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 preciously canceled claims 1-7. Applicant newly adds claims 24-26. Claims 8-26 are currently pending and 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in this action has been withdrawn in light of Applicant’s amendments and/or arguments.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 Statements filed April 27, 2026 has been considered.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 8-13 and 16-23 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Gunderson et al. (WIPO International Application Publication WO 2016/075204 A1 published May 19, 2016), cited on the IDS filed April 26, 2023.
Regarding claim 8, Gunderson teaches a method of preparing nucleic acids for a sequencing reaction (Title and [00142]). Gunderson teaches cluster generation by bridge amplification (Title and Pages 11-12, [0083]-[0085]). Gunderson teaches providing an array with a plurality of amplification sites (Pages 43-44, [00202]-[00203]). Gunderson teaches capture nucleic acids attached to amplification sites (Page 1, [0003], Pages 7-9, [0065]-[0068], Page 13, [0093] and Fig. 1). Gunderson teaches a first population of the plurality of capture nucleic acids comprises a cleavage site (Page 15, [00100], Pages 52-53, [00231] and Figs, 7B and 12A-B). Gunderson teaches a plurality of clonal double-stranded modified target nucleic acids (Pages 11-12, [0085] and Page 13, [0093]). 00326]). Gunderson teaches both strands of each double-stranded target nucleic acid are attached at their 5' ends to a capture nucleic acid (Page 57, [0256], Page 59, [00262] and Figs. 2-4 and 7A-B). Gunderson teaches one strand is attached to a capture nucleic acid that comprises the cleavage site (Page 15, [00100] and Page 79, [00334]). Gunderson teaches the cleavage site is positioned in a double-stranded region of each double-stranded molecule (Page 15, [00100], Pages 52-53, [00231] and Figs, 7B and 12A-B). Gunderson teaches contacting the array with a composition comprising an endonuclease to produce an abasic site at the cleavage site and an exonuclease comprising a 3' to 5' single-stranded DNA exonuclease activity (Pages 52-53, [00231], Page 15, [00109], Pages 18-19, [00118] and Page 77-78, [00330]). Gunderson teaches cleavage occurs at the cleavage site (Pages 52-53, [00231]). Gunderson teaches cleavage converts one strand of double-stranded target nucleic acids into a first strand attached to the amplification site and a second strand that is not attached to the amplification site (Pages 43-44, [00202]-[00203] and Fig. 7). Gunderson teaches a 3'-phosphate (Pages 2-3, [0016]-[0017] and Page 7, [0065]). Gunderson teaches single-stranded capture nucleic acids comprising a free 3’ end are reduced in length by the exonuclease (Pages 18-19, [00118], Page 54, [00236], Page 57, [00253] and Pages 77-78, [00330]).
Regarding claim 9, Gunderson teaches the composition comprises uracil DNA glycosylase (Pages 52-53, [00231]).
Regarding claim 10, Gunderson teaches the endonuclease is DNA glycosylase-lyase, Endonuclease VIII (e.g., USERTM mix, New England Biolabs comprises Uracil DNA Glycosylase and Endonuclease VIII; Page 94, [00376]).
Regarding claim 11, Gunderson teaches removal of the endonuclease and the exonuclease from the array (Page 15, [00104]-[00105], Pages 35-36, [0174]-[0175] and Fig. 14).
Regarding claim 12, Gunderson teaches subjecting the cleaved double-stranded target nucleic acids to conditions that remove the second strand that is not attached to the amplification site (Pages 11-12, [0085]-[0086], Pages 19-20, [00118]-[00119] and Pages 78-79, [00331]-[00335]).
Regarding claim 13, Gunderson teaches the conditions that remove the second strand comprise a denaturant, and the denaturant results in immobilized single-stranded nucleic acids comprising a target nucleic acid covalently attached to a second population of capture nucleic acid (Pages 11-12, [0085]-[0086], Pages 19-20, [00118]-[00119] and Pages 78-79, [00330]-[00335]). Gunderson teaches the second population of capture nucleic acids is attached to the amplification sites (Pages 43-44, [00202]-[00203] and Fig. 7).
Regarding claim 16, Gunderson teaches the cleavage site is positioned in the capture nucleic acid region of the double-stranded region of each double-stranded target nucleic acid (Pages 11-12, [0085]-[0086], Page 15, [00100] and Figs. 7 and 12).
Regarding claim 17, Gunderson teaches the cleavage site comprises a uracil, and an abasic site is generated by the uracil DNA glycosylase, and wherein the abasic site is cleaved by the endonuclease (Pages 52-53, [0231]).
Regarding claim 18, Gunderson teaches the exonuclease is Exonuclease I (Page 15, [00109] and Page 54, [00236]).
Regarding claim 19, Gunderson teaches hybridizing a sequencing primer to the immobilized single-stranded nucleic acids thereby preparing single-stranded nucleic acids for a sequencing reaction (Page 2, [0012], Page 5, [0041], Pages 11-12, [0085]-[0086], Page 13, [0093], Page 39, [00185], Pages 51-52, [00227]-[00230] and Pages 80-81, [00338]).
Regarding claim 20, Gunderson teaches performing a sequencing reaction to determine the sequence of at least one region of the immobilized single-stranded nucleic acids (Page 97, [00384]-[00385]).
Regarding claim 21, Gunderson teaches the sequencing reaction comprises sequencing-by-synthesis (Page 97, [00384]-[00385]).
Regarding claim 22, Gunderson teaches the array is produced by amplifying a plurality of target nucleic acids using the capture nucleic acids as amplification primers (Page 36, [00177]).
Regarding claim 23, Gunderson teaches amplifying comprises exclusion amplification (Abstract and Page 43, [00202]).
Gunderson teaches each and every limitation of claims 8-13 and 16-23, and therefore Gunderson anticipates claims 8-13 and 16-23.
Claim Rejections - 35 USC § 103
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 14-15 and 24-26 are rejected under 35 U.S.C. 103 as being unpatentable over Gunderson et al. (WIPO International Application Publication WO 2016/075204 A1 published May 19, 2016), cited on the IDS filed April 26, 2023, in view of Liu et al. (WIPO International Application Publication WO 2007/010251 A2 published January 25, 2007), cited on the IDS filed April 26, 2023.
Regarding claim 14, Gunderson teaches the denaturant may be a chemical denaturation (Page 79, [00334]-[00335]).
Regarding claim 15, Gunderson teaches the immobilized single-stranded nucleic acid as discussed above.
Regarding claim 24, Gunderson teaches hybridizing a sequencing primer to the immobilized partially single-stranded nucleic acids, thereby preparing single-stranded nucleic acids for a sequencing reaction (Page 2, [0012], Page 5, [0041], Pages 11-12, [0085]-[0086], Page 13, [0093], Page 39, [00185], Pages 51-52, [00227]-[00230] and Pages 80-81, [00338]).
Regarding claim 25, Gunderson teaches performing a sequencing reaction to determine the sequence of at least one region of the immobilized partially single-stranded nucleic acids (Page 97, [00384]-[00385]).
Regarding claim 26, Gunderson teaches the sequencing reaction comprises sequencing- by-synthesis (Page 97, [00384]-[00385]).
Gunderson does not teach or suggest the denaturant is explicitly formamide. Gunderson does not teach or suggest re-annealing the immobilized single-stranded nucleic acid to a member of the first population of capture nucleic acids to generate an immobilized partially single-stranded nucleic acids.
Liu teaches a method of preparing nucleic acids for a sequencing reaction (Title and Abstract). Liu teaches providing an array comprising a plurality of amplification sites (Page 2, Second and Third Paragraph, Page 4, Last Paragraph—Page 5, First Paragraph and Page 43, First-Fourth Paragraph). Roy teaches the amplification sites comprise a plurality of capture nucleic acids attached to the amplification sites (Page 43, First-Fourth Paragraph). Liu teaches a first population of the plurality of capture nucleic acids comprises a cleavage site (Page 6, First-Third Paragraph). Liu teaches a plurality of clonal double-stranded modified target nucleic acids (Page 49, First Paragraph, Page 14, Last Paragraph—Page 15, Third Paragraph, Page 6, Third Paragraph and Page 14, First Paragraph). Liu teaches both strands of each double-stranded target nucleic acid are attached at their 5' ends to a capture nucleic acid (Page 6, First Paragraph, Page 12, Second—Third Paragraph and Page 45, First Paragraph). Liu teaches one strand is attached to a capture nucleic acid that comprises the cleavage site (Page 7, Second Paragraph, Page 9, Second Paragraph, Page 14, Second Paragraph, Page 18, Second Paragraph and Page 47, First Two Paragraphs). Liu teaches the cleavage site is positioned in a double-stranded region of each double-stranded molecule (Figs. 1 and 2). Liu teaches contacting the array with a composition comprising at least one enzyme to produce an abasic site at the cleavage site (Page 7, Second Paragraph, Page 18, Last Paragraph and Claims 5 and 21). Liu teaches cleavage occurs at the cleavage site (Page 19, Second Paragraph). Liu teaches cleavage converts one strand of double-stranded target nucleic acids into a first strand attached to the amplification site and a second strand that is not attached to the amplification site (Abstract, Page 5, Second Paragraph and Figs. 1 and 3). Liu teaches performing a sequencing reaction to determine the sequence of at least one region of the immobilized single-stranded nucleic acids or the immobilized partially single-stranded nucleic acids (Page 30, Second Paragraph). Liu teaches the sequencing reaction comprises sequencing-by-synthesis (Page 46, Fourth Paragraph). Liu teaches the array is produced by amplifying a plurality of target nucleic acids using the capture nucleic acids as amplification primers (Page 8, Last Paragraph, Page 39, First Paragraph, Page 42, First Paragraph—Page 43, Second Paragraph). Liu teaches single-stranded capture nucleic acids comprising a free 3' end (Page 9, Second Paragraph, Page 20, Second Paragraph, Page 21, Third Paragraph, Page 29, First Paragraph and Page 39, Second Paragraph). Liu teaches an abasic site is generated using uracil DNA glycosylase and an endonuclease (Page 7, Second Paragraph). Liu teaches the endonuclease is DNA glycosylase-lyase Endonuclease VIII (Page 19, Second Paragraph). Liu teaches subjecting the cleaved double-stranded target nucleic acids to conditions that remove the second strand that is not attached to the amplification site (Abstract, Page 5, Second Paragraph, Page 10, First Paragraph and Page 12, Second—Fifth Paragraph). Liu teaches the conditions that remove the second strand comprise a denaturant, and the denaturant results in immobilized single-stranded nucleic acids comprising a target nucleic acid covalently attached to a second population of capture nucleic acid, as well as the second population of capture nucleic acids is attached to the amplification sites (Abstract, Page 5, Second Paragraph and Page 12, Second—Fifth Paragraph, Page 45, Last Paragraph and Figs. 1A-1E). Liu teaches the denaturant comprises formamide (Page 76, Last Paragraph). Liu teaches denaturing and subsequent re-annealing the immobilized single-stranded nucleic acid to a member of the first population of capture nucleic acids to generate an immobilized partially single-stranded nucleic acids (Page 30, Second and Last Paragraph). Liu teaches a sequencing reaction may then be initiated by hybridization of a sequencing primer to the single-stranded portion of the template (Page 30, Second Paragraph). Liu teaches that using this denaturation method and subsequent re-annealing of the cleaved strands that results in the production of a sequencing template which is partially or substantially single stranded is apparent to those skilled in the art (Pages 29, Last Paragraph—Page 30, Second Paragraph).
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Gunderson with the teachings of Lui, to use formamide for the denaturation and re-annealing the immobilized single-stranded nucleic acid to a member of the first population of capture nucleic acids to generate an immobilized partially single-stranded nucleic acids because Lui teaches using this denaturation method and subsequent re-annealing of the cleaved strands that results in the production of a sequencing template which is partially or substantially single stranded is known and apparent to those skilled in the art (Pages 29, Last Paragraph—Page 30, Second Paragraph). Additionally, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention to modify the denaturation of Gunderson with the denaturation of Liu, using specifically formamide, because Gunderson teaches that denaturing can include chemical denaturation which encompasses using formamide for the denaturing (Page 79, [00334]-[00335]), therefore the teachings of Liu are well suited for the systems of Gunderson and would obtain successful and expected results.
Response to Arguments
Applicant’s arguments and amendments, filed April 27, 2026 with respect to the rejections under 35 U.S.C. § 112(b) and 103 have been fully considered and are persuasive, therefore these rejections have been withdrawn.
However, new rejections under 35 U.S.C. § 102 and 103 are made in view of applicant’s amendments.
As discussed above, Gunderson discloses generating clusters by bridge amplification. Additionally Gunderson discloses using an endonuclease to create an abasic site, an exonuclease and a 3’ phosphate. Additionally, Gunderson and Liu disclose the use of formamide as the denaturation agent as well as the subsequent re-annealing the immobilized single-stranded nucleic acid to a member of the first population of capture nucleic acids to generate an immobilized partially single-stranded nucleic acids is known and apparent to those skilled in the art.
Therefore, all these reasons and those listed above, Gunderson and Gunderson in view of Liu are deemed to render the instant invention anticipated/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
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