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 Status
Claims 1-6 filed on 04/16/2026 are pending. Claims 9-23 are withdrawn from consideration as being drawn to a non-elected invention. Claims 4 & 6 are currently under examination directed to the elected species of the combination of i) and ii) in claim 4 and of SEQ ID NO: 3 in claim 6 (see response dated 11/03/2025). All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant application. Response to Applicant’s argument follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 112
Claim 6 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.
Regarding amended claim 6, the claim recites the limitation “the duplex stabilizer region” in lines 1-2 of the claim and there is insufficient antecedent basis for this limitation in the claim and it is unclear if “the duplex stabilizer region” is meant to refer back to “a duplex stabilizer domain” as amended to in claim 1, from which claim 6 depends from, or is referring to a different duplex stabilizer region.
Claim Rejections - 35 USC § 102
Claim(s) 1-5 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ho (Ho et al.; Nature Communications, Vol. 9, pages 1-11, August 2018), as cited in the IDS dated 03/24/2023.
Regarding amended claim 1, Ho teaches a recognition nanostructure comprising a modified DNA aptamer that binds strongly with polymerase to inhibit polymerase activity (binds to inactivate DNA polymerase) that has a conserved sequence region, a variable region (red and blue sequences of Fig. 3a in variable region) that comprises an inverter comprising an overhang segment and a duplex region (duplex stabilizer domain) that can be made complementary to the target DNA, in which the inverter comprising an overhang segment and the duplex region (red sequence of Fig. 3a in variable region) (target-specific inverter oligonucleotide comprising a portion that forms a duplex with the variable sequence region and a portion that forms an overhang) is complementary to the variable sequence region (blue sequence in Fig. 3a in variable region) (pg. 2 paragraph bridging column 1 & 2 lines 1-14; pg. 3 column 2 1st full paragraph lines 1-7; Fig. 1; Fig. 3; Supplementary Table 1). Ho also teaches that the duplex region (duplex stabilizer domain) is between the conserved region and the variable region and that inducing mismatches in the variable region of the nanostructure (comprising the duplex stabilizer domain) identified the duplex region conferring strong sequence sensitivity and the overhang region could accommodate more sequence variability (variation of length and/or composition of duplex domain can vary the conformational stability of the nanostructure) (pg. 3 2nd column 1st full paragraph lines 1-14; Fig. 3).
Regarding claim 2, Ho teaches that the variable sequence region is at least 8 nucleotides in length (variable region 8 nucleotides in Fig. 3a and sequence design with highly divergent (variable) regions of 40 bp) (pg. 9 column 1 3rd full paragraph lines 11-15; Fig. 3a; Supplementary Table 1).
Regarding claim 3, Ho teaches an inverter (target-specific inverter oligonucleotide) comprising a portion that forms overhang segment of at least 4 nucleotides and a portion that forms a duplex region (duplex stabilizer domain) (red sequence of Fig. 3a in variable region) (pg. 3 column 2 1st full paragraph lines 1-7; Fig. 1; Fig. 3; Supplementary Table 1).
Regarding amended claim 4, Ho teaches that inducing mismatches in the variable region of the nanostructure (comprising the duplex stabilizer domain) identified the duplex region (duplex stabilizer domain) conferring strong sequence sensitivity and the overhang region could accommodate more sequence variability (variation of length and/or GC content of duplex region can vary the conformational stability of the nanostructure) thereby altering sequence specificity and improvement of visual detection sensitivity through additional polymerase activity (pg. 3 2nd column 1st full paragraph lines 1-14; pg. 7-8 paragraph bridging column 1 & 2 lines 12-14; Fig. 3).
Regarding claim 5, Ho teaches that the duplex region (duplex stabilizer domain) is 4 nucleotides (duplex stabilizer domain length is in the range of 1 to 20 nucleotides) (Fig. 1; Fig. 3).
Claim(s) 1-5 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Shao (WO 2020/009660 A1), as cited on the IDS dated 03/24/2023.
The applied reference has a common applicant and joint inventors with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding amended claim 1, Shao teaches detecting target nucleic acids in a sample through providing a composition comprising at least one DNA polymerase enzyme and at least one recognition nanostructure wherein the recognition nanostructure comprises a DNA polymerase enzyme-specific DNA aptamer and an inverter oligonucleotide, wherein the adapter has a conserved region and a variable sequence region, wherein the variable sequence region comprises an overhang segment which is complementary to and forms a duplex (duplex stabilizer domain) with a portion of the inverter oligonucleotide (pg. 42 claim 1 lines 11-19). Shao also teaches that a longer sequence each for the duplex (duplex stabilizer domain) and overhang sequence stabilizes the aptamer binding to the DNA polymerase enzyme (variation of the length and/or composition of the duplex stabilizer region can vary the conformational stability of the nanostructure) (pg. 17 lines 21-24).
Regarding claim 2, Shao teaches that the variable sequence region comprises an overhang segment that is at least 10 nucleotides (variable sequence region is at least 8 nucleotides in length) (pg. 42 claim 1 lines 15-16; Figure 1).
Regarding claim 3, Shao teaches that the inverter oligonucleotide comprising a portion that forms a duplex with the variable sequence region and a portion that forms an overhang segment that is about half the length of the aptamer-inverter duplex, in which the inverter oligonucleotide is about 35 to 45 nucleotides in length providing an overhang segment that is 17 to 22 nucleotides in length (target-specific inverter oligonucleotide forms an overhang of at least 4 nucleotides) (pg. 42 claim 1 lines 15-19; pg. 44 claim 5 lines 1-2; pg. 44 claim 6 lines 1-3).
Regarding amended claim 4, Shao teaches that a longer sequence each for the duplex (duplex stabilizer domain) and overhang sequence stabilizes the aptamer binding to the DNA polymerase enzyme and produces an inhibitory effect to the enzyme and that the duplex region showed a higher sensitivity to sequence mismatches offering strong sequence specificity (increasing of the length of the duplex stabilizer domain can vary the conformational stability of the nanostructure) (pg. 17 lines 21-24; pg. 29 lines 5-14).
Regarding claim 5, Shao teaches that the duplex region (duplex stabilizer domain) is 4 nucleotides (duplex stabilizer domain length is in the range of 1 to 20 nucleotides) (Figure 1).
Response to Arguments
The response traverses the rejection. The response asserts that in Fig 3a of Ho, the double-stranded structure (i.e., the duplex region) is formed between the variable sequence of the inverter (the red sequence) and a part of the conserved sequence of the aptamer (the blue sequence) and that, to the contrary, the duplex stabilizer domain of independent claim 1 is a separate component in addition to the conserved region and variable region and lies between the conserved sequence region and the variable sequence region and thus the duplex region of Ho is not the same as the duplex stabilizer domain of the claimed invention. This argument has been thoroughly reviewed but was not found persuasive. First, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the duplex stabilizer domain is a fully separate component in addition to the conserved region and variable region (a fully separate component between the end of the conserved sequence region and the end of the variable sequence region)) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Independent claim 1, as currently amended, recites “a duplex stabilizer domain that lies between the conserved aptamer sequence region and the variable sequence region” in which the claim is given it broadest reasonable interpretation to encompass a duplex stabilizer region in between a conserved aptamer sequence and a variable sequence region. Further, Ho also teaches that the duplex region (duplex stabilizer domain) is between the conserved region and the variable region (duplex stabilizer domain lies between the conserved region and the variable region) (pg. 3 2nd column 1st full paragraph lines 1-14; Fig. 3).
The response also asserts that in Ho the mismatches are introduced in the complementary target sequence per se, which hybridizes to the variable region of the recognition nanostructure and that this is different from the variability of the duplex stabilizer domain according to independent claim 1, which is located in the aptamer and does not hybridize with the target per se. In addition, the response asserts that the introduced mismatches validate that the duplex region in Ho is able to confer strong sequence specificity, which is a different property compared to conformational stability as defined in claim 1 and therefore, Ho fails to disclose the feature “variation of the length and/or composition of the duplex stabilizer domain can vary the conformational stability of the recognition nanostructure” recited in independent claim 1. This argument has been thoroughly reviewed but was not found persuasive. First, strong sequence specificity enables a more stable conformation and therefore the teachings of Ho that the introduced mismatches (variation of the length or composition of the duplex stabilizer domain) validate that the duplex region is able to confer strong sequence specificity enables a more stable conformation (can vary the conformational stability). In addition, the claim as currently amended recites “variation of the length and/or composition of the duplex stabilizer domain can vary the conformational stability of the recognition nanostructure” in which Ho teaches that that inducing mismatches in the variable region of the nanostructure (comprising the duplex stabilizer domain) identified the duplex region conferring strong sequence sensitivity and the overhang region could accommodate more sequence variability (variation of length and/or composition of duplex domain can vary the conformational stability of the nanostructure) (pg. 3 2nd column 1st full paragraph lines 1-14; Fig. 3).
The response also asserts that, in view of the above, independent claim 1 is not anticipated in view of Ho and dependent claims 2-5 are not anticipated at least for the same reasons. This argument has been thoroughly reviewed but was not found persuasive for the reasons set forth above.
The response also asserts that Shao relates to the same work of Ho and therefore, the applicant submits that the above arguments regarding Ho also applies to Shao. Specifically, the response asserts that Shao fails to teach or disclose where the duplex stabilizer domain, according to independent claim 1, is a separate component in addition to the conserved region and variable region and lies between the conserved sequence region and the variable sequence region. This argument has been thoroughly reviewed but was not found persuasive. First, in response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the duplex stabilizer domain is a (a fully separate component between the end of the conserved sequence region and the end of the variable sequence region)) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Independent claim 1, as currently amended, recites “a duplex stabilizer domain that lies between the conserved aptamer sequence region and the variable sequence region” in which the claim is given it broadest reasonable interpretation to encompass a duplex stabilizer region in between a conserved aptamer sequence and a variable sequence region. Further, Ho also teaches that the duplex region (duplex stabilizer domain) is between the conserved region and the variable region (duplex stabilizer domain lies between the conserved region and the variable region) (pg. 3 2nd column 1st full paragraph lines 1-14; Fig. 3).
The response also asserts that, in Shao the mismatches are introduced in the complementary target sequence per se, which hybridizes with the variable region of the recognition nanostructure and that this is different from the variability of the duplex stabilizer domain according to independent claim 1, which is located in the aptamer and does not hybridize with the target DNA per se and further, the introduced matches validate that the duplex region in Ho is able to confer strong sequence specificity, which is also different to the conformational stability as defined in claim 1 and that, taken together, Shao fails to disclose the feature “variation of the length and/or composition of the duplex stabilizer domain can vary the conformational stability of the recognition nanostructure” recited in independent claim 1. This argument has been thoroughly reviewed but was not found persuasive. First, the response with regards to Ho in teaching the feature of “variation of the length and/or composition of the duplex stabilizer domain can vary the conformational stability of the recognition nanostructure” is discussed above. Second, Shao teaches that a longer sequence each for the duplex (duplex stabilizer domain) and overhang sequence stabilizes (conformational stability) the aptamer binding to the DNA polymerase enzyme (variation of the length and/or composition of the duplex stabilizer region can vary the conformational stability of the nanostructure) (pg. 17 lines 21-24) as discussed above in section 7.
The response also asserts that, in view of the above, independent claim 1 is not anticipated in view of Shao and dependent claims 2-5 are not anticipated at least for the same reasons. This argument has been thoroughly reviewed but was not found persuasive for the reasons set forth above.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Conclusion
Claims 1-6 are rejected.
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 BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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