DETAILED ACTION
The present application is a domestic application filed 29 February 2024, which is a continuation of PCT/US2022/042545, filed 02 September 2022, and claims priority to US Provisional Application No. 63/240,578, filed 03 September 2021.
Claims 1-23 are pending in the current application and are examined on the merits herein.
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 .
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.
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) 1-13 and 20-23 are rejected under 35 U.S.C. 103 as being unpatentable over Sommadossi et al. (US Patent Application Publication No. 2019/0201433, hereinafter the ‘433 Publication, cited in IDS submitted 25 September 2025) in view of Paparin et al. (US Patent Application Publication No. 2017/0198005, hereinafter the ‘005 Publication, cited in IDS submitted 25 September 2025).
The ‘433 Publication is drawn towards the use of 2’-substituted-N6-substituted purine nucleotides for RNA virus treatment (title). The nucleotide derivatives can be used to treat West Nile Virus (WNV), Zika, Yellow Fever Virus (YFV), and Dengue fever (para [0018]; claims 23-29). The ‘433 Publication teaches a method comprising administering an effective amount of a compound of Formula IIIe or Formula IVe, and exemplifies compound 205:
PNG
media_image1.png
108
306
media_image1.png
Greyscale
(claim 1, Table 5, see also para [0021]). Compound 205 had an EC50 towards DENV-2 of 0.8 µM, and an EC50 towards YFV. The ‘433 Publication teaches isomeric forms of compound 205, including:
PNG
media_image2.png
238
404
media_image2.png
Greyscale
,
PNG
media_image3.png
232
426
media_image3.png
Greyscale
,
PNG
media_image4.png
228
424
media_image4.png
Greyscale
(column 69, para [0679]). The drug can be in the form of an inorganic salt including sulfate (para [0720]).
While the ‘433 Publication teaches a 2’-methyl-2’-fluoro nucleoside derivative, the ‘433 Publication does not expressly disclose a 2’-fluoro-2’-chloro nucleoside analogues (title).
The ‘005 Publication teaches the following 2’-fluoro-2’-chloro derivative:
PNG
media_image5.png
174
292
media_image5.png
Greyscale
(col. 164, claim 1). The compounds can be used to treat Flaviviridae infections, including dengue fever and yellow fever (abstract). The ‘005 Publication teaches the preparation of 2’-dichloro nucleoside analogues 103 diastereomers 1 and 2:
PNG
media_image6.png
248
362
media_image6.png
Greyscale
(col. 143, 144). Compound 103a (diastereomer 2) had an EC50 of > 10 µM towards HCV Replicon , and a CC50 > 50 µM towards HCV Replicon Table 1). Compound 103a (diastereomer 1) had the same activity as diastereomer 2. The mixture had a higher EC50 activity of > 1 µM, and < 10 µM (Table 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify compound 205 of the ‘433 Publication at the 2’-position, to replace the 2’-methyl of compound 205 with a 2’-chloro group, to arrive at a 2’-fluoro-2’-chloro derivative.
The ordinary artisan would have started from compound 205, because it was identified by the ‘433 Publication as a lead compound, having strong antiviral activity towards dengue virus and yellow fever virus. The skilled artisan would have looked to the ‘005 Publication, because they are both concerned with preparing nucleoside analogues for the treatment of Flaviviridae infections. The compounds of the ‘433 Publication are very similar to compounds 103a of the ‘005 Publication, differing only at the 2’-position and the base. Furthermore, 2’-fluoro-2’-chloro derivatives were shown to have antiviral activity.
The ordinary artisan would have been motivated to substitute the 2’-methyl-2’-fluoro nucleoside for 2’-chloro-2’-fluoro with a reasonable expectation of arriving at a compound having similar Flaviviridae antiviral activity.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 14-19 are rejected under 35 U.S.C. 103 as being unpatentable over the '433 Publication and the '005 Publication as applied to claims 1-13 and 20-23 above, and further in view of Moussa et al. (US Patent No. 10,519,186, hereinafter the ‘186 Patent, cited in IDS submitted 25 September 2025).
The ‘433 Publication teaches as discussed above.
The ‘433 Publication does not expressly disclose a hemi-sulfate salt (present claims 14-19).
The ‘005 Publication teaches as discussed above.
The ‘186 Patent is drawn towards 2’-deoxy-2’-fluoro nucleoside hemi-sulfate salts for the treatment of hepatitis viral infections (title, abstract):
PNG
media_image7.png
230
470
media_image7.png
Greyscale
. The ‘186 Patent teaches hepatitis C is an RNA single-stranded virus (col.1:26-35). The ‘186 Patent teach they found the hemisulfate salt of compound 1, exhibited unexpected advantageous therapeutic properties, including enhanced bioavailability, and target organ selectivity over its free base, compound 1
PNG
media_image8.png
200
402
media_image8.png
Greyscale
(col.4:38-67).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify compound 205 of the ‘433 Publication at the 2’-position, to replace the 2’-methyl of compound 205 with a 2’-chloro group, and to prepare a hemi-sulfate salt of the compound for the treatment of a human host infected with a Flavivirus.
The ordinary artisan would have been motivated to prepare the hemi-sulfate salt as claimed, because in the same field of endeavor of administering 2’-fluoro nucleoside derivatives for the treatment of RNA viruses, the ‘433 Publication teaches preparing sulfate forms of compound 1, and the ‘186 Patent found the hemi-sulfate salt of compound 1 was significantly more bioavailable than the free base.
The skilled artisan would have had a reasonable expectation of success in treating a human host infected with a Flavivirus, because the ‘433 Publication teaches compound 1 was effective in treating Dengue virus infections and Yellow Fever infections, and the ‘005 Publication teaches 2’-fluoro-2’-chloro derivative for treating Flaviviridae infections, including dengue fever and yellow fever.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-52 of U.S. Patent No. 10,519,186 in view of Paparin et al. (US Patent Application Publication No. 2017/0198005, cited above).
The claims of the ‘186 Patent are drawn towards the following hemisulfate salt:
PNG
media_image7.png
230
470
media_image7.png
Greyscale
, and a method of administering it to treat a hepatitis C infection in a human.
The claims of the ‘186 Patent do not expressly disclose the 2’-chloro derivative, or treating a Flavivirus infection.
The ‘005 Publication teaches the following 2’-fluoro-2’-chloro derivative:
PNG
media_image5.png
174
292
media_image5.png
Greyscale
(col. 164, claim 1). The compounds can be used to treat Flaviviridae infections, including dengue fever and yellow fever (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the compound of the reference patent at the 2’-position, to replace the 2’-methyl of compound 205 with a 2’-chloro group, because like the ‘005 Publication, the compound was claimed as having antiviral activity. Substitution of methyl with chloro results in a compound having strong antiviral activity towards Flavivirus infections.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-52 of U.S. Patent No. 10,946,033 in view of Paparin et al. (US Patent Application Publication No. 2017/0198005, cited above), and further in view of Moussa et al. (US Patent No. 10,519,186, cited above).
The claims of the reference Patent are drawn towards the same compounds presently claimed for treating the same virus presently claimed, except they differ at the 2’-position (2’-methyl-2’-fluoro vs 2’-chloro-2’fluoro).
The claims of the reference Patent do not expressly disclose the hemi-sulfate salt.
The ‘005 Publication teaches the following 2’-fluoro-2’-chloro derivative:
PNG
media_image5.png
174
292
media_image5.png
Greyscale
(col. 164, claim 1). The compounds can be used to treat Flaviviridae infections, including dengue fever and yellow fever (abstract).
The claims of the ‘186 Patent are drawn towards the following hemisulfate salt:
PNG
media_image7.png
230
470
media_image7.png
Greyscale
, and a method of administering it to treat a hepatitis C infection in a human.
The claims of the ‘186 Patent do not expressly disclose the 2’-chloro derivative, or treating a Flavivirus infection.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the compound of the reference patent at the 2’-position, to replace the 2’-methyl of compound 205 with a 2’-chloro group, because like the ‘005 Publication, the compound was claimed as having antiviral activity. Substitution of methyl with chloro results in a compound having strong antiviral activity towards Flavivirus infections.
The ordinary artisan would have been motivated to prepare the hemi-sulfate salt as claimed, because in the same field of endeavor of administering 2’-fluoro nucleoside derivatives for the treatment of RNA viruses, the ‘433 Publication teaches preparing sulfate forms of compound 1, and the ‘186 Patent found the hemi-sulfate salt of compound 1 was significantly more bioavailable than the free base.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-52 of U.S. Patent No. 10,874,687 in view of Paparin et al. (US Patent Application Publication No. 2017/0198005, cited above).
The claims of the reference Patent are drawn towards administering the 2’-methyl-2’-fluoro derivative of the presently claimed compound (rather than the claimed 2’-fluoro-2’-chloro), and its hemi-sulfate form, for treating SARS-CoV-2 virus.
The claims of the reference Patent do not expressly disclose the 2’-chloro derivative, or treating a Flavivirus infection.
The ‘005 Publication teaches the following 2’-fluoro-2’-chloro derivative:
PNG
media_image5.png
174
292
media_image5.png
Greyscale
(col. 164, claim 1). The compounds can be used to treat Flaviviridae infections, including dengue fever and yellow fever (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the compound of the reference patent at the 2’-position, to replace the 2’-methyl of compound 205 with a 2’-chloro group, because like the ‘005 Publication, the compound was claimed as having antiviral activity. Substitution of methyl with chloro results in a compound having strong antiviral activity towards Flavivirus infections.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. 11,690,860 in view of Paparin et al. (US Patent Application Publication No. 2017/0198005, cited above).
The claims of the reference Patent are drawn towards administering the 2’-methyl-2’-fluoro derivative of the presently claimed compound (rather than the claimed 2’-fluoro-2’-chloro), and its hemi-sulfate form, for treating hepatitis C virus infected human.
The claims of the reference Patent do not expressly disclose the 2’-chloro derivative, or treating a Flavivirus infection.
The ‘005 Publication teaches the following 2’-fluoro-2’-chloro derivative:
PNG
media_image5.png
174
292
media_image5.png
Greyscale
(col. 164, claim 1). The compounds can be used to treat Flaviviridae infections, including dengue fever and yellow fever (abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the compound of the reference patent at the 2’-position, to replace the 2’-methyl of compound 205 with a 2’-chloro group, because like the ‘005 Publication, the compound was claimed as having antiviral activity. Substitution of methyl with chloro results in a compound having strong antiviral activity towards Flavivirus infections.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAHAR A CRAIGO whose telephone number is (571)270-1326. The examiner can normally be reached M-F: Noon-8pm ET.
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, Fereydoun Sajjadi can be reached at 571-272-3311. 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.
/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699
Prosecution Insights