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 1-28 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 1-28 are rejected under 35 U.S.C. 103 as being unpatentable over Li et. al. (US 2009/0069575 A1 – previously cited) (“Li”); in view of Xiao et. al. (CN 101270070 A – previously cited) (“Xiao”).
Regarding claim 1 and 13, 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). Further regarding claim 13, Li discloses the resolution can be carried out in the presence of an organic base, including pyridine, trialkylamines, diisopropylethylamine, triethylamine and the like (para. 0032, lines 1-4). Li further teaches that suitable resolution solvents include alcohols, such as isopropanol and butanol (a C4 alcohol), and aromatic solvents such as toluene and xylenes, and their mixtures (para. 0031). Li discloses their mixture of racemic II was heated in toluene with (R)-alpha-methylbenzylamine (chiral amine) and triethylamine (achiral amine with C6) until complete dissolution was observed, then cooled to room temperature. Li discloses they obtained 41% yield of the pure (S)-enantiomer, then funneled the (R)-enantiomer into their epimerization step, to produce more (S) and reduce wasted material further (Example 3, page 5).
Regarding claims 2-4 and 14-16, Li discloses that suitable resolution solvents include toluene, xylenes, and their mixtures (para. 0031, line 5).
Regarding claims 5-6 and 17-18, Li discloses that suitable resolution solvents include C1-C7 alcohols, such as butanol (para 0031, lines 1-2).
Regarding claim 7 and 19, it is noted that the courts have stated: similar properties may normally be presumed when compounds are very close in structure. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also In re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) (“When chemical compounds have very close’ structural similarities and similar utilities, without more a prima facie case may be made.”). Thus, evidence of similar properties or evidence of any useful properties disclosed in the prior art that would be expected to be shared by the claimed invention weighs in favor of a conclusion that the claimed invention would have been obvious. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563 F.2d 457, 461, 195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d 1013, 1016, 173 USPQ 560, 562 (CCPA 1972) (see MPEP 2144.08(d)).
Therefore, the claimed cyclohexanol is an obvious variant of Li’s C6 alcohol (para 0031, lines 1-2) of the cited the prior art.
Regarding claims 11-12 and 23-24, Li discloses suitable resolving agents include optically pure amine bases such as dehydroabietylamine (as recited in instant claims 12 and 24), and R-alpha-methyl benzylamine (reading on R-1-phenylethylamine – as recited in claims 11 and 23) (para 0030).
Regarding claims 25-26, Li discloses the resolution can be carried out in the presence of an organic base, including trialkylamines, like triethylamine (para. 0032, lines 1-4).
Regarding claims 27 and 28, the courts have stated that compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups, such as triethylamine, tripropylamine, and tributylamine) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). It is reiterated that the courts have stated that similar properties may normally be presumed when compounds are very close in structure.
Thus, the claimed tripropylamine of claim 27 and the tributylamine of claim 28 are obvious variants of the triethylamine of Li (para. 0032, lines 1-4). It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
While Li does not specifically teach: (i) their process at a temperature less than 80 °C (claim 1); or (ii) the process wherein the alkyl alcohol content is in the functionally equivalent mixed solvent from 1 to 90% or from 5 to 50% or from 5 to 30% by volume (claims 8-10 and 20-22). The teachings of Xiao are relied upon for these disclosures.
Xiao discloses the crude product of R-(+)-α-phenethylamine salt of (S)-α-ethyl-2-oxo-1-pyrrolidineacetic acid (instant Formula III) was recrystallized from a mixed solvent (toluene: methanol = 90:10) that is functionally equivalent to the instant invention (page 3 of translated disclosure, Embodiment 1, lines 11-12 – Obtained from Espacenet) – which is 10% by volume and reads on instant claims 8-10 and 20-22. Xiao discloses their mixture of Formula III was heated in toluene to a temperature of 70 °C for 30 minutes for dissolution prior to cooling and filtering (page 3, Embodiment 1).
Therefore, regarding heating to a temperature not higher than 80°C, as recited in instant claims 1 and 13, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to heat the racemic formula II in the toluene mixture with a chiral and achiral amine to about 70 °, as taught by Li and Xiao. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Li discloses their racemic acid in the toluene mixture with a chiral and achiral amine was heated until full dissolution, then cooled to room temperature prior to filtration; further because Xiao’s disclosures heating their acid mixture in toluene/ethanol to 70 °C for 30 min (presumably until full dissolution was observed), then cooling to room temperature and filtering. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR, 550 U.S. at 421, 82 USPQ2d at 1397.
Regarding the chiral resolution where the alcohol is in the solvent mixture from 1-90, 5-50, or 5-30% by volume, as recited in instant claims 8-10 and 20-22, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to use about 1-90, 5 to 50, or 5-30% by volume of a alkyl alcohol mixture in an aromatic solvent for the recrystallization of (S)-α-ethyl-2-oxo-1-pyrrolidineacetic acid prior to conversion into levetiracetam in view of Li’s disclosure that suitable resolution solvents include alcohols, such as isopropanol and butanol, and aromatic solvents, such as toluene and xylenes and their mixture; and Xiao’s disclosure of a 10% methanol/ toluene mixture. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in order to optimize chiral purity of their final (S)-α-ethyl-2-oxo-1-pyrrolidineacetamide or for efficient scale up and cost reduction, as taught by Li.
Further regarding the claimed temperature and volume ranges, 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.
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been added.
Telephonic Interview
Examiner acknowledges the phone communication and withdrawal of the claim objections.
Claim Rejections - 35 USC § 103
Applicant's arguments filed October 10th, 2025 have been fully considered but they are not persuasive.
Applicant argues that Li and Xiao are both silent about a specific impurity formation and its effect in the resolution process. Applicant states, after extensive investigation they’ve discovered this impurity can be avoided by carrying out the resolution in a mixed solvent of aromatics and an alcohol of formula C4-8 at a temperature not higher than 80 °C. Applicant states neither Li nor Xiao render the invention obvious.
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., formation of a specific impurity during the process or the effects of the impurity on the chiral resolution) are not recited in the rejected claim(s). 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).
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.
Applicant's arguments do not comply with 37 CFR 1.111(c) because they do not clearly point out the patentable novelty which he or she thinks the claims present in view of the state of the art disclosed by the references cited or the objections made. Further, they do not show how the amendments avoid such references or objections.
In the present case, Li discloses their chiral resolution, which may be done in solvents like alcohols, such as isopropanol and butanol, and aromatic solvents, such as toluene and xylenes, and their mixtures (para. 0031), in the presence of a chiral base and an achiral base, heating to dissolution (to about 70 °C, as taught by Xiao) then cooling to room temperature, and filtering to give 41% yield of the pure (S)-enantiomer, while the (R)-enantiomer is cycled back into the processed and epimerized to make more (S), thus minimizing waste.
The instant specification discloses Examples 1-3 (pages 9-10), which correspond to three consecutive crystallizations performed at 50 or 70 °C to give at 42% yield of the (S)-enantiomer (97.3: 2.7 ratio of S/R), while the (R)-enantiomer was presumably discarded in the mother liquor.
In response to applicant's argument that the discovery of formation of a specific impurity in the reaction profile at temperatures higher than 80 °C., the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Thus, instant claims stand rejected over Li in view of Xiao.
Double Patenting
The terminal disclaimers filed on October 10th, 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; and US Application No. 18/143,793 and 18/173,790 has been reviewed and is accepted. The terminal disclaimer has been recorded. The double patenting rejections have been withdrawn.
In the response filed October 10th, 2025, Applicant states a terminal disclaimer was filed over Application No. 18/143,785 (which is the instant Application). Examiner believes Applicant intended Application No. 18/143,790.
Conclusion
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 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