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 .
DETAILED ACTION
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 final rejection. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission dated 03/06/2026 has been entered pursuant to RCE filed on 03/06/2026.
Pursuant to the amendment dated 03/06/2026, claims 1-11 are cancelled and claims 12-21 are amended. Claims 12-21 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/US21/27535, filed on 04/15/2021 and claims benefit to provisional applications 63/107,893 filed on 10/30/2020, 62/705,288 filed on 06/19/2020, and 62/704,340 filed on 05/05/2020.
Information Disclosure Statement
The information disclosure statement (IDS) dated 03/06/2026 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
Withdrawn Objections
Applicant’s amendment, filed on 03/06/2026, with respect to the objection of the numbering of the claims has been fully considered and is persuasive. Applicant has renumbered the claims. The objection is hereby withdrawn.
Applicant’s amendment, filed on 03/06/2026, with respect to the objection claims 15-20 under 37 CFR 1.75(c) as being in improper form because multiple dependent claim 14 has been fully considered and is persuasive. None of the claims 15-20 are in multiple dependent form. The objection is hereby withdrawn.
Withdrawn Rejections
Applicant’s amendment, filed on 03/06/2026, with respect to the rejection of claim 12 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, has been fully considered and is persuasive. Applicant has successfully argued that monatepil and pancopride are not tradenames. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 03/06/2026, with respect to the rejection of claim 15 under 35 U.S.C. 103 as being unpatentable over Painter et al. (WO 2017/155923 A1, published 09/14/2017, see PTO-892 dated 01/09/2026) as applied to claim 12 and 14 above, and further in view of Sanders et al. (JAMA, published 04/13/2020, see PTO-892 dated 01/09/2026), has been fully considered and is not persuasive. The rejection has been withdrawn in favor of the modified/new rejection below. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 03/06/2026, with respect to the rejection of claims 13 and 14 under 35 U.S.C. 103 as being unpatentable over King et al. (US 2008/0124303 A1, published 05/29/2008, see PTO-892 dated 01/09/2026) has been fully considered and is persuasive. Applicant has amended claim 13 to remove azathioprine. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 03/06/2026, with respect to the rejection of claim 21 under 35 U.S.C. 103 as being unpatentable over Oost et al. (Bioorg. Med. Chem. Lett, published 03/06/2011, see PTO-892 dated 01/09/2026) has been fully considered and is persuasive. Applicant has amended claim 21 from a composition claim to a method of treating a subject with coronavirus. The rejection is hereby withdrawn.
New and Maintained rejections
Claim Rejections - 35 USC § 102
(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.
(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.
Claims 13 and 14 rejected under 35 U.S.C. 102(a)(1)(a)(2) as being anticipated by Chen et al. (US 2007/0160981 A1, published 07/12/2007, see PTO-892).
Chen is drawn to viral proteases of SARS-CoV PLP2 and methods of treatment of SARS-CoV (abstract). Chen discloses a method of treating an infection with SARS-CoV with an inhibitor of SARS-CoV PLP2 wherein the inhibitor is mercaptopurine (claims 17 and 21).
Accordingly, the prior art anticipates the claims.
Claim Rejections - 35 USC § 103
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.
Claims 12, 14, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Painter et al. (WO 2017/155923 A1, published 09/14/2017, see PTO-892 dated 01/09/2026).
Painter is drawn to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases and viral infections (abstract). Painter teaches the method of treating a viral infection comprising administering an effective amount of a pharmaceutical composition to a subject in need (page 3, lines 31-34). Painter teaches that the compounds disclosed can be used in combination with one additional drug selected from the group comprising amodiaquine, halofantrine, pyronaridine, hydroxychloroquine or mixture thereof (page 118, lines 3-12). The instant specification defines an anti-infective agent as an anti-viral such as one selected from the group consisting of entry-inhibiting drugs, uncoating inhibiting drugs, reverse transcriptase inhibiting drugs, antisense drugs, ribozyme drugs, protease inhibitors, assembly inhibiting drugs. and release inhibiting drugs (instant specification page 1, paragraph 00031). The instant specification states that hydroxychloroquine is an entry-inhibiting drug (instant specification page 67, paragraph 0097). Therefore, hydroxychloroquine meets the limitations of an anti-infective agent of instant claim 16 and an entry-inhibiting drug of instant claim 18.
Regarding instant claim 14, Painter teaches that the subject is diagnosed with a virus such as human coronavirus, SARS coronavirus, and MERS coronavirus (page 4, lines 8-11).
Painter does not exemplify the administration of halofantrine or pyronaridine.
It would have been prima facie obvious to before the effective filing date of the claimed invention to administer amodiaquine, halofantrine, pyronaridine, hydroxychloroquine or mixture thereof to a subject with a SARS-CoV infection as taught by Painter to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select administer comprising amodiaquine, halofantrine, pyronaridine, hydroxychloroquine or mixture thereof to a subject with a SARS-CoV infection because Painter teaches that the antiviral agents may be administered to a subject with SARS-CoV infection. One of ordinary skill in the art would have a reasonable expectation of success because Painter teaches that the antiviral agents may be administered to a subject with SARS-CoV infection.
Claims 12, 14, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Mamidala et al. (arXiv.org, accessed 04/25/2026, published 04/25/2020, see PTO-892).
Mamidala is drawn to the in-silico identification of clinically approved medicines against the main protease of SARS-CoV-2 (title). Mamidala tested 47 approved drugs including halofantrine (Table 1, pages 2-6). Mamidala teaches that halofantrine binds to the active site of the SARS-CoV-2 main protease site with high affinity (abstract). Mamidala teaches that halofantrine is a clinically approved drug that has been identified as a potent inhibitor against SARS-CoV-2 protease activity and that the outcome affords a strong foundation for the use of the drug for corona management. Mamidala teaches that further in vivo analysis in the termination of intracellular replication of corona virus should be conducted prior to the use as drugs in humans (page 16)
Mamidala does not exemplify the administration of halofantrine to a subject infected with SARS-CoV-2.
It would have been prima facie obvious before the effective filing date of the claimed invention to treat a subject infected with SARS-CoV-2 by administering a therapeutically effective amount of halofantrine to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to administer halofantrine to a subject infected with SARS-CoV-2 because Mamidala teaches testing the clinically approved compounds that have shown inhibitory ability against SARS-CoV-2, such as halofantrine, should be tested in vivo. One of ordinary skill in the art would have a reasonable expectation of success because Mamidala shows that halofantrine is a potent inhibitor against SARS-CoV-2 protease activity.
Allowable Subject Matter
Claim 21 is allowed.
Instant claim 21 is drawn to a method of treating a subject infected by a coronavirus comprising administering to a subject a therapeutically effective amount of RFM-011-200-5 or a pharmaceutically acceptable salt thereof. The applicant provided data (Table 1, instant specification page 9) that measured the antiviral effect in Hela-ACE2 cells and showed that RFM-011-200-5 had an EC50 of 4.24 µM.
PNG
media_image1.png
297
396
media_image1.png
Greyscale
The closest prior art, Oost et al. (Bioorg. Med. Chem. Lett, published 03/06/2011, see PTO-892 dated 01/09/2026) is drawn to the study of potent and selective oxindole-based vasopressin 1b receptor antagonists with improved pharmacokinetic properties. Oost exemplifies compound 18c which is a diastereomer of instant formula RFM-001-200-5. Oost further teaches that the diastereomers were either separated after the amination or after the sulfonylation stage. (Scheme 4, Page 3830). Oost does not teach that the vasopressin 1b receptor antagonists may be used to treat coronavirus and there is no teaching to modify the method to treat coronavirus with a vasopressin 1b receptor antagonist.
Consequently, the method of treating a subject infected by a coronavirus comprising administering to a subject a therapeutically effective amount of RFM-011-200-5 or a pharmaceutically acceptable salt thereof renders the claim non-obvious over the closest applicable prior art of Oost et al.
Response to Arguments
Applicant's arguments filed 03/06/2026 have been fully considered but they are not persuasive.
Applicant argues that the amendment removing arbidol, boceprevir, nelfinavir, and simeprevir from instant claim 12 overcomes the rejection over Painter. However, Painter also teaches halofantrine and pyronaridine from instant claim 12 and therefore, the rejection is maintained.
Conclusion
Claim 21 is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMANTHA LYNN SCHACHERMEYER whose telephone number is (703)756-5337. The examiner can normally be reached Monday thru Friday, alternate Fridays off, 7:30AM-5PM EST.
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 Goon can be reached on (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.
/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
Prosecution Insights