DETAILED ACTION
Claims 1 and 3-14 are currently pending in the instant application.
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 .
Response to Arguments
Applicant's arguments filed 10/02/2025 have been fully considered but they are not persuasive. Applicant argues the reference of Pramanik teaches a process for decarboxylating with NaOH and replacing the solvent and does not suggest use of a heterocyclic base for decarboxylation of 4-hydroxy-3,5-diisopropylbenzoic acid. Applicant further argues that CN ‘450 and JP ‘199 teaches decarboxylating in the presence of imidazole but decarboxylation is of a different reactant – JP ‘199 teaches decarboxylation of fluorosalicylic acid while CN ‘450 teaches decarboxylation of trihydroxy benzoic acid. Applicant argues that use of a reagent for decarboxylation reaction requires consideration of the nature of the reactant.
In response, although CN ‘450 and JP ‘199 teach decarboxylation of fluorosalicylic acid and trihydroxy benzoic acid rather than the 4-hydroxy-3,5-diisopropylbenzoic acid of Pramanik, one of ordinary skill in the art following the teachings of Pramanik would have found it prima facie obvious to utilize a known base as taught in CN ‘450 and JP ‘199 for the same reaction: decarboxylation of a substituted phenyl. One of ordinary skill in the art would have expected, prior to the filing of the instant application, that decarboxylation of 4-hydroxy-3,5-diisopropylbenzoic acid would occur with an imidazole base since decarboxylation with said base is taught by CN ‘450. As no evidence has been set forth to suggest the proposed reaction would not occur, the preponderance of the evidence supports a finding that it would have been obvious to substitute the base taught by CN ‘450 and JP ‘199 in the reaction of Pramanik as the chemical process that is occurring is an expected reaction.
Applicants further allege that the instantly claimed process has significantly higher yield and purity than a comparable process using triethanolamine. However, the prior art of Pramanik teaches HPLC purity of > 99.8% (see Scheme 1). Thus, Applicant’s do not appear to have met their burden of demonstrating unexpected results. See MPEP 716.02. Further, Applicant’s argument compares the results achieved to those when using triethylamine, which is different than the base used by the prior art. As a result, Applicants argument is unpersuasive and the prior art rejections have been maintained.
Election/Restrictions
Claims 11-14 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse on 06/16/2025.
Maintained 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 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.
Claims 1, 3-4 and 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over Pramanik et al (see Organic Process Research & Development, Vol. 18, 2014, p. 152-156) in view of Wangwei et al, see CN 101475450, hereafter referred to as CN ‘450, pub. 07/27/2011.
Pramanik teaches decarboxylating 4-hydroxy-3,5-diisopropylbenzoic acid to give 2,6-diisopropyl phenyl
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(see Scheme 1, p. 153). Pramanik teaches this process with NaOH in solvent rather than with a heterocyclic base comprising imidazole, an imidazole derivative, piperazine or pyrimidine.
CN ‘450 teaches decarboxylating gallic acid
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to pyrogallic acid
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using imidazole. The process is taught with 1 to 0.08-0.10 ratio of gallic acid to imidazole. CN ‘450 exemplifies the process without solvent at 145-150 ºC (see Embodiment 1). CN ‘450 is silent as to the time period over which decarboxylation is carried out. However, the adjustment of particular conventional working conditions (e.g. determining result effective amounts of the ingredients beneficially taught by the cited references), as well as adjustment of reaction temperature, reaction time and use of solvents, rearranging steps in a reaction sequence, is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan (See In re Mostovych, Weber, Mitchell and Aulbach, 339F.2d 455; 144 USPQ 38).
It would have been prima facie obvious to one of ordinary skill in the art to apply utilize a different base (i.e. imidazole as the heterocyclic base as taught by CN ‘450) rather than NaOH in the process of Pramanik since both CN ‘450 and Pramanik teach decarboxylation of a substituted phenyl. The Supreme Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398, 127 S. Ct. 1727, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper “functional approach” to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit.
Exemplary rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Note that the list of rationales provided is not intended to be an all-inclusive list. Other rationales to support a conclusion of obviousness may be relied upon by Office personnel.
The motivation to substitute a heterocyclic base comprising imidazole, imidazole derivative, piperazine or pyrimidine for NaOH in the art of Pramanik would derive from (B) or (C) from KSR. In the instant case, utilizing a different base as taught by CN ‘450 in the art of Pramanik, both of which are decarboxylation reaction would have been obvious to an artisan or ordinary skill in the art in order to optimize process yields for the synthesis of propofol. The enabled examples would have motivated one skilled in the art to modify the known process with the expectation that they would result in the same product of propofol.
Claims 1 and 4-10 are rejected under 35 U.S.C. 103 as being unpatentable over Pramanik et al (see Organic Process Research & Development, Vol. 18, 2014, p. 152-156) in view of Wangwei et al, see CN 101475450, hereafter referred to as CN ‘450, pub. 07/27/2011 as applied to claims 1 and 4-10 above, and further in view of Kazuto et al, see JPH09241199, hereafter referred to as JP ‘199, pub. 09/16/1997.
The limitations of claim 1 are taught as discussed above.
Regarding the use of solvent found in claim 5, JP ‘199 teaches decarboxylation of 4-fluorosalicyclic acid to 3-fluorophenol by heating without solvent or in the presence of solvent in the presence of a base with pyridine (a heterocyclic base) as a base – see p. 3, paragraph [0011] with 0.1 to 20 mol of base to 1 mol of starting material is used. JP ‘199 teaches solvents such as toluene (see p. 4, paragraph [0018]) in a temperature range of 150 to 230 ºC for 1 to 20 hours (see p. 4, paragraph [0021]). Thus, it would be reasonable to utilize toluene in the process of Pramanik, which is also a process directed towards decarboxylation of a substituted phenyl. It is known that the adjustment of particular conventional working conditions (e.g. determining result effective amounts of the ingredients beneficially taught by the cited references), as well as adjustment of reaction temperature, reaction time and use of solvents, rearranging steps in a reaction sequence, is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan (See In re Mostovych, Weber, Mitchell and Aulbach, 339F.2d 455; 144 USPQ 38).
Regarding the overlap in ranges for the temperature range and time found in claims 7-10, MPEP 2144.05 states In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
Conclusion
Applicant's amendment necessitated the new grounds 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 KAREN CHENG whose telephone number is (703)756-4699. The examiner can normally be reached M-F, 9AM-6PM PST.
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/KAREN CHENG/Primary Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623