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 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 filed on November 26, 2025 has been entered.
DETAILED ACTION
3. Claims 1, 3 – 6, 12, 14 – 15, 18 – 22, and 25 – 26 are pending in this application. Applicant’s Amendment and Remarks, filed November 26, 2025, is entered, wherein claims 1, 12, 19, 22, and 25 – 26 are amended, claims 3 – 4, 6, 12, 14, 19 – 22, and 25 – 26 are withdrawn, and claims 2, 7 – 11, 13, 16 – 17, 23 – 24, and 27 are canceled.
Therefore, claims 1, 5, 15, and 18 are currently examined.
Priority
4. This application is a national stage application of PCT/US2020/041133, filed July 8, 2020, which claims benefit of domestic application 62/872,070, filed July 9, 2019.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119€ or under 35 U.S.C. 120, 121, 365€, or 386€ 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. 119€ as follows:
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. 62/872,070, 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 domestic application 62/872,070 does not provide support for the limitation of “SARS-CoV-2” that recited in claim 2. Thus, the priority date of claim 2 is July 8, 2020.
Withdrawn Objections
5. The objection of claim 10 in the previous Office Action, mailed October 6, 2025, is withdrawn in view of the canceled claim 10.
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:
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.
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.
Claims 1, 15, and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Furuta et al. (Proceedings of the Japan Academy, 2017, Vol. 93, Issue 7, page 449 – 463, cited in the previous Office Action, mailed October 6, 2025) in view of da Silva et al. (Viruses, 2018, Vol. 10, Issue 5, cited in the previous Office Action, mailed March 24, 2025).
a. Regarding claims 1, 15, and 18, Furuta et al. teach that favipiravir (T-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an antiviral drug that selectively and potently inhibits the RNA-dependent RNA polymerase (RdRp) of RNA viruses. Favipiravir was discovered through screening chemical library for anti-viral activity against the influenza virus by Toyama Chemical Co., Ltd. Favipiravir is effective against a wide range of types of subtypes of influenza viruses, including strains resistant to existing anti-influenza drugs. Favipiravir shows anti-viral activities against other RNA viruses such as arenaviruses, bunyaviruses and filoviruses, all of which are known to cause fatal hemorrhagic fever. These unique anti-viral profiles will make favipiravir a potentially promising drug for specifically untreatable RNA viral infections (Abstract). Zika virus (ZIKV) is an emerging arbovirus of Flaviviridae, which is mainly transmitted by mosquito bites. Evidence to date suggests the association between fetal infection and microcephaly. Favipiravir inhibits the replication of ZIKV in Vero cells with an EC50 of 3.5 – 3.8 μg/mL, suggesting a therapeutic potential for the ZIKV infection (page 458, Left Col., para. 2). Furuta et al. also disclose that combination of anti-viral agents with a different mechanism of action is utilized to enhance therapeutic effects or to reduce the emergence of resistant virus clones. Synergistic effects are demonstrated by the combination of favipiravir with oseltamivir in a murine model of influenza virus (page 455, Left Col., para. 2). Favipiravir has been formulated as an oral treatment (page 453, Right Col., para. 2).
However, Furuta et al. do not teach a method for treating an RNA virus infection comprising administering a therapeutic combination as a combined formulation to a patient with an RNA virus infection and in need thereof, wherein the combination comprises a de novo nucleotide biosynthesis inhibitor (DNNBi), wherein the DNNBi is 6-methylmercaptopurine riboside (6-MMPR).
da Silva et al. teach that the antiviral activity of 6 MMpr is evaluated through RNA quantification, viral titration, and plaque reduction assay in Vero and SII-SY5Y neuronal cells. Vero and SII-SY5Y cells monolayers are infected with ZIKV PE243 at MOI 0.1 for 2 h at 37 ⁰C, washed, and additionated with four concentrations of 6 MMpr. The cell supernatants are collected 120 h.p.i. and submitted to qRT-PCR and virus titration. The results show that 6 MMpr inhibited viral RNA in a dose-dependent manner, and at 30.3 μM, the riboside decreased the viral RNA up to 99%. In addition, 30.3 and 60.5 μM of 6 MMpr reduced ZIKV titers by 77.24% and 99.45%, respectively (page 11, 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 combine favipiravir as taught by Furuta et al. with 6-MMPR in view of da Silva et al. to administering the combination to treat ZIKV viral infection. It would have been obvious for one of ordinary skill in the art to combine because both favipiravir and 6-MMPR are known separately in the prior art for the purpose of treating ZIKV viral infection, and it would have been obvious to combine them to treat the same disease. Furuta et al. teach that favipiravir is formulated as an oral treatment, one would have performed a routine experimentation to determine the formulation of the combination for the optimal treatment characteristics. For the dosing regimen, one would have performed a routine experimentation to determine the best dosing regimen for the optimal treatment characteristics. One of ordinary skill in the art would have had a reasonable expectation of success to combine favipiravir as taught by Furuta et al. with 6-MMPR in view of da Silva et al. because it is well known to combine drugs to treat the same disease, and further Furuta et al. teach that favipiravir can be used in combination with other drugs.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Furuta et al. (Proceedings of the Japan Academy, 2017, Vol. 93, Issue 7, page 449 – 463, cited in the previous Office Action, mailed October 6, 2025) in view of da Silva et al. (Viruses, 2018, Vol. 10, Issue 5, cited in the previous Office Action, mailed March 24, 2025) as applied to claims 1 – 2, 8, 10, 15, and 18 above, and further in view of Veljkovic (F1000Research, 2016, Vol. 5, cited in the previous Office Action, mailed March 24, 2025).
b. Regarding claim 5, Furuta et al. and da Silva et al. teach the limitations discussed above.
However, these references do not explicitly teach that 6-MMPR is able to treat influenza.
Veljkovic analyzes ZIKV E proteins using ISM. Results of this in silico analysis reveal that these viral proteins encode the highly conserved information which determines their interacting profile and immunological properties. Veljkovic also reports that the human interacting profile of HA1 from pdmH1N1 influenza viruses is characterized by the same information. The result suggests possible repurposing of the seasonal influenza vaccine containing pdmH1N1 for prevention of ZIKV infection (page 2, Left Col., para. 4).
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 treatment of ZIKV viral infection comprising administering favipiravir and 6-MMPR as taught by Furuta et al. and da Silva et al. into treating influenza in view of Veljkovic because Furuta et al. teach that favipiravir is able to treat influenza and Veljkovic teaches that ZIKV and influenza viruses are very similar in terms of their interacting profile. One would have been motivated to modify the treatment of ZIKV viral infection comprising administering favipiravir and 6-MMPR as taught by Furuta et al. and da Silva et al. into treating influenza in view of Veljkovic because Furuta et al. teach that favipiravir demonstrates promising therapeutic effects toward wide range of RNA virus, including influenza and Veljkovic suggests to repurpose the seasonal influenza vaccine for preventing ZIKV infection. One of ordinary skill in the art would have had a reasonable expectation of success modify the treatment of ZIKV viral infection comprising administering favipiravir and 6-MMPR as taught by Furuta et al. and da Silva et al. into treating influenza in view of Veljkovic because Furuta et al. teach that favipiravir is a promising treatment for influenza and Veljkovic teaches that ZIKV and influenza A are very similar, thereby, suggesting that similar treatment may be used.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed November 26, 2025, have been fully considered and are found to be not persuasive.
Applicant argues that the combination of antiviral nucleobase compounds with a DNNBi compound, such as 6-MMPR, in a cell viability assay exhibits synergistic effect which is surprising and unexpected. Applicant points to figures 4 – 12 and discussion and conclusions section on pages 21 – 24 as the evidence for the unexpected results. For example, figures 6A and 6B show that 6-MMPR strongly potentiates the anti-DENV activity of T-1105 without cellular toxicity and figures 8A and 8C show synergistic effect on inhibiting ZIKV replication when either T-1105 or favipiravir is in combination with 6-MMPR.
However, contrary to the disclosed results, the specification recites that “lower concentrations of 6-MMPR did not potentiate nucleobase anti-replicon activity” (page 21, lines 30 – 31). Therefore, the unexpected results disclosed are not commensurate in scope with the claims.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693