DETAILED ACTION Notice of Pre-AIA or AIA Status 1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. 2. Applicant's election with traverse of Group 1 in the reply filed on December 29, 2025 is acknowledged. The traversal is on the ground(s) that the shared contribution linking Groups I and II is the specific primer/probe architecture and its required cooperative use in the claimed amplification method (e.g., the particular stem-loop primer design parameters, probe pairing/placement, defined sequence regions/functional segments, and/or required relationships between primers and probes as recited in claims 9-15 and utilized in claims 1-8). Applicants argue that the claimed inventions share a common special technical feature that defines their contribution over the prior art and that the Office’s reliance on Arunachalam for the general proposition that stem-loop primers were known is too general. This argument has been fully considered. First it is noted that unity of invention is considered only in relation to the independent claims. Whether or not any particular technical feature makes a “contribution” over the prior art, and therefore constitutes a “special technical feature,” is considered with respect to novelty and invention step. The common feature to the claims is the Bw adapter primer having the structure (a) and the Fw adapter having the structure (c). However since the Bw adapter primer havi n g the structure (a) is known in the art and the Fw adapter having the structure (c) is obvious in view of the prior art (see art rejections set forth below), unity is lacking and there is no special technical feature common to all of the claims. The requirement is still deemed proper and is therefore made FINAL. 3. Claims 1-15 are currently pending. Claims 9-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on December 29, 2025. Nucleotide and/or Amino Acid Sequence Disclosures 4. Summary of Requirements for Patent Applications Filed O n Or After July 1, 2022, T hat Have Sequence Disclosures 37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted: 1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying: a. the name of the XML file b. the date of creation; and c. the size of the XML file in bytes; or 2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying: a. the name of the XML file; b. the date of creation; and c. the size of the XML file in bytes. SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS: This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that Table 5 contains a sequence that is not in the Sequence Listing. In particular miR-21-5p antisense strand needs to be included in the Sequence Listing because it has greater than 10 residues that are specifically defined and enumerated. Applicant must provide: • A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as • A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3); • A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4); • A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and • A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of: o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); o A copy of the amended specification without markings (clean version); and A statement that the substitute specification contains no new matter. Claim Rejections - 35 USC § 103 5. 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. 6. Claim s 1-5 are rejected under 35 U.S.C. 103 as being unpatentable over Al- maskri (Analytica Chimica Acta 1126 (8/22/2020) 1-6) in view of Desingu (Dumbbell-PCR: Blocking the 3' end of 3' Db-adapter is expected to avoid non-specific detection and increase the efficacy of this method, July 2015 - Comment accompanying Honda, Dumbbell-PCR: a method to quantify specific small RNA variants with a single nucleotide resolution at terminal sequences, Nucleic Acids Research, 43(12): e77 , July 2015) . Regarding Claim 1 Al- maskari teaches a miRNA RT-THSP-LAMP assay that consists of two hairpin DNA probes (SL and PS-H) and two primers, which are used in typical LAMP reactions. The principle underlying the amplification is based on the reverse transcription process that occurs in THSP and LAMP reactions. As shown in HYPERLINK "https://www.sciencedirect.com/science/article/pii/S0003267020306553?via%3Dihub" \l "sch1" Scheme 1 , the SL probe was first elongated after a reverse transcription reaction with the addition of miRNA. The elongated sequence at the 3′ end of the SL probe was complementary to part of the 3′ end of PS-H probe, both of which were then extended to form double-stranded DNA with the use of the strand-displacing polymerase Bst 2.0. Since the B1c and B2 region of the PS- H probe were phosphorothioated , the new double-stranded DNA could self-fold to create a foldback structure and extend along the 3′ end of the probe, which acted as a primer itself. Meanwhile, the inner primers, BIP and FIP, hybridized to the single-stranded loop in the foldback structure and initiated another round of strand displacement amplification (page 3, scheme 1) . Thus Al- maskari teaches a method for amplifying nucleic acids, comprising: step A : annealing a Bw adapter primer comprising the following structure (a): 5'-Blc-BL-B1-N3c-3' ... (a) to a target nucleic acid having a target region, synthesizing a base sequence complementary to a base sequence on a 5'-end side of the target region starting from a 3'-end of the Bw adapter primer, obtaining a first template nucleic acid comprising the following structure (b): 5'-Blc-BL-B1-N3c-N5c-3' ... (b) step B : annealing an Fw adapter nucleotide comprising the following structure (c): 5'-F1c-FL-F1-N5'-3' ... (c) and the first template nucleic acid, synthesizing a complementary strand of the Fw adapter nucleotide starting from a 3'-end of the first template nucleic acid, and obtaining a second template nucleic acid comprising the following structure (d): 5'-B lc-BL-B 1-N3c-N5c-F lc- FLc -F 1-3' ... (d) step C amplifying base sequence Nc of the second template nucleic acid by a LAMP method by using an Fw inner primer comprising the following structure (e): 5'-F1c-F2-3' ... (e) and a Bw inner primer comprising the following structure (f): 5'-B1c-B2-3' ... (f) with the second template nucleic acid as a template. Regarding Claim 2 Al- maskri teaches the sequence of the SL probe (Table S1). The N3c region of the SL probe is 6 base pairs long and is elongated using the miRNA as a template to produce the N5c region. Since miRNA are 21-25 bp, the reference teaches a method wherein the length of the base sequence Nc (N3c+ N5c = Nc) is 10 to 100 bases long. Regarding Claim 3 Al- maskri teaches a method wherein the target nucleic acid is miRNA (page 3). Regarding Claim 4 Al- maskri teaches that the reverse transcription process was first conducted. The reaction was completed in a 10 μL solution containing 400 nM SL probe, 1 μL of RT Mix, 1 μL of HiScript II Enzyme Mix and appropriate amount of target miRNA . The solution was treated with the following program: 25 °C for 5 min, 50 °C 15 min, and 85 °C for 5 min. Then, 200 nM PS-H probe was mixed with 2 μL of the RT product to form a 12.5 μL solution. The mixture was incubated at 95 °C for 5 min followed by slow cooling to room temperature at a rate of 0.1 °C/s (page 2). Since the PS-H probe (step B) was added to the solution containing the SL probe and target (step A), the reference teaches a method wherein step A and step B proceed in the same reaction system. Regarding Claim 5 Al- maskri teaches that the reverse transcription process was first conducted. The reaction was completed in a 10 μL solution containing 400 nM SL probe, 1 μL of RT Mix, 1 μL of HiScript II Enzyme Mix and appropriate amount of target miRNA . The solution was treated with the following program: 25 °C for 5 min, 50 °C 15 min, and 85 °C for 5 min. Then, 200 nM PS-H probe was mixed with 2 μL of the RT product to form a 12.5 μL solution. The mixture was incubated at 95 °C for 5 min followed by slow cooling to room temperature at a rate of 0.1 °C/s (page 2). Thus the reference teaches a step of heating the reaction product of step B to 85°C or higher after step B and before step C. Al- maskri does not teach a method wherein in step B: the annealing Fw adapter nucleotide comprises the following structure (c): 5'-F1c-FL-F1-N5'-3' ... (c) and has an extension inhibiting modification at the 3’ end. However Desingu teaches blocking the 3' end of the 3' adapter to avoid synthesis of cDNA from the 3' end of the stem loop, which would result in non-specific detection (Comment, paras. 2-4). Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Al- maskri by adding an extension inhibiting modification at the 3’ end of the Fw adapter as suggested by Desingu . One of skill in the art would have been motivated to add an extension inhibiting modification at the 3’ end since Desingu teaches that blocking the 3' end of the 3' adapter to avoid synthesis of cDNA from the 3' end of the stem loop, which would result in non-specific detection (Comment, paras. 2-4). 7. Claim s 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over Al- maskri (Analytica Chimica Acta 1126 (8/22/2020) 1-6) in view of Desingu (Dumbbell-PCR: Blocking the 3' end of 3' Db-adapter is expected to avoid non-specific detection and increase the efficacy of this method, July 2015 - Comment accompanying Honda, Dumbbell-PCR: a method to quantify specific small RNA variants with a single nucleotide resolution at terminal sequences, Nucleic Acids Research, 43(12): e77 , July 2015) as applied to claim 1 above and in further view of Dedent (US 2021/0254139 Filed 5/10/2019). The teachings of Al- maskri and Desingu are presented above. The combined references do not teach a method wherein after step C, a detection step of detecting the base sequence Nc using a probe that hybridizes to at least part of the base sequence Nc or at least part of a complementary strand of the base sequence Nc ( clm 6). The combined reference does not teach a method wherein in the probe, a length of a base sequence that hybridizes to the base sequence N3c is 5 bases long or less ( clm 7). The combined reference does not teach a method wherein a full-length base sequence of the probe is not contained entirely in one of the base sequence N3c and the base sequence N5c ( clm 8) . However Dedent discloses molecular beacon probes that bind to LAMP amplicons. Dedent discloses molecular beacon probes can bind to the DS region, the DS/Loop region, or the Loop region. Dedent teaches that in some embodiments the oligonucleotide probe comprises a sequence substantially complementary to the probe target sequence. In some embodiments, the probe target sequence overlaps the first region or the second region of the amplicon by at least 3 nucleotides. In some embodiments, the probe target sequence overlaps the first region or the second region of the amplicon by at least 7 nucleotides. In some embodiments, the probe target sequence overlaps the first region or the second region of the amplicon by at least 10 nucleotides. In some embodiments, the probe target sequence is located completely within the first region or the second region of the amplicon (para 0012). Dedent teaches that in some embodiments the probe target sequence overlaps with at least 3 nucleotides, at least 7 nucleotides, at least 10 nucleotides, or all of the F1 region, the F1c region, the B1 region, or the B1c region of the amplicon. In some embodiments, the probe target sequence is at least 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 nucleotides in length (para 0013). Different probe hybridization schemes are shown below in Fig 5. Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Al- maskri and Desingu by using molecular beacon probes to detect the amplicon produced by LAMP as suggested by Dedent . In particular Dedent teache s that o ligonucleotide probes have been used for sequence-specific detection of LAMP amplification. However, these probes specifically target only the loop region of the amplicon, specifically, the F2 region. This is consistent with primers used to generate amplicons during LAMP, which also bind to loop regions of the amplicon to continue amplification during LAMP. However, there are some drawbacks with the use of oligonucleotide probes, as they may interfere with LAMP amplification, and the sequences in the loop region may not provide the desired specificity, sensitivity, and reaction speed needed for an assay using oligonucleotide probes for detection. What is needed therefore, are new compositions and methods for LAMP amplicon detection that are rapid, sensitive and specific, and facilitate multiplexed detection. Thus one of skill in the art would have been motivated to design the claimed molecular beacon probes since they would be expected to provide benefits of rapid, sensitive and specific, multiplexed detection. 8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT AMANDA HANEY whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)272-8668 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday-Friday, 8:15am-4:45pm EST . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. 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For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AMANDA HANEY/ Primary Examiner, Art Unit 1682