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
The instant claims are the national stage entry of PCT/EP2021/073378 filed 24 August 2021. Acknowledgement is made of the Applicant’s claim of foreign priority to application GB2013383.1 filed 26 August 2020.
Examiner's Note
Applicant's amendments and arguments filed 31 March 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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. In the Applicant's response, filed 31 March 2026, it is noted that claim 1 has been amended and finds support in the claims as originally filed. No new matter or claims have been added.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 31 March 2026 has been entered.
Status of the Claims
Claims 1-12 and 14-18 are pending.
Claims 1-12 and 14-18 are rejected.
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 1-12 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over McKinnell et al. (WO 2013/163270) in view of Wuts et al. (Greene’s Protective Groups in Organic Synthesis, 2007) in view of Rajnikant Vyas et al. (US 2009/0187024).
McKinnell teaches synthesis of a diazole compound 5-4 in Scheme 5 (pg 21). The first step comprises the reaction of a protected pipecolic acid (when A is a 6 membered ring; pg 17, lns 1-6) with a compound of formula 5-1 (wherein X is bromo or chloro) to form the dicarbonyl compound 5-3. In one example, this step is carried out at room temperature (approx. 20-22 ºC) for 2 hours (pg 42, lns 15-22). Next, compound 5-3 is reacted with ammonium acetate in toluene (aromatic solvent) at 110-130 ºC overnight to form diazole 5-4 (pg 42, lns 25-27). Water (non-aromatic solvent) can also be involved in the washing process and thus reads on the method taking “place in the presence of a solvent” (id). McKinnell teaches that “Pg” is an amino protecting group and can be selected from any group described in Greene’s Protective Groups in Organic Synthesis (pg 15, lns 10-20).
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McKinnell does not teach the step of forming compound 5-2.
Wuts teaches that NH protecting groups include acetamide groups (pg 775-776) as well as N-benzyl groups (pg 701), wherein the acetamide reads on the protected amine of instant Formula (V). The acetamide can be formed by reacting the amine with acetyl chloride with or without base (pg 775).
Rajnikant Vyas teaches that the use of a phase transfer catalyst in the N-alkylation step of L-pipecolic acid derivatives improves chiral purity and reduces reaction time and temperature (abstract) [0019]. Without the use of the catalyst, such as sodium iodide, the reaction would be very time consuming [0019]. Alternatively, the catalyst can be tetrabutylammonium iodide wherein the counterion can be any halide, thus rendering obvious replacing the iodide with a bromide [0035].
It would have been prima facie obvious to prepare compound 5-4 of McKinnell by the steps of reacting 5-2 with bromo ethanone 5-1 to form diketone 5-3 and then reacting diketone 5-3 with ammonium acetate to form diazole 5-4. Since McKinnell teaches 5-2 comprises a protecting group and cites any group from Greene would be suitable, it would have been obvious to use any known protecting group such as an acetamide group. Regarding the formation step of II, it is noted that the presence of a base is recited in the claims as “optional.” The selection of protecting group would have been obvious to be acetamide as taught by Kauffman or, alternatively, an N-alkyl, as taught by Wuts and incorporated by reference into McKinnell. By further including a phase transfer catalyst, as taught by Rajnikant Vyas, the reaction time would have been accelerated and have improved chiral purity. With the inclusion of the phase transfer catalyst that provides chiral purity, it can be assumed that there is no change in chirality.
McKinnell teaches stirring at room temperature but does not teach away from using alternative temperatures wherein the temperature may affect the speed and efficiency of the reaction. That being said and in lieu of objective evidence of unexpected results, the temperature can be viewed as a variable which achieves the recognized result of completing the reaction in a desired length of time. The optimum or workable range of temperature can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). As such, instant claims 1-12 and 14-17 are obvious in view of the prior art.
Claims 1-12 and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over McKinnell et al. (WO 2013/163270) in view of Wuts et al. (Greene’s Protective Groups in Organic Synthesis, 2007) in view of Rajnikant Vyas et al. (US 2009/0187024) in view of Monument (https://monumentchemical.com/uploads/files/TDS/2-MeTHF-Brochure.pdf)
McKinnell, Rajnikant Vyas, and Wuts, as applied supra, are herein applied in their entirety for the teachings of a method forming the claimed Formula V.
McKinnell does not teach wherein the solvent is 2-methyltetrahydrofuran.
Monument teaches that 2-methyltetrahydrofuran is a green solvent that can be used as an alternative to dichloromethane in biphasic reactions (pg 1).
It would have been prima facie obvious to prepare the protected amine of Wuts and McKinnell wherein a phase transfer method was used, which is taught by Wuts as being one method for protecting an amine wherein a biphasic solvent system comprising a mixture of aqueous NaOH and methylene chloride is used. It would have been obvious to substitute 2-MeTHF in place of the dichloromethane since 2-MeTHF is taught as being a “green” solvent that can suitably be used in biphasic reactions in place of dichloromethane. Generally, it is prima facie obvious to substitute one equivalent component or process for another, each of which is taught by the prior art to be useful for the same purpose (see MPEP 2144.06). As such, claims 1-12 and 14-18 are rejected in view of the prior art.
Response to Arguments
Applicant's arguments filed 31 March 2026 have been fully considered but they are not persuasive. The Applicant argues, no page 6 of their remarks, that the cited prior art results in a carbamate, or is missing a carbonyl group, and does not read on instant Formula (II).
In response, the rejection has been modified to point to alternative protecting groups for amines in Wuts, including acetamide, which reads on the carbonyl group of Formula (V).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW S ROSENTHAL whose telephone number is (571)272-6276. The examiner can normally be reached M-F 8-5pm EST.
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/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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