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 371 of PCT/JP2022/004557 (02/04/2022)
and claims foreign priority to JAPAN 2021-033869 (03/03/2021).
Status
Rejections not reiterated are withdrawn.
Election/Restrictions
Applicant's election without traverse of Group I, claims 1-12, in the reply filed on 12/22/25 is acknowledged.
Applicant also elected the following species:
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As detailed in the following rejections, the generic claim encompassing the elected species was not found patentable. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn. MPEP 803.02; Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App. lnt. 1987).
Should applicant, in response to this rejection of the Markush-type claim, overcome the rejection through amendment, the amended Markush-type claim will be reexamined to the extent necessary to determine patentability of the Markush-type claim. See MPEP 803.02.
Claim Rejections - 35 USC § 103
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Yano et al. (US6299887) in view of Morodo et al. (Eur. J. Org. Chem. 2020, 5236–5277), and Mao et al. (ACS Omega 2020, 5, 9503−9509).
Regarding claims 1-3, Yano teaches methods for preparing asymmetric phosphoric triesters
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wherein R1, R2, and R3 are different and the alcohols are sequentially added to phosphorus oxyhalide (col 5, line4: “R1, R2, and R3 in the target phosphoric triester are different from one another, three different alcohols of R1—OH, R2—OH, and R3—OH, each in an equivalent amount by mol of phosphorus oxyhalide, are sequentially added and reacted.”). Yano teaches examples where the reaction temperature is 30C (cols 8-12).
Yano’s reaction differs from the claims in that it starts with phosphorus oxyhalide (POCl3) instead of phosphorus trihalide (PCl3). Yano also does not teach using a flow reactor with flow channels and mixers.
Morodo reviews continuous flow organophosphorus chemistry including well-known essential phorphorus-derived building blocks including organophosphites (Eq 11) and the oxidized organophosphates (Eq 12):
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Morodo reviews numerous successful examples of utilization of flow chemistry for control of organophosphorus reactions, including examples such as paraoxon:
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.and the reactions showed high yields (p. 5272-74). Morodo teaches examples of flow reactors utilizing continuous flow through flow channels and combining in mixers (Figures, p. 5272-74).
Mao teaches a continuous flow microreactor for synthesis of triphenylphosphites as in Scheme 1:
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Mao teaches that the use of the continuous flow microreactor provided advantages of simplified operation, short reaction time, excellent yields, and reaction conditions at 70C with flow rates of the reactants as 7.5 mL/min (p. 9506-07).
Regarding claim 4-5, Yano teaches the addition of a base including examples of pyridine (col 5, line 1-35). Regarding claim 6, Mao teaches success with imidazole (p. 9504, Table 2).
Regarding claim 7, Yano teaches stoichiometric ratios (Examples) as does Mao (Table 2).
Regarding claim 8, Mao teaches success with reaction temperatures of 40C (Table 2).
Regarding claim 9, Mao teaches optimization of residence time by altering the flow rate and provides examples (p. 9305, Table 3). Regarding claims 10-12, one of ordinary skill in the art would similarly consider optimization of the reaction residence time to improve yield as done by Mao including where the rates are different.
One of ordinary skill in the art following the teaching of Yano would have recognized that the improvements achieved with flow microreactors would be readily applicable to Yano’s reaction. One of ordinary skill in the art would have also readily considered the alternate reaction process of oxidizing the phosphite to obtain a asymmetric phosphoric triester because it was a well-known reaction step and is taught by Morodo (right side of Eqs 11-12). One of ordinary skill in the art would have been motivated to improve yields as taught by Mao and Morodo. One of ordinary skill in the art in constructing continuous flow reactions as suggested by Morodo would have known to utilize flow channels and mixes as successfully demonstrated by Morodo. The level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success.
Response to Remarks - 35 USC § 103
Applicant argues that the combined teaching of the prior art does not teach or suggest the method for producing an asymmetric phosphoric acid triester using a flow reactor as in the amended claims.
This argument is not persuasive one of ordinary skill in the art would have considered performing a continuous flow reaction to improve yields as taught by Morodo.
Applicant argues that Mao teaches away from the claimed invention because Mao performs an example above 40C.
This argument is not persuasive because Yano teaches examples where the reaction is performed at 30C which one of ordinary skill in the art would have considered and arrived at the claimed temperature with a reasonable expectation of success.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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 ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
