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:
PNG
media_image1.png
154
148
media_image1.png
Greyscale
as the elected compound species of Formula (I) are maintained.
Claims 15, 17, 25, 27, 28, 30, 35, 37, 40, 42 and 47 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Newly added claim 65 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 statement (IDS) submitted on 1/30/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The information disclosure statement (IDS) submitted on 6/10/2026 was filed after the mailing date of the Non-Final Office Action on February 2, 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on April 28, 2026, May 6, 2026 and May 26, 2026. Specifically, the amendment to claims filed on May 26, 2026 further amends claim 1 submitted on May 6, 2026. Collectively, the claims submitted after the mailing date of the Non-Final Office Action on February 2, 2026 amends claims 1, 21, and 43, newly added claims 63-65, and all other claims remain unchanged.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 3, 13, 15-17, 21-22, 24-28, 30, 35, 37, 40, 42-43, 45, 47 and 63-65 are pending.
Claims 15, 17, 25, 27, 28, 30, 35, 37, 40, 42 and 47 remain withdrawn.
Claim 65 is withdrawn.
Claims 1, 3, 13, 16, 21-22, 24, 26, 43, 45 and 63-64 are under examination in accordance with the elected invention and species.
Action Summary
Applicant’s arguments, see page 19, filed on April 28, 2026, with respect to rejection of claims 1, 3, 16, 21-22, 24 and 26 under 35 U.S.C. 102(a)(1) as being anticipated by Gerasimov et al. (J. Med. Chem., 1999. Vol. 42: 4257-4263) have been fully considered and are persuasive. The rejection of claims 1, 3, 16, 21-22, 24 and 26 has been withdrawn.
Claims 1, 3, 13, 16, 21-22, 24, 26, 43 and 45 rejected under 35 U.S.C. 103 as being unpatentable over Gerasimov et al. (J. Med. Chem., 1999. Vol. 42: 4257-4263) in view of Jasti et al. (WO 2005/066157 A1) and Harbeson et al. (Annual Reports in Medicinal Chemistry, Academic Press, 2011. Vol. 46: 403-417) are maintained, but revisited and modified in light of the claim amendments.
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.
Claims 63-64 are 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 (newly applied as necessitated by amendment).
Regarding claim 63, the limitation of “R5 comprises deuterium” is ambiguous, because it is unclear whether Applicant intends (i) R5 to be a deuterated C1-C6 alkyl group (i.e., one or more hydrogen atoms of the alkyl are replaced with deuterium), or (ii) R5 to include deuterium as an additional constituent separate from the C1-C6 alkyl group recited in claim 1. Clarification of the intended scope is required for examination. Appropriate clarifying language may include, for example, reciting that "at least one hydron atom of R5 is replaced with deuterium" or otherwise expressly defining R5 as a deuterated C1-C6 alkyl group. Accordingly, claim 64 is rejected based on its dependency on a rejected base claim. In order to advance prosecution, the Examiner has reasonably construed claim 63 in light of the elected compound species (i.e.,
PNG
media_image1.png
154
148
media_image1.png
Greyscale
).
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 remain rejected and claims 63-64 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)(partially newly applied as necessitated by amendment).
Gerasimov et al. teaches a compound 5, (R,S)-(±)-3-(N-Methylpyrrolidin-3-yl)-4-hydroxyindole, having the structure of:
PNG
media_image2.png
128
129
media_image2.png
Greyscale
(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)
PNG
media_image3.png
266
265
media_image3.png
Greyscale
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):
PNG
media_image4.png
222
483
media_image4.png
Greyscale
.
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.
Response to Arguments
Applicant submitted another amendment to the claims on May 26, 2026, which is filed after the submission of amendment to claims on April 28, 2026 and May 6, 2026. Applicant’s arguments with respect to the rejection(s) of record are presented in the reply filed on April 28, 2026. It is respectfully noted that the replies filed on April 28, 2026, May 6, 2026 and May 26, 2026 are fully considered by the Examiner, and they are addressed in the instant Office Action.
Applicant's arguments filed on April 28, 2026 with respect to the rejection of claims 1, 3, 13, 16, 21-22, 24, 26, 43 and 45 under 35 U.S.C. 103 as being unpatentable over Gerasimov et al. (J. Med. Chem., 1999. Vol. 42: 4257-4263) in view of Jasti et al. (WO 2005/066157 A1) and Harbeson et al. (Annual Reports in Medicinal Chemistry, Academic Press, 2011. Vol. 46: 403-417) have been fully considered but they are not persuasive for the reasons set forth below.
In sum, Applicant amends claim 1 by deleting the limitation of “n is 2 and m is an integer selected from 0 to 8”, and replacing the recitation of “C1-6alkyleneP(O)(OR9)P(O)(OR9)2” with “C1-6alkyleneP(O)(OR9)2”; and further amends claim 43 by deleting the Compound I-24 to I-31, I-37, I-40 and I-41 from the list of compound of Formula (I). Applicant newly added claims 63-65, and therefore, the rejection of record has been revisited and modified in light of the claim amendments.
In Summary, Applicant argues even though Jasti et al. mentions various isotopes, including 2H, it fails to single out 2H deuterium, provide an example of a compound comprising said deuterium, or disclose deuterium at the R12 position of its Formula (I) (corresponding to R4 of instant Formula (I)). Applicant further argues while Harbeson outlines the theoretical basis of the deuterium isotope effect, there is an unpredictability surrounding which effect deuterium may have on a drug's metabolism. Applicant argues one of ordinary skill in the art would not have reasonably expected that deuterating the particular site of Gerasimov et al. would provide the alleged benefit, because deuteration may alter metabolic fate and broader biological behavior in ways whose direction and magnitude depend on the specific substrate, pathway, and enzyme involved. Applicant further argues the deuteriation of drugs, e.g., sildenafil, discussed by Harbeson et al. does not share structural similarity. Applicant further argues the cited references do not provide a reasoned basis to deuterate the particular sites recited in the instant claims, do not narrow the available deuteration options to a finite number of identified, predictable solutions, and do not establish a reasonable expectation that the claimed substitutions would achieve the objective asserted in the Office Action.
In response, applicant’s arguments are not found persuasive for the reasons set forth below:
First, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In the present case, Applicant’s arguments improperly evaluate each reference individually rather than considering the combined teachings of the reference as a whole. For instance, applicant argues there is unpredictably surrounding the development of deuterated compound(s) by citing the teachings of Harbeson et al.; However, applicant fails to consider Jasti et al. teaches a structurally-related compound represented by Formula (I):
PNG
media_image5.png
267
277
media_image5.png
Greyscale
can be prepared by incorporating isotopes of hydrogen, e.g., 2H (see e.g., p. 13, line 6-11); and isotopically labelled compounds are popular in drug and/or substrate tissue distribution and target occupancy assays, e.g., isotopically labeled compounds are particularly useful in SPECT and in PET (see e.g., p. 13, line 11-15). In other words, the teachings of Jasti et al. aligns with the claimed invention to substitute atoms(s) of 3-(heterocyclic)indoles with alternated isotope thereof, e.g., substituting hydrogen with an exemplified isotope 2H; and therefore, the collective teachings of the prior art(s) set forth in rejection of record clearly suggested the claimed invention to one of ordinary skill in the art with a reasonable expectation of success.
According to MPEP 2123, I, “[a] reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)”. In the present case, the mere fact that Jasti et al. fails to exemplify a compound with deuterium or a compound with deuterium at the R12 position of Formula (I) does not mean the prior art is discouraging one of ordinary skill in the art to arrive at isotopically labelled compounds, including replacing the hydrogen atom(s) present at any position of Formula (I) with its isotopes. In addition, MPEP 2141.02, VI states: “‘the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…’ In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). See also MPEP § 2123”. Same logic is applicable to instant product claim(s), it may well be true that Jasti et al. teaches other isotopes, such as 3H, 11C, 14C, and 13N, in addition to 2H that can be incorporated to prepare isotopically labelled compounds; However, more than one alternated isotope does not constitute a teaching away from incorporating 2H as an isotope of hydrogen because such disclosure does not criticize, discredit, or otherwise discourage the incorporation of any of these isotopes to the 3-(heterocyclic)indoles to arrive at a compound with the same activity of modulating 5-HT receptor subtype. Thus, the collective teachings of the prior art(s) set forth in rejection of record clearly suggested the claimed invention to one of ordinary skill in the art with a reasonable expectation of success.
Moreover, it is respectfully noted that MPEP 2143.03 states: “[c]onclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018)”. In other words, absolute certainty or 100% effectiveness in modulating 5-HT receptor subtype is not a requirement to establish the obviousness-type rejection under 35 U.S.C. 103. The examiner recognized that obviousness may be established as long as there is some teachings, suggestion or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. If applicant contends interchanging any available atom with alternated isotope thereof, including interchanging hydrogen with alternated isotope thereof (e.g., 2H), changes the effect of modulating 5-HT receptor, said objective evidence is respectfully required. Please note MPEP 716.01(c) states “[o]bjective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See, for example, In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984)”.
Therefore, in view of the foregoing, applicant’s arguments are not found persuasive.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Chihyi Lee whose telephone number is (571)270-0663. The examiner can normally be reached Monday - Friday 8:30 am - 5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
Prosecution Insights