Office Action 2: Notice of Allowance (2025-01-16)

CLAIMS:
AMENDMENTS TO THE CLAIMS

Application No.: 18/739,955

1.-96. (Cancelled)295

97\. (Currently Amended) A method of converting a methylated cytosine residue in an isolated eukaryotic nucleic acid molecule to a modified cytosine residue, the method comprising:(a) contacting said isolated eukaryotic nucleic acid molecule with a polypeptide that converts said methylated cytosine residue to \[\[a\]\]said modified cytosine residue, wherein said polypeptide comprises a TETl polypeptide, a TET2 polypeptide, a TET3 polypeptide, or a CXXC4 polypeptide, or a catalytically active fragment thereof; andSVG {EMBED HERE} 0.1531.417(b) contacting said isolated eukaryotic nucleic acid molecule with a glucosyltransferase polypeptide to derivatize said modified cytosine residue, wherein said glucosyltransferase polypeptide comprises (BGT) or a-glucosyltransferase (AGT).

98\. (Previously Presented) The method of claim 97, wherein said polypeptide comprises said TETl polypeptide or said catalytically active fragment of said TETl polypeptide.

99\. (Currently Amended) The method of claim 98, wherein said TETl polypeptide or said catalytically active fragment of said TETl polypeptide comprises a sequence having at least 90% sequence identity to: SEQ ID NO:27\[\[,\]\]; a catalytically-active fragment of SEQ ID NO:27\[\[,\]\];
or a variant thereof.

100\. (Currently Amended) The method of claim 97, further comprising detecting a methylation status of said isolated eukaryotic nucleic acid molecule based on a presence or an absence of said modified cytosine residue.

101\. (Currently Amended) The method of claim 100, wherein said detecting comprises contacting said isolated eukaryotic nucleic acid molecule with bisulfite.

102\. (Previously Presented) The method of claim 97, wherein (b) further comprises contacting said isolated eukaryotic nucleic acid molecule with a glucose molecule or a glucose-derivative donor substrate.

103\. (Previously Presented) The method of claim 97, wherein said glucosyltransferase polypeptide comprises said BGT.

Application No.: 18/739,955

104\. (Previously Presented) The method of claim 97, wherein said glucosyltransferase polypeptide comprises said AGT.

105\. (Previously Presented) The method of claim 97, wherein said isolated eukaryotic nucleic acid molecule is obtained from a cell sample or a tissue sample of a subject.

106\. (Previously Presented) The method of claim 97, wherein said isolated eukaryotic nucleic acid molecule is obtained from an extracellular fluid sample.

107\. (Previously Presented) The method of claim 97, wherein said isolated eukaryotic nucleic acid molecule is obtained from a subject having cancer or suspected of having cancer.

108\. (Previously Presented) The method of claim 97, wherein said polypeptide comprises said TET2 polypeptide or said catalytically active fragment of said TET2 polypeptide.

109\. (Currently Amended) The method of claim 108, wherein said TET2 polypeptide or said catalytically active fragment of TET2 polypeptide comprises a polypeptide having at least 90% sequence identity to SEQ ID NO: 28, a catalytically-active fragment of SEQ ID NO:28, or a variant thereof.

110\. (Currently Amended) The method of claim 109, wherein said polypeptide having at least 90% sequence identity to SEQ ID NO: 28 or said catalytically-active fragment of SEQ ID NO:
28 comprises a conservatively-substituted variant of SEQ ID NO: 28, a conservatively- substituted catalytically active fragment of SEQ ID NO: 28, or a variant thereof.

111\. (Currently Amended) The method of claim 110, wherein said TET2 comprises a SEQ ID NO: 28.

112\. (Previously Presented) The method of claim 97, wherein said polypeptide comprises said TET3 polypeptide or said catalytically active fragment of said TET3 polypeptide.

113\. (Previously Presented) The method of claim 97, wherein said polypeptide comprises said CXXC4 polypeptide or said catalytically active fragment of said CXXC4 polypeptide.

114\. (Previously Presented) The method of claim 97, further comprising indirectly labeling said modified cytosine residue with a fluorophore or a biotinyl group.

115\. (Currently Amended) The method of claim 114, wherein said modified cytosine residue\[\[s\]\] is indirectly labeled with said fluorophore.

Application No.: 18/739,955

116\. (Previously Presented) The method of claim 114, wherein said modified cytosine residue is indirectly labeled with said biotinyl group.

117\. (Currently Amended) The method of claim 97, wherein (a) comprises contacting said isolated eukaryotic nucleic acid molecule with a polypeptide having at least 90% sequence identity to; any one of SEQ ID NOs: 27, 28, or 29\[\[,\]\]; a catalytically active fragment of any one of SEQ ID NOs: 27, 28, or 29 \[\[,\]\]; or a variant thereof.

118\. (Previously Presented) The method of claim 117, wherein said polypeptide comprises SEQ ID NO: 1 or a variant thereof.

119\. (Currently Amended) The method of claim 97, wherein said glucosyltransferase polypeptide comprises said BGT or \[\[a\]\]said conservatively-substituted variant of BGT.

120\. (Previously Presented) The method of claim 119, wherein said BGT comprises the polypeptide sequence of RCSB Accession No. 1J39, or a conservatively substituted variant thereof.

121\. (Previously Presented) The method of claim 120, wherein said BGT comprises residues 100-103, 231, and 311 relative to RCSB Accession No. 1J39.

122\. (Currently Amended) The method of claim 97, wherein said modified \[\[base\]\] cytosine residue is a hydroxymethylated cytosine residue.

123\. (Cancelled)

OFFICE ACTION:
Information Disclosure Statement
The information disclosure statement submitted on 10/3/2024 has been considered by the examiner.
EXAMINER'S AMENDMENT
An examiner’s amendment to the record appears below. Should the changes and/or additions be unacceptable to applicant, an amendment may be filed as provided by 37 CFR 1.312. To ensure consideration of such an amendment, it MUST be submitted no later than the payment of the issue fee.
The application has been amended as follows:
119.	The method of claim 97, wherein said glucosyltransferase polypeptide comprises said BGT or [[said]]a conservatively-substituted variant of BGT.
Reasons for Allowance
The following is an examiner’s statement of reasons for allowance: With the claim amendment received 11/26/2024, the rejections under 35 U.S.C. 112(b) and 112(d) are overcome.  With the terminal disclaimer received and approved 11/26/2024, the double patenting rejections over co-pending applications 18/588930 and 18/588987 and U.S. Patents 9816986, 10443091, 10731204, 10767216 and 12018320 are overcome.  Thorough searching has confirmed that, with the examiner’s amendment set forth above, the claims are in condition for allowance.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 97-122 are allowed.

APPLICANT REBUTTAL: REMARKS
Claims 97-123 were pending prior to entry of the abovementioned amendments. Claims 97, 99-101, 109, 110, 111, 115, 117, 119, and 122 have been amended for clarification and antecedent basis purposes. The amendments to the claims are fully supported by the application as originally filed, U.S. Patent App. No. 18/588,987, now U.S. Patent Pub. No. 2024/0318235 (the "Application"), and the original claims. Claim 123 has been cancelled. No new matter is added. Accordingly, upon entry, claims 97-122 will be pending.
Reconsideration is respectfully requested in light of the abovementioned amendments and following remarks.
35 U.S.C.
112(b)
Claim 111 stands rejected under 35 U.S.C. § 112(b) as indefinite.
Without conceding to the validity of the rejection, and solely to expedite prosecution, claim 111 has been amended. Applicant submits this amendment fully addresses the § 112(b) rejection and requests withdrawal of the rejection under § 112(b).
35 U.S.C.
112(d)
Claim 123 stands rejected under 35 U.S.C. as being of improper dependent form.
Without conceding to the validity of the rejection, and solely to expedite prosecution, claim 123 has been cancelled, rendering the rejection moot. Applicant respectfully requests withdrawal of the rejection under § 112(d).
DOUBLE PATENTING
Various claims stand rejected on the ground of double patenting as being unpatentable over one or more of claims 31-38, 45-46, 48-54 and 57-58 of copending Application No. 18/588,930 (reference application; herein "'930"), claims 31-34 and 36-50 of copending Application No. 18/588,987 (reference application; herein "'987"), claims 1-8 of U.S. Patent No. 9,816,986 (herein "'986"), claims 1-13 of U.S. Patent No. 10,443,091 (herein "'091"), claims 1- 19 of U.S. Patent No. 10731204 (herein "'204"), claims 1-16 of U.S. Patent No. 10,767,216
(herein "'216"), and claims 1-13 of U.S. Patent No. 12,018,320 (issues 6/25/2024 from application 17/675502; herein "'320").
Applicant respectfully disagrees, but solely for the purpose of advancing prosecution, Applicant submits herewith a terminal disclaimer over each of the above-cited patents. Applicant respectfully submits that the double patenting rejections are obviated in view of the terminal disclaimers.
Entry of the foregoing and prompt and favorable consideration of the subject application on the merits are respectfully requested. The Applicant has amended the claims to expedite prosecution of preferred embodiments. The Applicant reserves the right to prosecute any cancelled subject matter in continuation, divisional or continuation-in-part applications, claiming priority to this application.
In the event that there are any questions concerning this amendment or the application in general, the Examiner is respectfully urged to telephone the undersigned so that prosecution of this application may be expedited.
FEE AUTHORIZATION
The Director is hereby authorized to charge fee deficiencies or credit overpayments associated with the instant filing, in above-referenced matter to NIXON PEABODY LLP Deposit Account No. 50-4181, referencing Attorney Docket Number 701039-063007USX6. Any overpayments should also be credited to said Account.
November 26, 2024
Respectfully submitted,