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 .
Claims 1-34 are pending. Claims 14-16 are being examined on the merits. Claims 1-13 and 17-34 are withdrawn.
Election/Restrictions
Applicant’s election without traverse of Group III (claims 14-16), and the species of a T7 promoter, in the reply filed on April 1, 2026 is acknowledged.
Claims 1-13 and 17-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 1, 2026.
The Restriction Requirement mailed October 2, 2025 also included an Election of Species requirement for Group III, requiring, in part, an election between a T7 promoter, as recited in claim 14, and strand displacement at nicks, as recited in claim 16. As noted, Applicant elected the species of the T7 promoter in the reply filed April 1, 2026, which would have resulted in claim 16 being withdrawn. However, in searching the elected species, art was also found for the non-elected species. Thus, the election of species requirement for Group III is withdrawn.
Information Disclosure Statement
The Information Disclosure Statement submitted April 24, 2024 has been considered, except for Foreign Patent Document No. 1, to Illumina, which was not submitted here or in parent application US 16/945,638. The Information Disclosure Statement submitted June 17, 2025 has been considered.
Specification
The use of the terms for various nucleic acid assay reagents or kits, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Specifically, the trademarks include, at least, “Quant-iT” (e.g., p. 17), “YOYO” (e.g., p. 18), “RiboGuard” (e.g., p. 20), “Cy3” (e.g., p. 20), “NEBuffer” (e.g., p. 21), “ATTO-[X]” (e.g., p. 21), “CutSmart” (e.g., p. 21), and “Alexa Fluor[X]” (e.g., p. 34).
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.
Claims 14-16 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.
Claim 14 recites the limitations “the binding regions” in step (a) and the “the binding
region” in step (c), the meaning of which is unclear. Specifically, since the first instance is plural and the second is singular, it is not clear how many binding regions (i.e., one or at least one) are present in the substrate. Claim 15 is rejected with the same reasoning.
Claim 16 depends from claim 15, and consequently incorporates the indefiniteness issue of claim 15.
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.
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 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Charlot (Elongated unique DNA strand deposition on microstructured substrate by receding meniscus assembly and capillary force, Biomicrofluidics, 8(1):014103, 2014) in view of Pushkarev (WO 2013/036929 A1), Kaykov (Molecular Combing of Single DNA Molecules on the 10 Megabase Scale, Scientific Reports, 6: 19636, 2016) and Hite (Factors affecting fidelity of DNA synthesis during PCR amplification of d(C-A)n-d(G-T)n microsatellite repeats, Nucleic Acids Research, 24(1): 2429-2434, 1996), as evidenced by New England Biolabs (DNA Polymerase Strand Displacement Activity, 2026).
Regarding independent claim 14, Charlot teaches …
A method of on surface DNA sequencing library generation, the method comprising: a)
providing a micropatterned substrate, the micropatterned substrate comprising: at least one binding region having a first width; and at least one non-binding region having a second width; wherein the binding regions and the non-binding regions alternate across at least a portion of the substrate (Fig. 2A: patterned PDMS substrate comprising binding regions (wells) alternating with non-binding regions (areas in between the wells);
b) contacting the micropatterned substrate with a solution comprising at least one
molecule of DNA, wherein one end of at least one molecule of DNA attaches to the binding region of the micropatterned substrate (Figs. 2A-C; p. 3, paras. 4-6: DNA adsorbs to the PDMS substrate);
c) combing the at least one molecule of DNA such that the at least one molecule of DNA
extends from the binding region into at least a portion of an adjacent non-binding region (Figs. 2A-C: DNA that is attached to the well at one end is extended over the area in between the wells; p. 3, paras. 4-6). Charlot also teaches that DNA combing is performed at 25°C (p. 3, bottom para.).
Kaykov teaches that DNA combing is useful for the analysis of repetitive sequences in
genomes (p. 1, para. 2). Hite teaches that repetitive microsatellite DNA sequences can be analyzed with amplification techniques, such as PCR (e.g., abstract), and teaches that using lower amplification temperatures tends to improve polymerase fidelity in microsatellite analysis (p. 2433, left col., para. 3).
Pushkarev teaches amplifying partitioned target nucleic acids using any amplification
technique known in the art, thereby forming an amplification product, eluting the amplification product from the device and generating a sequencing library with the amplification product (Fig. 1; p. 4, para. 2; p. 19, para. 10). Pushkarev additionally teaches that the target nucleic acid may comprise an adapter with a T7 promoter (p. 36, para. 2).
Regarding independent claim 15 and dependent claim 16, Charlot teaches …
A method of DNA sequencing library generation, the method comprising: a) providing a micropatterned substrate, the micropatterned substrate comprising: at least one binding region having a first width; and at least one non-binding region having a second width; wherein the binding regions and the non-binding regions alternate across at least a portion of the substrate (Fig. 2A: patterned PDMS substrate comprising binding regions (wells) alternating with non-binding regions (areas in between the wells);
b) contacting the micropatterned substrate with a solution comprising at least one molecule of DNA, the at least one molecule of DNA wherein one end of at least one molecule of DNA attaches to the binding region of the micropatterned substrate (Figs. 2A-C; p. 3, paras. 4-6: DNA adsorbs to the PDMS substrate);
c) combing the at least one molecule of DNA such that the at least one molecule of DNA
extends from the binding region into at least a portion of an adjacent non-binding region (Figs. 2A-C: DNA that is attached to the well at one end is extended over the area in between the wells; p. 3, paras. 4-6). Charlot teaches that DNA combing is performed at 25°C (p. 3, bottom para.).
Kaykov teaches that DNA combing is useful for the analysis of repetitive sequences in
genomes (p. 1, para. 2). Hite teaches that repetitive microsatellite DNA sequences can be analyzed with amplification techniques, such as PCR (e.g., abstract), and teaches that using lower amplification temperatures tends to improve polymerase fidelity in microsatellite analysis (p. 2433, left col., para. 3).
Pushkarev teaches amplifying partitioned target nucleic acids using any amplification
technique known in the art, thereby forming an amplification product, eluting the amplification product from the device and generating a sequencing library with the eluted amplification product (Fig. 1; p. 4, para. 2; p. 19, para. 10). Pushkarev additionally teaches that the target nucleic acid may comprise an adapter with a T7 promoter (p. 36, para. 2). Finally, as noted, Pushkarev teaches amplifying partitioned target nucleic acids using any amplification
technique known in the art, and explicitly teaches the isothermal amplification techniques of strand displacement amplification, NASBA and RCA (p. 45, para. 1).
Prior to the effective filing date of the instant invention, it would have been prima facie obvious to use the Charlot molecular combing method to perform analysis of microsatellite repeats because molecular combing is recognized in the art to be suitable for that purpose, as taught by Kaykov. It would have been further obvious to use an amplification technique to analyze the microsatellite repeats because such techniques are recognized in the art to be suitable for that purpose, as taught by Hite. See MPEP 2144.07. Finally, it would have been obvious to use the Pushkarev isothermal amplification technique because Charlot teaches that DNA combing is performed at 25°C, and strand displacing polymerases, such as phi29, work at that temperature range, as evidenced by New England Biolabs. In addition, Hite teaches that lower amplification temperatures tend to improve polymerase fidelity in microsatellite analysis. Thus, the ordinary artisan would have been motivated to use an isothermal amplification technique in a library prepared from amplicons generated, in part, through DNA combing, because doing so would result in the expected advantage of a lower cost assay (as additional heating/thermal cycling capabilities would not be required) and a more accurate assay (as lower temperatures improves polymerase fidelity). The ordinary artisan would have had an expectation of success as the design and modification of nucleic acid assays is well-known the art.
Conclusion
Claims 14-16 are being examined, and are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN GREENE whose telephone number is (571)272-3240. The examiner can normally be reached M-Th 7:30-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CAROLYN L GREENE/Primary Examiner, Art Unit 1681
Prosecution Insights