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 .
Status of the Application
Claims 1, 4, 8-14, 16-20, 26-28, 30, 36-37, 40, 44-45, and 63-64 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 05/11/2026 are acknowledged. Claims 1, 37, 40, and 44 are amended and new claims 63-64 are added. Claims under consideration in the instant office action are claims 1, 4, 8-14, 16-20, 26-28, 30, 36-37, 40, 44-45, and 63-64.
Applicants' arguments, filed 05/11/2026, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
Claims 1, 4, 8-14, 16-20, 26-28, 30, 36-37, 40, 44-45, and 63-64 are rejected under 35 U.S.C. 103 as being unpatentable over Iverson (WO 2019/046201, as disclosed in IDS) in view of Napoli et al. (A Panel of Broad-Spectrum Antivirals in Topical Ophthalmic Medications from the Drug Repurposing Approach during and after the Coronavirus Disease 2019 Era, Journal of Clinical Medicine, 2020, 9 (2241), pp. 1-16, as disclosed in IDS).
Iverson is drawn towards methods of inhibiting side effects associated with vaccination in a human subject comprising administering a composition comprising a NSAID such as indomethacin and a co-agent such as ketotifen (see abstract; claims 1-2). Iverson teaches such compositions suitable for oral administration and daily administration in one or multiples doses (paragraphs 0030, 0038; claim 7). Iverson teaches administration essentially simultaneously with vaccination (paragraph 0022). Iverson teaches examples of typical amounts of NSAIDS, including about 150mg to about 900 mg for naproxen and ibuprofen (paragraphs 0029-0032). Iverson teaches ketotifen formulated in an amount of from about 0.5 mg to about 3 mg (claim 12).
Iverson does not teach a method for treating a coronavirus infection comprising administering a NSAID and ketotifen. Iverson does not teach administering indomethacin in the recited amounts.
Napoli et al. teaches methods of treating coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using antiviral treatments (see abstract). Napoli et al. teaches indomethacin and ketotifen as broad spectrum antivirals for such treatment (pg. 2, paragraphs 5-6; see Table 3). Regarding claims 5 and 28, Napoli et al. teaches that some patients with COVID-19 are asymptomatic or those with conjunctivitis as an early symptom may test negative for a conjunctival sac SARS-CoV-2 test (see abstract; pg. 9, 6th paragraph). Regarding claim 6, Napoli teaches COVID-19 as an infectious disease, wherein SARS-CoV-2 can be transmitted through the eye (pg. 2, lines 3-10). Regarding claims 9-11, Napoli et al. is drawn towards treatments for the SARS-CoV-2 virus in general (see abstract), which would read on the recited patient populations, variants, and attendant symptoms.
It would have been obvious to one of ordinary skill in the art to administer the composition orally or at the time of vaccination for beta coronavirus or SARS-CoV-2, as suggested by Napoli, and produce the claimed invention.
One of ordinary skill in the art would have been motivated to do so since Napoli teaches that indomethacin and ketotifen provide antiviral activity in patients with SARS-CoV-2 (pg. 2, paragraphs 5-6; see Table 3), with a reasonable expectation of success absent evidence of criticality of the particular steps.
Even though the range for dosages as taught by Iverson is not the same as the claimed dosages, Iverson does teach an overlapping range of dosages, and it has been held that in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). See MPEP § 2144.05(I). Furthermore, the determination of dosages is well within the purview of those skilled in the art through routine experimentation, and it has been held that “it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP § 2144.05(II). It would have been obvious to one of ordinary skill in the art to optimize the dosages in order to obtain the desired efficacy depending on the subject being treated (paragraph 0029).
The amounts of active agents to be used, the pharmaceutical forms, e.g., tablets, etc; mode of administration, flavors, surfactant are all deemed obvious since they are all within the knowledge of the skilled pharmacologist and represent conventional formulations and modes of administration.
Furthermore, no unobviousness is seen in the ratio claimed because once the usefulness of a compound is known to treat a condition, it is within the skill of the artisan to determine the optimum ratio.
With regards to the limitation claimed in instant claims 45 and 63-64, which claims a dose of about 40 mg to about 200 mg of indomethacin, Iverson does not specifically teach the exact amounts claimed in instant claims 45 and 63-64. However, it would be within the skill of an ordinary artisan to be able to modify the dosage in order to obtain the desired efficacy depending on the subject being treated (paragraph 0029). It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Response to Arguments
Applicant argues that “Neither Iversen nor Napoli teaches the synergistic antiviral effects of using naproxen or indomethacin in combination with ketotifen to treat a beta-coronavirus infection, as demonstrated in the Examples section of the present disclosure. Further, there is no actual disclosure in either Iversen or Napoli of treating a betacoronavirus infection.” The Examiner respectfully disagrees since although Iversen and Napoli do not explicitly teach treating a betacoronavirus infection by administering naproxen or indomethacin in combination with ketotifen in a synergistic manner, Napoli does teach that indomethacin and ketotifen as broad spectrum antivirals that have repurposing potential for SARS-CoV-2 treatment (pg. 2, paragraphs 5-8; see Table 3), and one of ordinary skill in the art would thus be motivated to try such antivirals for treating coronavirus infections.
Applicant also argues that “the combination of naproxen and ketotifen or indomethacin and ketotifen, as recited in claim 1, provides a synergistic and/or unexpected effect for inhibiting a beta-coronavirus infection better than each agent alone. This effect is neither taught nor suggested by either Iversen or Napoli, whether taken alone or in combination.” The Examiner respectfully disagrees since although Applicant has demonstrated some synergy when 50 µM of ketotifen is administered with indomethacin or naproxen against SARS-CoV-2 (see Tables 2-4), such results are not commensurate in scope with the claims, such as the concentrations of the agents in combination, particularly ketotifen, or for the full genus of betacoronavirus infections.
Conclusion
Claims 1, 4, 8-14, 16-20, 26-28, 30, 36-37, 40, 44-45, and 63-64 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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