CTNF 18/571,719 CTNF 77002 DETAILED CORRESPONDENCE Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. This action is in response to the papers filed June 16, 2024. Currently, claims 1-12 are pending. Priority This application is a 371 of PCT/EP2022/066736, filed June 20, 2022 and claims priority to UK 2108853.9, filed June 21, 2021. Drawings The drawings are acceptable. Sequence Rules This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Required response – Applicant must provide: Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers; AND/OR A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of: A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version); 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 §101 Claim 10 is rejected under 35 U.S.C. 101 because the claimed invention fails to recite a claim within one of the statutory classes and is thus directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because Claim 10 provides for the use of the polynucleotide but fails to provide any recited steps. MPEP 2173.05(q) provides that “use” claims that do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 101 because a “use” is not among the categories of patentable inventions specified in 101. There are not active steps in Claim 10. Claim 10 is directed to an assay for SARS-CoV-2 is indefinite because it merely recites a use without any active positive steps delimiting how this use is actually practiced. Claim Rejections - 35 USC § 112- Second Paragraph 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. 07-34-01 AIA 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 pre-AIA the applicant regards as the invention. 07-34-08 Regarding claim 3, the phrase "preferable" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claims 1-9 require the LTD sequence is at or near the terminus of the ORF9c. The term “near” in claim 1 is a relative term which renders the claim indefinite. The term “near” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. SEQ ID NO: 5 and 6 are listed on Page 18 of the specification as having a label. SEQ ID NO: 5 and 6 do not have a label in the sequence listing. It is not clear whether the claims directed to SEQ ID NO: 5 and 6 require a label or not. Clarification is required. Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 1, 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Andres et al. (bioRxiv preprint, “SARS-CoV-2 ORF9c is a Membrane-Associated protein that suppresses antiviral responses in cells”, August 19, 2020) in view of Khan et al. (ACS Synth. Biol. Vol. 9, pages 2861-2880, 2020) . Andres teaches SARS-CoV-2 ORF9c is a membrane associated protein that suppresses antiviral responses in cells. Andres teaches alignment of the gene sequence showing the position of the stop codon in ORF14 orthologs and 3 codon extension in ORF9c (Figure 1). Figure 1B illustrates the alignment of SARS-CoV-2 and the addition 3 amino acids, namely LTD. The SARS-CoV-2 is the only sequence with the additional LTD sequence. Andres teaches a single nucleotide mutation in SARS-CoV-2 ORF9c altered a termination codon, enabling the reading frame to extend by 3 amino acids (page 5, last line). Figure 1C illustrates the nucleic acid sequence flanking the mutation in SARS-CoV-2 ORF9c. PNG media_image1.png 134 578 media_image1.png Greyscale Andres does not teach generating cDNA from the RNA present in the sample and amplifying to detect the LTD sequence. However, Kahn teaches isothermal detection of SARS-CoV-2. Kahn teaches SARS-CoV-2 may be detected using an array of different testing means including LAMP, RPA, NEAR, RCA, MDA and Smart. Each of these methods relies upon generating cDNA and amplifying the sequences of interest. Kahn teaches mutations within SARS-CoV-2 may be analyzed using these methods, including MDA (page 2875, col. 2). Kahn reviews the array of different testing means and their advantages and disadvantages. Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have detecting the single nucleotide mutation in SARS-CoV-2 ORF9c to detect the SARS nucleic acid using a DNA detection method taught in the art including those that amplify the DNA. The ordinary artisan would have been motivated to have detected the known mutation using any known method in the art . 07-22-aia AIA Claim s 2-9, 11-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Andres et al. (bioRxiv preprint, “SARS-CoV-2 ORF9c is a Membrane-Associated protein that suppresses antiviral responses in cells”, August 19, 2020) in view of Khan et al. (ACS Synth. Biol. Vol. 9, pages 2861-2880, 2020) as applied to Claim s 1 and 10 above and further in view of Alladin-Mustan et al. (Analytica Chimica Acta, Vol. 1149, December 17, 2020) . Andres in view of Kahn does not teach a RT-LIDE method for detecting the SARS-CoV-2 specific sequence. However, Alladin-Mustan teaches reverse transcription lesion-induced DNA amplification isothermal method that is instrument free (RT-LIDE). Alladin-Mustan teaches RT-LIDE performed RNA transcription followed by cDNA amplification detection at room temperature. Alladin-Mustan teaches using aggregated DNA_AuNP beads for detecting a color change and the presence of the target sequence. Alladin-Mustan teaches the design of LIDA primers is simple in contrast to LAMP. LIDA requires an 18 nucleotide conserved region of the RNA to target for reverse-transcription followed by cDNA amplification. Each half of the DNA sequence complementary to the RNA target sequences constitutes the first pair of DNA primers. Looking and Andres, generating a 9mer upstream and a 9mer downstream of the mutation to be detected is P2p and P2*, namely SEQ ID NO: 4 and 5. Alladin-Mustan teaches the design of the abasic and csp oligonucleotides also. Alladin-Mustan teaches disDNA was designed such that it consisted of 8 or the 9 nucleotides in one of the primers as well as the complementary sequence to the 9-nt overhang of RNA-I’ (page 7, col. 1). Therefore, it would have been primar facie obvious prior to the effective filing date of the claimed invention to have modified the isothermal detection method of Andres in view of Kahn to use RT-LIDE as taught by Alladin-Mustan. The ordinary artisan would have recognized that RT-LIDE is an isothermal method that does not require instrumentation and may be performed at room temperature at a good sensitivity based on a colorimetric readout. Alladin-Mustan teaches the method is simple, instrument-free and uses a small number of reagents and simple reaction vessels. With respect to the sequences of SEQ ID NO: 3-7, Alladin-Mustan teaches the design of RT-LIDE primers. Andres specifically teaches the flanking sequence of the 3 amino acids that encode the nucleic acid of TTGACAGAT. The ordinary artisan would have followed the instructions of Alladin-Mustan for designing the RT-LIDE primers and oligonucleotides and arrived at SEQ ID NO: 3-8. Thus, designing SEQ ID NO: 3-8 would have been obvious at the time the invention was made . Conclusion No claims allowable over the art. 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Wu et al. (Genbank NC_045512, July 18, 2020) teaches the SARS-CoV-2 nucleic acid sequence. Jungreis et al. (Virology, Vol. 558, pages 145-151, March 17, 2021) teaches ORF9C is 73 codon in length for SARS- CoV and is located at position 28,734-28,952. Jungreis further teaches the ORF9c was previously called ORF9b and ORF14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on (571)272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. 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. /JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682 March 12, 2026 Application/Control Number: 18/571,719 Page 2 Art Unit: 1682 Application/Control Number: 18/571,719 Page 3 Art Unit: 1682 Application/Control Number: 18/571,719 Page 4 Art Unit: 1682 Application/Control Number: 18/571,719 Page 5 Art Unit: 1682 Application/Control Number: 18/571,719 Page 6 Art Unit: 1682 Application/Control Number: 18/571,719 Page 8 Art Unit: 1682 Application/Control Number: 18/571,719 Page 9 Art Unit: 1682