CTNF 17/918,407 CTNF 98171 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 Claims 1 – 9 are pending in this application and are examined on the merits herein. Applicant’s preliminary amendment, submitted October 12, 2022, is entered, wherein claims 2 – 3 and 5 – 6 are amended and claims 7 – 9 are new. Priority This application is a national stage application of PCT/IB2022/051502, filed February 21, 2022, which claims benefit of foreign priority document IN202121042313, filed September 18, 2021. 02-26 AIA Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. 02-09 AIA Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 365(c) or 386(c) as follows: 02-10 AIA The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc. , 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). The disclosure of the prior-filed application, Application No. IN202121042313 , fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The foreign priority IN202121042313 does not provide support for the limitation of “20 – 70 ⁰C” recited in claim 2 and “1 – 14 hours” recited in claim 3. Thus, the priority date of claims 2 – 3 is February 21, 2022 . Information Disclosure Statement The information disclosure statement (IDS) submitted on 10/12/2022 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. Claim Objections 07-29-01 AIA Claim s 1 – 7 and 9 are objected to because of the following informalities: Claim 1, lines 3 and 8, the structure of formula (I) and formula (V) should be presented immediately after their textual reference to ensure clarity. Claims 2 – 7, line 1, “;” should be replaced with “,”. The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not). Misnumbered claim 8 has been renumbered claim 9 . Appropriate correction is required. 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. 07-34-01 Claim 3 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. Claim 3 recites the phrase “more preferably” in line 3. The claim is indefinite because the inclusion of “more preferably” renders the scope of the claim ambiguous. The use of “more preferably” introduces uncertainty as to whether the narrower range is intended to be a required limitation or merely a suggested, non-limiting embodiment of the broader range. The use of the phrase prevents one of ordinary skill in the art from determining the precise boundaries of the claim. Claim Rejections - 35 USC § 102 07-06 AIA 15-10-15 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. 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. 07-15 AIA Claim s 1, 5 – 6, and 8 – 9 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Gopalsamuthiram et al. (ChemRxiv, June 2021, Reference included with PTO-892) . a. Independent claim 1 is directed to a process for the preparation of Molnupiravir compound of formula (I): PNG media_image1.png 190 201 media_image1.png Greyscale comprises using water as solvent for reacting compound of formula (IV): PNG media_image2.png 172 236 media_image2.png Greyscale with hydroxyl amine sulfate at suitable reaction conditions to obtain compound of formula (V): PNG media_image3.png 185 252 media_image3.png Greyscale and converting compound of formula (V) to formula (I). Dependent claims 5 – 6 are directed to the process, wherein converting of compound of formula (V) to formula (I) is carried out at temperature in the range of 20 – 40 ⁰C and at time in the range of 1 – 10 hours. Dependent claim 8 is directed to the process, wherein the reaction is to be carried out at temperature of 25 – 35 ⁰C. Dependent claim 9 is directed to the process, wherein the reaction is to be carried out at time of 1 – 8 hours. Gopalsamuthiram et al. teach a scalable four step synthesis of Molnupiravir from cytidine. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents, such as water, isopropanol, acetonitrile, and acetone (Abstract). Gopalsamuthiram et al. disclose the reaction scheme as follows (page 2, Scheme 3): PNG media_image4.png 482 535 media_image4.png Greyscale . In Scheme 3, Gopalsamuthiram et al. disclose step 4, wherein compound 6 is converted to Molnupiravir in 5 hours without elevated temperature. It is interpreted that step 4 is performed under room conditions , which addresses the limitations of claims 5 and 8. For these reasons above, Gopalsamuthiram et al. anticipate the claimed invention . Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 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. 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. 07-23-aia AIA The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: i. Determining the scope and contents of the prior art. ii. Ascertaining the differences between the prior art and the claims at issue. iii. Resolving the level of ordinary skill in the pertinent art. iv. Considering objective evidence present in the application indicating obviousness or nonobviousness. 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 – 9 are rejected under 35 U.S.C. 103 as being unpatentable over Gopalsamuthiram et al. (ChemRxiv, June 2021, Reference included with PTO-892). Claims 1, 5 – 6 and 8 – 9 are rejected here because they have been rejected by the primary reference under 102 . b. Regarding claims 1 – 9, Gopalsamuthiram et al. teach a scalable four step synthesis of Molnupiravir from cytidine. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents, such as water, isopropanol, acetonitrile, and acetone (Abstract). Gopalsamuthiram et al. disclose the reaction scheme as follows (page 2, Scheme 3): PNG media_image4.png 482 535 media_image4.png Greyscale . The first method involves recrystallization of crude 6 from 2.5 V of isopropyl acetate. The mass recovery using this method is 66% and the purity is 98 wt% (page 4, Right Col., para. 2). Gopalsamuthiram et al. also disclose that the methods afford product 6 of > 96% purity (page 4, Right Col., para. 3). It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the reaction conditions, such as temperature and time, as taught by Gopalsamuthiram et al. because it is known in the art that reaction conditions, such as temperature, are routinely optimized by the skilled artisan. One would have performed routine experimentation to discover the best reaction conditions for the optimal balance of reaction efficiency and product purity. In Scheme 3, Gopalsamuthiram et al. disclose step 4, wherein compound 6 is converted to Molnupiravir in 5 hours without elevated temperature. It is interpreted that step 4 is performed under room conditions, which addresses the limitations of claims 5 and 8. Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success in modifying reaction conditions, such as temperature, to discover the best conditions for optimal yield, since it is well-established that such parameters are recognized variables whose effects on reaction outcome are predictable, and adjusting them through routine experimentation falls within the skill of the art. Conclusion No claim is found to be allowable. Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOI YAN LEE whose telephone number is 571-270-0265. The examiner can normally be reached Monday - Thursday 7:30 - 17:30. 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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. /H.Y.L./Examiner, Art Unit 1693 /SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693 Application/Control Number: 17/918,407 Page 2 Art Unit: 1693 Application/Control Number: 17/918,407 Page 3 Art Unit: 1693 Application/Control Number: 17/918,407 Page 4 Art Unit: 1693 Application/Control Number: 17/918,407 Page 5 Art Unit: 1693 Application/Control Number: 17/918,407 Page 6 Art Unit: 1693 Application/Control Number: 17/918,407 Page 7 Art Unit: 1693 Application/Control Number: 17/918,407 Page 8 Art Unit: 1693 Application/Control Number: 17/918,407 Page 9 Art Unit: 1693