NUCLEOSIDES AND NUCLEOTIDES ANALOGS AS ANTIVIRAL AGENTS

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 . Continued Examination Under 37 CFR 1.114 A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on July 17, 2026, has been entered. Allowable Subject Matter The indicated allowability of claims 1-14, 19, 34, 63, and 117 is withdrawn in view of the newly discovered reference(s) to Changzhou Andi Sanitary Products Technology Co. ltd. CN 111548384B (Changzhou) and Wuhan Kangmat Biotechnology Co. ltd. Huazhong Agricultural University CN111135184A (Wuhan). Rejections based on the newly cited reference(s) follow. 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, 5-9, 19, 34, and 63 is/are rejected under 35 U.S.C. 103 as being unpatentable over Changzhou Andi Sanitary Products Technology Co. ltd. CN 111548384B (Changzhou). Claims 1-2, 5-9, and 19 are drawn to a method of treating or preventing a Coronaviridae, Bunyaviridae, or Togaviridae infection, comprising administering a treatment or preventative amount of a compound of Formula (A) to a patient in need of treatment or prevention thereof. Claim 34 is drawn to a method for treating or preventing a Coronaviridae, Bunyaviridae, or Togaviridae infection, comprising administering a treatment or preventative amount of a compound of Formula (A) to a patient in need of treatment or prevention thereof. Claim 63 is drawn to a method for treating or preventing a Coronaviridae, Bunyaviridae, or Togaviridae infection, comprising administering a treatment or preventative amount of a compound of Formula (A) or Formula (A1) to a patient in need of treatment or prevention thereof. Changzhou relates to N4-hydroxycytidine derivatives having substitution, prodrugs and pharmaceutical compositions containing the same, and methods of using the compositions for treating viral infections (Technical Field). In particular, the invention relates to methods and compounds for treating infections by viruses of the Paramyxoviridae, Orthomyxoviridae, Coronaviridae and Filoviridae families, and pharmaceutical compositions thereof. The invention particularly relates to a method and a compound for treating the infection of novel coronavirus (COVID-19 or SARS-Cov-2) and influenza virus and a medicinal composition thereof. Changzhou teaches that the compounds have the following structural formula (I) or are stereoisomers, prodrugs, active metabolites or pharmaceutically acceptable salts, solvates or crystalline forms thereof: PNG media_image1.png 194 220 media_image1.png Greyscale . See [0014]. Changzhou explicitly teaches compound PNG media_image2.png 138 182 media_image2.png Greyscale . See [0089]. Changzhou further discloses its anti-beta-coronavirus COVID-19 activity. See Example 15. PNG media_image3.png 318 710 media_image3.png Greyscale Changzhou teaches that the compounds and compositions of the invention are also used in combination with other active ingredients for the treatment of viral infections, in particular infections with one or more of the virus families paramyxoviridae, orthomyxoviridae, coronaviridae. Preferably, the further active therapeutic agent is active against infection by a virus of the family Paramyxoviridae, Orthomyxoviridae, Coronaviridae. Non-limiting examples of these other active therapeutic agents are: corticosteroids, anti-inflammatory signal transduction modulators, beta 2-adrenoceptor agonists bronchodilators, anticholinergics, mucolytics, or mixtures thereof. Wherein the at least one other therapeutic agent of the composition is ribavirin, palivizumab, mevizumab, RSV-IGIV, MEDI-557, A-60444, MDT-637 or BMS-433771, formoterol, salmeterol, an anticholinergic, or a mixture thereof. Changzhou is limited to in vitro data. Thus, Changzhou differs from the instantly claimed invention in that Changzhou does not explicitly teach the administration of PNG media_image2.png 138 182 media_image2.png Greyscale to an instant patient in need of treatment or prevention thereof; however, this deficiency would have been obvious. In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983). In considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom. In the instant case, although not explicitly disclosed, Changzhou teaches or reasonably suggests the administration of PNG media_image2.png 138 182 media_image2.png Greyscale to an instant patient in need of treatment or prevention thereof. See Example 15. Thus, claims 1-2, 5-9, 19, 34, and 63 would have been obvious based on the preponderance of evidence. Claim(s) 63 and 117 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wuhan Kangmat Biotechnology Co. ltd. Huazhong Agricultural University CN111135184A (Wuhan). Claim 63 is drawn to a method for treating or preventing a Coronaviridae, Bunyaviridae, or Togaviridae infection, comprising administering a treatment or preventative amount of a compound of Formula (A) or Formula (A1) to a patient in need of treatment or prevention thereof. Claim 117 is drawn to a method for treating or preventing a Coronaviridae, Bunyaviridae, or Togaviridae infection, comprising administering a treatment or preventative amount of a compound of one of the following formulas to a patient in need of treatment or prevention thereof: PNG media_image4.png 628 544 media_image4.png Greyscale . Wuhan discloses application of GS-441524 in preparation of a novel coronavirus SARS-CoV-2 inhibitor (Abstract). The results of in vitro cell experiments show that: GS-441524 can remarkably inhibit SARS-CoV-2 from infecting normal cells, has an inhibitory effect on novel coronavirus SARS-CoV-2 at a cell level, can remarkably reduce the virus price in the cells, and inhibits the proliferation of the virus in the cells, and has dose dependence. Therefore, GS-441524 can be used as a novel coronavirus SARS-CoV-2 inhibitor, and has the potential of treating COVID-19 pneumonia caused by human being infected by the virus, or other diseases caused by animal infection. PNG media_image5.png 200 238 media_image5.png Greyscale (GS-441524) Wuhan is limited to in vitro results. Thus, Wuhan differs from the instantly claimed invention in that Wuhan does not explicitly teach the administration of GS-441524 to an instant patient in need of treatment or prevention thereof; however, this deficiency would have been obvious. In determining the differences between the prior art and the claims, the question under 35 U.S.C. 103 is not whether the differences themselves would have been obvious, but whether the claimed invention as a whole would have been obvious. Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 218 USPQ 871 (Fed. Cir. 1983); Schenck v. Nortron Corp., 713 F.2d 782, 218 USPQ 698 (Fed. Cir. 1983). In considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom. In the instant case, although not explicitly disclosed, Wuhan teaches or reasonably suggests the administration of PNG media_image5.png 200 238 media_image5.png Greyscale to an instant patient in need of treatment or prevention thereof. See Abstract. Thus, claims 63 and 117 would have been obvious based on the preponderance of evidence. Conclusion Claims 1-14, 19, 34, 63, 73, 80, 91, 102, 111, and 117 are pending. Claims 1-2, 5-9, 19, 34, 63, and 117 are rejected. Claims 3-4 and 10-14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Claims 73, 80, 91, 102, and 111 are allowed. Contacts Any inquiry concerning this communication or earlier communications from the examiner should be directed to PATRICK T LEWIS whose telephone number is (571)272-0655. The examiner can normally be reached Monday to Friday, 10 AM to 4 PM EST (Maxi Flex). 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, Renee Claytor can be reached at (571) 272-8394. 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. /PATRICK T LEWIS/Primary Examiner, Art Unit 1691 /PL/