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 amendment of claim 1, 12, 16, 120, 121, 140 and 141, in the paper of 11/5/2025, is acknowledged. Applicants' arguments filed on 11/5/2025, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 1, 2, 7, 12, 13, 16, 19, 22, 23, 26, 49, 50, 63, 65, 80, 84, 86, 97, 103, 112, 115, 120, 121, 139-143 are still at issue and are present for examination.
Election/Restrictions
Applicant's election of the invention of Group 1, claims 1, 2, 12, 13, 16, 19, 22, 26, 49, 50, 63, 80, 120, 121,140-143, drawn to a fusion polypeptide/protein, in the paper of 7/18/2025, is acknowledged. Applicant's election of the following species: SEQ ID NO:1, SEQ ID NO:39, SEQ ID NO:47 and SEQ ID NO:41, in the paper of 7/18/2025, is acknowledged.
Claims 7, 84, 86, 97, 103, 112, 115, 139, 141 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claim Objections
Claims 13 and 121 is objected to because of the following informalities:
Claim 13 depends from rejected claim 12.
Claim 121 depends from rejected claim 120.
Appropriate correction 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 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Doucette-Stamm and Bush (US 6,380,370).
This rejection was stated in the previous office action as it applied to previous claims 1 and 2. In response applicants have amended the claims and traverse the rejection as it applies to the newly amended claims. It is noted that applicants have amended the claims from having at least 80% sequence identity to SEQ ID NO:1 to having at least 90% sequence identity to SEQ ID NO:1. Applicants traverse the rejection on the basis that applicants amendment of the claims is cause for the withdrawal of the rejection. This is not found persuasive for the following reasons. The original rejection is repeated herein.
Doucette-Stamm and Bush (US 6,380,370) teach a number of nucleic acid and amino acid sequences relating to Staphylococcus epidermidis for diagnostics and therapeutics use. Doucette-Stamm and Bush disclose a polypeptide comprising the amino acid sequence of SEQ ID NO: 2954 which has at least 89% sequence identity to instant SEQ ID NO:1 (see alignment below) and comprises the amino acid sequence of instant SEQ ID NO:33. Additionally the polypeptide taught by Doucette-Stamm and Bush comprises 4 amino acids on the amino terminus and 4 amino acids on the carboxy terminus thus meeting the limitation of a fusion polypeptide comprising amino acid sequence that is heterologous to the first amino acid sequence having 80% sequence identity to SEQ ID NO:1.
Query Match 90.6%; Score 557; Length 120;
Best Local Similarity 89.7%;
Matches 104; Conservative 7; Mismatches 5; Indels 0; Gaps 0;
SEQ 1: 1 MKTTTQELKQYITRLFQLSNNETWECEALEEAAENILPERFINNSLLAHLTLNTYTYYND 60
|||||||||||:||||||||||||||| ||||||||||:||||:| |||| | ||||||:
370: 5 MKTTTQELKQYMTRLFQLSNNETWECETLEEAAENILPKRFINDSPLAHLILETYTYYNN 64
SEQ 1: 61 ELHELSIYPFLMYANDQLISIGYLDHFDMDFLYLTDTKNTIIDERHLLKQGENNHE 116
|||||||||||||:|:|||||||||||||||||||||||||||||||||:| ||||
370: 65 ELHELSIYPFLMYSNNQLISIGYLDHFDMDFLYLTDTKNTIIDERHLLKEGGNNHE 120
SEQ 33
Applicants amendment of the claims and applicants traversal based upon this amendment is acknowledged and has been carefully considered, however, is not found persuasive for the reasons previously stated and for those reasons repeated herein.
Based upon the previously presented alignment of the polypeptide amino acid sequence disclosed by Doucette-Stamm and Bush, has 5 mismatches out of 116 residues. Thus 111 of 116 positions is 95.6%. Further, 104 of 116 positions is 89.7%. While it is admitted that the above alignment comprises some conservative residues these are considered identical based upon applicants specification which states “When sequences differ in conservative substitutions, the percent sequence identity may be adjusted upwards to correct for the conservative nature of the substitution” (page 31, line 12 thru page 32, line 36).
Thus, claim(s) 1, 2 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Doucette-Stamm and Bush (US 6,380,370).
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 rejection of claim(s) 1, 2, 12, 13, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and DATABASE UniParc UNIPROT, UPI0007698A58, “s, AUREUS URACIL dna GLYCOSYLASE INHIBITOR,” 2016 is withdrawn based upon applicants amendment of the claims and applicants arguments presented in the paper of 11/5/2025. Specifically applicants statement that “the designation of the UNIPROT UPI0007698A58 sequence as a UGI was not added to the RefSeq entry until February 17, 2022, which is after the effective filing date of the present application, July 15, 2021” is persuasive in causing the withdrawal of the rejection.
The rejection of claim(s) 16 under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and DATABASE UniParc UNIPROT, UPI0007698A58, “S. AUREUS URACIL dna GLYCOSYLASE INHIBITOR,” 2016 as applied to claims 1, 2, 12, 13, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of UNIPROT A0A2R2Z4D8 11-DEC-2019 is withdrawn based upon applicants amendment of the claims and applicants arguments presented in the paper of 11/5/2025. Specifically applicants statement that “the designation of the UNIPROT UPI0007698A58 sequence as a UGI was not added to the RefSeq entry until February 17, 2022, which is after the effective filing date of the present application, July 15, 2021” is persuasive in causing the withdrawal of the rejection.
The rejection of claim(s) 22 under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and DATABASE UniParc UNIPROT, UPI0007698A58, “S. AUREUS URACIL dna GLYCOSYLASE INHIBITOR,” 2016 as applied to claims 1, 2, 12, 13, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of Crawley et al., US Patent No. 11,162,114 is withdrawn based upon applicants amendment of the claims and applicants arguments presented in the paper of 11/5/2025. Specifically applicants statement that “the designation of the UNIPROT UPI0007698A58 sequence as a UGI was not added to the RefSeq entry until February 17, 2022, which is after the effective filing date of the present application, July 15, 2021” is persuasive in causing the withdrawal of the rejection.
The rejection of claim(s) 140 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and DATABASE UniParc UNIPROT, UPI0007698A58, “S. AUREUS URACIL dna GLYCOSYLASE INHIBITOR,” 2016 as applied to claims 1, 2, 12, 13, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of UNIPROT A0A2R2Z4D8 11-DEC-2019 and Crawley et al., US Patent No. 11,162,114 is withdrawn based upon applicants amendment of the claims and applicants arguments presented in the paper of 11/5/2025. Specifically applicants statement that “the designation of the UNIPROT UPI0007698A58 sequence as a UGI was not added to the RefSeq entry until February 17, 2022, which is after the effective filing date of the present application, July 15, 2021” is persuasive in causing the withdrawal of the rejection..
Claim(s) 1, 2, 12, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019.
Liu et al. disclose strategies, systems, reagents, methods, and kits that are useful for the targeted editing of nucleic acids, including editing a single site within the genome of a cell or subject, e.g., within the human genome. Liu et al. disclose fusion proteins comprising a Gam protein, a napDNAbp (DNA binding protein that complexes with a guide RNA), and a cytidine deaminase. Liu et al. disclose the taught fusion proteins further comprise a UGI (uracil glycolase inhibitor or uracil stabilizing polypeptide) domain and nuclear localization signals, wherein said fusion protein is within a cell and is a RNA-guided nuclease/nickase polypeptide that complexes with a guide RNA. Liu et al. disclose methods for targeted nucleic acid editing wherein the target DNA is within a cell, reagents and kits for the generation of targeted nucleic acid editing proteins, e.g., fusion proteins of a Gam protein, a cytidine deaminase and nucleic acid editing proteins or domains. Liu et al. teach a number of base editors, for example, base editor 2 (BE2) or base editor 3 (BE3), may be converted into high fidelity base editors by modifying the Cas9 domain to generate high fidelity base editors, for example, high fidelity base editor 2 (HF-BE2) or high fidelity base editor 3 (HF-BE3). Liu et al. teach that the base editor 2 (BE2) comprises a deaminase domain, a dCas9, and a UGI domain. Liu et al. teach that in some embodiments, base editor 3 (BE3) comprises a deaminase domain, anCas9 domain and a UGI domain. Liu et al. teach nucleic acids encoding the above fusion proteins located on a plasmid with a nucleic acid encoding a RNA guide under control of a heterologous promoter.
Uniprot Accession No. A0A3S7GYQ1, Dec 2019 discloses S. hominus SAUGI (S. aureus uracil glycolase inhibitor) protein and its amino acid sequence which has greater than 92% sequence identity to instant SEQ ID NO:1 and it comprises the amino acid sequence of instant SEQ ID NO:39.
One of skill in the art before the effective filing date would have been motivated to practice the methods taught by Liu et al. using the tools taught by Liu et al. with substutions of the various domains of the fusion proteins taught by Liu et al. as a means of adding versatility to the methods and compositions taught by Liu et al. One of skill in the art before the effective filing date would have been motivated to substitute the S. aureus uracil DNA glycosylase inhibitor protein taught by Uniprot Accession No. A0A3S7GYQ1 for the UGI for the same functional domain in the fusion proteins taught by Liu et al. to practice the methods taught by Liu et al. The expectation of success is high based upon the high level of recombinant protein engineering as exemplified by Liu et al. who teach all the techniques necessary to prepare the obvious fusion proteins.
Thus claim(s) 1, 2, 12, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 as applied to claims 1, 2, 12, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of UNIPROT A0A2R2Z4D8 11-DEC-2019.
The teachings of Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 and that which is obvious over the references is stated above.
UNIPROT A0A2R2Z4D8 11-DEC-2019 disclose an Apolipoprotein B mRNA editing enzyme catalytic polypeptide comprising 230 amino acids which is a deaminase and which is 100% identical to the amino acid sequence of instant SEQ ID NO:47.
As stated above, one of skill in the art before the effective filing date would have been motivated to practice the methods taught by Liu et al. using the tools taught by Liu et al. with substitutions of the various domains of the fusion proteins taught by Liu et al. as a means of adding versatility to the methods and compositions taught by Liu et al. One of skill in the art before the effective filing date would have been motivated to substitute the S. aureus uracil DNA glycosylase inhibitor protein taught by DATABASE UniParc UNIPROT, UPI0007698A58 for the UGI for the same functional domain in the fusion proteins taught by Liu et al. to practice the methods taught by Liu et al.
One of skill in the art before the effective filing date would have been further motivated to substitute the Apolipoprotein B mRNA editing enzyme catalytic polypeptide comprising 230 amino acids which is a deaminase taught by UNIPROT A0A2R2Z4D8 11-DEC-2019 for the deaminase domain in the above fusion protein made obvious over by Liu et al. and DATABASE UniParc UNIPROT, UPI0007698A58, “S. AUREUS URACIL dna GLYCOSYLASE INHIBITOR,” 2016 to practice the methods taught by Liu et al. As above, the expectation of success is high based upon the high level of recombinant protein engineering as exemplified by Liu et al. who teach all the techniques necessary to prepare the obvious fusion proteins.
Thus claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 as applied to claims 1, 2, 12, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of UNIPROT A0A2R2Z4D8 11-DEC-2019.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 as applied to claims 1, 2, 12, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of Crawley et al., US Patent No. 11,162,114.
The teachings of Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 and that which is obvious over the references is stated above.
Crawley et al., US Patent No. 11,162,114 disclose an RNA guided nuclease comprising 1070 amino acids which is greater than 80% identical to the amino acid sequence of instant SEQ ID NO:41.
As stated above, one of skill in the art before the effective filing date would have been motivated to practice the methods taught by Liu et al. using the tools taught by Liu et al. with substitutions of the various domains of the fusion proteins taught by Liu et al. as a means of adding versatility to the methods and compositions taught by Liu et al. One of skill in the art before the effective filing date would have been motivated to substitute the S. aureus uracil DNA glycosylase inhibitor protein taught by DATABASE UniParc UNIPROT, UPI0007698A58 for the UGI for the same functional domain in the fusion proteins taught by Liu et al. to practice the methods taught by Liu et al.
One of skill in the art before the effective filing date would have been further motivated to substitute the RNA guided nuclease comprising 1070 amino acids which is greater than 80% identical to the amino acid sequence of instant SEQ ID NO:41 taught by Crawley et al., US Patent No. 11,162,114 for the RNA guided nuclease in the above fusion protein made obvious over by Liu et al. and DATABASE UniParc UNIPROT, UPI0007698A58, “S. AUREUS URACIL dna GLYCOSYLASE INHIBITOR,” 2016 to practice the methods taught by Liu et al. As above, the expectation of success is high based upon the high level of recombinant protein engineering as exemplified by Liu et al. who teach all the techniques necessary to prepare the obvious fusion proteins.
Thus claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 as applied to claims 1, 2, 12, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of Crawley et al., US Patent No. 11,162,114.
Claim(s) 140 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 as applied to claims 1, 2, 12, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of UNIPROT A0A2R2Z4D8 11-DEC-2019 and Crawley et al., US Patent No. 11,162,114.
The teachings of Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 and that which is obvious over the references is stated above.
UNIPROT A0A2R2Z4D8 11-DEC-2019 disclose an Apolipoprotein B mRNA editing enzyme catalytic polypeptide comprising 230 amino acids which is a deaminase and which is 100% identical to the amino acid sequence of instant SEQ ID NO:47.
Crawley et al., US Patent No. 11,162,114 disclose an RNA guided nuclease comprising 1070 amino acids which is greater than 80% identical to the amino acid sequence of instant SEQ ID NO:41.
As stated above, one of skill in the art before the effective filing date would have been motivated to practice the methods taught by Liu et al. using the tools taught by Liu et al. with substitutions of the various domains of the fusion proteins taught by Liu et al. as a means of adding versatility to the methods and compositions taught by Liu et al. One of skill in the art before the effective filing date would have been motivated to substitute the S. aureus uracil DNA glycosylase inhibitor protein taught by DATABASE UniParc UNIPROT, UPI0007698A58 for the UGI for the same functional domain in the fusion proteins taught by Liu et al. to practice the methods taught by Liu et al.
One of skill in the art before the effective filing date would have been further motivated to substitute the Apolipoprotein B mRNA editing enzyme catalytic polypeptide comprising 230 amino acids which is a deaminase taught by UNIPROT A0A2R2Z4D8 11-DEC-2019 for the deaminase domain in the above fusion protein made obvious over by Liu et al. and DATABASE UniParc UNIPROT, UPI0007698A58, “S. AUREUS URACIL dna GLYCOSYLASE INHIBITOR,” 2016 and to substitute the RNA guided nuclease comprising 1070 amino acids which is greater than 80% identical to the amino acid sequence of instant SEQ ID NO:41 taught by Crawley et al., US Patent No. 11,162,114 for the RNA guided nuclease in the above fusion protein made obvious over by Liu et al. and DATABASE UniParc UNIPROT, UPI0007698A58, “S. AUREUS URACIL dna GLYCOSYLASE INHIBITOR,” 2016 to practice the methods taught by Liu et al. As above, the expectation of success is high based upon the high level of recombinant protein engineering as exemplified by Liu et al. who teach all the techniques necessary to prepare the obvious fusion proteins.
Thus, Claim(s) 140 is/are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (US 2020/0190493) and Uniprot Accession No. A0A3S7GYQ1, Dec 11 2019 as applied to claims 1, 2, 12, 19, 23, 26, 49, 50, 63, 65, 80, 120, 142 and 143 above, and further in view of UNIPROT A0A2R2Z4D8 11-DEC-2019 and Crawley et al., US Patent No. 11,162,114.
Remarks
No claim is allowed.
Conclusion
Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 11/5/2025 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). 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 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
3/13/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652