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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/22/2026 has been entered.
Claims 1-6 and 8 are pending in the instant application. Claims 1, 2, 4-6, 8 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
Claim 3 is under consideration in this Office Action.
In view of the claim amendment dated 05/22/2026 the previous rejections of the claim have been withdrawn in favor of the instant claim rejection(s) stated below.
Although claim 6 has been amended to claim depend from claim 1, amended claim 6 does not depend from claim elected claim 3 and has been withdrawn. Further, amended claim 6 would be rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for because there is insufficient antecedent basis for enantiomerically enriched preparation of S3a having the recited percentage amounts stated in claim 6.
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 of this title, 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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over WO2018071320 (04/19/2018; IDS filed 10/11/2024) in view of US20030003552 (01/02/2003; reference of record), US20060003428 (01/05/2006; reference of record), US20230193163 (06/22/2023; reference of record), US Patent 5514589 (05/07/1996; PTO 892)
WO2018071320 teaches process for the preparation of (1r,3r)- and (1s,3s)-2,2-dihalo-3-(substituted phenyl)cyclopropanecarboxylic acids where the process involves chemical resolution of a racemic mixture of a trans-2,2-dichloro-3-(substituted phenyl)cyclopropanecarboxylic acid with an enantiomeric amine, isolation of a diastereomeric amine salt and finally treatment of the salt with an acid. WO2018071320 teaches in Examples 1-4 representative compounds encompassed by S2a and S3a recited in the instant claim. See entire publication and claims especially pages 6-10 and claims 1-10. The teachings of the reference differ from the claims in that the reference does not teach the claimed process comprising hydrolyzing S2a to S3a using one or more carboxylic ester hydrolases.
US20030003552 teaches method of kinetic resolution of racemates of alcohols or carboxylic acid esters, where fluorine phase marking of the quicker or more slowly reacting enantiomer is obtained by lipase-catalysed reaction of racemic alcohols with fluorinated carboxylic acid esters of racemic alcohols with water, and the enantiomers are then extractively separated by division between an organic and a fluorine phase (see entire publication and claims especially paragraphs [0007]-[0051], Examples 1-7, and claims 1-12).
US20060003428 teaches process for enzymatically resolving a mixture of R- and S-enantiomers of an α-substituted carboxylic acid or an ester or thioester thereof, in which a Carica papaya lipase is used as a biocatalyst to effect the resolution as desired (see entire publication and claims especially paragraphs [0016]-[0029]. US20060003428 teaches the following in the claims:
1. A process for enzymatically resolving a mixture of R- and S-enantiomers of an α-substituted carboxylic acid or an ester or thioester thereof of formula (I):
wherein
X represents —O— or —S—;
Y is a halogen or a methyl group;
R1 represents: a straight-chain or branched saturated or unsaturated C1-C20 aliphatic group optionally substituted with one to three substituents selected from the group consisting of halo, amino, cyano, hydroxy, —SH, —COOH, —CF3, —OCF3, —SCF3, —CONH2, a C1-C6 alkoxy group and an aryl group; an aryl group, an aryloxy group or a C3-C12 heterocyclic group containing one to three heteroatoms selected from O, S and N, each group being optionally substituted with one to three substituents selected from the group consisting of halo, amino, cyano, hydroxy, —SH, —COOH, —CF3, —OCF3, —SCF3, —CONH2, a C1-C6 alkoxy group, an aryl group and a C3-C12 heterocyclic group containing one to three heteroatoms selected from O, S and N; and
R2 represents: H; a straight-chain or branched saturated or unsaturated C1-C12 aliphatic group optionally substituted with one to three substituents selected from the group consisting of halo, amino, cyano, hydroxy, —CF3, —OCF3, —SCF3, —Si(CH3)3, a C1-C4 alkyloxy group, a C1-C4 alkylthio group, an aryl group, vinyl and a 2-alkenyl group having 3 to 12 carbon atoms; an aryl group or a C3-C12 heterocyclic group containing one to three heteroatoms selected from O, S and N, each group being optionally substituted with one to three substituents selected from the group consisting of halo, amino, cyano, hydroxy, —SH, —COOH, —CF3, —OCF3, —SCF3, —CONH2, a C1-C6 alkoxy group, an aryl group and a C3-C12 heterocyclic group containing one to three heteroatoms selected from O, S and N;
with the proviso that Y and R1 cannot be methyl at the same time; the process comprising subjecting the mixture of R- and S-enantiomers of the α-substituted carboxylic acid or ester or thioaster thereof of formula (I) to an enzymatic resolution catalyzed by a Carica papaya lipase in a liquid phase.
2. The process of claim 1, wherein the liquid phase comprises a solvent system selected from an aqueous solution, an anhydrous organic solvent, an organic solvent saturated with water, and combinations thereof forming a biphasic solution.
3. The process of claim 1, wherein the liquid phase comprises an organic solvent selected from isooctane, heptane, hexane, cyclohexane, pentane, decane, toluene, benzene, carbon tetrachloride, t-butanol, t-pentanol, isopropyl ether, methyl t-butyl ether, methyl isobutyl ether, and combinations thereof.
4. The process of claim 1, wherein the mixture is a racemic mixture of the α-substituted carboxylic acid or ester or thioester thereof of formula (I).
5. The process of claim 1, wherein the Carica papaya lipase is prepared from a latex exudate of a plant of Carica papaya.
6. The process of claim 1, wherein the enzymatic resolution of the mixture by the Carica papaya lipase is conducted in a liquid phase comprising an organic solvent in combination with an organic base.
7. The process of claim 6, wherein the organic solvent is selected from isooctane, heptane, hexane, cyclohexane, pentane, decane, toluene, benzene, carbon tetrachloride, t-butanol, t-pentanol, isopropyl ether, methyl t-butyl ether, methyl isobutyl ether, and combinations thereof.
8. The process of claim 6, wherein the organic base is selected from the group consisting of tertiary amines, amidines, guanidines, phosphazene bases, and combinations thereof.
9. The process of claim 8, wherein the organic base is selected from the group consisting of triethylamine, tributylamine, trioctylamine, 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene, 1,8-diazabicyclo [5,4,0] undec-7-ene, 1,4-diazabicyclo [2.2.2] octane, t-butylimino-tris(pyrrolidino)phosphorane, t-butylimino-tris(dimethylamino)phosphorane, 1-t-butyl-4,4,4-tris(dimethylamino)-2,2-bis[tris(dimethylamino)-phosphoranylidenamino]-2λ54λ5-catenadi(phosphazene), diethylaminomethyl-polystyrene, and combinations thereof.
10. The process of claim 8, wherein the organic base is carried on a support selected from an organic support and an inorganic support.
11. The process of claim 8, wherein the organic base is carried on an anion-exchange resin.
12. The process of claim 1, wherein the enzymatic resolution of the mixture by the Carica papaya lipase is conducted at a temperature ranging from 20° C. to 90° C.
13. The process of claim 1, wherein the mixture comprises R- and S-enantiomers of an α-substituted carboxylic acid ester or thioester of formula (I), and wherein the enzymatic resolution of the mixture by the Carica papaya lipase is conducted in a liquid phase comprising a solvent system selected from an aqueous solution, a water-saturated organic solvent and combinations thereof forming a biphasic solution, such that either R-form or S-form of the α-substituted carboxylic acid ester or thioester of formula (I) is enantioselectively hydrolyzed by the Carica papaya lipase.
14. The process of claim 13, wherein the α-substituted carboxylic acid ester or thioester of formula (I) is at least any one of the following compounds: an ethyl, propyl, butyl, hexyl, phenyl or tritluoroethyl ester of naproxen, fenoprofen, ibuprofen, ketoprofen, suprofen, flurbiprofen, 2-phenyl propionic acid, 2-(4-chlorophenoxy)propionic acid or 2-chloro-2-phenylacetic acid; an ethyl, propyl, butyl, hexyl, phenyl or trifluoroethyl thioester of naproxen, fenoprofen, ibuprofen, ketoprofen, suprofen, flurbiprofen, 2-phenyl propionic acid, 2-(4-chlorophenoxy)propionic acid or 2-chloro-2-phenylacetic acid; and diclofog methyl ester.
15. The process of claim 13, wherein the liquid phase further comprises an organic base selected from the group consisting of tertiary amines, amidines, guanidines, phosphazene bases, and combinations thereof.
16. The process of claim 15, wherein the organic base is selected from the group consisting of triethylamine, tributylamine, trioctylamine, 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene, 1,8-diazabicyclo [5,4,0] undec-7-ene, 1,4-diazabicyclo [2.2.2]octane, t-butylimino-tris(pyrrolidino)phosphorane, t-butylimino-tris(dimethylamino)phosphorane, 1-t-butyl-4,4,4-tris(dimethylamino)-2,2-bis [tris(dimethylamino)-phosphoranylidenamino]-2λ5,4λ5-catenadi(phosphazene), diethylaminomethyl-polystyrene, and combinations thereof.
17. The process of claim 1, wherein the mixture comprises R- and S-enantiomers of an α-substituted carboxylic acid ester or thioester of formula (I), and wherein the enzymatic resolution of the mixture by the Carica papaya lipase is conducted in a liquid phase comprising an anhydrous organic solvent in combination with an alcohol, such that either R-form or S-form of the α-substituted carboxylic acid ester or thioester of formula (I) is enantioselectively transesterified by the Carica papaya lipase using said alcohol.
US20230193163 teaches Pseudomonas stutzeri lipase and use in washing agents or cleaning agents (see entire publication and claims especially claims 1-5)
US Patent 5514589 teaches an enzymatic method for the preparation of (2S,3S)-threo-alkyl-2-hydroxy-3-(4-methoxyphenyl)-3-(2-X-phenylthio)propionate, where X=NO2, NH2, NHCOCH3, NHCOCF3, NHCO2CH3, NHCO2C(CH3)3 or NHCHO and R is an alkyl group, e.g., CH3, or CH2CH3 in an essentially anhydrous organic solvent is described, where in this method a lipase which stereospecifically acylates the (2R,3R)-enantiomer of the racemic mixture is used (see entire patent and claims especially claims 1-6). US Patent 5514589 teaches the following in column 2, last full paragraph, lines 47- 67:
“As biocatalysts different commercial lipases were tested either as such or immobilized on solid supports (Celite and Chromosorb). Of the lipases tested Mucor miehei (Biocatalysts) , Candida lypolytica (Biocatalysts) , Candida cylindracea (Sigma), Candida cylindracea (AY 30, Amano), Aspergillus. niger (AP-6, Amano) and Pseudomonas cepacia (lipase PS, Amano), the lipase PS of Amano suits best for the purpose. In most cases it acts practically enantiospecifically, i.e. the reaction stops at 50% conversion and the products of the resolution (the unreacted enantiomer of the racemic mixture (2S,3S)-1 and the reaction product (2R,3R)-2) can be isolated as optically pure substances with almost 100% yields. The activity of the immobilized lipase PS is multiple when compared to the activity of an untreated enzyme and the activity of the immobilized enzyme lasts longer in reuse.”
The arguments filed 05/22/2026 have been considered but are not persuasive. According to MPEP 2111, claims must be given their broadest reasonable interpretation in light of the specification. Thus, while claims must be given their broadest reasonable interpretation consistent with the specification, limitations of the specification cannot be read into the claims to thereby narrow the scope of the claims. Claim 3 has not been amended to recite that the process produces an enantiomeric enriched product of S3a as stated in the arguments filed 05/22/2026. Further applicants have not provided specific evidence and references that the Pseudomonas stutzeri lipase of US20230193163 cannot make the claimed products when the said lipase is contacted with S2a in the presence of water and optionally an aqueous buffer.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by contacting any of the compounds taught by WO2018071320 with the Pseudomonas stutzeri lipase of US20230193163 to make the claimed products. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain simple method to obtain the recited products by enzymatic activity of lipase. One of ordinary skill in the art before the effective filing date of the claimed invention would have a reasonable expectation of success in view of the reference teachings especially US Patent 5514589 showing the use of lipases. Hence, the claimed invention as a whole is prima facie obvious.
Amending claim 3 to recite a process for producing an enatonmerically enriched preparation of S3a wherein the enantiomeric excess of the S3a (R,R)-enantiomer is greater than 80%, greater than 90%,=or greater than 95%, greater than 96%, greater than 97%, or greater than 98% would aid in overcoming the rejection.
Conclusion
No claim is allowed.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652
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