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
1. The Amendment filed August 22, 2025 in response to the Office Action of May 27, 2025 is acknowledged and has been entered. Claims 2-5 and 12-16 have been cancelled. Claims 1, 10, and 11 have been amended.
2. Claims 1, 6-11, 17-19 and 21-30 are pending.
3. Claims 6, 9, 10, 17-19 and 21-30 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or invention, there being no allowable generic or linking claim.
4. Claims 1, 7, 8, and 11 are currently under consideration.
Priority
5. Claims 1, 7, 8, and 11 have a priority date of March 5, 2021 for the reasons of record which were not specifically traversed.
New Grounds of Rejection
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.
6. Claim(s) 1, 7, 8, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/154687 A1 (Cihlar et al. Aug. 05, 2021, effectively filed Feb. 14, 2020, of record), “Cihlar” evidenced by Remdesivir (National Center for Biotechnology Information (2025). PubChem Compound Summary for CID 121304016, Remdesivir. Retrieved May 21, 2025 from https://pubchem.ncbi.nlm.nih.gov/compound/Remdesivir of record) in view of Kim et al. (Yonsei Med J. 2020 Sep;61(9):826-830, published online Aug. 27, 2020, of record), “Kim” and in view of Mathias et al. (Clin. Pharmacology & Therapeutics March 2010 87 (3): 322-329), “Mathias”.
Cihlar teaches methods of treating or preventing SARS-CoV-2 by administering a therapeutically effective amount of a compound of Formula I. See abstract, ¶¶ 0005-0010 and claims 1-162,
Cihlar teaches methods include administering remdesivir/Compound 32. See ¶¶ 0008, 0201-0205, Example 9 and claims 55-56 and Remdesivir-1.1 2D Structure.
Cihlar teaches pharmaceutical compositions with a compound of Formula I/remdesivir and additional therapeutic agents for treatment. See ¶¶ 0010-0011.
Cihlar teaches the additional agents include cobicistat. See ¶¶ 0214, 0234, 0244, and 0260 and claims 126 and 158.
Cihlar teaches that the effective dose of active ingredient depends at least on the nature of the condition being treated, toxicity, whether the compound is being used prophylactically or against an active viral infection, the method of delivery, and the pharmaceutical formulation, and will be determined by the clinician using conventional dose escalation studies. Cihlar teaches that the daily candidate dose for an adult human of approximately 70 kg body weight will range from 1 mg to 1000 mg, preferably between 5 mg and 500 mg, and may take the form of single or multiple doses. See ¶ 0196.
Cihlar teaches that the effective dose of a compound of the present invention for treating the 2019-nCoV infection can depend on whether the dose is to be used prophylactically or to treat a human already suffering from 2019-nCoV infection. See ¶ 0196. Cihlar teaches that larger doses may be necessary for treating humans testing positive for 2019-nCoV infection and for humans showing symptoms of 2019-nCoV infection as compared to humans receiving prophylactic treatment. See ¶ 0197.
Cihlar teaches as set forth above, but does not provide a working example of a composition comprising cobicistat and remdesivir, with cobicistat at an amount higher than 150 mg.
Kim teaches treating critically ill SARS-CoV-2 infected patients with darunavir-cobicistat (800–150 mg) therapy. Kim teaches that the darunavir-cobicistat patients had lower mortality and a significant survival benefit. See Abstract, Table 2 and Fig. 2.
Mathias teaches GS-9350/cobicistat is a new chemical entity under development as a potent, mechanism-based inhibitor of human cytochrome P450 3A (CYP3A) isoforms. Its intended use is to increase the systemic exposure of co-administered agents that are metabolized by CYP3A enzymes. See abstract.
Mathias teaches single-dose escalation from 50 to 400 mg resulted in a 164-fold increase in GS-9350/cobicistat exposure, whereas multiple-dose escalation in the dosage range of 50–300 mg resulted in a 47-fold increase in exposure. GS-9350/cobicistat potently inhibited midazolam apparent clearance (95% reduction), similar in effect to ritonavir 100 mg. GS-9350/cobicistat was generally well tolerated at all doses, and there was no evidence of dose-limiting toxicity. See abstract, p. 324- GS-9350 pharmacokinetics, Figure 2 and Table 1.
Mathias teaches that it is well established that “boosting” the systemic exposure of antiretrovirals (ARVs), particularly those of HIV-1 protease inhibitors, by inhibiting their primary route of metabolism (which takes place through cytochrome P450 3A (CYP3A)) leads to improved treatment outcomes, in treatment-naive patients as well as in those already undergoing therapy. See p. 322-left column.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Cihlar, Kim and Mathias make a composition for the treatment or prophylaxis of SARS-CoV-2 patients comprising remdesivir and darunavir-cobicistat with cobicistat amounts higher than 150 mg because Cihlar teaches treating SARS-CoV-2 patients with remdesivir, cobicistat, and darunavir (see ¶¶ 0238 and 0244 for darunavir, cobicistat, Cihlar teaches that the effective dose of an active ingredient depends on multiple factors, Cihlar teaches that larger doses may be necessary for treating humans testing positive for 2019-nCoV infection, Cihlar teaches doses between 5 mg and 500 mg, Kim teaches that the darunavir-cobicistat treated patients had lower mortality and a significant survival benefit, Mathias teaches single-dose escalation from 50 to 400 mg resulted in a 164-fold increase in GS-9350/cobicistat exposure, whereas multiple-dose escalation in the dosage range of 50–300 mg resulted in a 47-fold increase in exposure, and Mathias teaches GS-9350/cobicistat was generally well tolerated at all doses, and there was no evidence of dose-limiting toxicity. Thus given the benefits of darunavir-cobicistat taught by Kim in treating SARS-CoV-2 patients one would have been motivated to make a composition for the treatment or prophylaxis of SARS-CoV-2 patients comprising remdesivir, cobicistat, and darunavir to optimize the doses for treatment because Cihlar teaches that the effective dose of an active ingredient depends on multiple factors with potential need for larger doses and Mathias teaches escalation of the dose of GS-9350/cobicistat led significant increases in its exposure, which would increase the ability GS-9350/cobicistat to boost the activity of co-administered anti-viral drugs.
Response to Arguments
7. In the remarks of August 22, 2025, Applicant argues that evidence that the claimed invention is unexpectedly superior in one of a spectrum of common properties over the prior art can be enough to establish non-obviousness. See In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1988); In re Sebek, 465 F.2d 904, 907 (C.C.P.A. 1972), In re Chupp, 816 F.2d 643, 646 (Fed. Cir. 1987).
The instant specification teaches, on page 16, that
Interestingly, maximum plasma concentrations achievable through standard dosing of cobicistat (150mg/day as a booster for HIV-1 protease inhibitors) (Deeks 2014) were well below (~1 mM) most IC50 values obtained in our experiments (Figure 2C). In line with this, clinical testing of the HIV-1 protease darunavir, boosted by standard concentrations of cobicistat, did not yield clinical benefit to SARS-CoV-2 infected patients (Chen et ai. 2020).
Thus, the specification teaches that cobicistat at an amount higher than 150 mg show an advantageous property that cannot be achieved by using the booster dose of cobicistat at 150 mg. The claimed composition is superior compared to that of the cited references.
Applicant’s arguments have been considered, but have not been found persuasive. Applicant’s data show that increasing the dose of cobicistat increases the concentration of cobicistat in plasma which is closer to the IC50 value of cobicistat . See Fig. 2C and the description of Fig. 2 on pp. 22-23. Increasing the concentration of cobicistat by increasing the dose of cobicistat is not unexpected because Mathias teaches, as set forth above, that escalation of the cobicistat dose increased in GS-9350/cobicistat exposure.
Additionally, the evidence of nonobviousness must be commensurate in scope with the claims to rebut the prima facie case of obviousness. See MPEP 716.02 (d). The provided evidenced does not provide any evidence of nonobviousness of the claimed composition comprising cobicistat and a further claimed drug like remdesivir. Thus, Applicant’s arguments for unexpectedly superior properties are not found persuasive and the rejection is made and maintained for the reasons set forth above.
Conclusion
8. All other objections and rejections recited in the Office Action of May 27, 2025 are withdrawn in view of Applicant’s amendments and arguments.
9. No claims allowed.
10. 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 extension fee 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 date of this final action.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached on M-F 8:30-5:30 Eastern Time
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/Peter J Reddig/
Primary Examiner, Art Unit 1642