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
Per Applicant’s amendment to the claims, submitted on 11/25/2025, claims 16-17, 19-20, and 35 are amended, claims 1, 26-27, and 36-41 are canceled, and claims 43-51 are newly added. Currently, claims 5, 7-9, 11-17, 19-20, 28-29, 31-35, and 42-51 are pending in the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/28/2025 and 09/09/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant has elected the following invention, without traverse, in response to the Restriction requirement:
II. Claims 5, 7-9, 11-17, 19-20, 28-29, 31-34, and 42 drawn to compounds of Formula (I) as recited in claim 31 and methods of use of said compounds in treatment of mental illness
The claims of the elected invention newly added claims as well as newly added claims 42-51 are pending examination in the instant application.
Claim Objections
Claims 11-12 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.
Claim Rejections - 35 USC § 112 – Second Paragraph
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 46-47, and 51 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.
Claim 46 is indefinite for reciting R6 as being “selected from CH3, CD2H, CDH2, CD3, CF2H, CFH2, CF3” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. The limitations regarding variable R6 lists the indicated C1 species, which appear to lie outside of the limitations for R6 established in parent claim 45. Claim 45 establishes variable R6 as a moiety selected from a Markush group which excludes C1 species unless said C1 species are linked to ZR14 or a ring moiety.
Claim 47 is indefinite for the same reasons as claim 46, as it also recites C1 moieties for variable R6 which lie outside the established limitations of claim 45.
Claim 51 is indefinite for reciting variable R12 as “CH2CH2F” because a person of ordinary skill in the art would not reasonably be able to understand the metes and bounds of the claim. Variable R12 in parent claim 50 is defined by a Markush group which does not include the species CH2CH2F.
Claim Rejections - 35 USC § 102
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.
Claim(s) 31, 5, and 7-9 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Nivorozhkin (WO 2024/046837 A1).
Claim 31 recites a compound of Formula (I):
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Nivorozhkin teaches compounds as 5HT2 receptor agonists for use in treatment of 5HT2 related diseases. Among the compounds taught by Nivorozhkin is the following compound I-38 (page 232):
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225
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The above compound anticipates a compound of Formula (I) wherein:
X is S
R1, R2, R3, R4, and R5 are each H
R6 is C1 alkyl
R7, R8, R9, and R10 are each H
R11 is C1 alkyl
R12 is CH2CH2F
Claim 5 further limits the compound of claim 1 wherein R6 is selected from:
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Compound I-38 of Nivorozhkin is compound of claim 1 wherein R6 is C1 alkyl.
Claim 7 further limits the compound of claim 31 wherein:
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Compound I-38 of Nivorozhkin is a compound of claim 1 wherein each of R7-R10 is H.
Claim 8 further limits the compound of claim 31 wherein:
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Compound I-38 of Nivorozhkin is a compound of claim 1 wherein each of R7-R10 is H.
Claim 9 further limits the compound of claim 31 wherein:
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Compound I-38 of Nivorozhkin is a compound of claim 1 wherein R11 is C1 alkyl.
Claim(s) 13, 14, and 31 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sosic (J. Med. Chem. 2015, 58, 9712−9721).
Claim 13 further limits the compound of claim 31 wherein:
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Sosic teaches compounds as tryptamine based inhibitors of bacterial transglycolase. Among the compounds taught by Sosic is the following compound 10 (page 9714, Scheme 1):
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Compound 10 of Sosic anticipates the compound of the instant claim wherein:
X is S
R1 is H
R2 is C1 alkyl
R3, R4, and R5 are each H
R6 is C1 alkyl
R7, R8, R9, and R10 are each H
R11 and R12 together with the nitrogen atom between, form a 9 membered ring comprising 2 C=O groups
Claim 14 further limits the compound of claim 31 wherein:
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As indicated in the claim 13 rejections, Sosic teaches a compound wherein the corresponding R11 and R12 groups form a 9 membered ring containing two C=O groups. As tautomers are an inherent interconversion for any given compound, each of the indicated C=O groups would have a tautomeric form wherein the double bonded O moieties form an OH group. Accordingly, the inherent tautomeric forms of the compound would anticipate the instant claim.
Claim(s) 15-16 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Nivorozhkin.
Claim 15 further limits the compound of claim 31 wherein R6 is:
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As indicated previously, compound I-38 of Nivorozhkin is a compound of claim 31 wherein R6 is CH3
Claim 16 further limits the compound of claim 31 wherein R11 is selected from the recited species.
Nivorozhkin teaches an additional compound I-37 represented by the following structure:
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The above compound anticipates a compound of the instant claim wherein R11 is CH2CF3.
Claim(s) 17 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sosic.
Claim 17 further limits the compound of claim 31 wherein R11 and R12 come together to form a 3-10 membered heterocyclic ring selected from the recited species.
Compound 10 of Sosic anticipates a compound of the instant claim wherein the combined heterocyclic ring of R11 and R12 is
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.
Claim(s) 28-29, 32-34 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Nivorozhkin.
Claim 28 recites a pharmaceutical composition comprising one or more compounds of claim 31 and a pharmaceutically acceptable carrier.
Nivorozhkin teaches pharmaceutical compositions comprising their compounds together with diluents, adjuvants, excipients, or carriers (page 133, lines 14-22)1.
Claim 29 recites a method of treating a mental illness, comprising (Previously Presented) administering a therapeutically effective amount of one or more compounds of claim 31 to a subject in need thereof, wherein the mental illness is selected from anxiety disorders, generalized anxiety disorder, social anxiety disorder, depression, cancer-related depression, major depressive disorder (MDD), treatment-resistant depression (TRD), postpartum depression (PPD), anxiety, alcohol addiction, drug addiction, opioid addiction, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and combinations thereof.
Nivorozhkin teaches the use of their compounds in the treatment of CNS disorders, including major depressive disorder (MDD) and treatment-resistant depression (TRD), as well as other related conditions (page 187)2.
Claim 32 further limits the compound of claim 31 wherein:
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Nivorozhkin teaches the following compound I-39 (page 231):
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Compound I-39 appears to anticipate a compound of the instant claim wherein:
R2-R5 are each H
R6 is C1 alkyl
R7-R10 are each H
R11 is C1 alkyl
R12 is CH2CHF2
Claim 33 further limits the compound of claim 31 wherein:
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Compound I-38 of Nivorozhkin anticipates a compound of the instant claim wherein:
R2, R4, and R5 are each H
R6 is CH3
R7-R10 are each H
R11 is CH3
R12 is CH2CH2F
Claim 34 further limits the compound of claim 31 wherein:
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Compound I-38 of Nivorozhkin meets each of the limitation of the instant claim, wherein:
R2, R4, and R5 are each H
R6 is CH3
R7-R10 are each H
R11 is CH3
R12 is CH2CH2F
Claim 35 further limits the compound of claim 31 wherein:
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Nivorozhkin teaches the following compound I-11 (page 224):
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The above compound I-11 anticipates a compound of the instant claim wherein:
R2, R4, and R5 are each H
R6 is CHF2
R7-R10 are each H
R11 is CD3
R12 is CD3
Claim 43 further limits the compound of claim 31 wherein:
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Compound I-38 of Nivorozhkin anticipates a compound of the instant claim wherein:
R2, R4, and R5 are each H
R6 is C1 alkyl
R7-R10 are each H
R11 is C1 alkyl
Claim 44 further limits the compound of claim 43 wherein:
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507
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Compound I-38 of Nivorozhkin anticipates a compound of the instant claim wherein:
R2, R4, and R5 are each H
R6 is C1 alkyl
R7-R10 are each H
R11 is C1 alkyl
Claim 46 further limits the compound of claim 45 wherein:
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515
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Compound I-38 of Nivorozhkin anticipates a compound of the instant claim wherein:
R2, R4, and R5 are each H
R6 is CH3
R7-R10 are each H
R11 is CH3
Claim 47 further limits the compound of claim 46 wherein:
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Compound I-38 of Nivorozhkin anticipates a compound of the instant claim wherein:
R2, R4, and R5 are each H
R6 is CH3
R11 is CH3
Claim 48 further limits the compound of claim 44 wherein:
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Compound I-38 of Nivorozhkin anticipates a compound of the instant claim wherein:
R4 and R5 are each H
R6 is CH3
R11 is CH3
Claim 49 recites a compound of Formula (I):
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Nivorozhkin teaches the following compound I-38 (page 232):
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The above compound anticipates a compound of Formula (I) wherein:
X is S
R1, R2, R3, R4, and R5 are each H
R6 is C1 alkyl
R7, R8, R9, and R10 are each H
R11 is C1 alkyl
R12 is CH2CH2F
Claim 50 further limits the compound of claim 49 wherein:
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Nivorozhkin teaches the following compound I-39 (page 231):
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Compound I-39 of Nivorozhkin anticipates a compound of the instant claim wherein:
R2, R4, and R5 are each H
R6 is C1 alkyl
R7-R10 are each H
R11 is C1 alkyl
R12 is CH2CHF2
Claim 51 further limits the compound of claim 50 wherein:
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Compound I-38 of Nivorozhkin anticipates a compound of the instant claim wherein:
R2, R4, and R5 are each H
R6 is C1 alkyl
R7-R10 are each H
R11 is CH2CH2F
R12 is CH2CHF2
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.
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.
Claim(s) 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chadeayne (US 2021/0085671 A1) in view of Martino (previously referenced).
Claim 19 recites a table of compounds, including the following:
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Chadeayne teaches compositions comprising serotonergic drugs, and methods of use for said composition in treating depressive disorders. Among the serotonergic drugs taught by Chadeayne is N,N-Dimethyl-5-methylthio-T (page 30, claim 3), represented by the following structure:
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While Chadeayne does not explicitly teach the indicated compounds recited in the instant claim, it would have been obvious for a person of ordinary skill in the art to arrive at such compounds because the recited compounds are deuterated analogs of N,N-Dimethyl-5-methylthio-T, and Martino teaches that such deuterium replacements are a commonplace technique in the art, and are used to manipulate pharmacodynamic or pharmacokinetic properties of pharmaceutical compounds.
Martino provides an overview on the use of deuterium in pharmaceutical drug discovery. In particular, Martino indicates that the replacement of hydrogen for deuterium may provide improvements to the pharmacokinetic or toxicity profile of drugs, thereby providing benefits to safety and efficacy (page 1) . Such improvements are indicated to be a result of the deuterium kinetic isotope effect (DKIE) wherein C-D bonds are more stable and difficult to cleave relative to original C-H bonds (pages 2-3) . Furthermore, Martino indicates that such deuterated compounds are bioisosteres of their source compounds, meaning that they elicit similar biological effects despite being structurally distinct (page 2) . Accordingly, there would be reasonable expectation that deuteration of the compounds of Chadeayne would yield bioisosteric compounds with potentially improved safety and/or efficacy.
Given that each of the identified compounds of the instant claim are deuterated analogs of N,N-Dimethyl-5-methylthio-T, the teachings of Chadeayne indicating the use of N,N-Dimethyl-5-methylthio-T to treat depressive disorders, and the teachings of Martino with regards to drug deuteration, it would have been prima facie obvious at the time of invention for a person of ordinary skill in the art to develop the compounds of the instant claim by routine experimentation. N,N-Dimethyl-5-methylthio-T has multiple, but limited sites for deuterium replacement of hydrogen. N,N-Dimethyl-5-methylthio-T as a serotonergic drug is indicated as having use in the treatment of depressive disorders, and a person of ordinary skill in the art would have reasonable expectation that deuterated analogs of such compounds would be effective in treating said disorders while potentially imparting improvements to safety or efficacy.
Claim 20 recites a table of compounds, including the following:
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As discussed above in the claim 19 rejection, Chadeayne teaches compositions comprising N,N-Dimethyl-5-methylthio-T as a serotonergic drug, and methods of use of such compositions for the treatment of depressive disorders, while Martino teaches the commonplace practice of deuteration in pharmaceutical drug discovery. The instant claim recites a deuterated analog of N,N-Dimethyl-5-methylthio-T. Accordingly, the instant claim would be obvious for the same obviousness reasons as indicated in the claim 19 rejection.
Allowable Subject Matter
Claims 11-12 contain allowable subject matter. Accordingly, the claims are objected to for depending upon a previously rejected claim (see Claim Objections).
Conclusion
Claims 5, 7-9, 13-17, 19-20, 28-29, 31-35, and 42-51 are rejected.
Claims 11-12 are objected to.
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 ERIC TRAN whose telephone number is (571)272-7854. The examiner can normally be reached Mon-Fri 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “Also disclosed herein is a pharmaceutical composition comprising a compound of Formula (I) through (V), or a pharmaceutically acceptable salt, stereoisomer, tautomer, solvate, polymorph, or prodrug thereof, and a pharmaceutically acceptable vehicle… The term “vehicle” refers to a diluent, adjuvant, excipient, or carrier…”
2 “In some embodiments, the disease or disorder is a central nervous system (CNS) disorder, including, but not limited to, major depressive disorder (MDD), treatment-resistant depression (TRD), post-traumatic stress disorder (PTSD), bipolar and related disorders…”