplifying the deamination product to produce amplification products and sequencing the amplification products to produce sequence reads) (paragraph [0059] lines 1-18; paragraph [0060] lines 1-31; paragraph [0077] lines 12-14). Farzadfard also teaches that this method of deaminase domains that are capable of deaminating cytosine nucleotides in double-stranded DNA facilitate specific and efficient editing of targeted sites withing the genome of a cell or subject with low off-target effects (abstract lines 1-12).
Fauser and Farzadfard are considered to be analogous to the claimed invention because they are all in the same field of deaminating cytosines in target double-stranded DNA with a deaminating enzyme. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of deaminating double-stranded DNA with a cytidine toxin-derived deaminase (TDD) in Fauser to incorporate the amplification and sequencing of the deaminated target sequence comprising the modified cytosine to identify the methylated (modified) cytosines in the target nucleic acid as taught in Farzadfard because Farzadfard teaches that doing so would provide a method capable of deaminating cytosine nucleotides in double-stranded DNA facilitate specific and efficient editing of targeted sites withing the genome of a cell or subject with low off-target effects.
Regarding claims 9 & 11, Fauser does not teach pre-treatment with a TET methylcytosine dioxygenase and DNA beta-glucosyltransferase (see claim 9) or pre-treatment with a TET methylcytosine dioxygenase but not DNA beta-glucosyltransferase (see claim 11).
Farzadfard teaches a method for deaminating double-stranded (ds) DNA in which dsDNA-specific deaminases, including dsDNA-specific deaminases that deaminate cytosine nucleotides, deaminate target nucleotides in double-stranded DNA (paragraph [0008] lines 1-5; paragraph [0018] lines 1-13; paragraph [0019] lines 1-14; paragraph [0023] lines 1-8; paragraph [0143] lines 1-5; paragraph [0144] lines 1-8; paragraph [0199] lines 1-13). Farzadfard teaches that the target double-stranded cytosine methylated DNA can be first converted to oxidized forms using TET2 and BGT enzyme treatment (dsDNA substrate is pretreated with a TET methylcytosine dioxygenase and DNA beta-glucosyltransferase) (paragraph [0528] lines 19-24). Farzadfard also teaches that the target double-stranded cytosine methylated DNA can be treated with TET to convert 5-mC and 5-hmC to uracil (the dsDNA substrate is pretreated with a TET methylcytosine dioxygenase but not DNA beta-glucosyltransferase) (paragraph [0526] lines 1-9). Farzadfard also teaches that this method of deaminase domains that are capable of deaminating cytosine nucleotides in double-stranded DNA facilitate specific and efficient editing of targeted sites withing the genome of a cell or subject with low off-target effects (abstract lines 1-12).
Fauser and Farzadfard are considered to be analogous to the claimed invention because they are all in the same field of deaminating cytosines in target double-stranded DNA with a deaminating enzyme. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of deaminating double-stranded DNA with a cytidine toxin-derived deaminase (TDD) in Fauser to incorporate pre-treatment of the double-stranded DNA with a TET methylcytosine dioxygenase and DNA beta-glucosyltransferase or pre-treatment of the double-stranded DNA with a TET methylcytosine dioxygenase but not DNA beta-glucosyltransferase as taught in Farzadfard because Farzadfard teaches that doing so would provide a method capable of deaminating cytosine nucleotides in double-stranded DNA facilitate specific and efficient editing of targeted sites withing the genome of a cell or subject with low off-target effects.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fauser (WO 2022/067122 A1, September 2021), in view of Vaisvila (Vaisvila et al.; Genome Research, Vol. 31, pages 1280-1289, June 2021), as cited on the IDS dated 11/22/2022.
The teachings of Fauser with respect to claim 1 is discussed above and incorporated herein.
Regarding claim 7, Fauser does not teach that the double-stranded DNA is human cfDNA.
Vaisvila teaches a method for deaminating unmodified cytosines in DNA with an enzyme and sequencing the deaminated libraries produced, in which the libraries were made with genomic cell-free human DNA (abstract lines 1-14; pg. 1286-1287 lines 7-10). In addition, Vaisvila teaches that this method outperformed the standard method of bisulfite-converted libraries in coverage, duplication, and sensitivity, displayed better correlations across DNA inputs and accuracy of cytosine methylation calls, and was effective with the use of a small amount of DNA (abstract lines 9-14).
Fauser and Vaisvila are considered to be analogous to the claimed invention because they are all in the same field of deaminating cytosine in target DNA with a deaminating enzyme. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of deaminating double-stranded DNA with a cytidine toxin-derived deaminase (TDD) in Fauser to incorporate the use of human genomic cfDNA as taught in Vaisvila because Vaisvila teaches that doing so would provide better sensitivity and would be effective with the use of a small amount of DNA.
Claim(s) 14 & 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fauser (WO 2022/067122 A1, September 2021), in view of Xiong (Xiong et al.; Royal Society of Chemistry, Vol. 13, pages 9960-9972, August 2022).
The teachings of Fauser with respect to claim 1 is discussed above and incorporated herein.
Regarding claims 14 & 15, Fauser teaches that any type of cell comprising eukaryotic or prokaryotic cells may be targeted for base editing with cytidine toxin-derived deaminase that operates on double-stranded DNA (the double-stranded DNA substrate is bacterial DNA (paragraph [0053] lines 1-8; paragraph [0054] lines 1-6; paragraph [00112] lines 1-2).
Fauser does not teach that the double-stranded DNA comprises at least one N4mC.
Xiong teaches a method for genome-wide mapping of 4NmC at single-base resolution through enzyme-mediated deaminated sequencing in various strains of bacterial DNA (DNA substrate comprises N4mC and is bacterial DNA) (abstract lines 1-15). In addition, Xiong teaches that this method enabled genome-wide mapping of N4mC modifications in uncharacterized bacterial strains therefore providing the ability to facilitate further investigations of N4mC functions (abstract lines 8-15).
Farzadfard and Xiong are considered to be analogous to the claimed invention because they are all in the same field of deaminating cytosine in target DNA with a deaminating enzyme. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of deaminating double-stranded DNA with a cytidine toxin-derived deaminase (TDD) in Fauser to incorporate the use of bacterial DNA that comprises at least on N4mC as taught in Xiong because Xiong teaches that doing so would provide the ability to further investigate N4mC functions.
Claim(s) 17 & 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Fauser (WO 2022/067122 A1, September 2021), in view of Desantis (CA 3223501 A1, August 2022).
The teachings of Fauser with respect to claim 1 is discussed above and incorporated herein.
Regarding claims 17 & 18, Fauser does not teach ligating a hairpin adapter to a double-stranded DNA to produce a ligation product.
Desantis teaches a method of preparing a nucleic acid library comprising obtaining double-stranded nucleic acids, ligating a first adapter comprising a hairpin and a double-stranded region comprising a nickable site to each end of the double-stranded nucleic acid (ligating a hairpin adapter to a double-stranded fragment of DNA to produce a ligation product), contacting the double-stranded region comprising the nickable site with an enzyme and then denaturing the double-stranded nucleic acids to obtain single-stranded nucleic acids comprising a hairpin (enzymatically generating a free 3’ end in double-stranded region of the hairpin adapter in the ligation product), and extending the hairpin in the presence of a conversion-resistant cytosine analog, in which that conversion-resistant cytosine analog is selected from 5-methyl dCTP (modified dCTP is 5mdCTP) (extending the free 3’ end in a dCTP-free reaction mix that comprises strand-displacing or nick-translating polymerase, dGTP, dATP, dTTP, and modified dCTP), and ligating a Y-adapter to the end of the extended hairpins to obtain library polynucleotides, and further in which the library of polynucleotides can be converted through deamination (paragraph [0076] lines 1-5; paragraph [0090] lines 1-11; paragraph [0091] lines 1-8; paragraph [0092] lines 1-5; paragraph [0093] lines 1-5). In addition, Desantis teaches that this method can be used to determine the methylation level and pattern in a nucleic acid sample and that the methylation status of nucleic acids contains important information useful in many biological assays (paragraph [0066] lines 1-4; paragraph [0067] lines 1-7).
Fauser and Desantis are considered to be analogous to the claimed invention because they are all in the same field of deaminating cytosine in target DNA. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of deaminating double-stranded DNA with a cytidine toxin-derived deaminase (TDD) in Fauser to incorporate the ligation of a hairpin adapter with a double-stranded region comprising a nickable site to a double stranded nucleic acid before converting through deamination as taught in Desantis because Desantis teaches that doing so would provide a method to determine important information in the methylation status and levels in nucleic acids.
Response to Arguments
The response traverses the rejection. The response asserts that each of the rejected dependent claims, claims 7, 14, 5, 17, & 18, require a double-stranded DNA deaminase having at least 80% identity to SEQ ID NO: 11 and that the office action does not identify SEQ ID NO: 11 in any reference, nor does it identify any double-stranded DNA deaminases that has at least 80% identity to SEQ ID NO: 11. Further, the response asserts that no combination of Farzadfard with the secondary references (Vaisvila, Xiong, DeSantis) cure these deficiencies as the secondary references use an unrelated deaminase or lack disclosure of any double-stranded DNA deaminase. This argument has been thoroughly reviewed but was not found persuasive as SEQ ID NO: 33 is rejoined with SEQ ID NO: 11 in claims 1, 8, 10, 12, 16, & 19 and the prior art of Fauser, as applied to amended independent claim 1 as necessitated by amendment, teaches every element of claim 1 as discussed above.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Double Patenting
Claim 1-5, 9, 11, 13, & 34-38 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-3, 6-8, 13, 15, 17, 18, & 19-21 of copending Application No. 18/323,143 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because each patent application provides a method for deaminating dsDNA with a dsDNA deaminase and sequencing the deamination product.
Regarding amended claim 1 & claims 2 & 4, the instant application claims a method for deaminating a double-stranded nucleic acid comprising contacting a dsDNA substrate that comprises modified cytosines and a dsDNA deaminase having an amino acid sequence that is at least 80% identical to any of SEQ ID NOs: 40 & 63 to produce a deamination product and then sequencing the deamination product. Copending Application No. 18/323,143 claims a method for sequencing comprising contacting a dsDNA substrate with a dsDNA deaminase that has sequence bias for cytosine in a CpG context and is modification sensitive and sequencing the deamination product in which the dsDNA deaminase has an amino acid sequence that is at least 80% identical to any of SEQ ID NOs: 40 & 63 (see claims 1-3, 8, & 13).
Regarding claims 9 & 11, the instant application claims wherein the dsDNA substrate is pre-treated with a TET methylcytosine dioxygenase and DNA beta-glucosyltransferase and wherein the dsDNA substrate is pre-treated with a TET methylcytosine dioxygenase but not DNA beta-glucosyltransferase. Copending Application No. 18/323,143 claims wherein the dsDNA substrate is pre-treated with a TET methylcytosine dioxygenase, and optionally is pre-treated with a DNA beta-glucosyltransferase (see claim 7).
Regarding claim 13, the instant application claims wherein the dsDNA substrate is not pre-treated with either a TET methylcytosine dioxygenase or DNA beta-glucosyltransferase. Copending Application No. 18/323,143 claims wherein the dsDNA substrate is not pre-treated with either a TET methylcytosine dioxygenase or DNA beta-glucosyltransferase (see claim 6).
Regarding amended claim 1 & claims 3-5, the instant application claims a method comprising a dsDNA deaminase having an amino acid sequence that is at least 80% identical to any of SEQ ID NOs: 4, 5, 16, & 99, wherein the modified cytosine is 5fC, 5caC, 5mC, 5hmC, N4mC, 5ghmC, or pyrrolo-C, and wherein the method further comprises analyzing the sequence reads to identify a modified cytosine in the dsDNA substrate. Copending Application No. 18/323,143 claims a method comprising a dsDNA deaminase having an amino acid sequence that is at least 80% identical to any of SEQ ID NOs: 4, 5, 16, & 99, further comprising analyzing the sequence reads to identify a modified cytosine in the dsDNA substrate, and wherein the modified cytosine is one or more of 5fC, 5caC, 5mC, 5hmC, N4mC, or 5ghmC (see claims 1, 15, 17, & 18).
Regarding amended claim 1, the instant application claims a method for deaminating a double-stranded nucleic acid comprising contacting a dsDNA substrate that comprises cytosines and a dsDNA deaminase having an amino acid sequence that is at least 80% identical to any of SEQ ID NOs: 40, 49, 50, & 63 to produce a deamination product that comprises deaminated cytosines. Copending Application No. 18/323,143 claims a method for deaminating a double-stranded nucleic acid comprising contacting a dsDNA substrate that comprises cytosines and a dsDNA deaminase having an amino acid sequence that is at least 80% identical to any of SEQ ID NOs: 40, 49, 50, & 63 to produce a deamination product that comprises deaminated cytosines (see claim 19).
Regarding claim 2, the instant application claims wherein the dsDNA substrate further comprises a modified cytosine. Copending Application No. 18/323,143 claims wherein the dsDNA substrate further comprises a modified cytosine (see claim 20).
Regarding claim 3, the instant application claims wherein the modified cytosine is 5fC, 5caC, 5mC, 5hmC, N4mC, 5ghmC, or pyrrolo-C. Copending Application No. 18/323,143 claims wherein the modified cytosine is 5fC, 5caC, 5mC, 5hmC, N4mC, 5ghmC, or pyrrolo-C (see claim 21).
Regarding new claims 34-38, the instant application claims a method comprising a dsDNA deaminase having an amino acid sequence that is at least 80% identical to any of SEQ ID NOs: 10 & 96 wherein the modified cytosine is 5fC, 5caC, 5mC, 5hmC, N4mC, 5ghmC, or pyrrolo-C, and wherein the method further comprises analyzing the sequence reads to identify a modified cytosine in the dsDNA substrate. Copending Application No. 18/323,143 claims a method comprising a dsDNA deaminase having an amino acid sequence that is at least 80% identical to any of SEQ ID NOs: 10 & 96 further comprising analyzing the sequence reads to identify a modified cytosine in the dsDNA substrate, and wherein the modified cytosine is one or more of 5fC, 5caC, 5mC, 5hmC, N4mC, or 5ghmC (see claims 1, 15, 17, & 18).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant’s response does not provide any arguments and requests that the provisional nonstatutory double patenting rejection be held in abeyance until patentable subject matter in the co-pending application has been identified. Therefore, these rejections are maintained, and modified to address the claims as currently amended, from the previous office action.
Conclusion
Claims 1-7, 9, 11, 13-15, 17-19, & 34-38 are rejected. Claims 8, 10, 16, & 39-42 are objected to as being dependent from rejected claims. It is noted, as discussed previously, that double-stranded DNA deaminases having an amino acid sequence that is at least 90% identical to SEQ ID NOs: 11, 27, & 40 were searched and found free of the prior art.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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