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 .
Response to Amendment
The Amendment filed 12/04/2025 in which claims 15, 20 were amended, new claims 26-28 were added, and claims 17, 19, 21-25 were canceled, has been entered. Claims 1-14 were previously withdrawn.
Claims 15, 16, 18, 20, 26-28 are under examination on the merits.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings submitted on 12/04/2025 have overcome the objection previously set forth in the Non-Final Office Action mailed 09/11/2025.
Nucleotide and/or Amino Acid Sequence Disclosures
(Previous objection, withdrawn) Applicant’s amendments to the Drawings and Specification concerning nucleotide and/or amino acid sequence disclosures submitted on 12/04/2025 have overcome the objections previously set forth in the Non-Final Office Action mailed 09/11/2025.
Claim Objections
(Previous objections, withdrawn as to claim 20). Applicant’s amendments to claim 20 have overcome previous objections to claim 20.
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.
(Previous rejection, withdrawn as to claim 18) Claim 18 was rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly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.
See claim 18 as submitted on 12/04/2025.
Applicant’s amendment to claim 15 has overcome previous rejection to claim 18.
(New rejection, necessitated by the addition of claim 27) Claim 27 was 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 27 recites “and a colorimetric substrate to the captured digoxigenin labeled double-stranded nuclease protection probes to visibly show the presence of the target nucleic acid sequence in the sample.” There is insufficient antecedent basis for this recitation in the claim because claim 27 depends on claim 20 which has no mention of captured digoxigenin labeled double-stranded nuclease protection probes. Further, a digoxigenin label is not mentioned until claim 26. For purposes of compact prosecution and applying prior art, claim 27 was herein interpreted to be dependent on claim 26 which mentions a digoxigenin label.
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.
(previous rejection, withdrawn as to claims 17 and 19, maintained and modified as to claims 15, 16, 18, 20) Claims 15, 16, 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Seligmann, in view of Aveyard et al. and Nilsson et al. (prior art of record)
See claims 15, 16, 18 and 20 as submitted on 12/04/2025.
The previous rejections of claims 17 and 19 are moot in view of Applicant’s cancelation of these claims.
Regarding claim 15, it is noted that the amended claim recites the following new limitations:
A lateral flow assay system for the detection of presence, concentration, and/or quantity of a target nucleic acid sequence in a sample (lines 1-3)
(e) a protection zone comprising,
a plurality of nuclease protection probes, wherein each nuclease protection probe in the plurality of nuclease protection probes comprises a label for detection;
(h) a rolling circle amplification (RCA)
(l) a lateral flow assay strip
However, these new limitations are already taught by the cited prior art. Specifically the cited prior art teaches these limitations as follows:
A lateral flow assay system for the detection of presence of a target nucleic acid sequence in a sample is taught by Aveyard et al. (Abstract, page 1)
(e) a protection zone is taught by Seligmann (¶¶ [0024], [0029])
a plurality of nuclease protection probes is taught by Seligmann (¶¶ [0024], [0029]), wherein each nuclease protection probe in the plurality of nuclease protection probes comprises a label for detection is taught by Seligmann (¶¶ [0015], [0024], [0026])
(h) a rolling circle amplification (RCA) is taught by Seligmann (¶¶ [0051], [0084])
(l) a lateral flow assay strip is taught by Aveyard et al. (Abstract, Fig. 1, page 1).
With respect to all other limitations as recited in amended claim 15, as previously explained these limitations are taught as follows. Seligmann teaches a system for the detection of a target nucleic acid sequence in a sample (Abstract, ¶ [0001]), the system of Seligmann comprises the following elements:
a platform (claim 60, ¶¶ [0003], [0022]);
one or more heaters (¶¶ [0030], [0084]);
a sample loading zone (¶¶ [0038], [0095]);
a channel (¶¶ [0010], [0058]);
a padlock probe zone (¶ [0051]) comprising,
a plurality of padlock probes, each padlock probe comprising a 5' end, a 3' end, and a central region, wherein the 5' ends and the 3' ends of the padlock probes comprise sequences complementary to the target nucleic acid sequence and the central regions comprise a sequence that matches a sequence on the nuclease protection probes (Fig. 9; ¶ [0051]);
a ligation zone comprising (¶ [0024]),
a plurality of ligases (¶¶ [0024], [0032], [0054]);
a ligation buffer (¶¶ [0058], [0088]);
and a plurality of adenosine triphosphate (ATPs) (¶ [0054]);
a rolling circle amplification (RCA) zone suited for an RCA reaction (¶¶ [0051], [0084]) comprising,
a plurality of DNA or RNA polymerases (¶¶ [0020], [0088]);
a plurality of dNTPs (¶ [0020]);
a protection zone comprising (¶¶ [0024], [0029]),
a plurality of nuclease protection probes (¶¶ [0024], [0029]);
a nuclease digestion zone comprising (¶ [0029]),
a plurality of nucleases (claim 24, ¶ [0030]);
and a nuclease buffer (¶ [0032]);
a detection zone (claim 1, ¶¶ [0001], [0029]);
While Seligmann teaches RCA amplification in detail (¶¶ [0051], [0084]), Seligmann does not explicitly teach, bovine serum albumin, and an absorbent pad.
However, Aveyard et al. teach a system comprising a lateral-flow device for detection of nucleic acids after amplification (Abstract, page 1). Aveyard et al. further teach the lateral-flow device system functions by sandwiching amplification products between reporter oligonucleotides covalently attached to gold nanoparticles (GNPs) and capture oligonucleotides covalently attached to a nitrocellulose chromatographic strip such that unpurified amplification products can be detected with the unaided eye (Abstract, page 1). The lateral-flow device of Aveyard et al. further comprises a absorbent pad which allows for migration of the sample toward a test line (Fig. 1, page 1).
Nilsson et al. are cited for teaching the use of bovine serum albumin BSA in an RCA reaction (page 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teachings of Seligmann, Aveyard et al., and Nilsson et al. to formulate a system of detection of RCA products comprising an absorbent pad for the benefit of detection with the unaided eye. One of ordinary skill in the art would have been motivated to do so given that Seligmann and Nilsson et al. teach an RCA system and Aveyard et al. teach lateral-flow device comprising an adsorbent pad for detection of unpurified nucleic acid amplification products. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in combining the system of Seligmann with the BSA of Nilsson et al. and the adsorbent pad of Aveyard et al. given that the methods of RCA reactions and detection on an absorbent pad are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 16, it is noted that no amendments were introduced to claim 16 in the amendment filed on 12/04/2025. As previously explained, Seligmann further teaches padlock probes comprising a 5' -phosphate modification (¶¶ [0051], [0035])
Regarding claim 18, it is noted that no amendments were introduced to claim 16 in the amendment filed on 12/04/2025. As previously explained, Seligmann further teaches wherein each nuclease protection probe comprises a label for detection, wherein the label is a fluorescent label (¶¶ [0015], [0024], [0026]).
Regarding claim 20, it is noted that all of the amendments were made to overcome the previous rejections under 35 U.S.C. 112(b), second paragraph set forth in the Non-Final Office Action mailed on 09/11/2025. No new limitations were introduced in the amendment filed on 12/04/2025. As previously explained, Seligmann further teaches wherein the protection probes further comprise 5' biotin for clean of the reaction mixture (¶ [0041]).
(New rejection, necessitated by the addition of new claims 26-28) Claims 26-28 are rejected under 35 U.S.C. 103 as being unpatentable over Seligmann, Aveyard et al. and Nilsson et al. (prior art of record) as applied to claims 15, 16, 18, and 20 above; further in view of Guesdon JL. “Immunoenzymatic techniques applied to the specific detection of nucleic acids.” A review. J Immunol Methods. 1992;150(1-2):33-49. See PTO-892: Notice of References Cited.
See claims 26-28 as submitted on 12/04/2025.
Regarding claim 26, Seligmann, Aveyard et al. and Nilsson et al. in combination teach the LFA of claim 15. Seligmann teaches the use of biotin or other haptans for capturing ((¶ [0041]). Neither Seligmann, nor Aveyard et al. nor Nilsson et al. explicitly teach the haptan digoxigenin as a label.
However, Guesdon teaches method of labeling nucleic acid probes for specific detection of nucleic acids (Abstract). Guesdon further teaches a digoxigenin label which can be added to either side of a nucleic acid (3’ or 5’) and is not sensitive to elevated temperatures, extended incubations times, detergents and organic solvents (Abstract, page 8).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have incorporated a digoxigenin label into the protection probes as taught by Seligmann, Aveyard et al., and Nilsson et al. to formulate an LFA for detection of RCA products, wherein the protection probes are not sensitive to elevated temperatures, extended incubations times, detergents and organic solvents which represents a significant advantage in nucleic acid detection. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in incorporated a digoxigenin label into the protection probes as taught by Seligmann, Aveyard et al., and Nilsson et al. given that the methods of RCA reactions and labeling of nucleic acid probes are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claims 27 and 28, Seligmann and Guesdon teach a biotin/streptavidin conjugation of protection probes (Seligmann [¶ [0041]; Guesdon [page 10]). Guesdon further teaches reporter enzyme labeling (for example, with HRP) of avidin, streptavidin or antibodies for detection (pages 10 and 11) and a substrate such as an anti-digoxigenin antibody to capture the probes bound to target nucleic acids comprising a colorimetric label such that the target nucleic acid can be visualized (pages 10 and 11).
Accordingly, claims 26-28 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed 12/04/2025 have been fully considered but they are not persuasive.
Applicant contends on page 13 of the Remarks submitted on 12/04/2025:
The cited references do not, either alone or in combination, disclose nor suggest the lateral flow assay system which comprises a lateral flow strip for the ultrasensitive detection of target nucleic acids as currently claimed. Applicant notes that Seligmann does not teach a platform which is the physical foundation of a lateral flow assay (see, e.g., FIG. 7 of the present application). Seligmann, by contrast, recites a "platform" throughout the disclosure only in reference to next-generation sequencing, e.g., the 454 Sequencing "platform" or Solexa Sequencing "platform."… Further, Aveyard does not disclose nor mention detecting nucleic acids amplified via RCA amplification, let alone the specific detection methods described in the present application, including labeling nuclease protection probes with 5' biotin and/or 3' digoxigenin labels as a proxy for the target nucleic acid sequence… Nilsson also does not disclose or suggest incorporating a lateral flow assay for detection and quantification of RCA products as is recited in the currently amended claims.”
In response:
Applicant's arguments against the references individually are not persuasive because one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As explained above and previously, the combination of the references cited teach the exact LFA with all of its element as instantly claimed along with clear motivations to combine such teachings.
Conclusion
No claims are allowed.
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 MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672