DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election without traverse of Group I (Claims 1-3, 6-11, and 20-21) in the reply filed on 17 March 2026 is acknowledged.
Claims 12, 13 and 15-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 17 March 2026.
Claims 1-3, 6-11, and 20-21, submitted on 17 March 2026, represent all claims currently under consideration.
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.
Priority
This application is a 371 of PCT/US2022/21598, filed 23 March 2022, which claims priority to provisional US 63/165,510, filed 24 March 2021. The effective filing date is 24 March 2021.
Information Disclosure Statement
Four Information Disclosure Statements (IDSs), submitted on 22 September 2023, 30 January 2024, 20 May 2024, and 16 September 2025, are acknowledged and have been considered.
Claim Objections
Claim 1 is objected to because of the following informalities: The phrase “corona virus” should read “coronavirus”. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: The claim should read “an agent/target virion complex” rather than “a agent/target virion complex”, and there is a missing comma following “fuse with”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 –
(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 1, 3, 8, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cummins (WO 2008/036747; Publication Date: 27 March 2008).
Cummins (See IDS, 22 September 2023) discloses a pharmaceutical composition and method for modulating an immune response in a warm-blooded vertebrate animal. The method comprises administering an immunomodulatory composition comprising an anthelmintic benzimidazole compound. The anthelmintic compound is selected from the group consisting of fenbendazole, thiabendazole, mebendazole, and albendazole (Abstract). The methods can be applied to warm-blooded vertebrate animals, including but not limited to humans (Page 10, Lines 9-10). The anthelmintic benzimidazole compounds disclosed herein may be used to treat DNA and RNA viruses, including coronaviruses (Page 11, Line 31- Page 12, Line 4).
Regarding Claims 3 and 21, the method of Cummins does not explicitly disclose what is claimed; however, administering mebendazole to a patient suffering from a coronavirus infection will inherently result in these functions occurring.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. 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 1-3, 6-11, and 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over Cummins (WO 2008/036747; Publication Date: 27 March 2008) in view of Farag (ChemRxiv, Posted 14 May 2020), Doshi (December 2020, arXiv:2012.02151v1, 3 December 2020), Frieman (US 2017/0027975; Publication Date: 2 February 2017), and Weisberg (Pharm Res, 2020, 37:167).
Cummins, as described previously, teaches the use of mebendazole for the treatment of coronavirus infections.
Cummins fails to teach the treatment of SARS-CoV-2, or a combination with tyrosine kinase inhibitors such as imatinib.
Farag adopted a repositioning approach using in-silico molecular modeling to screen FDA-approved drugs with established safety profiles for potential inhibitory effects against SARS-CoV-2. The authors used structure-based drug design to screen more than 2000 FDA approved drugs against SARS-CoV-2 main protease enzyme (Mpro) substrate-binding pocket, focusing on two potential sites to identify hits based on their binding energies, binding modes, interacting amino acids, and therapeutic indications. High-scoring candidates were then screened for antiviral activity against infectious SARS-CoV-2 in a cell-based viral replication assay, and counterscreened for toxicity. Atovaquone, mebendazole, and ouabain exhibited antiviral efficacy with IC50 values well within their respective therapeutic plasma concentrations and limited toxic effects. Notably, all three were predicted in docking studies to covalently bind SARS-CoV-2 Mpro, underscoring the utility of this in-silico approach for identifying putative antivirals for repurposing. These results do not confirm efficacy in models or in humans, but serve as a starting point for testing antiviral potential of select FDA-approved drugs, either individually or in combination (Abstract).
Doshi (See IDS, 22 September 2023) explored a computational data-driven methods for drug repurposing and propose a dedicated graph neural network based drug repurposing model called Dr-COVID. The authors provide a detailed analysis of 150 potential drugs predicted by Dr-COVID for COVID-19 from different pharmacological classes. Of these 150 drugs, 46 are currently in clinical trials (Abstract). Dr-COVID predicts nucleotide analogue antivirals like acyclovir, valaciclovir, cidofovir, and entecavir have shown positive results in terminating RNA synthesis catalyzed by polymerases of coronaviruses. Mebendazole is another similar anti-parasitic drug that Dr-COVID ranked high. Figure 2 shows that mebendazole is a drug predicted to be effective in the treatment of SARS-CoV-2.
Frieman (See IDS, 22 September 2023) provides methods for treating a coronavirus infection. The treatment may be affected by administering compounds including a kinase signaling inhibitor or an anti-parasitic agent (Abstract). Representative coronavirus which may be treated using this method include but are not limited to Middle East respiratory syndrome coronavirus or severe acute respiratory syndrome coronavirus (Paragraph 0029). Representative examples of useful kinase signaling inhibitors include but are not limited to imatinib mesylate (Paragraph 0030). Three inhibitors of kinase signaling pathways were identified, two (imatinib mesylate and dasatinib) that are active against both MERS-CoV and SARS-CoV. Imatinib is a known inhibitor of the ABL1 pathway. Imatinib mesylate inhibits SARS-CoV and MERS-CoV with micromolar EC50 values and low toxicity. SARS-CoV appears more sensitive to ABL1 inhibitors (Paragraph 0072). Imatinib was found to have an effect on virus replication (Paragraph 0075). Imatinib blocks either viral envelope fusion with the endosomal membrane or a step before that such as spike cleavage, endosomal protein trafficking/maturation, or entry of virions into the endosomes (Paragraph 0078). In vivo studies performed in the mouse model of viral infection showed that imatinib was more effective than dasatinib in blocking dissemination of the virus, and this was attributed to the immunosuppressive effects of dasatanib (Paragraph 0083).
Weisberg (See IDS, 30 January 2024) characterized more than 30 approved kinase inhibitors in terms of their antiviral potential due to their measured potency against key kinases required for viral entry, metabolism, or reproduction. The authors also highlight inhibitors with potential to reverse pulmonary insufficiency because of their anti-inflammatory activity, cytokine suppression, or antifibrotic activity (Abstract). Table 1 lists imatinib as a kinase inhibitor which shows antiviral activity against SARS-CoV-2, SARS-CoV, and MERS-CoV. Recent, unpublished results reported as a preprint suggest that imatinib inhibits SARS-CoV-2 in vitro, among 17 other FDA-approved drugs with IC50 values similar to those observed for SARS-CoV and MERS-CoV; concentrations showing antiviral activity were not cytotoxic (Page 5). It has been proposed that imatinib may inhibit the function, localization or activity of TMPRSS2. This suggests that this may be a promising drug:target match that could be further explored as a potential treatment for SARS-CoV-2 infection since this virus uses the ACE2 receptor and the protease TMPRSS2 to enter host cells (Page 6).
Cummins, Farag, Doshi, Frieman, and Weisberg are considered analogous to the claimed invention as all are involved in the repurposing of known medications for the treatment of coronavirus infections. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to use mebendazole for the treatment of coronavirus infections as taught by Cummins for the specific treatment of SARS-CoV-2 infections as Farag and Doshi both state that their in silico modeling predicts that this compound would be useful in inhibiting the virus, and further combine the use of mebendazole with imatinib as both Frieman and Weisberg provide evidence that imatinib is useful for the prevention of viral replication. The artisan would be motivated to combine these two treatments as they are individually shown to be effective in the treatment of coronavirus infections, and it would flow from the art to combine them into one treatment. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (See MPEP § 2144.06 I). The artisan would have both a motivation and reasonable expectation of success in choosing imatinib as Frieman states that imatinib was found to have an effect on virus replication (Paragraph 0075), and that imatinib blocks either viral envelope fusion with the endosomal membrane or a step before that such as spike cleavage, endosomal protein trafficking/maturation, or entry of virions into the endosomes (Paragraph 0078).
Regarding Claims 3 and 21, the method of Cummins does not explicitly disclose what is claimed; however, administering mebendazole to a patient suffering from a coronavirus infection will inherently result in the inhibition of viral entry, inhibition of viral fusion, or inhibition of viral replication.
Conclusion
Claims 1-3, 6-11, and 20-21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
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/P.M.R./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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