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 Claims
The amendment filed on 05/22/2026 has been entered. Claim 1 has been amended. Thus claims 1-2, 4-7, 9, 11 and 18-25 are currently pending and under examination.
Withdrawn Objections and Rejections
The objection to the specification has been withdrawn in view of the amendment filed on 05/22/2026.
Claim 1 has been narrowed to now recite a solution consisting of a base in methanol. Applicant’s arguments in view of the amendment with respect to Ismagilov (Ismagilov, N. G. et al. “Reactions of fluoro monomers. I. Mechanism of reaction of 1,1-dichloro-2,2-difluoroethene with methanol under conditions of base catalysis” J. Cen. Chem. (1993), 63(1), 198-204; cited in IDS 08/18/2023), which uses a solution of a base, methanol and CCl4 in the reaction for the preparation of methoxyflurane, have been considered in the entirety and were found persuasive. Thus, the 103 rejection over Ismagilov (Ismagilov, N. G. et al. “Reactions of fluoro monomers. I. Mechanism of reaction of 1,1-dichloro-2,2-difluoroethene with methanol under conditions of base catalysis” J. Cen. Chem. (1993), 63(1), 198-204; cited in IDS 08/18/2023) in view of Plutschack (Plutschack, M. B. et al. “The Hitchhiker’s Guide to Flow Chemistry” Chem. Rev. 2017, 117, 11796−11893; cited in IDS 08/18/2023) has been withdrawn.
Claim Objections
Claims 20-25 stand objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4-5, 7, 9, 11 and 18 are newly rejected under 35 U.S.C. 103 as being unpatentable over Simakov (Simakov, B. V. et al. “Study of the Kinetics of Production of 2,2-dichloro-1,1-difluoroethylmethyl ether” Termodinam. i Kinet. Khim. Protsessov, L. 1981, pages 78-80) in view of Plutschack (Plutschack, M. B. et al. “The Hitchhiker’s Guide to Flow Chemistry” Chem. Rev. 2017, 117, 11796−11893; cited in IDS 08/18/2023).
Regarding claims 1 and 18, Simakov teaches a method for preparing 2,2-dichloro-1,1-difluoroethylmethyl ether (methoxyflurane) by reacting CF2=CCl2 and a solution consisting of KOH (base) and methanol. The reference further teaches 0.003 N or 0.005-0.06 N of KOH, a temperature of 6-20° C, and the amount of the base in the solution for 0.06 N is about 0.42 wt% based on the total weight of the solution (calculated by first converting 0.06 N to (0.06 molar)KOH/(1 L)MeOH or (3.37 g)KOH/(791 g)MeOH; thus wt%base = [3.37g/(3.37g+791g)]x100).
Regarding claim 1, while Simakov teaches the use of badge reaction, the reference fails to teach the use of the flow reactor as instantly claimed and wherein Cl2C=CF2 is introduced in the flow reactor continuously and separately from the solution of the base in methanol.
The deficiency is however cured by Plutschack.
Regarding claims 1-2 and 4-5, Plutschack teaches the use of continuous flow chemistry for different types of reactions. Plutschack provides different types of reactor units utilized in the flow chemistry, such as chip, coil, or packed bed (Fig. 16). The coil-based reactor units have an inner diameter of 0.01” (equivalent to 0.254), 0.02”, 0.03”, 0.04”, 1/16” (equivalent to 1.5875 mm), etc. (bridging pages 11809-11810). Thus, based on the inner diameter, the internal cross sectional area ranges between 0.05067-1.9793 mm2 (calculated by Area = (π * (inner diameter)^2) / 4). Furthermore, Plutschack teaches a typical continuous flow setup for synthetic applications can be broken into different zones, in which separate reagent A and reagent B supplied to the reactor via a mixing port (Figure 11). Similarly, the instant specification describes that the base/alkanol solution and the XClC═CF2 compound is fed, for example pumped, through inlet (26) into a line that interjects the tubular flow line at a mixing port (MP) and the base/alkanol solution and the XCIC=CF2 compound mix to form the reaction mixture, which flows downstream of the mixing port through the coiled tubular flow line (27) (pg. 31, lines 20-31).
The reference teaches that flow chemistry involves the use of channels or tubing to conduct a reaction in a continuous stream rather than in a flask and that it provides chemists with unique control over reaction parameters enhancing reactivity. Thus, a skilled artisan would have been motivated to use the continuous flow chemistry of Plutschack in the place of the use of the batch reactor of Simakov with a reasonable expectation of success in enhancing the reactivity of Simakov’s production of methoxyfurane.
Regarding claims 7, 9 and 11, Plutschack teaches on page 11813:
There are a plethora of important parameters for distinguishing a flow chemical process from a conventional batch reactor setup;
The residence time can be varied either via changing the flow speed (ν) or the length/volume of the flow path (V);
Prediction of the residence time is therefore relatively simple for single-phase transformations since the reactor volume as well as the flow rate is set by the user.
As such, it would be within the purview of the skilled artisan to control and determine through routine experimentation an optimal workable range of flow rate and residence time with a reasonable expectation in optimizing the reaction using the flow reactor.
It would thus have been prima facie obvious to a skilled artisan before the effective filing date of the instant invention to conduct a process for continuous preparation of methoxyflurane, the process comprising a step of introducing in a flow reactor reaction components comprising (i) Cl2C=CF2, and (ii) a solution consisting of a base in methanol, wherein a) the flow reactor comprises one or more tubular flow line(s) having an internal cross-sectional area of less than 115 mm2 through which the reaction components flow as a reaction mixture, and b) the methoxyflurane is formed at least upon the reaction components mixing, with the so formed methoxyflurane flowing out of the flow reactor in a reactor effluent, wherein the solution of the base in methanol is fed into the flow reactor at room temperature or below, wherein the base is used in a sub-stoichiometric molar amount relative to the Cl2C=CF2, and the base is used in an amount of between 1% and 30% by weight relative to the total weight of the solution and is introduced continuously into the flow reactor, wherein the Cl2C=CF2 is used at room temperature or below, and is introduced into the flow reactor continuously and separately from the solution, and wherein the base comprises an alkali metal base cation, an ammonium base cation, or a phosphonium base cation in view of the teachings of Simakov and Plutschack.
Claim 6 is newly rejected under 35 U.S.C. 103 as being unpatentable over Simakov (Simakov, B. V. et al. “Study of the Kinetics of Production of 2,2-dichloro-1,1-difluoroethylmethyl ether” Termodinam. i Kinet. Khim. Protsessov, L. 1981, pages 78-80) in view of Plutschack (Plutschack, M. B. et al. “The Hitchhiker’s Guide to Flow Chemistry” Chem. Rev. 2017, 117, 11796−11893; cited in IDS 08/18/2023) as applied to claims 1-2, 4-5, 7, 9, 11 and 18 above, and further in view of Krasberg (Krasberg, N. et al. “Selection of Technical Reactor Equipment for Modular, Continuous Small-Scale Plants” Processes 2014, 2, 265-292; doi:10.3390/pr2010265; cited in PTO-892 03/07/2025).
The teachings of Simakov and Plutschack have been set forth above.
Regarding claim 6, the above references, alone or in combination, fail to teach that the one or more tubular flow line(s) has/have a total internal volume of at least 100 mL. The deficiency however is cured by Krasberg.
Krasberg teaches different flow reactors comprising tubular flow line(s) including helically coiled tubular reactors (CT) made of standard tubing with 3, 6 and 8 mm outer diameters and an SMX-type static mixer reactor (SMX) with an 8-mm outer diameter (Table 2). The reference teaches that each element of the CT provides a tube length of 4.75 m and consists of 15 coils (0.1 m coil diameter) (Figure 4, Table 2). Among the coiled tubular reactors, the inner diameter (di) for CT6 and CT8 are 6 and 8 mm, respectively (Table 2). Thus, based on the aforementioned inner diameters and tube length of 4.75 m (L0), the internal volumes for CT6 and CT8 are 134.3 and 238.76 mL, respectively.
Accordingly, a skilled artisan would have been motivated to use teachings of Krasberg in the combination of Simakov and Plutschack in determining the internal volume that can be used in the process for the continuous preparation of methoxyflurane.
It would thus have been prima facie obvious to a skilled artisan before the effective filing date of the instant invention to conduct a process for continuous preparation of methoxyflurane according to claim 1 and wherein the one or more tubular flow line(s) has/have a total internal volume of at least 100 ml in view of the teachings of Simakov, Plutschack and Krasberg.
Claim 19 is newly rejected under 35 U.S.C. 103 as being unpatentable over Simakov (Simakov, B. V. et al. “Study of the Kinetics of Production of 2,2-dichloro-1,1-difluoroethylmethyl ether” Termodinam. i Kinet. Khim. Protsessov, L. 1981, pages 78-80) in view of Plutschack (Plutschack, M. B. et al. “The Hitchhiker’s Guide to Flow Chemistry” Chem. Rev. 2017, 117, 11796−11893; cited in IDS 08/18/2023) as applied to claims 1-2, 4-5, 7, 9, 11 and 18 above, and further in view of Ismagilov (Ismagilov, N. G. et al. “Reactions of fluoro monomers. I. Mechanism of reaction of 1,1-dichloro-2,2-difluoroethene with methanol under conditions of base catalysis” J. Cen. Chem. (1993), 63(1), 198-204; cited in IDS 08/18/2023).
The teachings of Simakov and Plutschack have been set forth above.
Regarding claim 19, the above references, alone or in combination, fail to teach adding water to the reactor effluent. However, Ismagilov teaches a similar reaction as Simakov in which methoxyflurane is prepared from the reaction of CF2=CCl2, CH3ONa (base) and binary CH3OH-CCl4. Ismagilov further teaches that 0.1 M HCl, which is known to be aqueous solution, is added to stop the reaction (page 150, 2nd col.). Thus, a skilled artisan would have been motivated in using the methods of Ismagilov in adding aqueous HCl solution in the process of Simakov with a reasonable expectation of success in stopping the reaction process.
It would thus have been prima facie obvious to a skilled artisan before the effective filing date of the instant invention to conduct a process for continuous preparation of methoxyflurane according to claim 1 and wherein water is added to the reactor effluent in view of the teachings of Simakov, Plutschack and Ismagilov.
Allowable Subject Matter
The subject matter of claims 20-25 is free of prior art. The closest prior art references have been set forth above, in which the workup of the reaction product mixture comprises washing with aqueous HCl. However, none of the references teach the purification step of claims 20-25.
Conclusion
Claims 1-2, 4-7, 9, 11 and 18-19 are rejected and no claims are allowed.
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 MEDHANIT W BAHTA whose telephone number is (571)270-7658. The examiner can normally be reached Monday-Friday 8am-5pm.
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, Scarlett Goon can be reached at 571-270-5241. 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.
/MEDHANIT W BAHTA/Primary Examiner, Art Unit 1692
Prosecution Insights