Office Action 2: Notice of Allowance (2024-09-29)

CLAIMS:
AMENDMENTS TO THE CLAIMS

Application No: 18/588,987

1.-30. (Cancelled)229

31\. (Currently Amended) A method comprising contacting a nucleic acid molecule with an isolated enzyme comprising a TET polypeptide, a catalytically active fragment thereof, a variant thereof, or any combination thereof in an amount effective to convert 5-methylcytosine of said nucleic acid molecule to an oxidized derivative thereof.

32\. (Currently Amended) The method of claim 31, wherein said isolated enzyme is present in an amount effective to convert all of said 5-methylcytosine of said nucleic acid molecule to said oxidized derivative thereof.

33\. (Previously Presented) The method of claim 31, wherein said isolated enzyme comprises an isolated dioxygenase.

34\. (Previously Presented) The method of claim 33, wherein said isolated dioxygenase comprises a recombinantly expressed dioxygenase.

35\. (Cancelled)

36\. (Currently Amended) The method of claim \[\[35\]\]31, wherein said TET polypeptide comprises a TETl polypeptide, TET2 polypeptide, or CXXC4 polypeptide,and comprises a polypeptide having at least 90% sequence identity to any one of SEQ ID NOs: 27, 28, or 29.

37\. (Currently Amended) The method of claim 36, wherein said TET olypeptide further comprises SEQ ID NO: 1.

38\. (Currently Amended) The method of claim 31, wherein said TET polypeptide comprises a TET2 polypeptide or a catalytically-active fragment thereof 39. (Previously Presented) The method of claim 38, wherein said TET2 polypeptide or said catalytically active fragment of said TET2 polypeptide comprises a polypeptide having at least 90% sequence identity to SEQ ID NO: 28, or a catalytically active fragment of SEQ ID NO: 28.

Application No: 18/588,987

40\. (Previously Presented) The method of claim 39, 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 SEQ ID NO: 1.

41\. (Previously Presented) The method of claim 40, wherein said polypeptide having at least 90% sequence identity to SEQ ID NO: 28 comprises a conservatively-substituted variant of SEQ ID NO: 28 or a conservatively-substituted catalytically active fragment of SEQ ID NO: 28.

42\. (Currently Amended) The method of claim 41, wherein said TET2 polypeptide comprises a polypeptide comprising SEQ ID NO: 28.

43\. (Previously Presented) The method of claim 31, wherein said nucleic acid molecule comprises isolated eukaryotic genomic DNA.

44\. (Previously Presented) The method of claim 43, wherein said isolated eukaryotic genomic DNA is from a somatic cell.

45\. (Previously Presented) The method of claim 31, further comprising adding a sugar residue to said oxidized derivative of said 5-methylcytosine in said nucleic acid molecule.

46\. (Previously Presented) The method of claim 45, wherein adding said sugar residue to said oxidized derivative of said 5-methylcytosine in said nucleic acid molecule comprises adding a glucose molecule or a glucose-derivative donor substrate to said oxidized derivative of said 5- methylcytosine in said nucleic acid molecule.

47\. (Currently Amended) The method of claim 46, wherein said adding a glucose molecule or a glucose-derivative donor substrate to said oxidized derivative of said 5-methylcytosine in said nucleic acid molecule comprises contacting said oxidized derivative of said 5- methylcytosine in said nucleic acid molecule with an a-glucosyltransferase (AGT) polypeptide or a variant thereof.

48\. (Currently Amended) The method of claim 46, wherein said adding said glucose molecule or said glucose-derivative donor substrate to said oxidized derivative of said 5-methylcytosine in said nucleic acid molecule comprises contacting said oxidized derivative of said 5- -3-

Application No: 18/588,987

methylcytosine in said nucleic acid molecule with said p-glucosyltransferase (BGT) polypeptide or a conservatively-substituted variant of said BGT polypeptide.

49\. (Previously Presented) The method of claim 48, wherein said BGT polypeptide comprises the polypeptide sequence of RCSB Accession No. 1J39.

50\. (Previously Presented) The method of claim 49, wherein said BGT polypeptide comprises residues 100-103, 231, and 311 relative to RCSB Accession No. 1J39.

51\. (Previously Presented) The method of claim 47, wherein said AGT polypeptide comprises the polypeptide sequence of RCSB Accession No. 1YA6.

52\. (Previously Presented) The method of claim 51, wherein said AGT polypeptide comprises residues 114-116 of AGT relative to RCSB Accession No. 1YA6.

OFFICE ACTION:
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.
Authorization for this examiner’s amendment was given in an interview with Mark FitzGerald on 9/20/2024 followed up by voicemail on 9/23/2024.
The application has been amended as follows:
42.	The method of claim [41]]38, wherein said TET2 polypeptide comprises a polypeptide comprising SEQ ID NO: 28.
48.	The method of claim 46, wherein said adding said glucose molecule or said glucose-derivative donor substrate to said oxidized derivative of said 5-methylcytosine in said nucleic acid molecule comprises contacting said oxidized derivative of said 5-methylcytosine in said nucleic acid molecule with
Information Disclosure Statement
The information disclosure statement submitted on 7/3/2024 has been considered by the examiner.
Reasons for Allowance
The following is an examiner’s statement of reasons for allowance: The claims are novel and non-obvious over the prior art and are enabled for the scope of the claims as evidenced by the original disclosure (for example, [0308-333]). The terminal disclaimer filed and approved on 9/11/2024 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patents 9816986, 10443091, 10533213, 10731204, 10767216, 12018320, 10612076 and 11072818 and co-pending applications 18/588930 and 18/588956.  With the filing and approval of the terminal disclaimer, the claims are now 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 31-34 and 36-52 are allowed.

APPLICANT REBUTTAL: REMARKS
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Claims 31-52 were pending prior to entry of the abovementioned amendments. In this

response, claims 31, 32, 36, 37, 38, and 42 have been amended, and claim 35 has been cancelled. Accordingly, claims 31-34 and 36-52 are pending. The amendments to claim 31 are fully supported by the application as originally filed, U.S. Patent App. No. 18/588,987 (the "Application"), such as at paragraph \[0013\]. Claims 32, 36, 37, 38, and 42 have been amended for clarity or for antecedent basis. The amendments to the claims do not add new matter.

Reconsideration is respectfully requested in light of the abovementioned amendments and following remarks.

35 U.S.C. & 112(b)

Claims 32 and 42 stand rejected under 35 U.S.C. § 112(b) as indefinite.

Without conceding to the validity of the rejection, and solely to expedite prosecution, claims 32 and 42 have been amended. Applicant submits these amendments fully address the § 112(b) rejections and requests withdrawal of the rejections under § 112(b).

35 U.S.C. 4 112(a)

Claims 31-34 and 43-52 stand rejected under 35 U.S.C. § 112(a) as failing to comply with the written description requirement.

Without conceding to the validity of the rejection, and solely to expedite prosecution,

claim 31 has been amended to recite subject matter from claim 35, which was not rejected under § 112(a). Applicant submits that the amendment to claim 31 fully addresses the § 112(a) rejections and requests their withdrawal.

Double Patenting
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Various claims stand rejected on the ground of double patenting as being unpatentable over one or more of claims 31-38, 41-42, 45-46 and 49-58 of copending Application No. 18/588930 (reference application; herein "'930"), claims 5-6 and 16-29 of copending Application No. 18/588956 (reference application; herein "'956"), claims 1-8 of U.S. Patent No. 9816986

(herein "'986"), claims 1, 6-8 and 10-15 of U.S. Patent No. 10323269 (herein "'269), claims 1-13 of U.S. Patent No. 10443091 (herein "'091"), claim 1 of U.S. Patent No. 10533213 (herein "'213"), claims 1, 13 and 16-17 of U.S. Patent No. 10612076 (herein "'076"), claims 1-3, 6-10, 13-15 and 19 of U.S. Patent No. 10731204 (herein "'204"), claims 1-3, 8-11, 13 and 16 of U.S. Patent No. 10767216 (herein "'216"), claims 1-9 of U.S. Patent No. 11072818 (herein "'818"), and/or claims 1-13 of U.S. Patent No. 12018320 (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.

CONCLUSION
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Applicant respectfully submits that the indefiniteness, written description, and double patenting rejections have been fully addressed herein. Applicant submits that where no other rejections are raised, the claims are now in allowable form.

Applicant does not acquiesce in the Examiner's characterizations of the art including the alleged motivation to combine references. For brevity and to advance prosecution, however, applicants may have not addressed all characterizations of the art and reserve the right to do so in further prosecution of this or a subsequent application. The absence of an explicit response by the applicants to any of the Examiner's positions does not constitute a concession of the Examiner's positions. The fact that applicants' comments have focused on particular arguments does not constitute a concession that there are no other arguments for patentability of the claims. All of the dependent claims are patentable for at least the reasons given with respect to the claims on which they depend.

Accordingly, Applicant respectfully requests early and favorable action finding the

claims allowable. If the Office has additional constructive comments or suggestions to expedite prosecution, Applicant sincerely encourages the Examiner to contact the undersigned attorney of record by telephone so that prosecution of the application can be expedited.

AUTHORIZATION TO CHARGE DEPOSIT ACCOUNT
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The Director of the USPTO is hereby authorized to charge any fee deficiencies associated with the instant filing except excess claims fees and credit any overpayments to NIXON PEABODY LLP Deposit Account No. 50-4181, from which the undersigned is authorized to withdraw.

Date: September 11, 2024 Respectfully submitted,

/Mark J. FitzGerald/

Customer No.: 50828 David S. Resnick (Reg. No. 34,235)

Mark J. FitzGerald (Reg. No. 45,928)Nixon Peabody LLP Exchange Place, 53 State Street Boston, MA 02109 Phone: 617-345-6057 / 1058 Fax: 617-345-1300 patentdocketing(anixonpeabody.com