DETAILED ACTION
Status of the Claims
Claims 1-2, 4-6, 9-11, 15-17, 19, 22-24, and 26-29 are currently pending.
Claims 1, 10, 15-16, and 19 are amended.
Claims 1-2, 4-6, 9-11, 15-17, 19, 22-24, and 26-29 are examined herein.
The following Office Action is in response to Applicant’s communication dated 02/23/2026. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/23/2026 has been entered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Title
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
Claim Rejections – 35 U.S.C. 103(a)
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 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.
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.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Fraser et al. and Hughes et al.
Claims 1-2, 4-6, 9-11, 15-17, 19, 22-24, and 26-29 are rejected under 35 U.S.C. 103 as being unpatentable over Fraser et al. (WO 2015/033134 A1, cited in IDS of 05/26/2022, of record) in view of Hughes et al. (WO 2017/068379 A1, cited in IDS of 05/26/2022, of record).
Regarding claims 1 and 4-6, Fraser discloses a method for identifying nucleic acid segments which interact with a target nucleic acid segment or segments (e.g., as per the FIELD OF THE INVENTION section on p. 1), said method comprising the steps of:
(a) obtaining a nucleic acid composition comprising the target nucleic acid segment or segments (e.g., as per step (a) on page 4, Fig. 1, and/or Example 1);
(b) crosslinking the nucleic acid composition (e.g., as per step (b) on page 4, Fig. 1, and/or Example 1);
(c) fragmenting the crosslinked nucleic acid composition using an endonuclease enzyme (e.g., as per step (c) on page 4, wherein fragmentation can be performed by using an endonuclease, as per p. 11, lines 21-34, Fig. 1, and/or Example 1);
(d) filling the ends of the fragmented crosslinked nucleic acid segments with one or more nucleotides comprising a covalently linked biotin moiety (e.g., incorporating a biotin-labeled nucleotide as per p. 12, lines 1-19, Fig. 1, and/or Example 1);
(e) ligating the fragmented nucleic acid segments obtained from step (d) to produce ligated fragments (e.g., as per step (d) on p. 4, Fig. 1, and/or Example 1);
(g) enriching for fragments comprising the biotin moiety of step (d) (e.g., purifying using, for example, streptavidin as per pp. 12-13, Fig. 1, and/or Example 1);
(h) enriching fragments comprising the target nucleic acid segment or segments (e.g., with the use of baits as per p. 11, Fig. 1, and/or Example 1) in the presence of sequences which prevent the binding of ligated fragments to other ligated fragments through complementarity of adaptor sequences or blocker sequences (e.g., blockers during SCRiBL as per Example 1);
(i) sequencing the enriched fragments obtained in step (h) to identify the nucleic acid segments which interact with the target nucleic acid segment or segments (e.g., as per step (g) on p. 4, Fig. 1, and/or Example 1).
However, it is noted that Fraser is silent on the limitation of step (f) performing single step fragmentation and oligonucleotide insertion on the ligated fragments using a recombinase enzyme, as set forth in claim 1. Instead, Fraser discloses steps of sonication, end-repairing, A-tailing, and adaptor ligation, as per pp. 23-25 in Example 1 and/or Fig. 1.
Hughes discloses a method of performing single step fragmentation and oligonucleotide insertion on the ligated fragments using a recombinase enzyme, and specifically using tagmentation as a means to fragment and add adaptors to the sample prior to sequencing (e.g., as per pp. 13-14).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to perform a single step fragmentation and oligonucleotide insertion on the ligated fragments using tagmentation as per Hughes in the chromosome conformation capture method of Fraser. One of ordinary skill in the art would have been motivated to do so since this allows the replacement of four steps (sonicating, end-repairing, A-tailing, and ligation) with a single step in a single tube, which simplifies the procedure and greatly increases efficiency, as explained by Hughes in pages 13-14.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since tagmentation was well-known in the art at the time, including the availability of commercial kits to perform it.
Regarding claims 2 and 10, Fraser discloses the above method, wherein step (h) comprises addition of isolating nucleic acid molecules which bind to the target nucleic acid segment or segments, wherein said isolating nucleic acid molecules are labelled with a first half of a binding pair; and isolating fragments which contain the target nucleic acid segment or segments bound to the isolating nucleic acid molecules by using the second half of said binding pair (e.g., the use of biotinylated RNA baits as per p. 30).
Regarding claim 9, Fraser discloses the above method, wherein said oligonucleotide and/or adapter sequences are oligonucleotide sequences that enable subsequent library preparation and sequencing (e.g., as per Fig. 1 and/or claim 10 of Fraser).
Regarding claim 11, Fraser discloses the above method, wherein the target nucleic acid segment or segments is selected from: promoters, silencers, enhancers or insulators (e.g., as per pp. 9-10 and/or claim 2 of Fraser).
Regarding claim 15, Fraser discloses the above method, wherein the restriction enzyme used at step (c) is HindIII or DpnII (e.g., as per Example 1 at p. 18).
Regarding claims 16-17, Fraser discloses the above method, which additionally comprises at step (g), and prior to step (i), amplifying the enriched fragments comprising the biotin moiety (e.g., PCR as per pp. 53-54).
Regarding claim 19, Fraser discloses the above method, wherein said nucleic acid composition is derived from a mammalian cell nucleus and/or wherein the said nucleic acid composition is derived from a non-human cell nucleus (e.g., as per pp. 13-14).
Regarding claims 22-23, Fraser discloses the above method, further comprising quantifying a frequency of interaction between a nucleic acid segment and a target nucleic acid segment or segments and comparing the frequency of interaction in the nucleic acid composition from the individual with said disease state with the frequency of interaction in a normal control nuclear composition from a healthy subject, such that a difference in the frequency of interaction in the nucleic acid composition is indicative of a particular disease, wherein the disease state is selected from: cancer, an autoimmune disease, a developmental disease or a genetic disorder (e.g., as per p. 15).
Regarding claim 24, Fraser discloses a kit for identifying a nucleic acid segment which interacts with a target nucleic acid segment or segments, comprising buffers and reagents capable of performing the method of claim 1 (e.g., as per pp. 16-17, wherein the step (f) requires, for example, a transposase as taught by Hughes at pp. 12-13).
Regarding claim 26, Hughes discloses the above method, wherein the retroviral integrase is a mutant transposase, optionally wherein the mutant transposase is a hyperactive Tn5 transposase (e.g., as per pp. 12-13).
Regarding claim 27, Fraser discloses the above method, wherein the sequences are blocker sequences (e.g., as per p. 29).
Regarding claim 28, Fraser discloses the above method, wherein the mammalian cell nucleus is a human cell nucleus, or the non-human cell nucleus is a mouse cell nucleus or plant cell nucleus (e.g., as per pp. 12-13).
Regarding claim 29, Hughes discloses the above method, wherein the retroviral integrase or transposase enzyme is a mutant transposase, optionally wherein the mutant transposase is a hyperactive Tn5 transposase (e.g., as per pp. 12-13).
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Response to Arguments
The 02/23/2026 remarks argue: not all elements are taught and no reasonable expectation of success.
Applicant's arguments have been fully considered but they are not persuasive for at least the following reasons.
Specifically, the remarks at pages 7-8 assert that claim 1 has been amended to recite in step (h) that the fragments comprising the target nucleic acid segment or segments are enriched "in the presence of sequences which prevent the binding of ligated fragments to other ligated fragments through complementarity of adaptor sequences or blocker sequences" and that this feature is not taught or suggested by either of the cited references. In response, it is noted that the rejection has been amended to include this newly added limitation.
Next, the remarks at pages 8-9 reproduce the arguments in the previous response to Non-Final Office Action filed on October 1, 2025. To the extent that Applicant is merely repeating the previously presented arguments, the response to these arguments is incorporated by reference from the Final Rejection Office Action of 10/23/2025.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEREMY FLINDERS whose telephone number is (571)270-1022. The examiner can normally be reached M-F 10-6:00 EST.
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/JEREMY C FLINDERS/
Primary Examiner, Art Unit 1684
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