DETAILED ACTION
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 and Response to Amendments
The amendments filed on July 10, 2026 have been acknowledged and entered. Claims 21, 23-26, 28-32, 36-42, and 44-49 are pending. Claims 1-20, 22, 27, 33-35, and 43 are cancelled.
Status of Priority
The present application is a continuation of International patent application PCT/CN2023/098992, filed on June 7, 2023. This application also claims the benefits of foreign priority to CN202210637542.4, filed on June 8, 2022.
Election/Restriction
Examiner previously required a restriction of the claimed inventions. The requirement filed on December 10, 2025 was withdrawn in the last office action (i.e., non-final rejection dated April 1, 2026).
Specification - Disclosure
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Withdrawn Rejections
Applicant is notified that any outstanding rejection or objection that is not expressly maintained in this office action has been withdrawn or rendered moot in view of applicant's amendments and/or remarks.
Claim Objections
Claims 23, 26, and 48 are objected to because of the following informalities:
Currently, claim 23 recites:
“…to obtain a compound as shown in the formula Ib-3 and/or Ic-3
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1386
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754
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”
For clarity, Formula III and the first Formula IV that appears can be removed.
Claim 23 only refers to formulas III-a and III-b (not formula III) and Formula IV appears twice (so the first Formula IV that appears can be removed).
For grammatical consistency, claim 26 should read:
“…wherein a condition for the ring-closure reaction in step 2) comprises: a temperature of 45 oC – 80 oC…”
For clarity and consistency, claim 48 should read:
“…a molar ratio of the compound as shown in the formula IV, the compound as shown in the formula III-a and/or an enol tautomer thereof and the base is 1:0.8-1.2: 0.5-1.3.”
Appropriate correction is required.
--------------------------- Maintained Rejections ---------------------------
Note on 35 USC § 102 and § 103 Rejections
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.
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.
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 42, 45, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over:
Frank-Foltyn et al. (Frank-Foltyn) (EP3130589A1; published February 15, 2017) and
Ashenhurst, J. “How to use a pKa Table” Master Organic Chemistry.https://www.masterorganicchemistry.com/2010/09/29/how-to-use-a-pka-table/ (Accessed March 23, 2026; Original date: 09/29/2010).
Frank-Foltyn teaches how to synthesize ethyl 4-(2-methoxyethoxy)-3-oxobutanoate (i.e., the compound of instant formula (III-a) which comprises the following steps (pg. 16, para. 0089):
React 2-methoxyethanol with sodium hydride (i.e., a base);
To the reaction mixture recited in (1), add ethyl 4-chloro-3-oxobutanoate (i.e., same as ethyl 4-chloroacetoacetate) that is dissolved in THF;
The product obtained is the compound of instant formula (III-a) which can tautomerize to form the compound of instant formula (III-b).
Frank-Foltyn, therefore, teaches the same starting materials, the same base-promoted formation of a 2-methoxyethoxide species, and the same subsequent substitution reaction used to produce the presently claimed Formula III-a product (which can tautomerize to form the compound of instant formula III-b).
Frank-Foltyn does not teach how to deprotonate 2-methoxyethanol with a base that is one or more selected from the group consisting of the bases recited in instant claim 42 (which includes sodium alkoxide). Ashenhurst teaches how to use a pKa table to select a base that can be used to deprotonate an alcohol.
Ashenhurst teaches the use of known acid-base relationships and pKa values to select a base suitable for deprotonating an alcohol. For example, section 4 of Ashenhurst, entitled “Using pKa values and the Principle of Acid-Base Mediocrity to Predict Acid-Base Reactions,” discusses the use of an alkoxide base to deprotonate an alcohol. Ashenhurst thus establishes that a person of ordinary skill in the art would have understood how to select an alkoxide base capable of converting an alcohol into its corresponding alkoxide salt.
Note: The teachings of Ashenhurst can be found on the Master Organic Chemistry website which is known to be a useful resource for undergraduate students who are learning introductory organic chemistry. Ashenhurst is the founder of the website.
Therefore, one of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the claimed invention to substitute the sodium hydride employed by Frank-Foltyn with a known alkoxide base (such as sodium ethoxide, sodium methoxide, potassium methoxide, and potassium ethoxide) that is suitable for deprotonating alcohols including 2-methoxyethanol, based on established pKa relationships. A POSITA would have been motivated to make this substitution because Frank-Foltyn expressly requires base-promoted formation of the 2-methoxyethoxide, and Ashenhurst teaches that alkoxide bases are conventionally selected based on established acid-base relationships to perform that known deprotonation function.
The substitution of NaH for sodium ethoxide, for instance, would merely involve the use of one known base in place of another known base to accomplish the same recognized purpose: formation of the 2-methoxyethoxide species that reacts with ethyl 4-chloroacetoacetate in the subsequent substitution step (see MPEP 2144.06, II: Substituting equivalents known for the same purpose). Because each recited alkoxide is a known base suitable for alcohol deprotonation, a POSITA would have had a reasonable expectation that the substituted base would generate a reaction material containing a salt of 2-methoxyethanol and thereby permit the known reaction taught by Frank-Foltyn to then proceed to form the compound of instant Formula III-a and/or Formula III-b.
Furthermore, selection of reaction conditions, including temperature, would have been within the routine skill of the art. Alkoxide bases are commonly employed in their corresponding alcohol solvents such that conducting the reaction at temperatures consistent with the boiling point of the corresponding alcohol solvent represents routine optimization of reaction conditions and does not render the claimed invention nonobvious.
Response to Applicant’s arguments regarding unexpected results:
Applicant argues that the presently recited base provides unexpectedly superior yields relative to the sodium hydride process of Frank-Foltyn. Specifically, Applicant states that the sodium hydride process of non-limiting Example 3 produced a yield of 53.6%, Frank-Foltyn reported a yield of 62%, and the sodium ethoxide process of non-limiting Example 4-3 produced a yield of 87.6%. Applicant contends that this improvement constitutes objective evidence of nonobviousness.
However, Examiner does not find Applicant’s response persuasive over the combined teachings of Frank-Foltyn and Ashenhurst.
Frank-Foltyn already teaches the claimed reaction, including formation of the same 2-methoxyethoxide from 2-methoxyethanol and subsequent reaction of 2-methoxyethoxide with ethyl 4-chloroacetoacetate to produce the same compound of instant Formula III-a (which can tautomerize to form a compound of instant formula III-b). The claimed modification does not introduce a different reaction mechanism, starting material, or product. Rather, it merely changes the base used to generate the same 2-methoxyethoxide intermediate required by the known reaction.
Because the prior art establishes both the need to form the 2-methoxyethoxide species and the suitability of known alkoxide bases for deprotonating alcohols, a POSITA would have had reason to evaluate conventional alkoxide bases as alternatives to sodium hydride. In conducting that routine evaluation, the skilled artisan would have sought a base and associated reaction conditions that efficiently generated the desired alkoxide while maximizing conversion and isolated yield. The discovery that one of the conventional candidate bases provides a higher yield represents the type of improvement that ordinarily results from optimizing a known reaction variable (i.e., substituting NaH for a sodium alkoxide is mere routine optimization).
Hence, claims 42, 45, and 47 are rendered obvious.
Allowable Subject Matter
Claims 21, 24, 25, 28-32, 36-41, 44, 46, and 49 are allowed. Claims 23, 26, and 48 are objected to but would be allowed once the appropriate corrections are made.
Conclusion
Claims 21, 24, 25, 28-32, 36-41, 44, 46, and 49 are allowed. Claims 23, 26, and 48 are objected to. Claims 42, 45, and 47 are rejected.
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.
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/KRISTEN W ROMERO/Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
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