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 .
Election/Restrictions
Applicant’s election without traverse of the formula II and IIb as the species in the reply filed on 7/13/2026 is acknowledged.
Claims 1-22 are currently pending and under consideration.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements filed on 6/25/2024 and 11/12/2025 are acknowledged and have been considered except where lined through.
Claim Interpretation
For examination purposes, the examiner will be interpreting equivalents to be molar equivalents consistent with organic chemical synthesis.
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.
Claims 1-22 are 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.
Regarding claim 1, claim 1 recites the limitation “additional base”, but does not set forth that there is already a base present within the reaction conditions. Assuming arguendo that “R3OMgHal” is considered to supply implicit support for the “first” base, it is unclear if the “additional” base needs to be different than the “first” base. For example, if a reaction proceeds with 1 equivalent of the first base, an additional 0.2 or 1 equivalent of first base may be construed as an additional base.
Regarding claims 11-14, the claims recite equivalents of the additional base based on a compound of the general formula (II). However, it is unclear what the equivalents of the additional base would be if based on a compound of formula (IIa) or II(b).
Regarding claim 19, claim 19 recites “…wherein the base used is a combination of a tertiary amine or of a pyridine base with an amide base.” In the instant case, it is unclear whether “the base” is the additional base or “the” first base which is not specifically recited
Regarding 22, claim 22 recites that the compounds of general formula (IV) are generated via a Grignard reaction, specifically with the following combination of reagents:
R5MgHal and R6R7CO where
R5 is C1-C6 alkyl, aryl, or benzyl (Note: the Examiner has inserted an “OR” which it is suggested applicants amend to incorporate as well).
R6, R7 are H, C1-C6-alkyl, aryl, and the resulting radical definition, and (Note: the Examiner has inserted an “AND” which it is suggested applicants amend to incorporate as well)
R3 corresponds to R5R6R7C. Thus, the definition of R3 in claim 22 appears to lack antecedent basis to the definition set forth in claim 1. Also note: It is unclear what the claim is referring to by reciting “the resulting radical definition”.
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.
Claim(s) 1-11, 15-18, 20 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/228985 (IDS) in view of Kanemasa et al. (Tetrahedron Letters 1992; 33(10): 1357-1360).
The WO document teaches herbicidally active 3-phenylisoxazoline-5-carboxamides of tetrahydro and dihydrofuran carboxylic acids and esters (Title). Specifically, the WO document teaches the synthesis of said compounds, wherein the synthesis comprises the following steps:
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(Page 21). Note: It is noted that the specification teaches that the compounds of general formulae (II) and (III) are known from WO2018/228985 (see page 9, line 21). Accordingly, the Examiner is taking this as an admission that the compounds of Formula II and III are found within the Scheme above.
While the prior art teaches, generically, the conditions for the generation of the nitrile oxide (reaction 4) and 1,3-dipolar cycloaddition (reaction 5), the prior art does not specifically teach the base for the generation of the nitrile oxide or use of a reactive species R3OMgHal (IV) for the cycloaddition.
Kanemasa et al. teach the regiocontrolled cycloaddition of nitrile oxides to allyl alcohols (Title). Specifically, Kanemasa et al. teach the following reaction sequence:
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, wherein the cycloadditions of benzonitrile oxide to (E)-2-buten-1-ol leads to 4a and 5a(Scheme 1) under the following conditions:
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(See Scheme 1 and Table 1). In particular, Kanemasa et al. found that when 2 equivalents of magnesium alkoxide 1a (X=MgBr) were also used as a base for the generation of nitrile oxide (3), higher yields of 4a resulted (Entries 9 and 10) which was in stark contrast with a similar reaction using only 1 equivalent of 1a (Entry 8) (page 1358, 2nd full paragraph). Moreover, Kanemasa et al. found that both the selectivity and yield were found to depend upon the equimolar amount of n-BuOMgBr in the reaction of nitrile oxide 3 generated from 2/NEt3 and free alcohol 1a and nBuOMgBr (see entries 1-4 vs. 5-6 below):
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, wherein the reaction has the following scheme:
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(page 1359, Scheme 2, Table 2 and 2nd full paragraph). As such, Kanemasa et al. concludes that the highly effective regiocontrol to produce 2-isoxazoline-5-methanol derivatives has been accomplished by the reactions of nitrile oxide, generated through a usual method of using hydroximoyl chloride precursors and triethylamine, with substituted allyl alcohols in the presence of more than one equimolar amount of a magnesium alkoxide, wherein it is no doubt that the chelated transition state A (Scheme 1) is responsible for the high regiocontrol (page 1360, Conclusion paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the method taught by the WO document to use a base such as triethylamine for the formation of the nitrile oxide and use of a magnesium alkoxide for the cycloaddition in view of the teachings of Kanemasa et al.. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- Kanemasa et al. concludes that the highly effective regiocontrol to produce 2-isoxazoline-5-methanol derivatives has been accomplished by the reactions of nitrile oxide, generated through a usual method of using hydroximoyl chloride precursors and triethylamine, with substituted allyl alcohols in the presence of more than one equimolar amount of a magnesium alkoxide, wherein it is no doubt that the chelated transition state A (Scheme 1) is responsible for the high regiocontrol.
Regarding the selection of solvent, it is noted that Kanemasa et al. teach that the reactions were performed in either dichloromethane or THF. Thus, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
In the instant case, the Examiner is interpreting the addition of the triethylamine for the formation of the nitrile oxide to the be the additional base.
Claim(s) 12-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/228985 (IDS) in view of Kanemasa et al. (Tetrahedron Letters 1992; 33(10): 1357-1360), as applied above for claims 1-11, 15-18, 20 and 22, in further view of Kanemasa and Kobayashi (Bull. Chem. Soc. Jpn 1993; 66: 2685-2693, IDS).
The combination of the WO document and Kanemasa et al. have been discussed above and are incorporated herein.
While the combination teaches that the nitrile oxide is generated through a usual method of using hydroximoyl chloride precursors and triethylamine, the combination does not specifically teach that equivalents of triethylamine.
Kanemasa and Kobayashi teach the lewis acid coordinated nitrile oxide and nitrile imine 1,3-dipoles and the syn-selective cycloadditions to 2-(1-hydroxyalkyl) acrylates (Title). Specifically, Kanemasa and Kobayashi teach the generation of Nitrile Oxide in 94% yield using triethyl amine at 1 equivalent to the carbohydroximoyl chloride (see Scheme 1, formation of 2a and Table 1, entry 1).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the synthesis taught by the combination of the WO document and Kanemasa et al. so as to use at least 1 equivalent of triethylamine for the formation of the nitrile oxide in view of the teachings of Kanemasa and Kobayashi. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- Kanemasa and Kobayashi teach the generation of Nitrile Oxide in 94% yield using triethyl amine at 1 equivalent to the carbohydroximoyl chloride.
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/228985 (IDS) in view of Kanemasa et al. (Tetrahedron Letters 1992; 33(10): 1357-1360), as applied above for claims 1-11, 15-18, 20 and 22, in further view of Kolarovic and Jakubec (Adv. Synth. Catal. 2021; 363: 4110-4158)..
The combination of the WO document and Kanemasa et al. have been discussed above and are incorporated herein.
The combination does not specifically teach that the compounds are further crystallized to increase the diastereomer ratio.
Kolarovic and Jakubec teach that crystallization-induced diastereomer transformation (CIDT) enables isolation of the target compounds in high enantio and diastereomeric purities and with up to quantitative yields simply by filtration (abstract).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to modify the synthesis taught by the combination of the WO document and Kanemasa et al. so as to further crystallize the product to increase the diastereomeric ration in view of the teachings of Kolarovic and Jakubec. One of ordinary skill in the art would have been motivated to make such a modification, with a reasonable expectation of success, because:
- Kolarovic and Jakubec teach that crystallization-induced diastereomer transformation (CIDT) enables isolation of the target compounds in high enantio and diastereomeric purities and with up to quantitative yields simply by filtration.
Conclusion
Therefore, No claim is allowed. Regarding claim 19, Kanemasa and Kobayashi (cited above) teach that the general method of generating 1,3-dipoles consists of the treatment of precursor chlorides such as carbohydroximoyl and carbohydrazonoyl chlorides with tertiary amine bases such as triethylamine (page 2685, 1st column, 1st paragraph). The prior art does not teach or suggest using a combination of a tertiary amine or pyridine base with an amide base. Accordingly, claim 19 appears to be free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
Prosecution Insights