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 . 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
The instant application is a 371 of PCT/US2021/070624 filed on 05/27/2021, which claims domestic benefit to US provisional application no. 63/200,334 filed on 03/02/2021, and US provisional application no. 63/071,560 filed on 08/28/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/28/2023 and 06/24/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Claims
The preliminary claim amendments filed on 02/28/2023 is acknowledged. Claims 3-5, 7-8, 10, 12, and 14-17 are amended.
Accordingly, claims 1-17 are pending and being examined on merits herein.
Claim Objections
Claims 1 and 8 are objected to because of the following informalities:
Claim 1 recites “Formula (I)” is recited twice.
Claim 8 is missing a period at the end.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 recites “The method according to claim 11”, however claim 11 recites “The pharmaceutical composition according to claim 1”. Therefore, there is insufficient antecedent basis for this limitation in the claim because there is no prior reference to a method.
For purposes of examination, claim 13 is interpreted as being dependent upon claim 12.
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.
Claim(s) 1-2 and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by European Medicines Agency (published 04/03/2020 in PTO-892).
European Medicines Agency discloses that remdesivir finished product contains the excipients betadex sulfobutyl ether sodium, hydrochloric acid and/or sodium hydroxide (see page 9 under section “Pharmaceutical Development”). Here, the remdesivir of European Medicines Agency meets the limitation of the recited compound of Formula (I) shown in instant claims 1 and 11 as evidenced by the instant specification, page 9 lines 11-12, which states that the compound is otherwise known as remdesivir. Furthermore, the hydrochloric acid of European Medicines Agency meets the limitation of an acid recited in claim 1. European Medicines Agency discloses that the remdesivir product should be diluted into intravenous fluids prior to IV administration and discloses 150 mg remdesivir diluted in 250 mL infusion bags of 0.9% sodium chloride in water and 5% glucose (see page 9 under section “Pharmaceutical Development”). European Medicines Agency discloses this formulation is stable at room temperature under ambient room lighting for up to 24 hours (see page 9 under section “Pharmaceutical Development”).
Therefore, claims 1 and 5 are anticipated.
In regards to instant claim 2, European Medicines Agency does not disclose that a cyclodextrin is present in their remdesivir formulation disclosed on page 9. Therefore, this formulation anticipates a composition that is free of cyclodextrin.
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.
Claim(s) 1-6, 8-9, and 11-17 are rejected under 35 U.S.C. 103 as being unpatentable over Seeberger et al. (US20210292296A1 in PTO-892, filed on 06/22/2020 and an effective filing date of 03/23/2020).
Seeberger et al. discloses a composition comprising 1,2,4-trioxane compound that are effective inhibitors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, and thus useful to treat COVID-19 (see Abstract). Seeberger et al. discloses pharmaceutical compositions that comprise at least one compound comprising at least one 1,2,4-trioxane moiety and at least one additional agent, wherein the at least one additional agent is selected from chloroquine, hydroxychloroquine, remdesivir, lopinavir, ritonavir, triazavirin, and/or dexamethasone (see claims 14-15). Here, the remdesivir of Seeberger meets the limitation of the recited compound of Formula (I) shown in instant claims 1 and 11 as evidenced by the instant specification, page 9 lines 11-12, which states that the compound is otherwise known as remdesivir. Seeberger et al. discloses that wetting agents, emulsifiers and lubricants, such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, release agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the compositions (see paragraph 0125). Seeberger et al. discloses several suitable antioxidants including cysteine hydrochloride and among others (see paragraph 0126). Seeberger et al. discloses liquid dosage forms for oral administration that include pharmaceutically acceptable emulsions, microemulsions, solutions, teas, coffees, suspensions, syrups and elixirs (see paragraph 0133). Seeberger et al. discloses that in addition to the active ingredients, the liquid dosage forms may contain inert diluent commonly used in the art and exemplifies water or other solvents, solubilizing agents and emulsifiers, such as ethyl alcohol (ethanol), benzyl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and among others as well as mixtures thereof (see paragraph 0133). Here, the fatty acid esters of sorbitan meets the limitation of a polysorbate recited in claim 9. Seeberger et al. discloses their preparation may be given orally, pulmonary, parenterally, topically, or rectally (see paragraph 0138) and may be administered in tablet or capsule form as well as by injection (see paragraph 0139).
Even though Seeberger et al. does not provide an exact embodiment for the recited composition of the instant invention, it would have been prima facie obvious before the effective filing date of the claimed invention to have selected remdesivir for the additional agent in the composition of Seeberger comprising a 1,2,4-trioxane compound and an additional agent and to further include an antioxidant such as cysteine hydrochloride and solvents/emulsifiers such as ethanol and fatty acid esters of sorbitan to arrive at the claimed invention. One of ordinary skill in the art would have made these selections with a reasonable expectation of success because Seeberger et al. provides guidance that all of the recited components can be included in their pharmaceutical compositions to treat COVID-19. Therefore, an ordinary skilled artisan could have chosen from a finite number of identified, predictable solutions, with a reasonable expectation of success.
Furthermore, while Seeberger et al. does not necessarily teach that their disclosed cysteine hydrochloride is an excipient as recited in the instant claims, the cysteine hydrochloride would necessarily function as an excipient because the cysteine hydrochloride is the same as recited in the instant claims, and Seeberger provides guidance to include this compound alongside antiviral compounds such as remdesivir. MPEP 2112 section I recites "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable”. Furthermore, MPEP 2112.01 section II recites “Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
In regards to claim 2, Seeberger does not disclose adding a cyclodextrin in any embodiments of their pharmaceutical compositions. Therefore, claim 2 is also prima facie obvious.
Claim(s) 7 is rejected under 35 U.S.C. 103 as being unpatentable over Seeberger et al. (US20210292296A1 in PTO-892, filed on 06/22/2020 and an effective filing date of 03/23/2020), as applied to claims 1 and 5 above, and further in view of Peralta et al. (US20200237689A1 in PTO-892, filed 03/25/2020) and Moore et al. (US20210059958A1 in PTO-892, filed 09/02/2020 and an effective filing date of 03/24/2020).
Seeberger et al. teaches the compositions recited in claims 1 and 5 as described above. Furthermore, Seeberger et al. discloses other dosages form including lotions and gels and among others (see paragraph 0136).
The difference between Seeberger and the claimed invention is that Seeberger et al. does not disclose the recited % w/w ranges for the recited components in claim 7.
Peralta et al. discloses a nanoemulsion composition with certain surfactant blend ratios that impart enhanced permeability. Peralta et al. discloses that such compositions are useful for mucosal and intranasal applications and allow for the greater delivery of one or more active agents to the application site to prevent infection by coronavirus (see Abstract). Peralta et al. discloses that the active agent may include any active agent that kills, or inactivates a coronavirus and exemplifies SARS-CoV-2 (see paragraph 0157). Peralta et al. discloses that suitable antiviral compounds include remdesivir and among others (see paragraph 0157). Peralta et al. discloses that the agent may be present in a concentration of 0.01% - 10% (see paragraph 0159), which equates to around 0.01% - 10% w/w at around 1 g/ml density for each component in solution. Peralta et al. discloses that the surfactant in their nanoemulsion composition is a nonionic surfactant selected from a polysorbate and among others (see paragraph 0021). Peralta et al. discloses that their compositions comprise (a) about 5 vol. % to about 50 vol. % of aqueous phase; (b) about 30 vol. % to about 90 vol. % of oil phase; and (c) about 3 vol. % to about 15 vol. % of surfactant (see paragraph 0023). Here, the vol. % to 15 vol. % surfactant equates to roughly 3-15% w/w based on polysorbate, aqueous phase, and oil phase all having an approximate density of 1 mg/mL. Peralta et al. discloses that their compositions can be applied topically in lotion form (see paragraph 0216).
Moore et al. discloses an enhanced moisturizing lotion composition comprising several ingredients as described in the Abstract. Moore et al. discloses that their lotions are mixed in a solvent such as water to form an aqueous solution (see paragraph 0045). Moore et al. discloses that the water can range from about 30-90 wt% concentration (see paragraph 0045). Moore et al. discloses that their lotion composition can include antioxidant agents in a concentration of about 0.01-5 wt% (see paragraph 0041). Moore et al. discloses that their composition can be used on skin to enhance the antimicrobial efficacy of one or more secondary compounds such as ethanol and among others that are also applied to the skin (see paragraph 0049). Moore et al. discloses that their composition for “antimicrobial use” is a use that targets, kills, inactivates, or slows the growth of microorganisms, and thus is defined broadly herein to include antibiotic uses, antibacterial uses, antiviral uses, and antiseptics uses (see paragraph 0011). Moore et al. discloses that coronaviruses such as SARS-CoV-2 can be efficiently inactivated within one minute in response to contact with a surface disinfectant comprising for example 62% to 71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite (see paragraph 0011).
It would have been prima facie obvious to combine Seeberger with Peralta and Moore et al. before the effective filing date of the claimed invention by preparing the composition of Seeberger et al. described above to have 3-10% w/w remdesivir, 0.01-5 wt% cysteine hydrochloride, and 30-90% ethanol based on the disclosures of Paralta and Moore et al. to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Paralta provides guidance of an overlapping range of 0.01% - 10% w/w for an antiviral compound such as remdesivir(see MPEP 2144.05 I) that are suitable for similar composition types as well as teaching or suggesting that these compositions are useful for the treatment of viral SARS-CoV-2 infection. Furthermore, Moore et al. provide guidance of an overlapping range of 0.01-5 wt% antioxidant agent as well as 30-90% water solvent in a similar composition useful for the treatment of SARS-CoV-2 infection. Therefore, an ordinary skilled artisan could have prepared these amounts for the cysteine hydrochloride, which is disclosed as an antioxidant in Seeberger, as well as the ethanol, which is disclosed as a solvent in Seeberger.
Claim(s) 10 is rejected under 35 U.S.C. 103 as being unpatentable over Seeberger et al. (US20210292296A1 in PTO-892, filed on 06/22/2020 and an effective filing date of 03/23/2020), as applied to claims 1 and 8 above, and further in view of Peralta et al. (US20200237689A1 in PTO-892, filed 03/25/2020), Moore et al. (US20210059958A1 in PTO-892, filed 09/02/2020 and an effective filing date of 03/24/2020), and De Flora et al. (FASEB, in PTO-892, published 08/11/2020).
Seeberger et al. teaches the compositions recited in claims 1 and 8 as described above. Furthermore, Seeberger et al. discloses other dosage forms including lotions and gels and among others (see paragraph 0136).
The difference between Seeberger and the claimed invention is that Seeberger et al. does not disclose the recited % w/w ranges for the recited components in claim 10.
The independent teachings of Peralta and Moore et al. are as described above.
De Flora et al. discloses the use of N-acetylcysteine (NAC) in both prevention and adjuvant therapy of COVID-19 (see Abstract). De Flora et al. discloses that NAC has been proposed as not only a mucolytic agent, but also as a preventive/therapeutic agent in a variety of disorders involving glutathione (GSH) depletion and oxidative stress. De Flora et al. discloses that the administration of NAC is likely to attenuate the risk of developing COVID-19 due its broad range of antioxidant and anti-inflammatory mechanisms (see Abstract). De Flora et al. discloses in Figure 1 (page 13187) the major mechanisms involved in the antioxidant and anti-inflammatory action of NAC.
It would have been prima facie obvious to combine Seeberger with Peralta, Moore, and De Flora et al. before the effective filing date of the claimed invention by further including the NAC of De Flora et al. to the modified composition as suggested by the combined teachings of Seeberger, Peralta, and Moore et al. described above as well as prepare the NAC at 0.01-5 wt% concentration and the surfactant at 3-15% w/w concentration as disclosed in Peralta and Moore to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because De Flora et al. provides guidance that NAC functions as an antioxidant and suggests administering NAC to treat COVID-19 based on these antioxidant properties. Furthermore, Seeberger, Peralta, and Moore all discloses similar compositions that include antioxidants for the treatment of viral SARS-CoV-2 infection. Therefore, an ordinary skilled artisan would have found it obvious to try and include NAC as an additional antioxidant for the treatment of viral SARS-CoV-2 infection. Lastly, Paralta and Moore et al. provide guidance of overlapping ranges of antioxidants and surfactants (see MPEP 2144.05 I) that are suitable for similar composition types as well as teaching or suggesting that these compositions are useful for the treatment of viral SARS-CoV-2 infection.
Conclusion
No claim is found allowable.
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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693