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. This application is the national stage entry of PCT/JP2022/022556 , filed 02 June 2022; and claims benefit of foreign priority document JAPAN 2021-092873 , filed 02 June 2021 . This foreign priority document is not in English. Claims 1-4 are pending in the current application and are examined on the merits herein. 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. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: 1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness . 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 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over McCuen et al. (J. Am. Chem. Soc., 2006, 128, p8138-8139, provided by Applicant in IDS filed 24 April 2025) in view of Roy et al. (Molecules, 2013, 18(11), p14268-14284, provided by Applicant in IDS filed 24 April 2025) . McCuen et al. teaches oligodeoxyribonucleotides (ODNs) bearing internucleotide borane phosphonate linkages (page 8138, left column, paragraph 1). McCuen et al. teaches a chemistry for synthesizing borane phosphonate DNA in high yield and having any combination of the four common bases as well as both phosphate and borane phosphonate internucleotide linkage s (page 8138, paragraph spanning left and right columns, and figure 1). McCuen et al. suggests the further development of borane phosphonate oligomers having, among others, phosphorothioate internucleotide linkages (page 8139, left column, paragraph 3). McCuen et al. teaches to date, the most successful synthesis approach has been conversion of deoxyoligonucleotide H-phosphonates (page 8138, left column, paragraph 2). McCuen et al. does not specifically disclose the embodiment of a nucleic acid oligomer comprising a phosphorothioate internucleotide linkage and a boranephosphonate linkage, and optionally a phosphate internucleotide linkage (claim 1). Roy et al. teaches a review on the chemical synthesis of DNA and RNA carried out using nucleoside phosphoramidites or H-phosphonates as synthons , including the synthesis and properties of certain DNA and RNA analogs that are modified at phosphorus such as boranephosphonates (page 14268, abstract). Roy et al. teaches the structure of a boranephosphonate (also referred to as boranophosphate in the literature) linkage can be described as one where one of the non-bridging phosphate oxygens is replaced by borane (compound 24a) , but the same linkage can equally be described as a P(III) compound complexed with a borane group (compound 24b) (page 14276, paragraph 1 and figure 1). The H-phosphonate method can be used for the synthesis of boranephosphonate DNA or methods for synthesis of oligonucleotides containing phosphodiester and boranephosphonate diester linkages (page 14277, paragraph 3; page 14278, Scheme 6 and paragraph 1). The H-phosphonate approach can also be used for the synthesis of a number of modified oligonucleotides such as phosphorothioates (page 14274, paragraph 2). Roy et al. further teaches the H-phosphonate approach to DNA/RNA synthesis where the coupling reaction is performed on a solid support (page 14275, Scheme 5). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine McCuen et al. in view of Roy et al. in order to obtain the nucleic acid oligomer comprising a phosphorothioate internucleotide linkage and a boranephosphonate linkage, and optionally a phosphate internucleotide linkage . One of ordinary skill in the art would have been motivated to combine McCuen et al. in view of Roy et al. with a reasonable expectation of success because McCuen et al. suggests it is desired to obtain borane phosphonate oligomers further having phosphorothioate internucleotide linkages and teaches the relevant field of art includes the chemical synthesis of DNA and RNA using H-phosphonates as synthons , and Roy et al. teaches the chemical synthesis of DNA and RNA including boranephosphonate and phosphorothioates was known in the art, suggesting one of ordinary skill in the art would have had a reasonable expectation of success to obtain this desired nucleic acid oligomer corresponding to the claimed compound wherein R1 is a hydrogen atom and R2 is a hydrogen atom . McCuen et al. in view of Roy et al. does not specifically describe the counter cations of the nucleic acid oligomer, however it would have been obvious to one of ordinary skill in the art that the anions in the depicted structures would have existed as ion pairs with counter cations, such as shown by Roy et al. for compound 20 in Scheme 5. Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over McCuen et al. (J. Am. Chem. Soc., 2006, 128, p8138-8139, provided by Applicant in IDS filed 24 April 2025) in view of Roy et al. (Molecules, 2013, 18(11), p14268-14284, provided by Applicant in IDS filed 24 April 2025) as applied to claim s 1-2 above, and further in view of Sato et al. ( J . Org. Chem., 2019, 84, p15032-15041, provided by Applicant in IDS filed 30 Nov 2023 ) and Zain et al. ( J. Org. Chem., 1996 , 61 , p 6617-6622 , cited in PTO-892 ). McCuen et al. in view of Roy et al. teaches as above. McCuen et al. in view of Roy et al. does not specifically teach the method for producing the nucleic acid oligomer comprising sequentially condensing a nucleotide monomer selected from the group consisting of a compound represented by General Formula (5) and a compound represented by General Formula (6) to obtain a precursor nucleic acid oligomer comprising a nucleotide unit represented by General Formula (8) and a nucleotide unit represented by General Formula (9) and optionally comprising a nucleotide unit represented by General Formula (10) (claim 3). Sato et al. teaches solid-phase synthesis of phosphate/ boranophosphate (PO/PB) chimeric DNA was achieved by the combination of the H - phosphonate and H- boranophosphonate methods (page 15032, abstract) . Sato et al. teaches the strategy for the synthesis of PO/PB chimeric DNA comprising sequentially coupling the H - phosphonate or H- boranophosphonate synthons to the oligomer on solid support (page 15034, scheme 1). Zain et al. teaches f ormation of H-phosphonothioate diesters via condensation of H-phosphonate monoesters . Optimal reaction conditions, which eliminate or significantly suppress the side reactions, have been designed and assessed in syntheses of dinucleoside H-phosphonothioate diesters (page 6617, abstract) . H-Phosphonothioate diesters are versatile synthetic intermediates, for example, they may serve as precursors to both phosphorothioate and phosphorodithioate diesters or to other analogues that are rather difficult to obtain by other routes (page 6617, right column, paragraph 2). Having in mind possible applications of H-phosphonothioates as precursor to various oligonucleotide analogues, Zain et al. undert ook systematic studies on this class of compounds (page 6617, right column, paragraph 4). Zain et al. teaches d inucleoside H-phosphonothioates 3 can be produced in a condensation reaction as in Scheme 1 using nucleoside H-phosphonothioates 1 as a synthon (page 6618, left column, paragraph 2 and Scheme 1 at right column). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine McCuen et al. in view of Roy et al. further in view of Sato et al. and Zain et al. in order to arrive at a method of producing the nucleic acid oligomer using H-phosphonothioate , H- boranophosphonate , and H - phosphonate synthons. One of ordinary skill in the art would have been motivated to combine McCuen et al. in view of Roy et al. further in view of Sato et al. and Zain et al. with a reasonable expectation of success because both McCuen et al. and Roy et al. teach the relevant field of art includes the method of producing the nucleic acid oligomer using H-phosphonate chemistry, Roy et al. suggests the H-phosphonate and H- boranophosphonate are known equivalents in the art and that the H-phosphonate synthons can be used to produce phosphorothioate oligonucleotide analogs, and Sato et al. and Zain et al. teach known methods of synthesis of phosphate/ boranophosphate or phosphorothioate oligonucleotide analogs. It would have been obvious to combine prior art elements of the methods of synthesis of oligonucleotide analogs using H-phosphonothioate , H- boranophosphonate , and H - phosphonate synthons according to known methods in order to yield the predictable results of producing the chimeric oligonucleotide analogs based on the combined teachings of McCuen et al. in view of Roy et al. further in view of Sato et al. and Zain et al. because Sato et al. and Zain et al. teach the synthesis using these synthons separately, and both McCuen et al. and Sato et al. teach the synthesis of a chimeric oligonucleotide analogs by using a combination of different synthons, suggesting one of ordinary skill in the art could have combined the elements acclaimed by known methods to give a predictable result. Conclusion No claim is found to be allowable. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Jonathan S Lau whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (571)270-3531 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday-Friday 9a-5p Eastern . 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, FILLIN "SPE Name?" \* MERGEFORMAT Scarlett Goon can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT (571)270-5241 . 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. /JONATHAN S LAU/ Primary Examiner, Art Unit 1693