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 with traverse of Group I (claims 1, 3-6 and 28) in the reply filed on 04/28/2026 is acknowledged. The traversal is on the ground(s) that “both Groups I and II are directed to a method for identifying one or more hydroxymethylated cytosines in a nucleic acid by contacting the nucleic acid sample with an oxidative reagent, converting the hydroxymethylated cytosines to modified thymine moieties each having the structure of Formula (I) or (II) to form a modified nucleic acid sequence, and amplifying the modified nucleic acid sequence. The only difference between Groups I and II is that Group I uses a peracid as the oxidative reagent, and Group II uses hydrogen peroxide and at least one transition metal as the oxidative reagent. This difference represents merely an alternative species for performing the same oxidation step within the claimed method, rather than two distinct groups of inventions, as both Groups I and II are linked by a generic linking claim - claim 1. The proper requirement should be the election of a single species of oxidative reagent from the peracid and hydrogen peroxide with at least one transition metal”. This is found persuasive and Groups I and II have been rejoined and claims 1 and 3-8 and 28 have been examined.
The requirement is still deemed proper and is therefore made FINAL.
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, 3-4 and 28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hayashi et al. "Base-Resolution Analysis of 5-Hydroxymethylcytosine by One-Pot Bisulfite-Free Chemical Conversion with Peroxotungstate", Journal of the American Chemical Society, vol. 138, no. 43, 21 October 2016 (2016-10-21), pages 14178-14181.
Hayashi et al. discloses a method of identifying one or more hydroxymethylated cytosines of a DNA sequence comprising: contacting a DNA sample with peroxotungstate , which converts 5hmC into trihydroxylated thymine, which corresponds to the compound of Formula (II) of claim 1 (Fig. 1 A). The reaction is better explained in D5 (referred to by D1 ). Scheme 2 of D5 shows that the oxidative reagent reacts with 5hmC to form epoxidation or dihydroxylation intermediates and subsequent hydrolysation forms the modified thymine. Hayashi et al. also discloses that to investigate whether the technique is applicable to a low copies of DNA sample such as genomic DNA, the peroxotungstate-treated ssDNA was PCR amplified before Sanger sequencing (p. 14179, right-hand col. par. 2). The Supporting Information describes the application of the method on human genomic DNA (p. S4-S5). Sequencing comparison with unoxidized DNA allows the identification of the 5hmC positions (Fig. S4).
Claim(s) 1, 3-4 and 28 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by YUAN FANG ET AL: "Bisulfite-free and base-resolution analysis of 5-methylcytidine and 5-hydroxymethylcytidine in RNA with peroxotungstate", CHEMICAL COMMUNICATIONS, vol. 55, no. 16, 19 February 2019 (2019-02-19), pages 2328-2331.
YUAN FANG ET AL discloses a method of identifying 5hmC in RNA using a similar method: contacting an RNA sample with peroxotungstate , which converts 5hmC into trihydroxylated thymine, which corresponds to the compound of Formula (II) of claim 1 (Fig. 1 a). The peroxotungstate-treated RNA was amplified by RT-PCR (Fig. 2b). Sanger sequencing of the PCR product from the oxidized RNA samples was also performed (Fig. 3). YUAN FANG ET AL further discloses that the method can be expanded to m5C sequencing in RNA by previously generating 5hmC from the oxidation of 5mC mediated by the TET enzyme (Fig. 4).
Claims 5-8 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm.
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/JEZIA RILEY/Primary Examiner, Art Unit 1681 11 July 2026
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