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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/13/2026 has been entered.
Election/Restrictions
Applicant’s election without traverse of Group (II) with the addition of the compound-Ie
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which is a compound of the formula (I)
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where R1 and R2 are C1-alkyl (methyl), and R3 is a straight C3-alkyl, R4, R6, R7, R8, and R9 are each hydrogen, and X- X- is a pharmaceutically acceptable anion, in the reply filed on 10/07/2024 is maintained.
Priority
This application is a Continuation-in-Part that claims priority to PCT International Application No. PCT/US2020/047791, filed on August 25, 2020, which claims priority to U.S. Provisional Application No. 62/891,388, filed on August 25, 2019, U.S. Provisional Application No. 63/007,653, filed on April 9, 2020, and U.S. Provisional Application No. 63/053,976, filed on July 20, 2020; and this application claims priority to U.S. Provisional Application No. 63/139,976, filed on January 21, 2021.
Claims Status
Claims 54-73 are pending. Claims 54-60 and 62-73 are withdrawn. Claim 61 is examined in accordance to the expanded compound species.
Action Summary
Claim 61 rejected under 35 U.S.C. 103 as being unpatentable over Stamets (US2018/0021326 A1) in view of Patani et al (Chem. Rev. 1996, 96, 3147−3176), is maintained, but, modified and revisted.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 61 is rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The compound of formula (I) of claim 61 which uses the compound of claim 54 encompasses a broad genus defined by multiple independently variables substituents (R1-R9 and X-). Claim 61 also incorporates this genus into a method of preventing or treating a psychological disorder.
The specification does not reasonably convey to one of ordinary skill in the art that Applicant was in possession of the full scope of the claimed genus at the time of filing.
The specification discloses only a limited number of species (approximately eleven compound species; see paragraph [038]), which represent a small subset of the compounds encompassed by the claimed genus. The specification further fails to identify structural features common to the genus that correlate with the asserted biological activity.
Additionally, the experimental data (Table 5) paragraph [144]) demonstrates:
Only one compound (4-OH-TMTI) exhibits measurable receptor activity;
Closely related analogs (e.g., 4AcOTMTI) show not activity;
Structurally similar compounds exhibit divergent activity profiles.
These results indicate that the disclosed species are not representative of the claimed genus and that activity is not predictable based on structure.
Accordingly, the specification does not demonstrate possession of the full scope of the claimed genus, and the written description requirement is satisfied.
Claim 61 is rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 61 encompasses:
A broad genus of compounds (claim 54);
Treatment and prevention of psychological disorders; and
Prophylactic administration (“preventing”).
Undue experimentation is required when the factors as set forth in in re Wand are considered.
Wands Factors
(1) Breadth of the claims:
The claims are broad covering numerous compounds and a wide range of phycological
disorders, including both treatment and prevention.
(2) Nature of the art/predictability:
The art is unpredictable, as small structural changes in tryptamine analogs result in
significant differences in biological activity as evidenced by Applicant’s own data. (Spec. at paragraph [125]. Further, prior art Stamets cited in the 103 rejections below) demonstrates that specific tryptamine compounds exhibit activity, but does not establish that structurally modified analogs will retain such activity., reinforcing unpredictability. (See Stamets paragraph [0016] and claims 18-20.)
(3) Amount of guidance in the specification:
The specification provides limited guidance, consisting primarily of in vitro receptor
binding data for a small number of compounds, with no clear structure-activity relationship.
(4) Working examples:
Only a small number of compounds were tested, and most show little or no activity,
demonstrating that biological activity is not predictable across the claimed genus and that one ordinary skill in the art would be required to screen to identify operative species. Additionally, the specification provides only in vitro receptor binding data and does not demonstrate any correlation between such data and in vivo therapeutic efficacy for the treatment or prevention of psychological disorders. Accordingly, the specification fails to provide working examples to enable the full scope of the claimed invention without undue experimentation.
(5) Quantity of experimentation required:
One of ordinary skill in the art would need to screen a large number of compounds with the claimed genus to identify those relevant activity and then determine appropriate therapeutic use. Such experimentation would be extensive and iterative.
Treatment Embodiments not enabled
The claim encompasses treatment of a broad genus of phycological disorders, yet
The specification provides no in vivo or clinical data:
There is no demonstrated correlation between receptor binding and therapeutic efficacy’
There is no guidance for specific disorders, dosing or administration.
Accordingly, undue experimentation would be required to determine whether the
claimed compound are effective across the full scope of psychological disorders.
Prevention embodiment no enabled
Under the broadest reasonable interpretation, “preventing” includes administration to the subject prior to disease onset.
The specification;
Provides no disclosure of prophylactic use;
Does not identify which subjects would benefit from prevention’
Does not disclose dosing or timing for prevention.
Thus, undue experimentation would be required to practice the prevention
embodiments.
In view of breath of the claims, the unpredictability of the art, the limited and
inconsistent data, and the lack of guidance, the specification does not enable the full scope of the claimed invention without undue experimentation.
Examiner note: The rejection under 35 U.S.C 103. and 35 U.S.C. 102(a) are consistent. The legal standard for obviousness and enablement are distinct and addresses different inquiries. The rejection under 103 is based on whether or not one of ordinary skill in the art would have been motivated to modify the prior art with a reasonable expectation of success that some structurally related compounds would retain biological activity. In contrast, the rejection under 102(a) addresses whether the specification enables the full scope of the claimed invention without undue experimentation. Here, while Stamets in view of Patani provides a reasonable expectation that certain tryptamine analogs may exhibit similar activity, the specification does not provide sufficient guidance to identify which compounds within the broad claimed genus will be operative, nor does not enable their use across the full scope of the claimed psychological disorders, including prophylactic embodiments. Thus, the positions are no inconsistent: a claim may be obvious to try or reasonably expect to yield some operative embodiments, yet still fail to be enabled across its full scope.
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 non-obviousness.
Claims 61 is rejected under 35 U.S.C. 103 as being unpatentable over Stamets (US2018/0021326 A1) in view of Patani et al (Chem. Rev. 1996, 96, 3147−3176).
The fact the term “prevention” which is not defined in the specification, implies that the Examiner can broadly reasonably construe it as the disease has not yet occurred.
Stamets teaches a method for improving neurological health comprising: administering a daily dose of a composition for at least one month to a patient, wherein the composition comprises: one or more of about 0.1 to 10 mg of psilocybin, psilocin, baeocystin, norbaeocystin, or salts thereof, one or more of about 0.1 to 1 gram of psilocybin mushrooms, or combinations thereof; about 0.1 to 200 mg of one or more of erinacines, hericenones, or combinations thereof; and about 1 to 200 mg of niacin. (See claim 14.) Moreover, Stamets teaches the psilocybin includes N-methyl-N-propyl tryptamine (MPT) with possible salts such as fumarate, maleate, picrate, oxalate, tartrate and sulfate salts, which are typically more stable. (See paragraph [0016] and claim 18.) The structure of N-methyl-N-propyl tryptamine (MPT) Is
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. The salts would inherently chemically have to be a pharmaceutically acceptable anion. Moreover, Stamets teaches the method results in one or more of improved memory and cognition, improved motor skills and coordination, improved ability to solve complex computer coding challenges, improved hearing, improved vision, improved sensory function, improved learning or promotion of neurogenesis, or combinations thereof. (See claim 20.)
Stamets does not teach the compound species of the formula (I)
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Patani teaches the ability of a group of bioisosteres to elicit similar biological activity has been attributed to common physicochemical properties. In this review an attempt
has been made to quantitate, in specific instances, physicochemical effects such as electronegativity, steric size, and lipophilicity and to correlate these values to the observed biological activity. (See second paragraph of the left column of page 3148.) Moreover, Patani teaches the widespread application of the concept of isosterism to modify biological activity has given rise to the term bioisosterism. As initially defined by Friedman, bioisosteres were to include all atoms and molecules which fit the broadest definition for isosteres and have a similar type of biological activity, which may even be antagonistic. More recently this definition has been broadened by Burger as “Compounds or groups that possess near-equal molecular
shapes and volumes, approximately the same distribution of electrons, and which exhibit similar physical properties...”. The critical component for bioisosterism is that bioisosteres affect the same pharmacological target as agonists or antagonists and, thereby, have biological properties which are related to each other. (See fourth paragraph of the right column of page 3148.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the compound taught by Stamets in this case N-methyl-N-propyl tryptamine (MPT) by introducing an additional methyl substituent at the amine to form of the N,N-dimethyl analog (DMPT), as such modification represents a routine structural variation within the class of tryptamine derivatives.
It would have further been obvious to prepare the compound as a pharmaceutically acceptable salt, including iodide salt, as Stamets teaches the use of salts and such salts are routinely employed to improve stability, solubility, and formulation properties.
A person of ordinary skill in the art would have had a reasonable expectation of success that the modified compound would retain similar biological activity sufficient for therapeutic use because Stamets establish that tryptamine scaffolds, including MPT, are active in improving neurological function , Patani teaches that small structural modification, such as alkyl substitution at the amine, are expected to yield structurally related compounds with similar biological activity, and the modification from MPT to DMPT represent a minor and predictable structural change within a well-known class of compounds.
In conclusion, it would have been obvious to modify the compound of Stamets in view of Patani to arrive at the elected compound DMPT iodide) and to use such compound in a method of treating psychological disorders, with a reasonable expectation that such structurally related analogs would exhibit similar biological activity.
Applicant’s argument
Applicant argues that the modification from the dialkyl tryptamine (MPT) disclosed in Stamets to the claimed quaternary tryptammonium compound (DMPT iodide) results in a “completely different compound” with significantly different pharmacological properties, and therefore one of ordinary skill in the art would not have been motivated to make such modification.
Examiner’s answer
In response, Applicant’s argument is not commensurate with the scope of the rejection. The rejection is not premised on an expectation that all modified compounds will exhibit identical properties, but rather that one of ordinary skill in the art would have been motivated to make routine structural changes/modifications would yield compounds having similar or related biological activity sufficient to warrant investigation.
Stamets teaches that tryptamine-based compounds, including MPT, are used for improving neurological function. Patani teaches that modification of functional groups, including alkyl substitution at amine position, is a routine medicinal approach for generating structurally related analogs while exploring and potentially retaining biological activity. The modification of MPT to include an additional alkyl substituent on the amine nitrogen represents a routine homologous or alkylation modification within the class of tryptamine derivatives, rather than a departure from the core scaffold.
Applicant’s argument that dialkyl tryptamine (MPT) and quaternary tryptammonium compounds are completely different is not persuasive because the claimed compound retains the same tryptamine core structure, and the modification is limited to substation at the amine nitrogen, which is a recognized site for routine modification in medicinal chemistry. Such modifications are commonly performed to evaluate effects on properties such as solubility, stability, and biological activity.
Moreover, Applicant’s own specification demonstrates that structurally similar tryptamine analogs may exhibit differing levels of activity, which further supports that such compounds are routinely explored and evaluated in the art. This does not negate motivation, rather it underscores the optimization and variation within the class of compounds is expected and routinely undertaken.
To the extent Applicant argues that the pharmacological effect may differ, such argument is not overcome the rejection, as obviousness does not require absolute predictability or identical properties, but only a reasonable expectation that the modification would yield compounds with related biological activity or utility.
Accordingly, Applicant has not provided sufficient evidence or technical reasoning to but the conclusion that the modified DMT compound of Stamets in view of Patani would be expected to arrive at the claimed compound.
Applicant’s argument directed to Grimm’s Hydride Displacement Law are not persuasive because the present rejection does not rely on Grimm’s Hydride Displacement Law. Rather, the rejection is based on the well-established principle that routine structural modifications, including alkyl substitution at amine positions, are commonly employed in medicinal chemistry to generate structurally related analogs of known compounds for evaluation of biological activity. Accordingly, Applicant’s arguments regarding the interpretation of Grimm’s Law are not commensurate with the scope of the rejection.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim s 61 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 8 of copending Application No. 18/544,954 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application claims the same similar compound as the present application with the exception at least R4 is limited to C1-C6 alkoxy whereas the R4 of the instant application encompasses a broader genus, including C1-C6 alkoxy for R4.
The claimed subject matter of the instant application is not patentably distinct from that of the copending application because the limitation of R4 to C1-C6 alkoxy in the copending claims is fully encompassed within the broader scope of R4 recited in the instant claims.
It would have been obvious to one ordinary skill in the art at the time the invention was filed to include such known substituents within a broader genus of functionally similar substituents as recited in the instant claims.
Accordingly, the instant claims are not patentably distinct from the claims of the copending application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claim 61 is not allowed.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628
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