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 .
Priority
This application is a national stage entry of PCT/US2021/070300 filed on 03/23/2021 which claims the benefit of U.S. Provisional Application No. 62/993,121 filed on 03/23/2020.
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. 62/993,121, 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. There is no support for Applicant’s elected species of the ribose alcohol active metabolite of remdesivir as a species of the first anti-viral agent found in the provisional application.
Accordingly, the effective filing date for the claims being examined as they read on the elected species of the ribose alcohol active metabolite of remdesivir as a species of the first anti-viral agent is 03/23/2021.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 December 18, 2025 has been entered.
Response to Amendment
No amendment’s to the claims were made by Applicant’s reply filed on December 18, 2025. Claims 2-12 were previously canceled. Claims 15-20 are withdrawn.
Claims 1, 13 and 14 are currently presented for examination.
Response to Arguments
Applicant's arguments filed December 18, 2025 with respect to the rejection under 35 USC 103 have been fully considered but they are not persuasive. Specifically, Applicant argues that a supporting declaration under 37 C.F.R. §1.132 is included to provide factual evidence regarding the thermal instability of liposomes and their incompatibility with vaporization, addressing the evidentiary deficiencies identified in the previous Office Action. However, no such declaration has been received. Even though Applicant’s arguments are found not persuasive, upon further search and consideration, the previous rejection under 35 USC 103 is hereby withdrawn. Thus, Applicant’s arguments with respect to said rejection are moot in view of the withdrawal of the rejection. However, a new rejection under 35 USC 103 is detailed below. This action is non-final.
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.
Claims 1, 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Manning et al. (Drug Discovery Today, Volume 25, Number 6, June 2020, pages 956-958) in view of Laskin et al. U.S. Publication No. 2018/0305310 A1 and Clarke et al. EP-4088718 A1.
Claims 1, 13 and 14 of the instant application claim a pharmaceutical composition, comprising: two chemically linked anti-viral agents wherein the first anti-viral agent is the ribose alcohol active metabolite of remdesivir, and the second anti-viral agent is hydroxychloroquine or dexamethasone, and wherein the chemically linked anti-viral agents are combined with a carrier suitable for respiratory administration via vaporization wherein the heat of vaporization decouples the chemically linked anti-viral agents.
Manning et al. teaches three antivirals, including hydroxychloroquine, chloroquine, and remdesivir, for the treatment of a viral infection such as COVID-19 and the use of vaporization for the delivery of antivirals, with the bulk constituents having mild antiviral efficacy (abstract). Manning et al. teaches that bioactive vapors composed of organic species have the potential to deliver pharmaceutical agents efficiently and economically (page 956). Manning et al. focuses on the vaporization and delivery of hydroxychloroquine (page 956). Manning et al. teaches that hydroxychloroquine and chloroquine, both antimalarial agents, are being used for the treatment of COVID-19 and this coronavirus results in severe acute respiratory syndrome (SARS), indicating an inhalation route using an aerosol or vapor might offer a more effective treatment method compared with a pill, i.v. or an implant, assuming the drugs can be delivered at acceptable doses with little or no side effects (page 956). Manning et al. teaches a formulation that consists of three bulk constituents: 50% propylene glycol, 25% glycerin and 25% ethanol by volume (and 80% PG, 10% glycerin, 10% ethanol), was tested as a method to deliver a unique set of formulations with anti and pro-viral activities (page 956). Manning et al. teaches that glycerin has been used to fix viruses for decades, propylene glycol has been shown to inactivate viruses and ethanol is widely used as a viral disinfectant as well as to increase the solubility of some of the polar species (page 956). Manning et al. teaches hydroxychloroquine was tested at levels as high as 6% of the bulk solvent mass and remdesivir was also tested utilizing a commercially available vape device to vaporize the formulations (page 957). Manning et al. further teaches that when a coronavirus infects the lungs, specifically the primary alveolar epithelial cells, there is a rapid response by the cell’s immune system (page 957). Manning et al. teaches that the goal is to maintain or accelerate viral replication improving the efficacy of the drug during this vulnerable phase, and at the same time, the fatty acids, ethanol and glycerin provide antagonistic activity toward the virus at the molecular level (page 957). In the vaporization process, droplets composed of glycerin and propylene glycol can be in the tens to several hundreds of nanometers diameter range and these nanoparticles will rapidly release their bioactive species in the lungs owing to the high surface area:volume ratio (page 957). The inhalation approach enables lower doses to be administered (page 957).
Thus Manning et al. teaches and provides motivation to prepare a formulation comprising antiviral agents for vaporization for the treatment of COVID-19.
Manning et al. does not teach the ribose alcohol active metabolite of remdesivir. Manning et al. does not teach the combination of the ribose alcohol active metabolite of remdesivir and hydroxychloroquine. Manning et al. does not teach chemically linking the anti-viral agents via a carbamate or carbonate group.
Although Manning et al. does not teach the ribose alcohol active metabolite of remdesivir and the combination of the ribose alcohol active metabolite of remdesivir and hydroxychloroquine, Manning et al. teaches that both remdesivir and hydroxychloroquine are useful in the treatment of COVID-19 In addition, Clarke et al. teaches nucleoside and prodrugs thereof useful for treating Coronaviridae virus infections (abstract). Clarke et al. specifically teaches compound 1 which is GS-441524 the ribose active metabolite of remdesivir [0302]. Clarke et al. specifically teaches compound 32 which is remdesivir [0440]. Clarke et al. specifically demonstrates the antiviral activity of both GS-441524 and remdesivir against Coronaviridae virus infections (Table 4 paragraph [0475]). Claim 59 of Clarke et al. specifically claims a method of treating Coronaviridae virus infections in a human in need thereof comprising the administration of a therapeutically effective amount of compound 1 (GS-441524) or remdesivir.
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Manning et al. which teaches the preparation of antiviral compositions for vaporization for the treatment of coronavirus infections combined with a carrier for respiratory administration with the teachings of Clarke et al. which claims a method of treating Coronaviridae virus infections in a human in need thereof comprising the administration of a therapeutically effective amount of compound 1 (GS-441524) or remdesivir. Thus since GS-441524 and remdesivir are antiviral compounds useful for Coronaviridae virus infections, a person of ordinary skill in the art would have been motivated to prepare GS-441524 formulations as antiviral agents according to the teachings of Manning et al. with a reasonable expectation of success. Moreover, since the prior art recognizes both GS-441524 and hydroxychloroquine as useful for the treatment of coronavirus infections, it would have been obvious to a person of ordinary skill in the art to combine said compounds with a reasonable expectation of preparing an improved composition useful for the treatment of coronavirus infections. "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).
Although Manning et al. and Clarke et al. do not teach chemically linking the anti-viral agents via a carbamate or carbonate group, prior to the effective filing date of the claimed invention, conjugation of compounds was known in the art. Laskin et al. teaches preparing covalently conjugated compounds to improve the activity of the compounds wherein the compounds are linked through a carbamate linker [0039]-[0041]. Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to chemically link the combination of antiviral compounds rendered obvious over the teachings of Manning et al. and Clarke et al. since it was known in the art that covalently conjugated compounds through a carbamate linker will improve the activity of the compounds. Therefore, a person of ordinary skill in the art would have been motivated to chemically link the antiviral compounds with a reasonable expectation of improved success.
Thus the cited prior art teachings render obvious combining hydroxychloroquine and the nucleoside compound is GS-441524 by covalently conjugating the compounds through a carbamate linker, wherein the composition is formulated for respiratory administration via vaporization. Therefore the prior art renders obvious combining the compounds with a carrier suitable for respiratory administration via vaporization and thus the composition is necessarily capable of being administered by vaporization wherein the heat of the vaporization will necessarily decouple the chemically linked antiviral agents rendered obvious over the prior art teachings.
Claim 13 is rendered obvious since Manning et al. teaches that the formulation comprises glycerin, propylene glycol and ethanol which are disinfectants having antimicrobial properties (page 956).
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1, 13 and 14 are rejected. Claims 15-20 are withdrawn. Claims 2-12 are canceled. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached on (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM