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 filed on 03/16/2026 is a continuation application of US Application No. 19/189,862 filed on 04/25/2025, which is a continuation application of International Application No. PCT/IB2024/000644 filed on 11/12/2024, which claims the benefit of priority of U.S. Provisional Application No. 63/598,683 filed on 11/14/2023, and U.S. Provisional Application No. 63/598,703 filed on 11/14/2023.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 03/16/2026 and 08/18/2026, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Status of claims
Applicants’ amendments and arguments filed on 08/18/2026 have been received and have been fully considered. Claims 1, 3-4, 9-14, 19-23 and 26-28 were amended, claim 17-18 and 30 were canceled, and claims 31-33 were added.
Claims 1-16, 19-29 and 31-33 are pending.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claims 1 and 23 recite “…. C1-C6alkyleneC3-C7cycloalkyl, C1-C6alkyleneC3-C10heterocycloalkyl, C1-C6alkyleneC6-C10aryl and C1-C6alkyleneC5-C10heteroaryl, ….”
While instant specification defines cycloalkyl, heterocycloalkyl, etc. [Page 15], instant specification does not provide definition to the above alternatives. However, instant specification recites:
The suffix “ene” at the end of a group (for example “alkylene” or “alkenylene”) means that the group is bivalent, that is that itis bonded to two variables each on a different end of or location on the group. [Pg. 18, [0080]].
As such, C1-C6alkyleneC3-C7cycloalkyl is interpreted as –(CH2)1-6-C3-C7cycloalkyl. This interpretation is applied to the above alternatives.
However, Applicant submits that C1-C6alkylene would also include isomers, such as, without limitation, -(CH2)1-3C(CH3)2. This interpretation is supported by the definition of “alkyl” in the specification at [0052] as including isomers. Furthermore, the original specification provides examples of alkylene moieties other than n-alkylene, see, e.g., [00190] and [00191] of the specification. [Remarks, pg. 2, 1st para.]. In view of Applicant persuasive explanation, the C1-C6 alkylene is interpreted according to Applicant’s definition and interpretation.
Withdrawn Objection to Abstract
Objection to Abstract for improper language is withdrawn in view of Applicant’s amendment to the Abstract filed on 08/18/2026. Applicant’s argument is moot.
Withdrawn Objection to Specification
Objection to the disclosure for containing an embedded hyperlink and/or other form of browser-executable code, is withdrawn in view of Applicant’s amendment to the Abstract filed on 08/18/2026 that deletes the embedded hyperlink. Applicant’s argument is moot.
Withdrawn Claim Rejections - 35 USC § 112(a) (Written Description)
Rejection to claims 1-30 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement for reciting prodrug, is withdrawn in view of Applicant’s amendment filed on 08/18/2026 that deletes the term prodrug. Applicant’s argument is moot.
Withdrawn Claim Rejections - 35 USC § 112 (a) (Enablement)
Rejection of claims 17, 18 and 30 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement, is withdrawn in view of Applicant’s amendment filed on 08/18/2026 that cancelled claims 17, 18 and 30. Applicant’s argument is moot.
Withdrawn Claim Rejections - 35 USC § 103
Rejection of claims 1, 2, 3, 4, 5, 6, 10, 11, 12, 13, 14, 15, 16, 19, 20, 21, 22, 23, 24, 25 and 29 under 35 U.S.C. 103 as being unpatentable over Q. Meng et al. (US Patent No 5654431A, 08/05/1997) in view of Harbeson et al. (Annual Reports in Medicinal Chemistry, Academic Press, 2011. Vol. 46: 403-417), is withdrawn in view of Applicant’s amendment filed on 08/18/2026 that amended R6 of claim 1 to exclude C1-C6alkyleneC2-C10heterocycloalkyl and C1-C6alkyleneC2-C10aryl. Applicant argument is moot.
Rejection of claims 1, 2, 3, 5, 6, 9, 10, 11, 15, 16, 17, 18, 23, 24, 25, 26, 29 and 30 under 35 U.S.C. 103 as being unpatentable over A. Slassi et al. (USPN 6100291 A, 08/08/2000) in view of Harbeson et al. (Annual Reports in Medicinal Chemistry, Academic Press, 2011. Vol. 46: 403-417), is withdrawn in view of Applicant’s amendment filed on 08/18/2026 that amended R6 of claim 1 to exclude C3-C7cycloalkyl. Applicant argument is moot.
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 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.
§ 103 Rejection over Dukat in view of Harbeson
Claims 1-3, 5-6, 9, 11, 15-16, 23-26, and 29 rejected under 35 U.S.C. 103 as being unpatentable over M. Dukat et al. J. Med. Chem. (2008) 51 (3): 603–611, “Dukat” cited in the PTO-892) in view of Harbeson et al. (Annual Reports in Medicinal Chemistry, Academic Press, 2011. Vol. 46: 403-417, “Harbeson” cited in the PTO-892 dated on 05/21/2026).
Dukat teaches Benzenesulfonyltryptamine derivatives for binding to 5-HT6 serotonin receptor. [Abstract]. Dukat teaches Benzenesulfonyltryptamine derivative compound 8 below, [pg. 605, Scheme 1]:
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290
546
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Dukat’s compound 8 reads on claim 1 Formula (I), wherein:
X is O,
R1 is H,
R2 is CH2CH3,
R3 is H,
R4 is H,
R5 is H,
R6 is CH3,
R7 is H,
R8 is H, and
n is 0.
and differs from instant claim 1 in that Dukat’s R10 is CH3, whereas R10 in the instant claimed compound of formula (I), as depicted in the table below for facile comparison:
Dukat’s compound 8
Claim 1 compound of Formula (I)
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173
268
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228
366
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Harbeson 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 [p. 404, line 12-16]. Harbeson further teaches most deuterated compounds reported-to-date appear to retain full biochemical potency and selectivity [p. 415, line 5-8].
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of instantly claimed invention to substitute the H of Dukat’s compound 8 with D in view of the teachings of Harbeson. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Harbeson teaches that Deuterium are a powerful medicinal chemistry tool and incorporation of deuterium into pharmacologically active agents offers potential benefits, such as improved exposure profiles and the decreased production of toxic metabolites that could yield improvements in efficacy, tolerability, or safety. [Abstract]. Moreover, Harbeson teaches that deuterated compounds retain full biochemical potency and selectivity. [Abstract]. Furthermore, as well known in the art, hydrogen consists of three isotopes: (1) hydrogen or protium (P or H), (2) deuterium (D); and (3) tritium (T), with mass numbers 1, 2 and 3 respectively. The natural isotopic abundance of Hydrogen 1H is 99.985 % and that of 2H is 0.015 %. W. Meier-Augenstein et al., Stable Isotope Analysis: General Principles and Limitations, In Wiley Encyclopedia of Forensic Science, 1-15 (2012). Also, it is more common to find deuterium bonded to a protium atom to form hydrogen deuteride, which is written as HD or 1H2H. See A. M. Helmenstine, Deuterium Facts, 2019. Thus, deuterium is involved in every synthetic reaction in which hydrogen is employed. Thus, the combination of Dukat and Harbeson meet each and every limitation of claims 1-2 and 23-24.
Claim 3 is met because R6 is CH3.
Claims 5 and 6 are met because R7 and R8 are H.
Claim 9 is met because R6 is CH3.
Claim 11 is met because R3 is H.
Claim 25 is met because R1 is H.
Claim 26 is met because R6 is CH3.
Regarding claims 15-16 and 29, Dukat’s compound 8 was tested for human 5-HT6 receptor binding efficacy, wherein the compound is dissolved in docking solution (composition). [pg. 605, col. 1, last para.].
§ 103 Rejection over Nirogi in view of Harbeson
Claims 1-3, 5-6, 9, 11, 19-20 and 23-26 rejected under 35 U.S.C. 103 as being unpatentable over R. Nirogi et al. Asian Journal of Chemistry; Vol. 25, No. 16 (2013), 9293-9298, “Nirogi” cited in the PTO-892) in view of Harbeson et al. (Annual Reports in Medicinal Chemistry, Academic Press, 2011. Vol. 46: 403-417, “Harbeson” cited in the PTO-892 dated on 05/21/2026).
Nirogi teaches structure activity relationship of rigidized indolyl pyrrolidine derivatives as 5-HT6 receptor ligands [Abstract]. Nirogi teaches compound 10d below, [pg. 9297, Scheme 2]:
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274
544
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Nirogi’s compound 10d reads on claim 1 Formula (I), wherein:
X is O,
R1 is H,
R2 is H,
R3 is H,
R4 is H,
R5 is H,
R6 is CH(CH3)2,
R7 is H,
R8 is H, and
n is 0.
and differs from instant claim 1 in that Dukat’s R10 is CH3, whereas R10 in the instant claimed compound of formula (I), for example compound (R)-I-220, as depicted in the table below for facile comparison:
Nirogi’s compound 10d
Claim 1 compound of Formula (I)
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177
273
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100
172
media_image6.png
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Harbeson 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 [p. 404, line 12-16]. Harbeson further teaches most deuterated compounds reported-to-date appear to retain full biochemical potency and selectivity [p. 415, line 5-8].
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of instantly claimed invention to substitute the H of Nirogi’s compound 10d with D in view of the teachings of Harbeson. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Harbeson teaches that Deuterium are a powerful medicinal chemistry tool and incorporation of deuterium into pharmacologically active agents offers potential benefits, such as improved exposure profiles and the decreased production of toxic metabolites that could yield improvements in efficacy, tolerability, or safety. [Abstract]. Moreover, Harbeson teaches that deuterated compounds retain full biochemical potency and selectivity. [Abstract]. Furthermore, as well known in the art, hydrogen consists of three isotopes: (1) hydrogen or protium (P or H), (2) deuterium (D); and (3) tritium (T), with mass numbers 1, 2 and 3 respectively. The natural isotopic abundance of Hydrogen 1H is 99.985 % and that of 2H is 0.015 %. W. Meier-Augenstein et al., Stable Isotope Analysis: General Principles and Limitations, In Wiley Encyclopedia of Forensic Science, 1-15 (2012). Also, it is more common to find deuterium bonded to a protium atom to form hydrogen deuteride, which is written as HD or 1H2H. See A. M. Helmenstine, Deuterium Facts, 2019. Thus, deuterium is involved in every synthetic reaction in which hydrogen is employed. Thus, the combination of Dukat and Harbeson meet each and every limitation of claims 1-2 and 23-24.
Claim 3 is met because R6 is CH(CH3)2.
Claims 5 and 6 are met because R7 and R8 are H.
Claim 9 is met because R6 is CH(CH3)2.
Claim 11 is met because R3 is H.
Claim 25 is met because R1 is H.
Claim 26 is met because R6 is CH(CH3)2.
Claim 19 further differs from Nirogi’s compound 10d in that claim 19 compound (R)-I-220 includes an additional CH3 group at R6. As provided in MPEP 2144.09, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963). Nirogi’s compound and claim 19 compound 220 are homologs differs by addition of same group, CH3, see MPEP 2144.09 (In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978), In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979), In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978), In re Schechter, 205 F.2d 185, 98 USPQ 144 (CCPA 1953), In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963), In re Wiechert, 370 F.2d 927, 152 USPQ 247 (CCPA 1967), and In re Dillon, 919 F.2d 688, 693, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc). Claim 20 is met because claim 20 recites compound I-220.
Allowable Subject Matter
Claims 4, 7, 8, 10, 12-14, 21-22, 27-28, and 31-33 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Reasons for Allowance
The following is an examiner’s statement of reasons for allowance:
The closest prior art is considered to be J. Wallach et al. (WO 2022/256554 A1, 12/08/2022, “Wallach”, cited in the IDS dated 03/16/2026).
Wallach discloses compound of formula (I’), [page 20-23]. Wallach discloses the indole derivative 215 below as species of formula (I’), [page 197]:
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214
616
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Wallach’s compound 215 above reads on instant claims 1 and 23 wherein X is O; R6 is methyl; R1, R2, R3, R4, R7, R8 and R9 are H; and R10 is C3 cycloalkyl (cyclopropyl), and differs from instant claims 1 and 23 is that Wallach’s R5 is F, whereas R5 of the instant claims is H or C1-C6 alkyl, as depicted in the table below for facile comparison:
Wallach’s indole derivative
Claimed compound
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186
350
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253
396
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In order to arrive at a compound falling within the instant claims 27 and 28, one of ordinary skill in the art would have to modify the above Wallach’s compound 215 to replace the fluoro highlighted with circle (position R5 of instant claims) with H or C1-C6 alkyl. However, Wallach’s disclosure does not provide sufficient guidance and motivation to one of ordinary skill in the art to perform the functional modification to arrive at instantly claimed compounds of claims 27 and 28. Wallach’s disclosure directed to indole derivatives fluorinated at position R5. One of ordinary skill in the art would have no motivation to specifically replace the F at position 5 with H or C1-C6 alkyl. In order to arrive at a compound reads on claim 12-14, 21-22, 31 and 33, one of ordinary skill in the art would have to also replace the cyclopropyl ring at position R10 of instant claimed compound of Formula (I) with one of R10 variables listed on claims 12-14, 21-22, 27-28. However, Wallach’s disclosure does not provide sufficient guidance and motivation to one of ordinary skill in the art to perform the functional modification to arrive at instantly claimed compounds of claims 12-14, 21-22, 31 and 33. In In order to arrive at a compound falling within the instant claims 7-8 and 32, one of ordinary skill in the art would have to modify the above Wallach’s compound 215 to replace the hydrogen at the highlighted oval (position R9 of instant claims) with halo, alkyl, etc. However, Wallach’s disclosure does not provide sufficient guidance and motivation to one of ordinary skill in the art to perform the functional modification to arrive at instantly claimed compounds of claims 7 and 8. Therefore, Wallach does not anticipate or render claims 4, 7, 8, 10, 12-14, 21-22, 27-28 and 31-33 obvious.
Dukat’s compound 8 above does not render claims 4, 7-8, 12-14, 21-22, 27-28 and 31-33 obvious as depicted below:
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202
317
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Dukat does not provide guidance and motivation to one of ordinary skill in the art to perform the functional modification described above.
Nigori’s compound 10d does not render claims 4, 7-8, 10, 12-14, 21-22, 27-28 and 31-33 obvious as depiced below:
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177
367
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Nigori does not provide guidance and motivation to one of ordinary skill in the art to perform the functional modification described above.
Conclusion
Claims 1-3, 5-6, 9, 11, 15-16, 19-20, 23-26 and 29 are rejected and claims 4, 7-8, 10, 12-14, 21-22, 27-28 and 31-33 are objected to.
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 MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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