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 .
Election/Restrictions
Applicant’s election without traverse of Group and the species elections of the combination of i) and ii) in claim 4 and of i), specifically SEQ ID NO: 3, in claim 6 in the reply filed on 11/03/2025 is acknowledged. The species of SEQ ID NO: 1 from i) is rejoined with the species of SEQ ID NO: 3 from i) in claim 6. Group II, claims 9-19, Group III, claims 20-22, and Group IV, claim 23, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A first office action on the merits of claims 1-6 is set forth herein and claims 9-23 are withdrawn from consideration.
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 1-6 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 claim 1, the recitation of “variation of the length and/or composition of the duplex stabilizer region can vary the conformational stability of the nanostructure” in lines 6-7 of the claim is unclear as to what is encompassed in “vary the conformational stability of the nanostructure”. Does any change in length or composition of the duplex stabilizer region vary the conformation stability of the nanostructure? How is conformational stability measured? In addition, the claim recites the limitation “the nanostructure” in line 7 of the claim and it is unclear and there is insufficient antecedent basis for this limitation in the claim. It is unclear if “the nanostructure” is referring to the “recognition nanostructure” or if it is referring to a different nanostructure.
Regarding claim 4, the recitation of “kinetics of enzyme activation” in line 5 of the claim is unclear how kinetics of enzyme activation is altered by increasing the length and/or GC content of the duplex stabilizer region. Is the inactivation or activation of any enzyme altered? The inactivation or activation of a specific enzyme altered? An increase or decrease in enzyme activity? In addition, the recitation of “ability to measure inputs” in line 6 of the claim is unclear what inputs are being measured and how their ability to be measured is altered by increasing the length and/or GC content of the duplex stabilizer region.
Regarding claim 5, the claim recites the limitation “the duplex stabilizer domain” in line 2 of the claim and there is insufficient antecedent basis for this limitation in the claim.
Regarding claim 6, the recitation of “a nucleic acid sequence set forth in any of Tables 1 to 4” in line 3 of the claim is indefinite. As stated in MPEP 2173.05(s), the claims should be complete to themselves and the reference to a table in the specification renders the claim incomplete. Claims which recited tables are only permitted in exceptional circumstances where there is not practical way to define the invention in words or where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. In addition, the claim recites the limitation “the nucleic acid sequence” in lines 4 & 11 of the claim and there is insufficient antecedent basis for this limitation in the claim. In addition, the recitation of “SEQ ID NO: 52, SEQ ID NO: 53 and SEQ ID NO: 54” in lines 10 & 15 of the claim is unclear if SEQ ID NO: 53 and SEQ ID NO: 54 are a part of the same group of nucleic acid sequence, or if this is the result of a typographical error and should read “SEQ ID NO: 52, SEQ ID NO: 53, and SEQ ID NO: 54”.
Claims 2 & 3 are rejected due to their dependence on claim 1.
Claim Rejections - 35 USC § 102
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.
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 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 region) 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 region) is between the conserved region and the variable region and that inducing mismatches in the variable region of the nanostructure (comprising the duplex stabilizer region) 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 region 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 region) (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 claim 4, Ho teaches that inducing mismatches in the variable region of the nanostructure (comprising the duplex stabilizer region) identified the duplex region (duplex stabilizer region) 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 (target compatibility) and improvement of visual detection sensitivity through additional polymerase activity (kinetics of enzyme activation) (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 region) is 4 nucleotides (duplex stabilizer region 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 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 region) 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 region) 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 claim 4, Shao teaches that a longer sequence each for the duplex (duplex stabilizer region) and overhang sequence stabilizes the aptamer binding to the DNA polymerase enzyme and produces an inhibitory effect to the enzyme (altering kinetics of enzyme activation) and that the duplex region showed a higher sensitivity to sequence mismatches offering strong sequence specificity (target compatibility (increasing of the length of the duplex stabilizer region 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 region) is 4 nucleotides (duplex stabilizer region length is in the range of 1 to 20 nucleotides) (Figure 1).
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.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ho (Ho et al.; Nature Communications, Vol. 9, pages 1-11, August 2018), as cited in the IDS dated 03/24/2023, in view of Park (U.S. Patent Application Publication US 2017/0335381 A1), as cited in the IDS dated 03/24/2023.
The teachings of Ho with regard to claim 1 are discussed above and incorporated herein.
Regarding claim 6, Ho does not teach that the duplex stabilizer region comprises a nucleic acid sequence of SEQ ID NO: 1.
Park teaches a DNA aptamer that has a duplex region (duplex stabilizer region) that comprises SEQ ID NO: 21, in which SEQ ID NO: 21 comprises SEQ ID NO: 1 from the instant application (duplex stabilizer region comprises a nucleic acid sequence set for the in any of Tables 1 to 4, SEQ ID NO: 1) (paragraph [0005] lines 1-5; paragraph [0011] lines 1-17; paragraph [0059] lines 1-9). Park also teaches that this DNA aptamer can detect target molecules with high sensitivity based on the change in DNA polymerase activity (abstract lines 1-8).
Ho and Park are considered to be analogous to the claimed invention because they are all in the same field of detection of target nucleic acids with DNA enzyme specific DNA aptamer complexes. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the recognition nanostructure comprising a duplex stabilizer region in Ho to incorporate a duplex stabilizer region comprising a nucleic acid sequence of SEQ ID NO: 1 as taught in Park because Park teaches that doing so would allow for detection of target molecules with high sensitivity.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shao (WO 2020/009660 A1), as cited on the IDS dated 03/24/2023, in view of Park (U.S. Patent Application Publication US 2017/0335381 A1), as cited in the IDS dated 03/24/2023.
The teachings of Shao with regard to claim 1 are discussed above and incorporated herein.
Regarding claim 6, Shao does not teach that the duplex stabilizer region comprises a nucleic acid sequence of SEQ ID NO: 1.
Park teaches a DNA aptamer that has a duplex region (duplex stabilizer region) that comprises SEQ ID NO: 21, in which SEQ ID NO: 21 comprises SEQ ID NO: 1 from the instant application (duplex stabilizer region comprises a nucleic acid sequence set for the in any of Tables 1 to 4, SEQ ID NO: 1) (paragraph [0005] lines 1-5; paragraph [0011] lines 1-17; paragraph [0059] lines 1-9). Park also teaches that this DNA aptamer can detect target molecules with high sensitivity based on the change in DNA polymerase activity (abstract lines 1-8).
Shao and Park are considered to be analogous to the claimed invention because they are all in the same field of detection of target nucleic acids with DNA enzyme specific DNA aptamer complexes. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the recognition nanostructure comprising a duplex stabilizer region in Shao to incorporate a duplex stabilizer region comprising a nucleic acid sequence of SEQ ID NO: 1 as taught in Park because Park teaches that doing so would allow for detection of target molecules with high sensitivity.
Conclusion
Claims 1-6 are rejected.
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