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 .
Priority
This application is a national stage application under 35 U.S.C. § 371 of International
Application No. PCT/EP2020/076933, filed 09/25/2020, which claims the priority benefit of
United Kingdom Application No. 1913921.1, filed 09/26/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/01/2022, and 05/30/2024 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of claims
Claims 20-21, 23-30 and 40-47 are pending in this application. Claim 28 is amended. Claims 1-19, 22, and 31-39 have been cancelled by applicant without prejudice or disclaimer.
Applicant’s arguments, filed 06/26/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
The obviousness rejection below is repeated from the 03/30/2026 Office Action and modified in order to address the most recent amendments.
Claims 23 and 41-46 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 20-21, 24-30, 40 and 47, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 09/09/2024 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 20-21, 23-30 and 40-47 are currently under examination. They constitute the complete set presently being applied to the instant application.
Specification
The lengthy specification (166 pages) 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.
Claim Objections
Claims 26-27 and 29 objected to because of the following informalities: the phrase “which method comprises” needs to be replaced with –comprising—for clarity of the record. Appropriate correction is required.
Claim 47 is objected to because of the following informalities: a typo exists at the end of claim 47 wherein a “;” needs to be replaced by a period --.--. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 40 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 40, the phrase e.g. "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
This rejection may be overcome by amending the claim language to remove “e.g.” from the limitations.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 20-21, 23-30 and 40-47 are rejected under 35 U.S.C. 103 as being unpatentable over Boyle (WO 2018/197714 A1).
The instant claims are directed to a method of preparing a single atropisomer according to claim 20, or a pharmaceutically acceptable salt thereof, which method comprises the chiral separation of mixture of atropisomers of a racemic mixture of compound of formula (0), wherein the chiral separation is carried out by: (i) passing the mixture of atropisomers through a chiral chromatography column; e.g. a chiral HPLC column; or (ii) reacting the mixture of atropisomers of a compound of the formula (0) with a chiral acid to form salts of both of the atropisomers in the mixture, separating the salts and decomposing the salts to give the corresponding free bases of each of the atropisomers.
Boyle et al. teach “Optical isomers can be separated by a number of techniques including chiral chromatography (chromatography on a chiral support) and such techniques are well known to the person skilled in the art. As an alternative to chiral chromatography, optical isomers can be separated by forming diastereoisomeric salts with chiral acids such as (+)-tartaric acid, (-)-pyroglutamic acid, (-)-di-toluoyl-L-tartaric acid, (+)-mandelic acid, (-)-malic acid, and (-)-camphorsulphonic, separating the diastereoisomers by preferential crystallisation, and then dissociating the salts to give the individual enantiomer of the free base. Where compounds of the invention exist as two or more optical isomeric forms, one enantiomer in a pair of enantiomers may exhibit advantages over the other enantiomer, for example, in terms of biological activity. Thus, in certain circumstances, it may be desirable to use as a therapeutic agent only one of a pair of enantiomers, or only one of a plurality of diastereoisomers. Accordingly, the invention provides compositions containing a compound having one or more chiral centres, wherein at least 55% (e.g. at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%) of the compound of the formula (1) is present as a single optical isomer (e.g. enantiomer or diastereoisomer). In one general embodiment, 99% or more (e.g. substantially all) of the total amount of the compound of the formula (1) may be present as a single optical isomer (e.g. enantiomer or diastereoisomer).” (sic) (pg. 37, lines 7-14). Boyle discloses the compound of 4-[5-(4-chlorophenyl)-l-[2-(trifluoromethyl) phenyl] pyrrol-2-yl]-N-[2(dimethylamino)ethyl]benzamide in example 33 which is equivalent to the structure of formula (0) of instant claim 29. (pg. 72)
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Boyles example 33 (Left) Applicants formula (0) (Right)
Examiner notes the applicants specification teaches “Optical isomers can be separated by a number of techniques including chiral chromatography (chromatography on a chiral support) and such techniques are well known to the person skilled in the art. As an alternative to chiral chromatography, optical isomers can be separated by forming diastereoisomeric salts with chiral acids such as (+)-tartaric acid, (-) pyroglutamic acid, (-)-di-toluoyl-L-tartaric acid, (+)-mandelic acid, (-)-malic acid, and (-)-camphorsulphonic, separating the diastereoisomers by preferential
crystallisation, and then dissociating the salts to give the individual enantiomer of the free base.” (sic) (pg. 46, lines 1-9).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to prepare an atropisomer from the compound of formula (0) following the teachings of Boyle who disclosed the methods of chiral chromatography and separating optical isomers by forming diastereoisomeric salts with chiral acids wherein a derivative of formula 1 as example 33 is separated into single optical isomers.
A person of ordinary skill in the art would have been motivated to follow the teachings of Boyle who showed that compounds of formula 1 can be isolated into single isomeric forms where 55-99% of the compound of formula 1 is present in a single isomeric form. A skilled artisan would have had a reasonable expectation of success in separating the compound of instant claim formula (0) into the desired chiral form by using a chiral chromatography column or reacting the compound of formula (0) with a chiral acid with a reasonable expectation of success in isolating all optical isomeric forms including atropisomers using the disclosed chiral separation methods of Boyle.
Conclusion
All claims are rejected, no claims are allowed.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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/E.V./Examiner, Art Unit 1623 /SAMANTHA L SHTERENGARTS/Primary Examiner, Art Unit 1623
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