CTNF 18/562,911 CTNF 82308 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. Detailed Action This application is a national stage application of PCT/US2022/31381, filed May 27, 2022, which claims benefit of provisional application 63/193951, filed May 27, 2021. Claims 1, 2, 19, 33, 46, 55, 70, 85, 97, and 108-127 are pending in this application and examined on the merits herein. Applicant’s preliminary amendment submitted November 21, 2023, is acknowledged wherein claims 1, 2, 19, 33, 46, 55, 70, 85, 97, 109, 110, 118, and 122 are amended and claims 3-18, 20-32, 34-45, 47-54, 56-69, 71-84, 86-96, 98-107, and 128-134 are canceled. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claim 55 is 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. This claim, which depends from base claim 1, further requires that the compound has formula D, which is defined in the base claim as PNG media_image1.png 201 217 media_image1.png Greyscale . However, claim 55 also defines specific variables R 1 , R 2 , R 3 , and R 4 , which appear nowhere in formula D. Therefore it is unclear what these limitations actually mean and what limits they impose on the chemical structure, rendering claim 55 indefinite. 07-34-01 Claims 115 and 125 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. Claims 115 and 125 contain the trademark/trade name Jakafi®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph. See Ex parte Simpson , 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the JAK inhibitor compound ruxolitinb (See prescribing instructions included with PTO-892) and, accordingly, the identification/description is indefinite. Similarly, while the use of trademarks in the specification is acceptable, Applicant should ensure that they are properly designated as such wherein they appear in the specification. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-12-aia AIA (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. 07-15 AIA Claim 1 is rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Cappellacci et al. (Reference included with PTO-892) Independent claim 1 is directed to a compound having a formula selected from (A)-(H), wherein formula (E) is PNG media_image2.png 178 231 media_image2.png Greyscale . Cappellacci et al. discloses compounds falling within this formula (p. 1500 scheme 2 compounds 9, 11, 13, 14) thereby anticipating claim 1 . 07-15-03-aia AIA Claim s 1, 2, 33, 108, and 110-127 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Schinazi et al. (PCT international publication WO2022/217154, Reference included with PTO-892) Independent claim 1 is directed to a compound having a formula selected from (A)-(H), wherein formula (C) is: PNG media_image3.png 161 163 media_image3.png Greyscale , R 5 , R 8 , R 8’ , and R 9 can be H, R 10 can be methyl, and R 1 can be OH. Schinazi et al. discloses compounds for treating and preventing viral infections in a subject. (p. 2 last paragraph, p. 3 first paragraph) These compounds are nucleosides of formula A: PNG media_image4.png 200 400 media_image4.png Greyscale . (p. 11) More specifically, Schinazi et al. discloses the compound: PNG media_image5.png 200 400 media_image5.png Greyscale on p. 134 which anticipates present claim 1 and is one of the specific compounds recited in claim 108. Regarding dependent claims 2 and 33, these claims merely requires that the compound have this same formula (C), and that one of twelve provisos be true. Since certain of these provisos, such as X being methylene or Y and Z both being CH, are true claim 33 is anticipated as well. Regarding claim 110, Schinazi et al. discloses compositions of these compounds and a pharmaceutically acceptable carrier or excipient. (p. 3 fourth paragraph) Regarding claims 118-121, Schinazi et al. discloses methods comprising administering these compounds to a subject suffering from a viral infection, including for example SARS-CoV2 and other coronaviruses, as well as picornaviruses. (p. 4 last paragraph) Regarding claims 111-117 and 122-127, Section VI on pp. 37-61 discloses combination therapies with various additional active agents including all of the compounds recited in these claims . 07-15-02-aia The applied reference has a common assignee and some inventors in common with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. 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. 07-21-aia AIA Claim s 1, 110-112, and 118-123 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al. (PCT international publication WO2020/206289, Reference included with PTO-892) Independent claim 1 is directed to a compound having a formula selected from (A)-(H), wherein formula (E) is PNG media_image2.png 178 231 media_image2.png Greyscale . Lin et al. discloses a compound of formula (I): PNG media_image6.png 200 400 media_image6.png Greyscale wherein R 3 , R 4 , and R 5 are defined in ways substantially overlapping with the corresponding positions in formula (E) in present claim 1. (pp. 2-3 paragraph 6) A further embodiment (p. 35 paragraph 154) discloses the formula PNG media_image7.png 200 400 media_image7.png Greyscale wherein R 5 can be H or F and R 6 can be H. This structure differs from formula (E) in present claim 1 only in that the scope of groups R 1 allows for a large number of structures not specifically part of the scope of -X-R 1 in present claim 1. However, this formula does allow for R 1 to be -C 1 -C 6 alkyl-O-C 1 -C 6 alkyl, which when the first alkyl is C 1 alkyl, is the same structure “CH 2 -O-C 1-6 alkyl” appearing in formula (E) in present claim 1. Still further another compound is shown (compound 19 on p. 63) wherein this position is CH 2 -O-CH 3 , which clearly falls within the definition in present claim 1. It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to make an embodiment of formula I-J on p. 35 of Lin et al. wherein R 1 is -CH 2 -O-C 1-6 alkyl. One of ordinary skill in the art would have been motivated to try any of the finite, limited embodiments of R 1 listed for this structure, which include some that infringe present claim 1. Regarding claim 110, p. 26 paragraph 163 describes pharmaceutical compositions of these compounds with pharmaceutically acceptable carriers or excipients. Regarding claim 111, p. 50 paragraph 218 describes administering the compound with another active ingredient. Regarding claim 112, at the very least “agents of distinct or unknown mechanism” would encompass any additional active agent included in the composition as described by Lin et al. Regarding claims 118-123, Lin et al. discloses a method of treating diseases including COVID-19, a viral disease caused by the coronavirus SARS-CoV2. (p. 54 paragraph 233) For these reasons the claimed invention is prima facie obvious over Lin . 07-22-aia AIA Claim s 112-114 and 123-125 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al . as applied to claim s 1, 110-112, and 118-123 above, and further in view of Lin et al. 2021. (Infection (2021) 49:401–410, Reference included with PTO-892, distinct from Lin et al. WO2020/206289 cited above) The disclosure of Lin et al. WO2020/206289 is discussed above. Lin et al. WO2020/206289 does not disclose pharmaceutical composition or methods wherein the additional agent is an another antiviral nucleoside such as remdesivir. Lin et al. 2021 discloses that Remdesivir is an adenosine analog with broad-spectrum antiviral activity against RNA viruses. (p. 402 left column third paragraph) It is known to be effective at inhibiting replication of coronaviruses including SARS-CoV2. (p. 402 table 1) It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the compounds described by Lin et al. WO2020/206289 in combination with remdesivir, to a patient suffering from COVID-19. One of ordinary skill in the art would have seen it to be obvious to combine two therapeutic agents known to be useful for treating the same condition, to form a combination therapy for treating said condition. Therefore the invention taken as a whole is prima facie obvious . 07-22-aia AIA Claim s 112, 116, 123, and 126 are rejected under 35 U.S.C. 103 as being unpatentable over Lin et al . as applied to claim s 1, 110-112, and 118-123 above, and further in view of Shi et al. (Reference included with PTO-892) The disclosure of Lin et al. WO2020/206289 is discussed above. Lin et al. WO2020/206289 does not disclose pharmaceutical composition or methods wherein the additional agent is an anticoagulant. Shi et al. discloses a review of the use of heparin for treating COVID-19. (p. 2 left column last paragraph) Furthermore coagulopathy is described as common in COVID-19. (p. 3 section 3.2) Anticoagulation using heparin has been shown to reduce mortality in severe COVID-19 patients. (p. 3 section 3.3) It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the compounds described by Lin et al. WO2020/206289 in combination with heparin, to a patient suffering from COVID-19. One of ordinary skill in the art would have seen it to be obvious to combine two therapeutic agents known to be useful for treating the same condition, to form a combination therapy for treating said condition. Therefore the invention taken as a whole is prima facie obvious . 07-15 AIA Claim s 1, 110-113, 118, 119, and 122-124 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Roberts et al. (PCT international publication WO2004/028481, Reference included with PTO-892) Independent claim 1 is directed to a compound having a formula selected from (A)-(H), wherein formula (E) is PNG media_image2.png 178 231 media_image2.png Greyscale . Roberts et al. discloses compounds having the formula I: PNG media_image8.png 200 400 media_image8.png Greyscale which encompass within their scope compounds having formula (E) of present claim 1. (p. 4 line 5 – p. 6 line 20) In particular both R and R 1 are selected from a number of options including both hydrogen and alkyl. Specific compounds are described including compound 1 on p. 27: PNG media_image9.png 200 400 media_image9.png Greyscale and compound 4 on p. 28: PNG media_image10.png 200 400 media_image10.png Greyscale , both of which differ from the claimed compounds only in that they have a methyl group on the 2’- position rather than the 3’- position. It would have been obvious to one of ordinary skill in the art at the time of the invention to modify either of these compounds by switching the methyl group to the 3’- position, as this fairly conservative modification is within the broad scope of structures described by Roberts et al., and would therefore be among the modifications of these lead compounds which would be obvious to try. Regarding claim 110, Roberts et al. discloses pharmaceutical compositions comprising these compounds. (p. 59 lines 15-26) These compositions can further include pharmaceutically acceptable excipients. (p. 60 lines 22-31) Regarding claims 118 and 119, Roberts et al. discloses a method of treating HCV in a subject comprising administering a composition of one or more of said compounds to a subject. (p. 34 lines 7-12) Regarding claims 111, 112, and 119-123, the description of “one or more” compounds suggests administering compositions of two of these compounds, in which case the second compound would be an additional antiviral nucleoside as described in these claims. Therefore the invention taken as a whole is prima facie obvious . 07-21-02-aia AIA Claim s 19, 46, 55, and 109 are rejected under 35 U.S.C. 103 as being obvious over Schinazi et al. (PCT international publication WO2022/217154, Reference included with PTO-892) The disclosure of Schinazi et al. is discussed above. Schinazi et al. does not specifically disclose compounds of formula (B) and (D), specifically wherein the 3’- and 5’- positions are linked by a cyclic phosphate. However, Schinazi et al. does disclose said cyclic phosphates as formulae B: PNG media_image11.png 200 400 media_image11.png Greyscale and PNG media_image12.png 200 400 media_image12.png Greyscale . (See p. 16 and p. 19) Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to make a derivative of the compound PNG media_image5.png 200 400 media_image5.png Greyscale disclosed by Schinazi and referenced in the previous rejection under 35 USC 102, having a similar cyclic phosphate groups connecting the 3’- and 5’- hydroxyl groups. One of ordinary skill in the art would have seen it as being obvious to make such a modification of the specific compounds disclosed by the reference because of the disclosure of structures bearing this group as preferred embodiments of the disclosed antiviral agents. Furthermore with respect to claim 109, this claim recites a number of specific nucleosides including phosphoramidates and acyl esters of PNG media_image5.png 200 400 media_image5.png Greyscale . (see for example p. 26 of the claims) Schinazi et al. furthermore allows for such modifications in in fact discloses specific compounds bearing them, for example PNG media_image13.png 200 400 media_image13.png Greyscale , (p.127) or PNG media_image14.png 200 400 media_image14.png Greyscale . (p. 131) It would have been obvious to one of ordinary skill in the art at the time of the invention to make ester or phosphoramidite derivatives of the particular compounds disclosed by Schinazi, within the scope recited in claim 109 . The applied reference has a common assignee and some inventors in common with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02. Conclusion Claims 1, 2, 19, 33, 46, 55, 108, and 110-127 are rejected. Claims 70, 85, and 97 are objected to for depending from a rejected base claim but would be allowable if rewritten in independent form incorporating all the limitations of the rejected base claim and any intervening claims. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm. 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, Scarlett Y Goon can be reached at 571-270-5241. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ANDREA OLSON/Primary Examiner, Art Unit 1693 3/6/2026 Application/Control Number: 18/562,911 Page 2 Art Unit: 1693 Application/Control Number: 18/562,911 Page 3 Art Unit: 1693 Application/Control Number: 18/562,911 Page 4 Art Unit: 1693 Application/Control Number: 18/562,911 Page 5 Art Unit: 1693 Application/Control Number: 18/562,911 Page 6 Art Unit: 1693 Application/Control Number: 18/562,911 Page 7 Art Unit: 1693 Application/Control Number: 18/562,911 Page 8 Art Unit: 1693 Application/Control Number: 18/562,911 Page 9 Art Unit: 1693 Application/Control Number: 18/562,911 Page 10 Art Unit: 1693 Application/Control Number: 18/562,911 Page 11 Art Unit: 1693 Application/Control Number: 18/562,911 Page 12 Art Unit: 1693 Application/Control Number: 18/562,911 Page 13 Art Unit: 1693 Application/Control Number: 18/562,911 Page 14 Art Unit: 1693