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 .
Election/Restrictions
Applicant’s election without traverse of Group I, drawn to a compound of Formula (I) and pharmaceutically acceptable salts and/or solvates thereof; and a pharmaceutical composition comprising one or more compounds of claim 1 or a pharmaceutically acceptable salt and/or solvate thereof and pharmaceutically acceptable carrier; and a compound having the structure of:
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as the elected compound species of Formula (I) in the reply filed on January 8, 2026 is acknowledged.
Claims 15, 17, 25, 27, 28, 30, 35, 37, 40, 42 and 47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on January 8, 2026.
Expansion of Election of Species Requirement
A reasonable and comprehensive search of the elected species conducted by the Examiner
discover a prior art by Gerasimov et al. that anticipates the claimed invention; However, it is noted that the prior art does not teach the elected compound species of Formula (I). In light of this discovery, the search is expanded to the subject matter of the compound of Formula (I) to include the compound 5 of Gerasimov et al. in addition to the elected compound species of Formula (I) such that it does not encompass the full scope of the claim.
Priority
The instant application 18/265,286 filed on June 5, 2023 is a 371 of PCT/CA2021/051755 filed
on December 7, 2021, which claims priority to, and the benefits of U.S. Provisional Application No.
63/122,181 filed on December 7, 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 10/23/2024, 1/8/2026, 1/26/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on January 8, 2026, wherein claims 1, 3, 13, 22, 26 and 43 are amended; claims 2, 4-12, 14, 18-20, 23, 29, 31-34, 36, 38-39, 41, 44, 46, and 48-62 are canceled; claims 15-17, 21, 24-25, 27-28, 30, 35, 37, 40, 42, 45 and 47 are unchanged.
Claims 1, 3, 13, 15-17, 21-22, 24-28, 30, 35, 37, 40, 42-43, 45 and 47 are pending.
Claims 15, 17, 25, 27, 28, 30, 35, 37, 40, 42 and 47 are withdrawn.
Claims 1, 3, 13, 16, 21-22, 24, 26, 43 and 45 are under examination in accordance with the elected invention and species.
Claim Rejections - 35 USC § 102
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 following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3, 16, 21-22, 24 and 26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gerasimov et al. (J. Med. Chem., 1999. Vol. 42: 4257-4263).
Gerasimov et al. teaches a compound 5, (R,S)-(±)-3-(N-Methylpyrrolidin-3-yl)-4-hydroxyindole, having the structure of:
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(see e.g., p. 4259, left column, Scheme 3; p. 4261, right column, compound 5).
Please note the compound 5 of Gerasimov et al. is a compound of Formula (I)
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instantly claimed, wherein R1 is hydrogen; R2 and R3 are hydrogen; R4 is hydrogen;
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is single bond; n is 1 and m is 0; R6, R7 and R8 are hydrogen; Y is OH (i.e., Y is Q-A, wherein Q is O and A is hydrogen).
Therefore, the compound 5 taught by Gerasimov et al. anticipates the claimed invention.
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 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 13, 16, 21-22, 24, 26 43 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Gerasimov et al. (J. Med. Chem., 1999. Vol. 42: 4257-4263; cited in the IDS filed on 10/23/2024) in view of Jasti et al. (WO 2005/066157 A1; cited in the IDS filed on 10/23/2024) and Harbeson et al. (Annual Reports in Medicinal Chemistry, Academic Press, 2011. Vol. 46: 403-417).
Gerasimov et al. teaches a compound 5, (R,S)-(±)-3-(N-Methylpyrrolidin-3-yl)-4-hydroxyindole, having the structure of:
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(see e.g., p. 4259, left column, Scheme 3; p. 4261, right column, compound 5). Gerasimov et al. further teaches Compounds 4 and 5 have lower affinities at the 5-HT2A receptor than the more active enantiomers (R)-1 and (R)-3, respectively, but still have 2-3 fold higher affinities than the less active S enantiomers of 1 and 3 (see e.g., Table 1; p. 4259, right column, line 7-10).
Gerasimov et al. does not teach the elected compound species of Formula (I). Gerasimov et al. also teaches not teach the pharmaceutically acceptable carrier in claim 45.
Jasti et al. teaches compound 1, (R,S)3-(1-Methylpyrrolidin-3-yl)-1H-indole, is an exemplary compound of Formula (I)
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useful for modulating the activity of 5-HT receptor subtype (see e.g., abstract; page 1, line 3-9; p. 44, line 8-10). Jasti et al. further teaches compounds of Formula (I), wherein R11, R12, R13 and R14 whenever possible, independently represent, inter alia, hydrogen or (C1-C3)alkyl (see e.g., p. 2, line 8-21). Jasti et al. further teaches a pharmaceutical composition containing at least one compound of formula (I) either in pure or impure forms forming an active ingredient, together with pharmaceutically employed carriers, auxiliaries and the like (see e.g., p. 13, line 16-19). Jasti et al. further teaches there may be need to prepare radio-labelled compounds related to general structure (I), and suitable isotopes which can be prepared by incorporating isotopes of, inter alia, hydrogen, exemplified by 2H (see e.g., p. 13, line 6-15). Jasti et al. further teaches isotopically labelled compounds are popular in drug and/or substrate tissue distribution and target occupancy assays, for example, isotopically labeled compounds are particularly useful in SPECT (single photon emission computed tomography) and in PET (positron emission tomography) (see e.g., p. 13, line 11-15).
Harbeson et al. teaches the incorporation of deuterium into pharmacologically active agents offers potential benefits such as improved exposure profiles and decreased production of toxic metabolites, which could yield improvements in efficacy, tolerability, or safety (see e.g., p. 404, line 12-16). Harbeson et al. further teaches most deuterated compounds reported-to-date appear to retain full biochemical potency and selectivity (see e.g., p. 415, line 5-8).
In the present case, the difference between the compound 5 of Gerasimov et al. and the claimed compound (the elected compound species) is that the prior art compound contains the methylamine side chain rather than an amine, and the pyrrolidine contains hydrogen rather than deuterium (2H) shown below (see shaded):
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.
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to select compound 5 of Gerasimov et al. and then modify said compound by substituting the methyl on the amine group with a hydrogen, and then substituting the hydrogen atom(s) with 2H as the isotope of hydrogen to arrive at the claimed invention. One would have been motivated to do so, because Jasti et al. teaches compounds of Formula (I) have affinity towards 5-HT receptor can incorporating isotopes of hydrogen, such as 2H, useful for drug and/or substrate tissue distribution and target occupancy assays; and further teaches a list of R12, including hydrogen or (C1-C3)alkyl, that can be interchanged to give the pyrrolidine moiety; and Harbeson et al. teaches the incorporation of deuterium into pharmacologically active agents appear to retain full biochemical potency and selectivity, and offers potential benefits such as improved exposure profiles and decreased production of toxic metabolites, which could yield improvements in efficacy, tolerability, or safety. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the compound 5 of Gerasimov et al. and the compound of Formula (I) taught by Jasti et al. are position isomers (compounds having the same radicals in physically different positions on the same nucleus) with similar utilities (modulating 5-HT receptor subtype), and therefore, said compound 5 modified in view of the Formula (I) of Jasti et al. by substituting the methyl on the amine group with a hydrogen and substituting the hydrogens with 2H as the isotope of hydrogen would have successfully arrive at the compound that is similarly useful for modulating 5-HT receptor.
Regarding the limitation of “a pharmaceutical composition comprising one or more compounds of claim 1 or a pharmaceutically acceptable salt and/or solvate thereof and pharmaceutically acceptable carrier” in claim 45, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to incorporate the compound 5 of Gerasimov et al. with a pharmaceutically employed carrier taught by Jasti et al. to arrive at the claimed invention. One would have been motivated to do so, because Jasti et al. teaches the compound of formula (I) and pharmaceutically employed carriers can arrive at a pharmaceutical composition. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the compound 5 of Gerasimov et al. and the compound of Formula (I) taught by Jasti et al. are position isomers (compounds having the same radicals in physically different positions on the same nucleus) with similar utilities (modulating 5-HT receptor subtype), and therefore the compound 5 of Gerasimov et al. can successfully be combine with a pharmaceutically employed carriers taught by Jasti et al. to arrive at a pharmaceutical composition without any appreciable loss of activity. Please note the pharmaceutically employed carrier taught by Jasti et al. is a pharmaceutically acceptable carrier.
Therefore, the claimed invention is prima facie obvious to one of ordinary skill in the art at the time the application was filed, absent factual evidence to the contrary.
Conclusion
No claims are allowed.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628