DETAILED ACTION
Notice of Pre-AIA or AIA Status and New Examiner
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Please note that the examiner for this application has changed. Please address future correspondence to Robert T. Crow (Art Unit 1683) whose telephone number is (571) 272-1113.
Amendments and Status of the Claims
3. This action is in response to papers filed 23 April 2026 in which no claims were amended, no claims were canceled, and no new claims were added.
All previous objections and/or all previous rejections not reiterated below are withdrawn in view of the amendments.
Applicant’s arguments have been thoroughly reviewed and are addressed following the rejections.
4. Claims 173-177, 180-181, and 183-191 are under prosecution.
Interview Summary
5. The interview summary is acknowledged and the interview record is complete.
Claim Rejections - 35 USC § 112
6. 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.
7. Claims 173-177, 180-181, and 183-191 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.
A. Claim 173 (upon which claims 173-177, 180-181, and 183-187 depend) is indefinite in each of the following:
I. The recitation “the nucleic acid sample” in lines 3, 5, 6, and 7-8, which lacks antecedent basis in the previous recitation of “an isolated nucleic acid sample.”
It is noted that the limitation “the nucleic acid sample” is also present in each of claims 184-187.
II. The recitation “a modified Glu is enzymatically attached to 5-hydroxymethylcytosines” is indefinite as it is unclear how one (i.e., “a”) modified Glu can be attached to more than one 5-hydroxymethyl cytosine (i.e., the claimed plural recitation of “5-hydroxymethylcytosines” in line 5 of claim 173).
For the purposes of examination, the claims are interpreted as having one modified Glu on one 5-hydroxymethylcytosine.
It is also noted that the recitation “the 5-hydroxymethycytosines” also appears in line 6 of claim 173, as well as each of claims 184-186.
B. Claim 177 (upon which claims 180-181 and 183 depend) is indefinite in the recitation “attaching a detectable moiety or an isolation tag to X on the modified UDP-Glu molecule.” The claimed “attaching” is interpreted as an active method step; thus, it is unclear how a detectable moiety or insolation tag can be attached to X as the attachment will alter the azide or thiol of claim 173.
For the purposes of examination, the step of claim 177 is interpreted as an active method step occurring after the incorporation of the modified GLU is attached to a 5-hydroxymethylcytosine,as discussed above in the rejection of claim 173.
C. Claims 184-186 and 189-191 are each indefinite in the recitation “the glycosylated nucleic acid,” which lacks antecedent basis because there is no previous recitation of a “glycosylated nucleic acid.”
D. Claim 188 (upon which claims 189-191 depend) is indefinite in each of the following:
I. The recitations “the sample” in line 3, “the genomic DNA” in each of lines 5 and 6, and the recitation “ the nucleic acid sample” in lines 7-8, each of which lacks antecedent basis in the previous recitation “ a genomic DNA sample.”
It is noted that “the genomic DNA” also appears in each of claims 189-191.
II. The recitation “to attach the modified Glu to 5-hydroxymethylcytosines” in line 4is indefinite as it is unclear how one (i.e., “a”) modified Glu can be attached to more than one 5-hydroxymethyl cytosine (i.e., the claimed plural recitation of “5-hydroxymethylcytosines” in line 6 of claim 188).
For the purposes of examination, the claims are interpreted as having one modified Glu on one 5-hydroxymethylcytosine.
It is also noted that the recitation “the 5-hydroxymethycytosines” also appears in each of claims 189-191.
Claim Interpretation
8. The claims are subject to the following interpretation:
A. The recitation “a modified Glu” in claim 173 (upon which claims 173-177, 180-181, and 183-187) and claim 188 (upon which claims 189-191 depend) is interpreted as being the glucose residue having the “X” group as depicted in the structure at the end of claims 173 and 188, respectively.
B. As noted above, claim 177 (upon which claims 180-181 and 183 depend) in interpreted as comprising an active method step occurring after the incorporation of the modified GLU is attached to a (i.e., only 1) 5-hydroxymethylcytosine.
Double Patenting
9. 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.
10. Claims 173-177, 180-181, and 183-191 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 and 21 of copending Application No. 19/330,958 in view of Rao et al. (PCT International Application Publication No. WO 2010/037001 A1, published 1 April 2010).
Both sets of claims are drawn to methods using isolated nucleic acid molecules, genomic DNA, attaching a molecule, including biotin or beta-glucosyltransferase, and a UDP-Glu having a modification, in the form of an azide or thiol, at carbon 6 of the Glu moiety, biotin, primer extension, etc. Any additional limitations of the ‘958 claims are encompassed by the open claim language “comprising” found in the instant claims.
The ’958 claims do not discuss comparing to controls.
However, Rao et al. teach methods of labeling 5-hydroxymethylcytosines using beta-glucosyltransferase (Abstract and paragraph 0043), comparing to control samples (paragraph 0039), microarray hybridization, sequencing, and fluorescent labeling (paragraph 0152), and that the methods have the added advantage of aiding in the monitoring of the methylation status in cellular DNA (paragraph 0011). Thus, Rao et al. teach the known techniques discussed above.
It would therefore have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the ‘958 claims with the teachings of Rao et al. to arrive at the instantly claimed methods with a reasonable expectation of success. The ordinary artisan would have been motivated to make the modification because said modification would have resulted in methods having the added advantage of aiding in the monitoring of the methylation status in cellular CNA as explicitly taught by Rao et al. (paragraph 0011). In addition, it would have been obvious to the ordinary artisan that the known techniques of Rao et al. could have been applied to the ‘958 claims with predictable results because the known techniques of Rao et al. predictably result in methods useful for testing DNA in cells.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
11. With respect to Applicant’s arguments filed 23 April 2026, the examiner agrees that the use the specifically claimed UDP-Glu molecule having X as either thiol or azide with beta-glucosyltransferase to attach the modified Glu (as discussed above) to 5-hydroxymethylcytosein is free and clear of the cited prior art.
Conclusion
12. No claim is allowed
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert T. Crow whose telephone number is (571)272-1113. The examiner can normally be reached M-F 8:00-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Robert T. Crow
Primary Examiner
Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
Prosecution Insights