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 .
Status of the Claims
Claims 1-3 and 5-6 are pending in this application.
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.
Claims 1-3 and 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Li et. al. (US 2009/0069575 A1 – cited in IDS – previously cited); in view of Gupta et al. (Tet. Lett., 45, 2004, 1733–1736).
Regarding claim 1, Li discloses a process for the preparation of (S)-α-ethyl-2-oxo-1-pyrrolidineacetamide with formula (I) from the same racemic acid of formula (II) in the instant application. Li’s method comprises combining the racemic acid (II) with a chiral base amine in a resolution solvent and recrystallizing from that mixture (abstract). Li discloses the resolution can be carried out in the presence or absence of an organic base, including trialkylamines (reading on R1R2R3N, wherein R1, R2, and R3 are independently C1-C12), N,N-diisopropylethylamine (reading on 8 carbons total), triethylamine, and the like (para. 0032, lines 1-4).
Li further teaches ~1: 1.01 molar ratio of chiral amine to achiral amine (Example 3, page 5 – ratio calculated using the following values: triethylamine (89 g/ 101.19 gmol-1) and R-(+)-1-phenylethylamine (106 g/ 121.18 gmol-1)), reading on instantly most preferred ratio of 0.45: 0.55 (~0.8: 1 of chiral amine to achiral amine) in the specification (page 6, lines 16-20). Li’s Example 3 also discloses heating until a clear solution is observed (complete dissolution) then cooling to room temperature to recrystallize products, as done in the instant Examples 1-4 (page 10 of the spec.).
Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that where 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. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
While Li does not specifically mention wherein the optically inactive amine forms an ionic liquid with the compound of Formula II; the teachings of Gupta et al. are relied upon for these disclosures.
Gupta teaches trialkylammonium salt formation after proton transfer from an acidic species to tertiary amines (abstract). Gupta discloses that the presence of triethylamine in a reaction with a diketone (acidic species) increased the percentage of enol in equilibrium, presumably by forming ionic liquid [Et3NH]+[enolate]- (page 1733, col. 2, lines 3-10). Gupta discloses tributylamine and tripropylamine (Scheme 1; and Table 1, page 1734, entries 1-8) in reactions to form low density ionic liquids at room temperature after an acid/ base reaction.
Therefore, regarding the optically inactive amine forming an ionic liquid with the carboxylic acid compound of Formula II, it would have been prima facie obvious to one of ordinary skill that such “ionic liquid” intermediate would form in the presence of Li’s trialkylamine achiral base and the acidic compound of Formula II. One of ordinary skill would have been motivated to do so in view of Gupta’s teaching that trialkylamines can deprotonate acidic species to form ionic liquids under mild, room temperature conditions in various solvent systems (page 1733, col. 2, lines 3-13). One of ordinary skill would have had a reasonable expectation of success because Li discloses their process for the chiral resolution of levetiracetam in the presence of an achiral trialkylamine; and Gupta teaches that trialkylamines like tributyl or tripropylamines can easily form ionic liquids in the presence of an acidic species, thus pushing the reaction equilibrium towards product formation.
Therefore, if an ionic liquid forms under the instantly claimed conditions, one would expect the same ionic liquid to be present under Li’s nearly identical reaction conditions.
Regarding claims 2-3, Li discloses suitable resolving agents include optically pure amine bases such as dehydroabietylamine (as recited in instant claim 2), and R-alpha-methyl benzylamine (same as R-1-phenylethylamine – as recited in instant claim 3) (para 0030).
Regarding claims 5-6, Gupta discloses tripropylamine and tributylamine (Scheme 1; and Table 1, page 1734, entries 1-8).
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been added.
The objection of record to claim 4 was withdrawn as part of a phone call performed by the Examiner on May 16th, 2025. Reference to the phone interview is acknowledged. Claim 4 has been cancelled, see page 4 of the reply filed October 7th, 2025, thus the objection is also rendered moot.
Claim Rejections - 35 USC § 103
Applicant's arguments filed October 7th, 2025 have been fully considered but they are not persuasive.
Applicant argues that Li’s process is inefficient due to the need to recrystallize from toluene several times. Applicant also states that Li uses triethylamine in their process.
Regarding the use of triethylamine, Li states trialkylamines, in general, are appropriate for their process, and specifically mentions N,N-diisopropylethylamine (with 8 carbons) as a viable option (para. 0032, lines 1-4).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the number of times which Li recrystallizes their products) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Furthermore, while Li et al. doesn’t disclose specific enantiomeric ratios of the isolated product, they disclose that, not only can the R and S enantiomers of racemic formula II be separated, but the undesired enantiomer can be epimerized and funneled back into the process to form even more of the desired enantiomer, thus allowing for the formation of more than 50% of the desired enantiomer (see page 2, col. 1).
Examples 1 and 4 of the instant specification, which use xylene or a 9:1 mix of o-xylene/ cyclohexanol, respectively, and start with racemic formula II (without spiking with the S-enantiomer, as done with examples 2 and 3) (pages 10-11 of the specification) show consistent ratios of about 85:15 of the S and R enantiomers, respectively, while – for example 4 – the mother liquor contained about 18:81 ratio of the S and R enantiomers, which presumably was discarded, unless subsequent recrystallizations were performed. Example 6 shows an improved ratio of about 95:5 of the S and R enantiomers, respectively, after using a toluene/butanol solvent mixture and dehydroabietylamine acetate instead of R-phenylethylamine, though still the mother liquor contained about a 44:56 ratio of the S and R enantiomers, which would have to be discarded unless subsequent recrystallizations were performed.
Applicant argues that the present application discloses surprising resolution due to the use of an ionic liquid that can be formed in situ from the reaction of formula II and an achiral amine.
Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
In the present case, Li discloses the same reaction with the same materials. Therefore, if such a “ionic liquid” intermediate is formed as part of the instantly claimed reaction, then the same intermediate would be expected to form in Li’s reaction.
Thus, instant claims 1-3 and 5-6 stand rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Gupta et al., as set forth above.
Double Patenting
The terminal disclaimer filed on October 7th, 2025, disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11,384,050; Copending App. No. 18/143,785; and Copending App. No. 18/143,793 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Applicant’s arguments, see page 4, filed October 7th, 2025, with respect to obviousness-type double patenting rejections over US Patent No. 11,384,050; Copending App. No. 18/143,785; and Copending App. No. 18/143,793 have been fully considered and are persuasive. The obviousness-type double patenting rejections of the claims have been withdrawn.
Conclusion
Applicant's amendment necessitated the new ground(s) 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 JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627