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 Claims 1-10 are still pending and herein discussed on their merits. Information Disclosure Statement No information disclosure statement was filed at the time of this action. Claim Objections Claim 1 is objected to because of the following informalities: improper grammar . In claim 1, step (b), the word “has” is used twice and should be replaced with the word “having,” so that the sentence reads “…with one end of the amplified product having a sequence… and the other end having a biotin modification.” Appropriate correction is required. 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. Claim s 1 - 10 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. Claim 1 is rejected as indefinite because it recites a “sequence capable of synthesizing copper nanoclusters” (repeated in claims 4-6). Capability is a latent characteristic and the claims do not set forth the criteria by which to determine capability. That is, it is not clear as to whether the target gene sequence itself comprise s a sequence with the ability to synthesize copper nanoclusters, or if that ability is only present under some unspecified conditions or following modification of some kind. Amendment of the claim to make clear the nature of the sequence is suggested. Claim 1 also recites that the sample should contain either a wildtype sequence or a variant sequence or both in step (a), but then requires that both be present in step c (when the restriction enzyme produces both a digested and an undigested product). Therefore, in the case that only the wildtype or only the variant sequence were present in a sample , step c would render the claim contradictory . Clarification of which sequences are present in the test sample in claim 1 would help elucidate the limitations of claim 10 , the meaning and scope of which are unclear because both heterozygosity and the determination of proportion imply a plurality of gene targets and only a single gene sequence is recited in claim 10 or required in claim 1, step a . 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. Claims 1 , 3- 5 , and 9- 10 are rejected under 35 U.S.C. 102(a)(1) as unpatentable over Lai et al (published November 17, 2022; Lai et al. Analyst, 2022,147, 5732-5738). Lai teaches a method of detecting a single nucleotide variant in the BCR-ABL1 gene using copper nanoclusters. Regarding claim 1, Lai teaches a test sample with a target sequence that represents wild-type and /or single-nucleotide variant sequences (pg 5734, Scheme 1; pg 5736, Application in DNA samples) , using a specific primer pair to produce an amplified product having one end with a copper nanocluster synthesis sequence and the other with a biotin modification, (pg 5734, Scheme 1 ; Results and discussion, paragraph 1 ), digesting the amplified product with a restriction enzyme that digests only the wild-type sequence, wherein the digested product includes a fragment with the copper nanocluster synthesis sequence and a fragment with a biotin modification , using streptavidin-coated magnetic beads to precipitate the undigested and biotin-modified amplified to obtain a supernatant , and then conducting copper nanocluster synthesis in the supernatant , and determining the condition of the gene sequence based on the amount of DNA-templated copper nanoclusters (pg 5734, Results and discussion, 1 st paragraph ). It is a property of the assay taught by Lai that more copper nanoclusters are produced when the supernatant contains more digested fragments containing the copper nanocluster synthesis sequence (Results and discussion, 1 st paragraph). Regarding claim 3, Lai teaches gene amplification with polymerase chain reaction ( Results and discussion, 1st paragraph). Regarding claim 4, Lai teaches a copper nanocluster synthesis sequence at the 5’ end of the forward primer (Scheme 1 in the cutaway after the step of adding copper ions and sodium ascorbate; pg 5735, col 1, 1 st paragraph) and a biotin modification at the 5’ end of the reverse primer (Scheme 1 , forward and reverse primers ). Regarding claim 5, Lai teaches an AT repeat sequence on one end of the amplified product which is capable of synthesizing copper nanoclusters (Table S1; Results and discussion, first paragraph). Regarding claim s 9 and 10 , Lai teaches fluorescence spectrometry to obtain a quantitative result ( Results and discussion, 1st paragraph ) , which is used to identify mutant/wildtype heterozygotes (pg 5736, Application in DNA samples) . 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. Claims 1, 3-5, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al . (published September 11, 2018; Analytical Chemistry 2018 90 (19), 11599-11606), in light of Jia et al. (published March 14, 2012; ACS Nano 2012 6 (4), 3311-3317). Wang et al. teaches a method of detecting gene variants using streptavidin magnetic beads combined with PCR and restriction fragment release (Abstract). Regarding claims 1, 3-5, and 9, Wang teaches a test sample containing a wild-type target gene sequence and/or a variant, adding a specific primer pair to perform an amplification via PCR , wherein the reverse primer has a biotin modification on the 5’ end and the amplification product includes a biotin modification on one end (Figure 1), digesting the product with a restriction enzyme that is specific to the wildtype sequence (pg 11600, col 2, last paragraph), and interpreting the quantitative results of a fluorescence spectrometry analysis to determine the condition of the target gene (pg 11600, col 2, first and last paragraphs). Wang does not teach a sequence for copper nanocluster synthesis on the non-biotin-modified end of the amplified product. Wang also does not teach conducting copper nanocluster synthesis in the supernatant, where more digested fragments released into the supernatant generate more synthesis of copper nanoclusters, which allows for determining the condition of the target gene sequence based on the amount of nanoclusters. Jia teaches synthesis of copper nanoclusters using AT repeat sequences (pg 3315, col 1, first paragraph) where the amount of copper nanoclusters is used to determine the condition of the target gene sequences (pg 3312, col 1, first paragraph). Additionally, though Wang does not disclose copper nanoclusters, Wang does teach a fluorescent chromophore on the non-biotin-modified end of the amplified product (Figure 1), where more fluorescently-labeled digested fragments released into the supernatant lead to a larger signal, which is used for determining the condition of the target gene sequence (pg 11600, last paragraph). As the copper nanoclusters and the fluorescent chromophore are used for the same purpose (generating differential levels of fluorescence in a sequence-specific manner), it would be obvious to a person with ordinary skill in the art before the effective filing date of the invention to substitute the chromophore modification of Wang for the copper nanocluster synthesis sequence of Jia to arrive at the instant invention. One would be motivated to do so in order to achieve high selectivity in detection of DNA mismatches (Jia: pg 3311, col 2). Claims 6-8 are rejected under 35 U.S.C. 103 as unpatentable over Wang et al (published September 11, 2018; Analytical Chemistry 2018 90 (19), 11599-11606), in light of Jia et al. (published March 14, 2012; ACS Nano 2012 6 (4), 3311-3317) as applied to claims 1 and 5 above, and further in light of Song et al. (published February 2, 2015; Song et al. Chem Eur J 21(4), 2417-2422). Wang et al. and Jia et al. teach methods of detecting genetic variants, as described above. Regarding claims 6-8, the combination of Wang and Jia do not teach the use of AAT repeat sequences (including AAT, ATA, TAA, TTA, TAT, and ATT repeat sequences ) as sequences capable of synthesizing copper nanoclusters. Song et al. teaches AT, TA, AAT, and ATA in duplexed DNA as sequences capable of synthesizing copper nanoclusters (Figure 1, Figure S7, and pg 2419 col 1, last paragraph – col 2, first paragraph). Song also teaches copper nanocluster synthesis from ATA and AAT sequences sufficient to generate a qualitative result by direct observation (Figure S7, inset). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the invention to combine the use of AAT and ATA sequences for copper nanocluster synthesis and direct observation/detection of qualitative results with the teachings of Wang and Jia to arrive at the instant invention . One would have been motivated to do so to control the formation and distribution of copper nanoclusters onto DNA templates (Song: pg 2421, col 2) and in order to screen for sequence variation in specific segments of genomic DNA using differences in fluorescence intensity (Jia: pg 3312, col 1, first paragraph). Claim 2 is rejected under 35 U.S.C. 103 as unpatentable over Wang et al (published September 11, 2018; Analytical Chemistry 2018 90 (19), 11599-11606), in light of Jia et al. (published March 14, 2012; ACS Nano 2012 6 (4), 3311-3317), as applied to claim 1 above, and further in light of Escosura-Muñiz et al. (published January 13, 2016; Escosura-Muñiz et al. Small. 2016 Jan 13;12(2):205-13). Wang et al. and Jia et al. teach methods of detecting genetic variants, as described above. Regarding claim 2, the combination of Wang and Jia does not teach the use of recombinase polymerase amplification for gene amplification. Escosura-Muñiz teaches the use of recombinase polymerase amplification in the context of assay that uses optical detection of metal nanoparticles to detect the presence of DNA. It would be obvious to a person with ordinary skill in the art before the effective filing date of the invention to combine the references of Wang, Jia, and Escosura-Muñiz, in order to overcome the complications of traditional PCR ( Escosura-Muñiz : pg 206, col 1, 1 st full paragraph). Claim 10 is rejected under 35 U.S.C. 103 as unpatentable over Wang et al (published September 11, 2018; Analytical Chemistry 2018 90 (19), 11599-11606), in light of Jia et al. (published March 14, 2012; ACS Nano 2012 6 (4), 3311-3317), as applied to claims 1 and 9 above, and further in light of Zhou et al. (published Jan 20, 2022; Patent Publication No. US 2022/0017963). Wang et al. and Jia et al. teach methods of detecting genetic variants, as described above. Regarding claim 10, the combination of Wang and Jia does not teach the use of quantitative fluorescence analysis to determine if a sample ’s genotype is heterozygous . Zhou et al. teaches that samples containing both wildtype and single nucleotide variant gene sequences will produce a combination of fluorescent signals allowing for genotyping (paragraph 0106). Similarly, Wang teaches fluorescence intensity differences dependent on the copy number of the target gene sequence for genotyping, in the context of disease caused by gene duplication/deletion (Wang: pg 11602, col 1, last paragraph). It would be obvious to a person with ordinary skill in the art before the effective filing date of the invention to combine the principle of sequence-specific fluorescence intensity from Zhou with Wang and Jia in order to arrive at the invention of the instant application. One would be motivated to do so in order to determine gene dosage for the diagnosis of disease (Wang: pg 11602, col 1, last paragraph). Claim 2 is rejected under 35 U.S.C. 103 as unpatentable over Lai et al (published November 17, 2022; Lai et al. Analyst, 2022,147, 5732-5738), as applied to claim 1 above, in light of Escosura-Muñiz et al. (published January 13, 2016; Escosura-Muñiz et al. Small. 2016 Jan 13;12(2):205-13). Lai teaches methods of detecting genetic variants, as described above. Regarding claim 2, Lai does not teach the use of recombinase polymerase amplification for gene amplification. Escosura-Muñiz teaches the use of recombinase polymerase amplification in the context of assay that uses optical detection of metal nanoparticles to detect the presence of DNA. It would be obvious to a person with ordinary skill in the art before the effective filing date of the invention to combine the references of Lai and Escosura-Muñiz in order to overcome the complications of traditional PCR (Escosura-Muñiz: pg 206, col 1, 1 st full paragraph). Claims 6-8 are rejected under 35 U.S.C. 103 as unpatentable over Lai et al (published November 17, 2022; Lai et al. Analyst, 2022,147, 5732-5738), as applied to claims 1 and 5 above, in light of Song et al. (published February 2, 2015; Song et al. Chem Eur J 21(4), 2417-2422). Lai teaches methods of detecting genetic variants, as described above. Regarding claims 6-8, Lai does not teach the use of AAT repeat sequences (including AAT, ATA, TAA, TTA, TAT, and ATT repeat sequences) as sequences capable of synthesizing copper nanoclusters. Song et al. teaches AT, TA, AAT, and ATA in duplexed DNA as sequences capable of synthesizing copper nanoclusters (Figure 1, Figure S7, and pg 2419 col 1, last paragraph – col 2, first paragraph). Song also teaches copper nanocluster synthesis from ATA and AAT sequences sufficient to generate a qualitative result by direct observation (Figure S7, inset). It would have been obvious to a person with ordinary skill in the art before the effective filing date of the invention to combine the use of AAT and ATA sequences for copper nanocluster synthesis and direct observation/detection of qualitative results with the teachings of Lai to arrive at the instant invention. One would have been motivated to do so to control the formation and distribution of copper nanoclusters onto DNA templates (Song: pg 2421, col 2). Conclusion No claims are allowed. 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