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 .
Status of the Claims
Claims 52-65 are pending.
Claims 52-65 are rejected.
Priorities
It is acknowledged that instant application 18/719,695, filed on 2024, Jun. 13, is a National Stage entry of PCT/US2022/052879, filed on 2022, Dec. 14, which claims priority from Provisional Application 63,387,225, filed on 2022, Dec. 13, which claims priority from Provisional Application 63,290,037, filed on 2021, Dec. 15.
Information Disclosure Statements
The information disclosure statement(s) (IDS) submitted on 2024, Sept. 05, 2025, Jan. 27, 2025, May 02, 2025, Dec. 19, and 2026, Mar. 31 is/are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the examiner.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 52-53, and 60-65 and is/are rejected under 35 U.S.C. 103 as being unpatentable over Chakravarty (WO 2011/103433 A1; published 2011, Aug. 25) as evidenced by Heilig (Addiction as a brain disease revised: why it still matters, and the need for consilience. Neuropsychopharmacology, 2021, 46, 1715-1723. doi.org/10.1038/s41386-020-00950-y), evidenced by Moussa (Erectile dysfunction in common neurological conditions: a narrative review, Archivio Italiano di Urologia e Andrologia 2020, 92, 371-385. DOI: 10.4081/aiua.2020.4.371), and evidenced by Devillé (Dissociated disorders: between neurosis and psychosis. Case Rep Psychiatry, 2014, 425892. doi: 10.1155/2014/425892), and evidenced by Yates (Factitious disorder: a systematic review of 455 cases in the professional literature. General Hospital Psychiatry, 2016, 41, 20-28. doi.org/10.1016/j.genhosppsych.2016.05.002).
Claims 52-53 are directed to compounds of Formula (IA-2) or Formula (IB-2), or pharmaceutically acceptable salts or solvates thereof:
Table 1. Instantly claimed compound Formulas
Formula (IA-2)
Formula (IB-2)
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162
260
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198
234
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Wherein:
Each of R1,R2, R3 and R4 is independently hydrogen, halogen, -ORa, cyano, alkyl, heteroalkyl, aryl, arylalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, cycloalkyl, or heterocycloalkyl, wherein each alkyl, heteroalkyl, aryl, arylalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, cycloalkyl, or heterocycloalkyl is optionally substituted;
or any of R1 and R2,R2 and R3, or R3 and R4 are taken together with the carbon atoms to which they are attached to form an optionally substituted 5- or 6-membered ring;
R7 is hydrogen, alkyl, haloalkyl, cycloalkyl, or heterocycloalkyl, wherein each alkyl,haloalkyl, cycloalkyl, or heterocycloalkyl is optionally substituted; specifically, R7 = hydrogen or methyl and
Ra is hydrogen, alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, cycloalkyl, or heterocycloalkyl, wherein each alkyl, haloalkyl, heteroalkyl, aryl, arylalkyl, cycloalkyl,or heterocycloalkyl is optionally substituted.
Chakravarty teaches pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives, pharmaceutical compositions thereof, and methods of use in a variety of therapeutic applications including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder, and/or a neuronal disorder (title, abstract). Specifically, Chakravarty discloses compounds 62 and 68 (Table 2).
Table 2. Piperidine derivatives of Chakravarty
Compound 62
Compound 68
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344
282
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437
428
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Compound 62 reads on instant Formula (IB-2) when R7 = hydrogen, R2 = alkyl, and R7 = heterocycloalkyl. The instant specification defines heterocycloalkyl as a radical of the formula –Rz–heteroaryl, where Rz is an alkylene chain (page 15, paragraph 0046); wherein the alkylene chain refers to a divalent alkyl radical, such as the present case of –CH2CH(CH3)–, which may be optionally substituted as described for alkyl groups (page 8, paragraph 0028); wherein the CH atom of the alkylene chain may be substituted with ORx, where Rx may be hydrogen (page 8, paragraph 0027).
Compound 68 reads on instant Formula (IA-2) in the same manner as described above.
The difference between compounds 62 and 68 of Chakravarty and the instant application is that the above compounds fail to teach an azepino-based 7,5-fused ring system.
However, Chakravarty also teaches compounds with an azepino-based 7,5 fused ring system, for example compound 126 (Table 3).
Table 3. Azepine compound of Chakravarty
Compound 126
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313
326
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Chakravarty suggests that both piperidinyl-based 6,5 fused ring systems and azepino-based 7,5 fused ring systems have similar utility as neurotransmitter modulators for the treatment of neurodegenerative diseases (page 2, paragraph 0006). As such, one of ordinary skill in the art would have a reasonable expectation of success to homologate the piperidine ring of compounds 62 and 68 into the azepino derivative thus arriving at the azepino-based 7,5 fused ring system of the current invention.
Claim 60 is directed to a pharmaceutical composition comprising a compound of the above Formulas or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.
Chakravarty teaches pharmaceutical compositions comprising the above compounds and a pharmaceutically acceptable carrier or excipient (page 16, paragraph 0020), wherein the excipients used are defined on (page 36, paragraph 0074).
Claim 61 is directed to a method of promoting neuronal growth in a mammal comprising administering to the mammal a compound of the above Formulas, or any pharmaceutically acceptable salt or solvate thereof.
Chakravarty teaches the above compounds may be used to stimulate neurite outgrowth and/or promote neurogenesis and/or enhance neurotrophic effects in an individual comprising administering to an individual in need thereof an amount of a compound described or a pharmaceutically acceptable salt thereof effective to stimulate neurite outgrowth and/or to promote neurogenesis and/or to enhance neurotrophic effects (page 17, paragraph 0023), wherein an “individual” is defined as a mammal, including but not limited to a human (page 22, paragraph 0032).
Claims 62-63 are directed to a method for treating a neurological disease or disorder in a mammal, comprising administering to the mammal a compound of the above Formulas or any pharmaceutically acceptable salt or solvate thereof, wherein the neurological disease or disorder is a neurodegenerative, a neuropsychiatric, or a substance use disease or disorder
Chakravarty teaches a method of treating a neuronal disorder (page 15, paragraph 0018) (including neurodegenerative diseases (page 25, paragraph 0041)) and a method of treating ADHD (page 116, paragraph 0238), which is noted as being the most common child neuropsychiatric condition present in school-aged children (page 33, paragraph 0065). While Chakravarty does not explicitly state a method of treating substance use diseases or disorders, it is understood in the art that substance use has neurobiological components and by extension is considered a brain disease (see Heilig). Therefore, a reasonable expectation of success exists for treating substance use disorders when a subject is administered a compound that is taught to treat other neurological diseases and disorders.
Claims 64-65 are directed to the method above wherein the neurological disease or disorder is an injury and wherein the neurological disease or disorder is selected from the group consisting of an anxiety, mood, psychotic, personality, eating, sleep, sexuality, impulse control, substance use, dissociative, cognitive, developmental, and factitious disorders.
Chakravarty teaches the use of the compounds above in treating neuronal disorders (page 15, paragraph 0018), including injury-related mild cognitive impairment, traumatic brain injury, avulsion injury, and spinal cord injury (page 25, paragraph 0041). Chakravarty further teaches the treatment of anxiety (page 24, paragraph 0039), depression (page 24, paragraph 0039), psychotic disorder (page 15, paragraph 0018), schizophrenia (page 24, paragraph 0039), allergy diseases (page 25, paragraph 0040) including food allergy (page 34, paragraph 0067), canine cognitive dysfunction syndrome (page 25, paragraph 0041) which is noted as causing abnormal sleep-wake cycles (page 29, paragraph 0051), impulsivity and developmental in the form of ADHD (page 116, paragraph 0238), cognitive disorders (page 15, paragraph 0018), and substance use as described above. While Chakravarty does not explicitly teach methods for treating sexuality, dissociative, and factitious disorders, it is known in the art that these conditions have overlapping comorbidities with disorders described above. For example, erectile dysfunction is a type sexuality disorder that is frequently caused by spinal cord injury (see Moussa); dissociative disorders share many overlapping symptoms as schizophrenia (see Devillé); and many patients with factitious disorders also experience depression (see Yates). Therefore, one of ordinary skill in the art would have a reasonable expectation of success to treat any of sexuality, dissociate, and/or factitious disorders by using the methods taught by Chakravarty.
Claim(s) 52-59 and is/are rejected under 35 U.S.C. 103 as being unpatentable over Sames (US 2023/0382919 A1; published 2023, Nov. 30, priority claim to provisional filing on 2021, Feb. 8) in view of Chakravarty.
Claims 52-58 are directed to compounds of Formula (I2-A) and Formula (I2-B) above, wherein:
R7 is hydrogen or methyl;
Each of R1, R2, R3, and R4 is independently hydrogen, halogen, –Ora, cyano, or haloalkyl;
Each of R1, R2, R3, and R4 is hydrogen;
At least one of R1, R2, R3, and R4 is halogen, haloalkyl, or ORa, wherein Ra is haloalkyl, arylalkyl, or alkyl;
At least one of R1, R2, R3, R4 is benzyloxy, methoxy, fluoro, trifluoromethyl, or trifluoromethoxy;
R3 is benzyloxymethoxy, fluoro, trifluoromethyl, or trifluoromethoxy, and R1, R2, and R3 are each hydrogen.
Sames teaches a class of fused tetracyclic azepino[4.5b]indole derivatives for the treatment of neurological and psychiatric disorders (title, abstract). Specifically, Sames teaches compounds 1-2 (Table 4).
Table 4. Representative compounds of Sames
Compound 1
Compound 2
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88
176
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92
135
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Regarding claims 53-54 and 56-58, compound 1 reads on claim 53 when R7 is hydrogen, claim 54 when each of R1-R4 is independently hydrogen or haloalkyl, claim 56 when at least one of R1-R4 is haloalkyl, claim 57 when at least one of R1-R4, is trifluoromethyl, claim 58 when R3 is trifluoromethyl and R1, R2, and R4 are each hydrogen.
Regarding claim 53-55, compound 2 reads on claim 53 when R7 = methyl and claims 54-55 when each of R1-R4 is hydrogen.
The difference between the compounds taught by Sames and the instant application is that Sames teaches azepino-based 7,6 fused ring systems whereas instant claim 1 recites an azepino-based 7,5 fused ring system.
However, as discussed above, Chakravarty demonstrates homologation of the piperidinyl-based 6,5 ring system into the azepine-based 7,5 ring system is obvious.
A person of ordinary skill in the art could therefore combine the teachings of Chakravarty and Sames to arrive at an azepino-based 7,5 ring system, and would be motivated to do so because there is a reasonable expectation of success for structures with close structural similarity to have similar properties. For example, Chakravarty teaches the use of compounds 62, 68, and 126, inter alia in pharmaceutical compositions and methods of using in the treatment of cognitive disorders, psychotic disorders, neurotransmitter-mediated disorders, and/or neuronal disorders (title, abstract). Chakravarty further teaches these compounds modulate serotonin receptors (e.g., 5-HT2A, 5-HT2C, and/or 5-HT7) (page 17, paragraph 0024) and further demonstrates their efficacy on various 5-HT isoforms (page 177, Table 4). Similarly, Sames teaches the use of compounds 1 and 2 inter alia in pharmaceutical compositions to treat neurological disorders (page 3, paragraph 0090). Sames further teaches a method of using these compounds to activate 5-HT2A, 5-HT2C, or both (page 25, paragraph 0445) and further demonstrates their efficacy on various 5-HT isoforms (page 68, Table 2 and page 69, Table 4). Accordingly, said skilled artisan art would find it prima facie obvious to apply the azepino-based 7,5 ring system of Chakravarty to the teachings of Sames to arrive at the present invention.
Regarding claim 59, the combined teachings of Chakravarty and Sames discussed herein overlaps with the following instantly claimed compounds:
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96
145
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,
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98
144
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,
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94
166
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,
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90
160
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, and
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106
113
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, and
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84
129
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.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Paul Arcoria whose telephone number is (571)272-8719. The examiner can normally be reached Mon-Fri 8:00-5:00 EST.
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/P.A./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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