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
Claims 12-13 and 15-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 17 March 2026.
Current Status of 18/283,704
Claims 1, 3, 12, 18, and 21 have undergone amendments. Claims 7-11, 17, and 19-20 have been cancelled. Claims 12-13 and 15-19 remain withdrawn from consideration as drawn to a non-elected invention. Thus, Claims 1-3, 6, and 21, submitted on 9 July 2026, represent all claims currently under consideration.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 9 July 2026, is acknowledged and has been considered.
Response to Arguments
The objections to Claim 1 and Claim 21 are each withdrawn. Applicant has amended the claims to correct the informalities.
The 35 U.S.C. § 102 rejection of Claims 1, 3, 8 and 20 over Cummins is withdrawn. Applicant has amended Claim 1 to be drawn towards treating SARS-CoV-2, which is not taught by Cummins, obviating the rejection.
The 35 U.S.C. § 103 rejection of Claims 1-3, 6-11, and 20-21 over Cummins in view of Farag, Doshi, Frieman, and Weisberg is maintained. Applicant argues that there is no teaching, suggestion, or motivation to combine the teachings to arrive at the claimed invention. Applicant argues that the disclosure of Cummins does not suggest the use of mebendazole for the treatment of SARS-CoV-2, with examples only drawn to the use of fenbendazole for the treatment of bovine viruses. The Examiner does not find this argument persuasive. Cummins provides a group of four anthelmintic compounds, one of which is mebendazole, and states that these compounds may be used to treat both DNA and RNA viruses, and specifically states that these include coronaviruses, but does not state that SARS-CoV-2 can be treated. However, this provides a motivation to select one of these compounds for use in the treatment of coronaviruses. Applicant further argues that neither Farag nor Doshi correct the deficiency of Cummins of the use of mebendazole for the treatment of SARS-CoV-2 as these data do not demonstrate actual inhibition of viral activity. The Examiner does not find this argument to be persuasive. Farag shows that mebendazole has in vitro anti-viral activity against SARS-CoV-2. Figure 10 demonstrates that mebendazole has a dose-dependent inhibition of SARS-CoV-2, with Figure 11 demonstrating that it has an IC50 of between 0.25 and 1.2 µM in Vero E6 cells which were infected with SARS-CoV-2 in vitro. Thus, these data provide both a motivation and reasonable expectation of success in selecting mebendazole as the in vitro data supports the in silico and neural network data of Farag and Doshi. Applicant then argues that Frieman nor Weisberg provide a reason to select imatinib. The Examiner does not find this to be persuasive. Frieman teaches that imatinib inhibits coronavirus using imatinib, while Weisberg further argues that kinase modulators can be repurposed to modulate viral entry or reproduction of SARS-CoV-2. Taken together, these two references provide a motivation and reasonable expectation of success to combine imatinib, which is known to be useful for the treatment of coronavirus infections, with mebendazole, which similarly has utility in the treatment of SARS-CoV-2 infections.
Claim Rejections - 35 USC § 103- REJECTIONS MAINTAINED
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 6, and 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).
Determining the Scope and Contents of the Prior Art:
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).
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).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
Cummins teaches the use of mebendazole for the treatment of viral infections including coronaviruses but does not teach the specific treatment of SARS-CoV-2 using mebendazole. Farag and Doshi teach that mebendazole is useful for the treatment of SARS-CoV-2 infections in vitro and in silico, but does not teach the combination with imatinib. Frieman and Weisberg teach the use of kinase inhibitors including imatinib for the treatment of coronavirus infections, but do not teach the combination with mebendazole.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The artisan would have extensive training in immunology and the treatment of infectious diseases including viruses. This training would further include pharmacological methods of managing and treating these conditions.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
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, with Farag providing data demonstrating that mebendazole is a potent inhibitor of SARS-CoV-2 in vitro as well, 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, and 21 are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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