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. Art Unit Designation The art unit designation for correspondence to this Office Action has changed to 1681. This application has been transferred from Examiner Sarae L Bausch to Examiner Tian Yu. All future correspondence should be directed to Examiner Tian Yu whose contact information appears at the end of this Office Action. Information Disclosure Statement The information disclosure statements (IDS) submitted on 08/09/2023 and 12/05/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Status of Claims This office action is in response to Applicant's Response to Election / Restriction filed on January 13, 2026. Claims 1-4, 7, 9, 11, 14, 16, 47, 50, 52, 55-58 and 75-78 are pending, with Claims 1-2, 7, 9, 11, 47, 50, 52, 55-58, 75 and 77-78 withdrawn from further consideration. Claims 3-4, 14, 16 and 76 are under examination . This is the first action on the merits. Election/Restrictions In the restriction requirement mailed on 11/13/2025, claim 3 was inadvertently included in Group I. This inclusion appears to be a clerical error, as the system of claim 3 does not align with the description of Group I, which comprises a first and second reporter. In contrast, claim 3 does not recite any reporter. Similarly, claim 14 was inadvertently included in Group II. Claim 14 does not recite a first, second, third and fourth probe, as required by the inventions in Group II. Therefore, claims 3 and 14 should only belong to Group III, drawn to a system comprising a first nucleotide, second nucleotide and substrates. For clarity of the record, the corrected invention groups are as follows: Group I claims 1, 7, 11 , drawn to system comprising a first and second reporter. Group II, claims 2, 9, 75 , drawn to system comprising a first, second, third and fourth probe. Group III, claims 3-4, 14, 16, 76 , drawn to a system comprising a first nucleotide, second nucleotide and substrates. Group IV, claim 47, 55-56 , drawn to method for detecting a target sequence using a first and second reporter. Group V, claim 50, 77, drawn to method for detecting a target using a first and second probe. Group VI, claim 52, 57-58, 78 drawn to a method for detecting a target using a first and second nucleotide and providing substrates. Additionally, and for record clarity only, the PTO-326 form in the prior restriction requirement mailed on 11/13/2025 should reflect the pending claims that are subject to restriction requirement as 1-4, 7, 9, 11, 14, 16, 47, 50, 52, 55-58 and 75-78, consistent with the claims filed on 07/28/2023. Applicant’s election without traverse of Group III (claims 3-4, 14, 16, 76) in the reply filed on January 13, 2026 is acknowledged . Claims 1-2, 7, 9, 11, 47, 50, 52, 55-58, 75 and 77-78 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention. Examination on the merits commences on claims 3-4, 14, 16 and 76. Claim Objections Claims 14 and 16 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. See MPEP § 608.01(n). Here, claim 14 is improper for referencing the "system of claim 3" and "the second nucleotide sequence of claim 4." Claim 16 is improper for referencing the "system of claim 3" and " the second nucleotide sequence of claim 5" (claim 5 is a cancelled claim). Thus, the claims improperly reference to two sets of claims to different features. Accordingly, the claims 14 and 16 have not been further treated on the merits. Priority The priority date of the instant claim 3 is 06/04/2020, filling date of the US provisional application NO.63/034,824. Regarding claims 4, 14, 16 and 76, the earliest priority is 06/15/2020 because the priority document (US Provisional Application NO. 63/039,247) filed that date is the first to disclose (in Figure 3) a system comprising a “first nucleotide” probe and a “second nucleotide” probe comprising all the structural and functional features in claim 3 and further comprise thymine, as required by claim 76; and a system further comprising a "third nucleotide" probe and a "fourth nucleotide" probe, as required by claim 14; or "a first seed nucleotide" and "a second seed nucleotide" as required by claim 16. Claim Interpretation In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111. For the purpose of applying prior art, claim 3 recites the term " reversibly hybridize ," which is not expressly defined in the application's disclosure. Thus, under BRI, "reversibly hybridize" is interpreted to have the same meaning as "hybridize," since the hybridization of nucleic acid is already a reversible process . For the purpose of applying prior art, claim 3 recites "first enzymatic sequence ," "second enzymatic sequence ." Claim 4 further recites "third enzymatic sequence " and "fourth enzymatic sequence ." Neither the claim nor the specification explicitly defines the term " enzymatic sequence " with any structural features that distinguishes it from sequences known in the art. Therefore, under BRI, "enzymatic sequence" is interpreted as encompassing any nucleotide sequence and/or protein peptide sequence. Claim Rejections - 35 USC § 112(b) 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. Claims 3-4 and 76 are rejected under 35 U.S.C. 112(b), 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. A) Regarding claim 3 , it recites a " first nucleotide " and a " second nucleotide " comprising nucleotide sequences. This claim language is indefinite because the term "nucleotide" in the claim is used in a manner inconsistent with its ordinary and customary meaning in the art. A "nucleotide" is commonly understood as follows: “ nucleotide (NOO- klee -oh-tide) A molecule consisting of a nitrogen-containing base (adenine, guanine, thymine, or cytosine in DNA; adenine, guanine, uracil, or cytosine in RNA), a phosphate group, and a sugar (deoxyribose in DNA; ribose in RNA). DNA and RNA are polymers comprised of many nucleotides, strung together like beads in a necklace. ” ( see NCI Dictionary of Genetics Terms, Archived Jan 09, 2020 on WaybackMachine ) Accordingly, it is unclear how a "nucleotide," which is a single unit, can itself comprise a "nucleotide sequence," which is a polymer of many nucleotides like DNA and RNA. This term usage contradicts the commonly understood definition of "nucleotide" and creates ambiguity as to whether the claim is referring to a single nucleotide or a nucleic acid sequence. As the applicant acts as their own lexicographer by using "nucleotide" to refer to an entity comprising multiple nucleotide bases, and the specification fails to provide a clear and specific re-definition when the term is used in a manner divergent from it commonly understood meaning in the art, the claim is indefinite because it does not allow a skilled artisan to ascertain of the scope of the invention with reasonable certainty. See MPEP § 2111.01(IV) (“The only exceptions to giving the words in a claim their ordinary and customary meaning in the art are (1) when the applicant acts as their own lexicographer. . . .¶ An applicant is entitled to be their own lexicographer and may rebut the presumption that claim terms are to be given their ordinary and customary meaning by clearly setting forth a definition of the term that is different from its ordinary and customary meaning(s) in the specification at the relevant time”). Claims 4 and 76 are rejected for depending from claim 3 and not remedying the indefiniteness. Claim 4 similarly recites "third nucleotide" and "fourth nucleotide," which are also indefinite for the same reason discussed above. B) Claim 3 recites " enzymatically active dimer ," in the recitation : "wherein the first nucleotide and the second nucleotide are configured to dimerize to form a first enzymatically active dimer upon reversible hybridization of the first nucleotide sequence to the first target sequence and reversible hybridization of the second nucleotide sequence to the second target sequence." Thus, Claim 3 recites "first enzymatically active dimer" as a product formed through the process of hybridizing the "first nucleotide sequence" and "second nucleotide sequence" to their respective target sequences. The claim further recites : "wherein the first enzymatically active dimer is configured to convert the one or more first substrates into one or more first products. " These claim languages are indefinite because it is unclear what additional structural features define the "enzymatically active dimer" other than comprising "the first nucleotide and the second nucleotide," and whether it is required to possess features that support enzymatic activity or merely features that support active participation in an enzymatic reaction. The claim does not recite any structural features of the "enzymatically active dimer," and the term is not expressly defined in the specification. Further, there is no generally accepted definition in the art for "enzymatically active dimer" or for the phrase "enzymatically active." The term "enzymatically" is commonly understood as "in a way that involves enzymes, " which does not necessarily require that the entity itself has catalytic activity. Although the claim recites that the "enzymatically active dimer" is "configured to convert" substrates into products, this functional language does not require that the dimer itself performs enzymatic catalysis. Rather, it broadly encompasses entities that merely participate in a process that results in conversion of substrates to products. For example, the dimer may function as a double-stranded DNA template in a strand-displacement polymerase reaction, where the polymerase catalyzes conversion of a primer to an extended strand (see Yan in Fig. 5A). Alternatively, the dimer could function as probes that induce strand extension and ligation reactions converting dNTPs into a covalently linked sequence (see Yan in Fig. 5E). In such cases, the dimer participates in, but does not itself catalyze, the enzymatic reaction. Accordingly, because the claim does not clearly define the structural features or required functional properties of the recited "enzymatically active dimer," the metes and bounds of this limitation are not reasonably certain, rendering the claim indefinite. Claims 4 and 76 are rejected for depending from claim 3 and not remedying the indefiniteness. Claim 4 similarly recites "a second enzymatically active dimer," which is also indefinite for the same reason discussed above. For the purpose of compact prosecution and applying prior art under 35 USC§ 102 and 103, the term "first enzymatically active dimer" is interpreted as an entity comprising the first nucleotide and the second nucleotide, and is capable of participating in enzyme-mediated activity, but is not required to possess intrinsic catalytic function. Claim Rejections - 35 USC § 101 35 U.S.C. 101 reads as follows: Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title. Claims 3-4 and 76 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Independent claim 3 recites: A system of detecting a nucleic acid target comprising a first target sequence and a second target sequence, wherein the system comprises: a first nucleotide comprising a first nucleotide sequence and a first enzymatic sequence coupled to the first nucleotide sequence, wherein the first nucleotide sequence is configured to reversibly hybridize the first target sequence; a second nucleotide comprising a second nucleotide sequence and a second enzymatic sequence coupled to the second nucleotide sequence, wherein the second nucleotide sequence is configured to reversibly hybridize the second target sequence; wherein the first nucleotide and the second nucleotide are configured to dimerize to form a first enzymatically active dimer upon reversible hybridization of the first nucleotide sequence to the first target sequence and reversible hybridization of the second nucleotide sequence to the second target sequence; and one or more first substrates; wherein the first enzymatically active dimer is configured to convert the one or more first substrates into one or more first products. MPEP §2106.II on Patent Subject Matter Eligibility states : "It is essential that the broadest reasonable interpretation (BRI) of the claim be established prior to examining a claim for eligibility. " Regarding claim 3, it is drawn to a system comprising a first nucleotide and a second nucleotide, which encompass nucleic acid fragments with undefined sequence and length; and first substrates. Following the analysis below the claims are not patent eligible under 35 U.S.C. 101. Step 1 - Whether the Claim is to a Statutory Category : YES . The claims are drawn to a system, therefore to one of the four statutory categories. Step 2A According to MPEP § 2106, Step 2A is a two-prong inquiry, in which examiners determine in Prong One whether a claim recites a judicial exception, and if so, then determine in Prong Two if the recited judicial exception is integrated into a practical application of that exception. Together, these prongs represent the first part of the Alice/Mayo test, which determines whether a claim is directed to a judicial exception. Step 2A Prong 1 - Whether the Claim Recite an Abstract idea, Law of Nature, or Natural Phenomenon: Yes. The claims recite at nucleic acids without specifying any unique, markedly different characteristics compared to what occurs in nature. As stated in MPEP 2106.04(b)(I), laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. The courts have identified that " short, synthetic, single-stranded DNA molecule[s] that bind specifically to … intended targets nucleotide sequence[s] " are products of nature because they claim the same nucleotide sequence as naturally occurring DNA. See University of Utah Research Foundation v. Ambry Genetics Corp ., 774 F.3d 755, 761, 113 USPQ2d 1241, 1244 (Fed. Cir. 2014). See also MPEP 2106. Thus, the "first nucleotide" and "second nucleotide "comprising undefined nucleotide sequences are classified as nature-based products because they are not recited with any structural feature that can clearly distinguish these nucleic acids from the nucleic acids in nature, thus they could be either naturally occurring or they do not have markedly different characteristics compared to what occurs in nature. In conclusion, the claims recite nature-based products. Step 2A Prong 2 - Whether the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application: No. The claim as a whole do not integrates the exception into a practical application of that exception. For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must “transform the nature of the claim” into a patent-eligible application of the judicial exception, Alice Corp ., 573 U.S. at 217, 110 USPQ2d at 1981. The additional element in the claim is one or more first substrates that can be converted to products, but this element does not transform the claimed nature-based products to something that are markedly different than their naturally occurring counterparts in their natural state, nor does it integrate the recited judicial exception into a practical application of the exception. Mere combination of natural elements does not affect a change to any of the natural elements from their natural functions. See Funk Bros. Seed v. Kalo Inoculant Co ., 333 U.S. 127 (1948). Here, the “first substrate” can be broadly interpreted to include natural components including substrates involved in any natural enzymatic reactions, such as nucleic acids in exonuclease digestion, which naturally occurs in cellular metabolism. Although the claim recites first nucleotide and the second nucleotide "are configured to dimerize to form a first enzymatically active dimer," the claimed system does not actually require the formation of this "first enzymatically active dimer," it merely requires that the nucleotides be capable of forming the dimer. With the current interpretation under BRI, any nucleic acid composition can qualify as capable of forming "enzymatically active dimer" as long as it comprises two nucleotide sequences that bind to a hybridization target, along with additional sequences that may or may not hybridize to the target (i.e., enzymatic sequence), and is capable of participating in enzyme-mediated activities, such as naturally occurring nuclease digestion. Step 2B - Whether a Claim Amounts to Significantly More: No. According to MPEP§ 2106.05, The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc. , 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)). An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo , 566 U.S. at 72-73, 101 USPQ2d at 1966). In this instant case, the claims, when considered as a whole, do not recite any inventive concept with additional elements that amount to significantly more than the judicial exception. The claims do not appear to add markedly different characteristics that significantly modify or use the naturally occurring oligonucleotides in a manner that is not naturally occurring. Since Applicant does not claim any specific sequences or sequence lengths in claim 3, the nucleic acid fragments of the instant claims are equivalents of products of nature. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The dependent claims do not recite additional elements that amount to significantly more than the judicial exception. Although claim 76 additionally recites thymine bases capable of forming dimers upon UV light, this feature is naturally occurring and (see Smith-Carpenter JE, Taylor JS. Photocrosslinking of G-Quadruplex-Forming Sequences found in Human Promoters. Photochem Photobiol . 2019 Jan;95(1):252-266. doi : 10.1111/php.12991. Epub 2018 Sep 26. PMID: 30084501; PMCID: PMC6347517), therefore, constitutes a judicial exception and cannot amount to significantly more than the judicial exception. In conclusion, the claims are not patent eligible under 35 U.S.C. 101. However, if the claims are amended to specifically recite DNAzymes (see, for example, Fig. 9 in present disclosure), that would be sufficient to overcome the 101 rejection. While ribozymes comprising split probes are known in the art as naturally occurring, there are no reports of naturally occurring DNAzyme s . Claim Rejections - 35 USC § 102 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 ( i.e., changing from AIA to pre-AIA ) 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. 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. Claim 3 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yan (Yan et al. Isothermal amplified detection of DNA and RNA. Mol Biosyst . 2014 May;10(5):970-1003. doi : 10.1039/c3mb70304e. PMID: 24643211). Regarding claim 3, Yan teaches a system comprises: a first nucleotide (Fig. 37) comprising a first nucleotide sequence (Fig. 37, analyte binding arm) and a first enzymatic sequence coupled to the first nucleotide sequence(Fig. 37, substrate binding arm), wherein the first nucleotide sequence is configured to reversibly hybridize the first target sequence(Fig. 37); a second nucleotide (Fig. 37) comprising a second nucleotide sequence (Fig. 37, analyte binding arm) and a second enzymatic sequence coupled to the second nucleotide sequence(Fig. 37, substrate binding arm), wherein the second nucleotide sequence is configured to reversibly hybridize the second target sequence(Fig. 37); wherein the first nucleotide and the second nucleotide are configured to dimerize to form a first enzymatically active dimer upon reversible hybridization of the first nucleotide sequence to the first target sequence and reversible hybridization of the second nucleotide sequence to the second target sequence(Fig. 37, DNAzyme ); and one or more first substrates(Fig. 37, substrate); wherein the first enzymatically active dimer is configured to convert the one or more first substrates into one or more first products(Fig. 37). Claim 3 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhou (Zhou, Lu, et al. "Label-free fluorescence light-up detection of T4 polynucleotide kinase activity using the split-to-intact G-quadruplex strategy by ligation-triggered and toehold-mediated strand displacement release." Analyst 140.16 (2015): 5450-5453). Regarding claim 3, Zhou teaches a system comprising: a first nucleotide (Scheme 1, S2) comprising a first nucleotide sequence ( Scheme 1, S2, 5’-GCGGGT -3’) and a first enzymatic sequence coupled to the first nucleotide sequence (Scheme 1, S2, 5’-TGG -3’), wherein the first nucleotide sequence is configured to reversibly hybridize the first target sequence; a second nucleotide (Scheme 1, S1) comprising a second nucleotide sequence (Scheme 1, S1, 5’-GGTAGG -3’) and a second enzymatic sequence coupled to the second nucleotide sequence (Scheme 1, S2, 5’ - GTG -3’), wherein the second nucleotide sequence is configured to reversibly hybridize the second target sequence; wherein the first nucleotide and the second nucleotide are configured to dimerize to form a first enzymatically active dimer upon reversible hybridization of the first nucleotide sequence to the first target sequence and reversible hybridization of the second nucleotide sequence to the second target sequence (Scheme 1, ligated PS2.M; and one or more first substrates (Scheme 1, NMM); wherein the first enzymatically active dimer is configured to convert the one or more first substrates into one or more first products (Scheme 1). Claims 3-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dong (Dong et al. ; Amplified detection of nucleic acid by G-quadruplex based hybridization chain reaction. Biosens Bioelectron . 2012 Oct-Dec;38(1):258-63. doi : 10.1016/j.bios.2012.05.042. Epub 2012 Jun 8. PMID: 22739472 ). Regarding claim 3 , Dong teaches a system of detecting a nucleic acid target comprising a first target sequence (Scheme 1, a) and a second target sequence (Scheme 1, b), wherein the system comprises: a first nucleotide (Scheme 1, probe 1) comprising a first nucleotide sequence (Scheme 1, a*) and a first enzymatic sequence coupled to the first nucleotide sequence (Scheme 1, g2), wherein the first nucleotide sequence is configured to reversibly hybridize the first target sequence (Scheme 1, a*-a binding); a second nucleotide (Scheme 1, probe 2) comprising a second nucleotide sequence (Scheme 1, b*) and a second enzymatic sequence coupled to the second nucleotide sequence (Scheme 1, g1), wherein the second nucleotide sequence is configured to reversibly hybridize the second target sequence (Scheme 1, b*-b binding); wherein the first nucleotide and the second nucleotide are configured to dimerize to form a first enzymatically active dimer upon reversible hybridization of the first nucleotide sequence to the first target sequence and reversible hybridization of the second nucleotide sequence to the second target sequence (Scheme 1; Figure 2, dimer comprising probe 1 and probe 2 ); and one or more first substrates (Figure 2, ABTS and H2O2); wherein the first enzymatically active dimer is configured to convert the one or more first substrates into one or more first products (Green ABTS-). Regarding claim 4 , Dong teaches a third nucleotide (Scheme 1, 4th in line probe in DNA polymer, a GA2) comprising a third nucleotide sequence (Scheme 1, “a” in GA2) and a third enzymatic sequence coupled to the third nucleotide sequence (Scheme 1, g1); wherein the third nucleotide sequence is configured to reversibly hybridize the first nucleotide sequence (Scheme 1, a binds to a*); and a fourth nucleotide (Scheme 1, third in line probe in DNA polymer, the first GA1 probe that binds to GA2 in “ab”) comprising a fourth nucleotide sequence (Scheme 1, “b”) and a fourth enzymatic sequence coupled to the fourth nucleotide sequence (Scheme 1, g2), wherein the fourth nucleotide sequence is configured to reversibly hybridize the second nucleotide sequence (Scheme 1, b*-b binding); wherein the third nucleotide and the fourth nucleotide are configured to dimerize to form a second enzymatically active dimer upon reversible hybridization of the third nucleotide sequence to the first nucleotide sequence of the first enzymatically active dimer and the fourth nucleotide sequence to the second nucleotide sequence of the first enzymatically active dimer (Scheme 1), and wherein the second enzymatically active dimer is configured to convert the one or more first substrates into one or more first products (Figure 2). Claim Rejections - 35 USC § 103 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 ( i.e., changing from AIA to pre-AIA ) 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. 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. Claim 76 is rejected under 35 U.S.C. 103 as being unpatentable over Dong (Dong et al. ; Amplified detection of nucleic acid by G-quadruplex based hybridization chain reaction. Biosens Bioelectron . 2012 Oct-Dec;38(1):258-63. doi : 10.1016/j.bios.2012.05.042. Epub 2012 Jun 8. PMID: 22739472 ), in view of Gerling (Gerling et al. Sequence-programmable covalent bonding of designed DNA assemblies. Sci Adv. 2018 Aug 17;4(8):eaau1157. doi : 10.1126/sciadv.aau1157. PMID: 30128357; PMCID: PMC6097813). The teachings of Dong are recited above and applied as for base claim 3. Regarding claim 76, Dong teaches the first nucleotide and the second nucleotides are both DNA (Scheme 1, GA1 and GA2 are DNA probes forming DNA polymers). Dong teaches a system for amplified detection of nucleic acid using G-quadruplex based hybridization chain reaction (Abstract). Specifically, Dong teaches that, in the presence of a target sequence, hybridization of probe dimers (GA1-GA2) and their assemblage into polymers comprising G-quadruplex structures. These G-quadruplexes function as peroxidase mimicking DNAzymes that catalyze conversion of a clear substrate into a green colored product, thereby achieving colorimetric detection of the target sequence (Scheme 1, Fig. 2). As discussed above for base claim 3, Dong teaches a first and second nucleic acid probes (referred to in the claim as first and second "nucleotide") that are configured to hybridize to target sequences via complementary sequences. Although Dong does not explicitly teach that the hybridizing probes comprise thymine bases configured to dimerize upon exposure to ultraviolet (UV) light, this feature in known in the art and would have been obvious in the context of the DNA polymer structures in Dong, in view of Gerling. Gerling teaches methods for introducing additional covalent bonds in DNA nanostructures by placing additional thymidines at both strand termini at strand break sites (i.e., locations where single-stranded oligonucleotides are positioned in proximity through hybridization but are not covalently linked; see Gerling, Fig. 1A ). Gerling further teaches that UV irradiation induces dimerization of these thymidines , forming covalent cross-links that enhance structural stability and enhanced resistance against nuclease activity (Abstract). Regarding claim 76, Gerling teaches preparing DNA strands with additional thymidines at both strand termini (Fig. 1A, motif 1). Although these added bases will not be involved in forming Watson-Crick base pairs, they are positioned in close proximity at strand break sites, enabling formation of covalently bonded thymine dimers upon UV exposure (page 2 , left-hand col, lines 15-20). Gerling further explains that such modification address structural weaknesses in DNA nanostructures, such as DNA tile-brick objects, in which the double-helical domains are formed only between single-stranded oligonucleotides, containing hundreds of single-strand breaks, which represent weak points. This is because “ free ends enable not only the formation but also the dissolution of plectonemic double-helical domains .” (page 2 , left-hand col, lines 15-20). Similarly, the DNA polymers described in Dong comprise double-helical domains formed between individual oligonucleotides and therefore include analogous single-stranded break points. Accordingly, a person of ordinary skill in the art would have recognized that the teachings of Gerlingꟷ introducing covalent cross-links via UV-induced thymine dimerization ꟷ could be applied to improve the stability of the DNA polymers of Dong. In view of the above, it would have been prima facie obvious to modify Dong’s teaching of a system for target detection via generation of DNA polymers bearing G-quadruplexes, to further improve the stability of DNA polymers by incorporating additional thymidines at the termini of the hybridizing probes, such that, upon hybridization, the thymine bases are positioned in proximity and can form covalently linked dimers upon UV exposure, as taught by Gerling. The skilled artisan would have been motivated to make this modification to address the structural weakness associated with strand break sites in the DNA polymer of Dong, and to leverage the benefits described in Gerling, including increased stability and nuclease resistance. The person of ordinary skill would have had a reasonable expectation of success in making this modification because incorporating additional thymine bases at the 3' and 5' termini of oligonucleotide probes is a routine design modification that can be readily achieved using standard molecular biology techniques. Moreover, the teachings of the references are technically compatible. And Gerling further states that its teaching is applicable to a wide range of fields: "Because of the simplicity, sequence programmability, and scalability, covalent bonding by UV irradiation will help pave the way for applications of DNA nanostructures in a wide variety of conditions for a range of fields." (page 8, left-hand col, para 3, lines 5-8). Conclusion Claims 14 and 16 are objected to; claims 3-4 and 76 are rejected. No claim are allowed. 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