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 I, claims 1-21 & 26, and the species elections of 5mC in claim 4, of SEQ ID NO: 40 in claim 8, of SEQ ID NO: 49 in claims 9, 19-21, & 26, of 5hmC in claim 17, of 5mC in claim 21, and of SEQ ID NO: 4 in claim 18, in the reply filed on 11/28/2025 is acknowledged. The species of SEQ ID NO: 62 is rejoined with SEQ ID NO: 40 in claim 8, the species of SEQ ID NO: 55 is rejoined with SEQ ID NO: 49 in claims 9, 19-21, & 26, and the species of SEQ ID NO: 10 is rejoined with SEQ ID NO: 4 in claim 18. Group II, claims 22-25 & 27-32, and Group III, claims 33-36, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A first office action on the merits of claims 1-21 & 26 is set forth herein and claims 22-25 & 27-36 are withdrawn from consideration.
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. 63/264,513, 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, 63/264,513, does not have support for all of the limitations in claims 3-5, 8-12, 14, 17-21, & 26 of the instant application. The provisional application, 63/264,513, does not provide support for a double-stranded deaminase having an amino acid sequence that is at least 80% identical to SEQ ID NOS: 4, 10, 13, 16, 21, 40, 47, 49, 50, 55, 58, 59, 62, 63, 65, 67, 70, 71, 76, 99, 106, 107, 110, 112, 114, 117, 163, and 164, support for modification sensitivity, or linking the double-stranded DNA substrate to an adapter. Accordingly, claims 3-5, 8-12, 14, 17-21, & 26 are not entitled to the benefit of the prior applications. Therefore, claims 3-5, 8-12, 14, 17-21, & 26 are given a priority date of the date of filing 11/22/2022.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 8, 9, 18-21, & 26 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are broadly drawn to a method for deaminated a nucleic acid comprising contacting a double stranded DNA substrate with a double stranded DNA deaminase that has an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 4, 5, 10, 13, 16, 21, 40, 47, 49, 50, 55, 58, 59, 62, 63, 65, 67, 70, 71, 76, 96, 99, 106, 107, 110, 112, 114, 117, 163, and 164.
The claims therefore comprise a large number of structurally undefined amino acid sequences which possess the functionality of being a double stranded DNA deaminase.
Relevant to the lack of particular structural limitations in the rejected claims drawn to amino acid sequences, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
In the case of the instant claims, the functionality of being a double stranded DNA deaminase is a critical feature of the claimed methods.
The specification teaches the double stranded DNA deaminases can be naturally or non-naturally occurring DNA deaminases. Further, the specification teaches the non-naturally occurring double-stranded DNA deaminases may have a high degree of identity to a portion of a naturally occurring sequence but may lack structural and/or functional domains and further that non-naturally occurring double stranded DNA deaminases may have less than 100%-20% identity to a naturally occurring enzyme (pg. 11 of the specification of the instant application). Further, the specification teaches that in some embodiments a non-naturally occurring double stranded DNA deaminase lacks at least 10 to at least 100 of the N-terminal amino acids of the corresponding naturally-occurring protein (pg. 12 of the specification of the instant application). However, the specification does not teach which 80% identity to amino acid SEQ ID NOs: 4, 5, 10, 13, 16, 21, 40, 47, 49, 50, 55, 58, 59, 62, 63, 65, 67, 70, 71, 76, 96, 99, 106, 107, 110, 112, 114, 117, 163, and 164 function as a double-stranded DNA deaminase. Further, the specification does not teach what can be changed in the amino acid sequences, while maintaining at least 80% identity to the listed SEQ ID NOs, and still maintaining the claimed function of deaminated double stranded DNA. Further, the specification teaches the double stranded DNA deaminase has an amino acid sequence that is at least 80% identical to any of listed SEQ ID NOs and double stranded DNA deaminases that lack N-terminal amino acids, therefore contemplating shorter fragments in the listed SEQ ID NOs, however the specification does not teach which fragments maintain a function of being a double stranded DNA deaminase.
The specification provides guidance on naturally and non-naturally occurring DNA deaminases, however, the specification does not provide guidance on what variability of 80% identity to listed SEQ ID NOs provides the function of deaminating double stranded DNA from those that do not.
While the skilled artisan may be capable of making an amino acid sequence with at least 80% to any of the SEQ ID NOs listed in the claims with the claimed functionality of being a double stranded DNA deaminase, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims encompass a genus of structurally undefined amino acid sequence which require a specific functionality. However, the specification fails to teach how to distinguish members of the claimed genus of amino acid sequence which possess the claim functionality: being a double stranded DNA deaminase, from non-members, especially in light of the guidance of the specification which contemplates the amino acid sequences as listed in the claims and fragments of the amino acid sequence as listed in the claims.
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. Further, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Thus considering the breadth of the amino acid sequences required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
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.
Claims 8, 9, 15-21, & 26 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 8, the recitation of “the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 40, 62, 63, 65, 67, 71, 110, 112, 114, and 117” in lines 1-3 of the claim is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required.
Regarding claim 9, the recitation of “the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 47, 49, 50, 55, 58, 59, 70, 76, 106, 107, 163, and 164” in lines 1-3 of the claim is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required. In addition, the recitation of “an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 47, …, 106, 107, 163 and 164” in lines 2-3 of the claim is unclear is SEQ ID NOS: 163 and 164 are a part of the same double-stranded deaminase or if it is the result of a typographical error and should read “an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 47, …, 106, 107, 163, and 164”.
Regarding claim 15, the recitation of “analyzing sequence reads to identify a modified cytosine in the double-stranded DNA substrate” in lines 1-2 of the claim is unclear. It is unclear as claim 1, from which claim 15 depends from , recites “sequencing the deamination product”, therefore it is unclear if the “sequence reads” of claim 15 are from sequencing the deamination product or from sequencing the “double-stranded DNA substrate” which has not been treated with a double-stranded DNA deaminase.
Regarding claim 18, the recitation of “the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 4, 5, 10, 13, 16, 96, 99, and 106” in lines 1-3 of the claim is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required. In addition, the recitation of “an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 4, …, 16, 96, 99 and 106” in lines 2-3 of the claim is unclear is SEQ ID NOS: 99 and 106 are a part of the same double-stranded deaminase or if it is the result of a typographical error and should read “an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 4, …, 16, 96, 99, and 106”.
Regarding claim 19, the recitation of “the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 21, 40, 47, 49, 50, 55, 58, 59, 62, 63, 65, 67, 70, 71, 76, 106, 107, 110, 112, 114, 117, 163, and 164” in lines 4-6 of the claim is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required.
Regarding claim 26, the recitation of “an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 21, 40, 47, 49, 50, 55, 58, 59, 62, 63, 65, 67, 70, 71, 76, 106, 107, 110, 112, 114, 117, 163, and 164” in is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required.
Claims 16 & 17 are rejected due to their dependence on claim 15 and claims 20 & 21 are rejected due to their dependence on claim 19.
Claim Rejections - 35 USC § 102
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) 1-4, 6, & 10-15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Komor (Komor et al.; Nature Letter, Vol. 533, pages 420-436, May 2016), as cited on the IDS dated 06/16/2023.
Regarding claim 1, Komor teaches a deaminase assay on double-stranded DNA in which double-stranded DNA is contacted with a double-stranded DNA deaminase to produce a deamination product and then the deaminated product is sequenced (pg. 420 column 2 1st full paragraph lines 1-16; pg. 420 column 2 2nd full paragraph lines 1-11; pg. 421 paragraph bridging columns 1 & 2 lines 1-11; pg. 425 column 1 4th full paragraph lines 1-4; pg. 425 column 2 1st full paragraph lines 1-15; pg. 425 column 2 2nd full paragraph lines 1-19).
Regarding claim 2, Komor teaches the fusion double-stranded DNA deaminase contains APOBEC1 which is a cytosine deaminase (the double-stranded DNA deaminase has a sequence bias for cytosine) (pg. 420 column 2 2nd full paragraph lines 1-11; pg. 421 paragraph bridging columns 1 & 2 lines 1-11; pg. 425 column 1 4th full paragraph lines 1-4).
Regarding claim 3, the specification of the instant application teaches that the double-stranded DNA deaminase may be modification sensitive and, for example, a double-stranded DNA deaminase may deaminate cytosine but not deaminate 5mC or N4mC. Therefore, the claim is given its broadest reasonable interpretation to encompass a double-stranded DNA deaminase that modifies specific type of nucleotide.
Komor teaches the fusion double-stranded DNA deaminase specifically modifies and deaminates cytosines to convert to uracils (double-stranded DNA deaminase is modification sensitive) (pg. 420 column 2 1st full paragraph lines 1-3; pg. 420 column 2 2nd full paragraph lines 1-11; pg. 421 paragraph bridging columns 1 & 2 lines 1-11).
Regarding claim 4, Komor teaches the fusion double-stranded DNA deaminase specifically modifies and deaminates cytosines to convert to uracils (double-stranded DNA deaminase does not deaminate 5mC) (pg. 420 column 2 1st full paragraph lines 1-3; pg. 420 column 2 2nd full paragraph lines 1-11; pg. 421 paragraph bridging columns 1 & 2 lines 1-11).
Regarding claim 6, Komor teaches the double-stranded DNA substrate is not pre-treated with either TET methylcytosine dioxygenase or DNA beta-glucosyltransferase (pg. 425 column 2 1st full paragraph lines 1-15).
Regarding claims 10 & 11, Komor teaches that the double-stranded DNA substrates are combined with a Cy3-labelled primer that is complementary to the 3’ end of each double-stranded DNA substrate (the double-stranded DNA substrate further comprises a fragment linked to an adapter wherein the adapter comprises a primer) (pg. 425 paragraph bridging column 1 & column 2 lines 3-11).
Regarding claim 12, Komor teaches that the double-stranded DNA substrates are combined with a Cy3-labelled primer that is complementary to the 3’ end of each double-stranded DNA substrate (strands of the double-stranded DNA substrate are not linked together by an adapter) (pg. 425 paragraph bridging column 1 & column 2 lines 3-11).
Regarding claim 13, Komor teaches the fusion double-stranded DNA deaminase contains APOBEC1 and deaminates a double-stranded DNA substrate (the deamination product is double-stranded) (pg. 425 column 1 4th full paragraph lines 1-4).
Regarding claim 14, Komor teaches that the double-stranded DNA substrates are combined with a Cy3-labelled primer that is complementary to the 3’ end of each double-stranded DNA substrate (strands of the double-stranded DNA substrate are not linked together by an adapter and the double-stranded DNA substrate is not a multi-copy strand) (pg. 425 paragraph bridging column 1 & column 2 lines 3-11).
Regarding claim 15, Komor teaches analyzing the sequence reads to identify conversion of cytosine to uracil (identify a modified cytosine in the double-stranded DNA substrate) (pg. 421 paragraph bridging column 1 & column 2 lines 8-11; pg. 426 paragraph bridging column 1 & column 2 lines 1-3).
Claim Rejections - 35 USC § 103
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.
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) 5, 7, 16, & 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Komor (Komor et al.; Nature Letter, Vol. 533, pages 420-436, May 2016), as cited on the IDS dated 06/16/2023, in view of Schutsky (Schutsky et al.; Nature Biotechnology, Vol. 36, pages 1083-1094, November 2018).
The teachings of Komor with respect to claims 1, 2, & 15 are discussed above and incorporated herein.
Regarding claim 5, Komor does not teach that the double-stranded DNA deaminase is not modification sensitive.
Schutsky teaches a method of APOBEC-couple sequencing in which the APOBEC family DNA deaminase enzyme can discriminate between cytosine modifications and that this method can be used to detect 5mC and 5hmC in samples through enzymatic deamination (DNA deaminase can detect multiple types of cytosine modifications and is not modification sensitive) (abstract lines 1-8; pg. 1083 column 2 2nd full paragraph lines 1-7; pg. 1084 column 1 1st full paragraph lines 6-15). Schutsky also teaches that this method of enzymatic deamination overcomes many challenges posed by bisulfite-based methods and enables greater characterization of modified cytosines in genomic DNA (abstract lines 8-10; pg. 1089 column 2 1st full paragraph lines 22-25).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate in Komor to incorporate the use of APOBEC3A DNA deaminase that is not modification sensitive as taught in Schutsky because Schutsky teaches that doing so would provide a method that enables greater characterization of modified cytosines in genomic DNA and overcomes challenges posed by bisulfite-based methods.
Regarding claim 7, Komor does not teach that the double-stranded DNA substrate is pre-treated with TET methylcytosine dioxygenase.
Schutsky teach that to detect 5hmC specifically the sample may be treated with TET to enzymatically modify the 5hmC bases to 5ghmC and further that the sample may be treated with beta-glucosyltransferase (DNA substrate is pre-treated with a TET methylcytosine dioxygenase and optionally is pre-treated with DNA beta-glucosyltransferase) (pg. 1083 paragraph bridging column 1 & column 2 lines 9-14; pg. 1087 paragraph bridging column 1 & 2 lines 1-18). Schutsky also teaches that this method of enzymatic deamination overcomes many challenges posed by bisulfite-based methods and enables greater characterization of modified cytosines in genomic DNA (abstract lines 8-10; pg. 1089 column 2 1st full paragraph lines 22-25).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate that is not pre-treated with TET in Komor to incorporate the use of APOBEC3A DNA deaminase that is pre-treated with TET and optionally beta-glucosyltransferase as taught in Schutsky because Schutsky teaches that doing so would provide a method that enables greater characterization of modified cytosines in genomic DNA and overcomes challenges posed by bisulfite-based methods.
Regarding claim 16, Komor does not teach that a reference sequence is not used for analysis of the sequence reads.
Schutsky teaches that the sequence reads were analyzed through visualizing signals with Refseq transcript annotation as a reference in which the modified cytosines are indicated by upwards and downward ticks with the height of each tick representing the fraction of modification (analyzing the sequence reads to identify a modified cytosine wherein a reference sequence is not used for analyzing) (pg. 1092 paragraph bridging column 1 & 2 lines 1-8). Schutsky also teaches that this method of enzymatic deamination overcomes many challenges posed by bisulfite-based methods and enables greater characterization of modified cytosines in genomic DNA (abstract lines 8-10; pg. 1089 column 2 1st full paragraph lines 22-25).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate and analysis of the sequence reads to identify modified cytosines in Komor to incorporate analysis of the sequence reads without the use of a reference sequence as taught in Schutsky because Schutsky teaches that doing so would provide a method that enables greater characterization of modified cytosines in genomic DNA and overcomes challenges posed by bisulfite-based methods.
Regarding claim 17, Komor does not teach that the modified cytosine is 5hmC.
Schutsky teaches a method of APOBEC-couple sequencing in which the APOBEC family DNA deaminase enzyme can discriminate between cytosine modifications and that this method can be used to detect 5mC and 5hmC in samples through enzymatic deamination (wherein the modified cytosine is 5hmC) (abstract lines 1-8; pg. 1083 column 2 2nd full paragraph lines 1-7; pg. 1084 column 1 1st full paragraph lines 6-15). Schutsky also teaches that this method of enzymatic deamination overcomes many challenges posed by bisulfite-based methods and enables greater characterization of modified cytosines in genomic DNA (abstract lines 8-10; pg. 1089 column 2 1st full paragraph lines 22-25).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate to identify modified cytosines in Komor to incorporate analysis of 5hmC cytosine modifications as taught in Schutsky because Schutsky teaches that doing so would provide a method that enables greater characterization of modified cytosines in genomic DNA and overcomes challenges posed by bisulfite-based methods.
Claim(s) 8, 9, 17-21, & 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Komor (Komor et al.; Nature Letter, Vol. 533, pages 420-436, May 2016), as cited on the IDS dated 06/16/2023, in view of Farzadfard (U.S. Patent Application Publication US 2024/0318159 A1, January 2022).
The teachings of Komor with respect to claim 15 are discussed above and incorporated herein.
Regarding claim 8, it is noted as discussed above, the recitation of “the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 40, 62, 63, 65, 67, 71, 110, 112, 114, and 117” in lines 1-3 of the claim is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required. Further, the specification of the instant application teaches a double stranded DNA deaminase lacks at least 10 to at least 100 of the N-terminal amino acids of the corresponding naturally-occurring protein and that in some embodiments a double stranded DNA deaminase that is no more than 150-300 nucleotides in length (pg. 12 of the specification of the instant application), therefore contemplating fragments of double stranded DNA deaminases. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to include a double stranded DNA deaminase that has at least 80% identity to a fragment of amino acid sequence of SEQ ID NO: 62.
Komor does not teach that the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to a fragment of SEQ ID NO: 62.
Farzadfard teaches a method for deaminating double-stranded (ds) DNA in which dsDNA-specific deaminases, including dsDNA-specific deaminases that deaminate cytosine nucleotides, including 5hmC, deaminate target nucleotides in double-stranded DNA in which the double-stranded deaminase comprises SEQ ID NO: 16, in which SEQ ID NO: 16 is 100% identical to SEQ ID NO: 62, from positions 1 through 10, of the instant application (a double-stranded DNA deaminase having an amino acid sequence that is at least 80% identical to a fragment of SEQ ID NO: 62) (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 that this method enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease (paragraph [0114] lines 1-8).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate to identify modified cytosines in Komor to incorporate analysis of 5hmC cytosine modifications with a double-stranded DNA deaminase comprising SEQ ID NO: 16 (100% identical to a fragment of SEQ ID NO: 62 of the instant application) as taught in Farzadfard because Farzadfard teaches that doing so would provide a method that enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease.
Regarding claim 9, it is noted as discussed above, the recitation of “the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 47, 49, 50, 55, 58, 59, 70, 76, 106, 107, 163, and 164” in lines 1-3 of the claim is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required. Further, the specification of the instant application teaches a double stranded DNA deaminase lacks at least 10 to at least 100 of the N-terminal amino acids of the corresponding naturally-occurring protein and that in some embodiments a double stranded DNA deaminase that is no more than 150-300 nucleotides in length (pg. 12 of the specification of the instant application), therefore contemplating fragments of double stranded DNA deaminases. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to include a double stranded DNA deaminase that has at least 80% identity to a fragment of amino acid sequence of SEQ ID NO: 55.
Komor does not teach that the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to a fragment of SEQ ID NO: 55.
Farzadfard teaches a method for deaminating double-stranded (ds) DNA in which dsDNA-specific deaminases, including dsDNA-specific deaminases that deaminate cytosine nucleotides, including 5hmC, deaminate target nucleotides in double-stranded DNA in which the double-stranded deaminase comprises SEQ ID NO: 14, in which SEQ ID NO: 14 is 100% identical to SEQ ID NO: 55, from positions 144 through 153, of the instant application (a double-stranded DNA deaminase having an amino acid sequence that is at least 80% identical to a fragment of SEQ ID NO: 55) (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 that this method enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease (paragraph [0114] lines 1-8).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate to identify modified cytosines in Komor to incorporate analysis of 5hmC cytosine modifications with a double-stranded DNA deaminase comprising SEQ ID NO: 14 (100% identical to a fragment of SEQ ID NO: 55 of the instant application) as taught in Farzadfard because Farzadfard teaches that doing so would provide a method that enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease.
Regarding claims 17 & 18, Komor does not teach that the modified cytosine is 5hmC and that the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to SEQ ID NO: 10.
Farzadfard teaches a method for deaminating double-stranded (ds) DNA in which dsDNA-specific deaminases, including dsDNA-specific deaminases that deaminate cytosine nucleotides, including 5hmC, deaminate target nucleotides in double-stranded DNA in which the double-stranded deaminase comprises SEQ ID NO: 50, in which SEQ ID NO: 50 is 100% identical to SEQ ID NO: 10 of the instant application (a double-stranded DNA deaminase having an amino acid sequence that is at least 80% identical to SEQ ID NO: 10 and the modified cytosine is 5hmC) (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 that this method enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease (paragraph [0114] lines 1-8).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate to identify modified cytosines in Komor to incorporate analysis of 5hmC cytosine modifications with a double-stranded DNA deaminase comprising SEQ ID NO: 50 (100% identical to SEQ ID NO: 10 of the instant application) as taught in Farzadfard because Farzadfard teaches that doing so would provide a method that enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease.
Regarding claims 19-21, it is noted as discussed above, the recitation of “the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 21, 40, 47, 49, 50, 55, 58, 59, 62, 63, 65, 67, 70, 71, 76, 106, 107, 110, 112, 114, 117, 163, and 164” in lines 4-6 of the claim is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required. Further, the specification of the instant application teaches a double stranded DNA deaminase lacks at least 10 to at least 100 of the N-terminal amino acids of the corresponding naturally-occurring protein and that in some embodiments a double stranded DNA deaminase that is no more than 150-300 nucleotides in length (pg. 12 of the specification of the instant application), therefore contemplating fragments of double stranded DNA deaminases. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to include a double stranded DNA deaminase that has at least 80% identity to a fragment of amino acid sequence of SEQ ID NO: 55.
Komor teaches a deaminase assay on double-stranded DNA in which double-stranded DNA is contacted with a double-stranded DNA deaminase to produce a deamination product and then the deaminated product is sequenced (pg. 420 column 2 1st full paragraph lines 1-16; pg. 420 column 2 2nd full paragraph lines 1-11; pg. 421 paragraph bridging columns 1 & 2 lines 1-11; pg. 425 column 1 4th full paragraph lines 1-4; pg. 425 column 2 1st full paragraph lines 1-15; pg. 425 column 2 2nd full paragraph lines 1-19).
Komor does not teach that the modified cytosine is 5hmC and that the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to a fragment of SEQ ID NO: 55.
Farzadfard teaches a method for deaminating double-stranded (ds) DNA in which dsDNA-specific deaminases, including dsDNA-specific deaminases that deaminate cytosine nucleotides, including 5hmC (modified cytosine is 5hmC), deaminate target nucleotides in double-stranded DNA in which the double-stranded deaminase comprises SEQ ID NO: 14, in which SEQ ID NO: 14 is 100% identical to SEQ ID NO: 55, from positions 144 through 153, of the instant application (a double-stranded DNA deaminase having an amino acid sequence that is at least 80% identical to a fragment of SEQ ID NO: 55) (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 that this method enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease (paragraph [0114] lines 1-8).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate to identify modified cytosines in Komor to incorporate analysis of 5hmC cytosine modifications with a double-stranded DNA deaminase comprising SEQ ID NO: 14 (100% identical to a fragment of SEQ ID NO: 55 of the instant application) as taught in Farzadfard because Farzadfard teaches that doing so would provide a method that enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease.
Regarding claim 26, it is noted as discussed above, the recitation of “an amino acid sequence that is at least 80% identical to any of SEQ ID NOS: 21, 40, 47, 49, 50, 55, 58, 59, 62, 63, 65, 67, 70, 71, 76, 106, 107, 110, 112, 114, 117, 163, and 164” in is unclear. It is unclear if the double-stranded DNA deaminase requires at least 80% identity to the entirety or over the full length of the SEQ ID NO or if at least 80% identity to fragments of the SEQ ID NO is required. Further, the specification of the instant application teaches a double stranded DNA deaminase lacks at least 10 to at least 100 of the N-terminal amino acids of the corresponding naturally-occurring protein and that in some embodiments a double stranded DNA deaminase that is no more than 150-300 nucleotides in length (pg. 12 of the specification of the instant application), therefore contemplating fragments of double stranded DNA deaminases. Therefore, for the purposes of this rejection, the claim is given its broadest reasonable interpretation to include a double stranded DNA deaminase that has at least 80% identity to a fragment of amino acid sequence of SEQ ID NO: 55.
Komor teaches a deaminase assay on double-stranded DNA in which double-stranded DNA is contacted with a double-stranded DNA deaminase to produce a deamination product and then the deaminated product is sequenced (pg. 420 column 2 1st full paragraph lines 1-16; pg. 420 column 2 2nd full paragraph lines 1-11; pg. 421 paragraph bridging columns 1 & 2 lines 1-11; pg. 425 column 1 4th full paragraph lines 1-4; pg. 425 column 2 1st full paragraph lines 1-15; pg. 425 column 2 2nd full paragraph lines 1-19).
Komor does not teach that the double-stranded DNA deaminase has an amino acid sequence that is at least 80% identical to a fragment of SEQ ID NO: 55.
Farzadfard teaches a method for deaminating double-stranded (ds) DNA in which dsDNA-specific deaminases, including dsDNA-specific deaminases that deaminate cytosine nucleotides, including 5hmC, deaminate target nucleotides in double-stranded DNA in which the double-stranded deaminase comprises SEQ ID NO: 14, in which SEQ ID NO: 14 is 100% identical to SEQ ID NO: 55, from positions 144 through 153, of the instant application (a double-stranded DNA deaminase having an amino acid sequence that is at least 80% identical to a fragment of SEQ ID NO: 55) (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 that this method enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease (paragraph [0114] lines 1-8).
Komor and Schutsky are considered to be analogous to the claimed invention because they are all in the same field of detecting modified cytosines with DNA deaminases. 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 using a fusion double-stranded DNA deaminase containing APOBEC1 to deaminate a double-stranded DNA substrate to identify modified cytosines in Komor to incorporate analysis of 5hmC cytosine modifications with a double-stranded DNA deaminase comprising SEQ ID NO: 14 (100% identical to a fragment of SEQ ID NO: 55 of the instant application) as taught in Farzadfard because Farzadfard teaches that doing so would provide a method that enables precise editing of DNA allowing for efficient ability to correct a variety of point mutations relevant to human disease.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 6-8, 13, 17, 17, 18, 19-21, & 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 9, 11, & 13 of copending Application No. 18/058,115 (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 claims 1-3, 8, & 13, the instant application 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. Copending Application No. 18/058,115 claims a method for deaminating a double-stranded nucleic acid comprising contacting the 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 (see claims 1, 2, & 4).
Regarding claim 6, 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. 18/058,115 claims wherein the dsDNA substrate is not pre-treated with either a TET methylcytosine dioxygenase or DNA beta-glucosyltransferase (see claim 13).
Regarding claim 7, the instant application claims wherein the dsDNA substrate is pre-treated with a TET methylcytosine dioxygenase, and optionally is pre-treated with a DNA beta-glucosyltransferase. Copending Application No. 18/058,115 claims wherein the dsDNA 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 (see claims 9 & 11).
Regarding claims 1, 15, 17, & 18, 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, 10, 16, 96, & 99, further comprising analyzing the sequence reads to identify a modified cytosine in the dsDNA substrate, and wherein the modified substrate is one or more of 5fC, 5caC, 5mC, 5hmC, N4mC, or 5ghmC. Copending Application No. 18/058,115 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, 10, 16, 96, & 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 (see claims 1 & 3-5).
Regarding claims 19 & 26, 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. 18/058,115 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 that comprises deaminated cytosines (see claim 1).
Regarding claim 20, the instant application claims wherein the dsDNA substrate further comprises a modified cytosine. Copending Application No. 18/058,115 claims wherein the dsDNA substrate further comprises a modified cytosine (see claim 2).
Regarding claim 21, the instant application claims wherein the modified cytosine is 5fC, 5caC, 5mC, 5hmC, N4mC, or pyrrolo-C. Copending Application No. 18/058,115 claims wherein the modified cytosine is 5fC, 5caC, 5mC, 5hmC, N4mC, 5ghmC, or pyrrolo-C (see claim 3).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-21 & 26 are rejected.
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.
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, Winston Shen can be reached on (571) 272-3157. 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.
/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/ Primary Examiner, Art Unit 1682