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 .
Applicant canceled claims 2, 4, 7-8, 10-44 and 47. Applicant newly adds claim 60. Claims 1, 3, 5-6, 9, 45-46 and 48-60 are currently pending. Claim 6 remains withdrawn as being drawn to a nonelected species. Claims 1, 3, 5, 9, 45-46 and 48-60 are under examination.
Any objection or rejection of record in the previous Office Action which is not addressed
in this action has been withdrawn in light of Applicant’s amendments and/or arguments. This
action is FINAL.
Information Disclosure Statement
The Information Disclosure Statement filed November 19, 2025, has been considered.
Claim Rejections - 35 USC § 112
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.
Claim 60 is 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.
Claim 60 is considered vague and indefinite for the following reasons:
In claim 60, line 1, references Table 1 in the specification. It is improper to provide claim limitations by way of a table. The limitations from the table should be specifically listed in the claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 3, 5, 45-46 and 48-60, are rejected under 35 U.S.C 103 as unpatentable over Potapov et al. (“Comprehensive Profiling of Four Base Overhang Ligation Fidelity by T4 DNA Ligase and Application to DNA Assembly” ACS Synthetic Biology, (7)1, pgs., 2665-2674, published October 18, 2018), cited on the IDS filed July 29, 2025, in view of Field et al. (U.S. Patent Application Publication US 2018/0230455 A1, published Aug 16, 2018). This is a new rejection as necessitated by amendments.
Regarding claim 1, Potapov teaches a first partially double-stranded nucleic acid molecule, a second partially double-stranded nucleic acid molecule, and a DNA ligase (Figure 1). Potapov teaches the first partially double-stranded nucleic acid molecule comprises a first overhang and a second overhang, wherein the at least second partially double-stranded nucleic acid molecule comprises a third overhang and fourth overhang (Table 1 and Figures 1 and 4). Potapov teaches the second overhang and the third overhang are complementary to each other (Table 1). Potapov teaches the first overhang, the third overhang and the fourth overhang each comprise one of a 4-mer sequence, or a complement thereof, or a 4-mer triplet (Figures 1 and 4 and Table 1). Potapov teaches the 4-mer triplet comprises three 4-mer sequences, which yield a single fragment with at least 90% purity upon ligation of the first partially double-stranded nucleic acid molecule and the at least second partially double-stranded nucleic acid molecule (Page 2668, Left Column, Second Paragraph—Right Column, Last Paragraph, Figures 1 and 4 and Table 1). Potapov teaches wherein the first overhang, the third overhang and the fourth overhang each comprise a different 4-mer sequence (Figures 1 and 4 and Table 1). Potapov teaches a first partially double-stranded nucleic acid molecule and the second partially double-stranded nucleic acid molecule comprises a double-stranded portion (Figure 1).
Regarding claim 3, Potapov teaches at least one of the first overhang, the second overhang, the third overhang and the fourth overhang is 4 nucleotides in length (Page 2665, Right Column, First Paragraph, Page 2666, Left Column, First Paragraph, Table 1 and Figure 1). Potapov teaches the first overhang, the second overhang, the third overhang and the fourth 5' overhang are each 4 nucleotides in length (Page 2665, Right Column, First Paragraph, Page 2666, Left Column, First Paragraph, Table 1 and Figure 1).
Regarding claim 5, Potapov teaches the first and the at least second partially double-stranded nucleic acid molecules comprise XNA (Synthetic oligonucleotides, Page 2672, Left Column, Second Paragraph).
Regarding claim 9, Potapov teaches at least one of the first partially double-stranded nucleic acid molecule and the at least second partially double-stranded nucleic acid molecule that comprises a double-stranded portion that is at least 30 bp in length (Page 2667, Right Column, First Paragraph and Table S1).
Regarding claim 45, Potapov teaches the composition comprises a GC content from about 10% to about 90% (Page 2666, Left Column, Last Paragraph and Page 2668, Left Column, Last Paragraph).
Regarding claim 46, Potapov teaches the composition comprises a GC content of at least about 50% (Page 2666, Left Column, Last Paragraph and Page 2668, Left Column, Last Paragraph).
Regarding claim 48, Potapov teaches the first overhang, the second overhang, the third overhang, or the fourth overhang comprises a length from about 4 nucleotides to about 20 nucleotides (Page 2665, Right Column, First Paragraph, Page 2666, Left Column, First Paragraph, Table 1 and Figure 1).
Regarding claim 49, Potapov teaches the first partially double-stranded nucleic acid molecule or the second partially double-stranded nucleic acid molecule comprise at least one non-hybridized sequence, at least one non-symmetrical element, at least one hairpin, at least one G- quadruplex, at least one I-motif, at least one hemi-modified site, at least one CpG or any combination thereof (Figure 1).
Regarding claim 50, Potapov teaches the at least one non-hybridized sequence, at least one non-symmetrical element, at least one hairpin, at least one G-quadruplex, at least one I- motif, at least one hemi-modified site, at least on CpG or any combination thereof introduce at least one unique molecular identifier (UMI) regions (e.g., barcode, Figure 1).
Regarding claim 51, Potapov teaches the first partially double-stranded nucleic acid molecule or the second partially double-stranded nucleic acid molecule is attached to at least one solid support (Page 2673, Left Column, First Paragraph—Right Column, Second Paragraph).
Regarding claim 52, Potapov teaches the first partially double-stranded nucleic acid molecule or the second partially double-stranded nucleic acid molecule comprise at least one hairpin sequence (Figure 1).
Regarding claim 53, Potapov teaches the first partially double-stranded nucleic acid molecule and the second partially double-stranded nucleic acid molecule each comprise at least one hairpin sequence (Figure 1).
Regarding claim 54, Potapov teaches the at least one hairpin sequence comprises at least one restriction endonuclease site (Page 2672, Left Column, Last Paragraph—Right Column, First Paragraph).
Regarding claim 55, Potapov teaches the least one restriction endonuclease site comprises a Type II S restriction endonuclease site (Page 2672, Left Column, Last Paragraph—Right Column, First Paragraph).
Regarding claim 56, Potapov teaches the ligation of the first partially double- stranded nucleic acid molecule and the second partially double-stranded nucleic acid molecule comprises a coupling efficiency on average that is greater than about 99.9% (Page 2668, Left column Second Paragraph).
Regarding claim 57, Potapov teaches the first partially double-stranded nucleic acid molecule and the second partially double-stranded nucleic acid molecule comprises a double- stranded portion, wherein the double-stranded portion comprises a percent alignment of at least about 99% (Page 2668, Left column Second Paragraph and Right Column, Last Two Paragraphs) .
Regarding claim 58, Potapov teaches the first overhang, the second overhang, the third overhang, or the fourth overhang comprises a 5' overhang (Page 2666, Left Column, Last Paragraph—Right Column, First Paragraph).
Regarding claim 59, Potapov teaches the first overhang, the second overhang, the third overhang, or the fourth overhang comprises a 3' overhang (Figure 1).
Regarding claim 60, Potapov teaches the 4-mer triplet sequence is selected from table 1 (Supporting information S2-S4 and S8).
Potapov does not teach or suggest the double-stranded portion comprises a length from about 5 base pairs to about 40 base pairs.
Field teaches assembly of nucleic acids using multiple double stranded polynucleotides, with different overhangs (Abstract and Page 9, [0107]). Field teaches using ligase to assemble the polynucleotides (Page 9, [0108], Page 10, [0114]). Field teaches using XNA (Page 4, [0064]). Field teaches at least four overhangs comprising a 4-mer overhang (Page 1, [0015], Page 2, [0034]-[0035], Page 9, [0107] and Fig. 6). Field teaches the double- stranded portion comprises a length from about 5 base pairs to about 40 base pairs (Pages 7-8, [0099]-[0100] and Fig. 3). Field teaches using the methods of the present invention can advantageously be used to assemble multiple identical target sequences simultaneously and/or assemble multiple different target polynucleotide sequences simultaneously (Page 5, [0076]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Potapov with the teachings of Field wherein the double-stranded portion comprises a length from about 5 base pairs to about 40 base pairs. Using these methods would advantageously allow for assembly of multiple identical target sequences simultaneously and/or assemble multiple different target polynucleotide sequences simultaneously as taught by Field (Page 5, [0076]).
Response to Arguments
Applicant’s arguments and amendments filed November 11, 2025 with respect to the
rejections under 35 U.S.C. 102 and 112(b) have been fully considered and are persuasive. Therefore these rejections have been withdrawn.
Applicant’s arguments and amendments filed November 11, 2025 with respect to the
rejections under 35 U.S.C. 103 have been fully considered and these rejections are rendered moot due to the cancellation of claim 47. Therefore, these rejections are withdrawn.
However, upon further consideration, new grounds of rejections under 35 U.S.C. § 103 are made in view of Applicant’s amendments to claims. As discussed above, Potapov in view of newly cited Field, discloses the first partially double-stranded nucleic acid molecule and the second partially double-stranded nucleic acid molecule comprise a double-stranded portion, wherein the double- stranded portion comprises a length from about 5 base pairs to about 40 base pairs.
Therefore, for all these reasons, and those listed above, Potapov in view of Field are deemed to render the instant invention obvious.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JESSICA D PARISI/Examiner, Art Unit 1684 /HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684