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 the following species:
Claim 3 as the elected patient species shown as follows:
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Claim 2 as the elected diagnostic criteria species shown as follows:
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Claim 13 as the elected criteria species to identify the occurrence of a peak psychedelic experience shown as follows:
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Claim 22 as the elected assessment species for a clinical response shown as follows:
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Claim 24 as the elected assessment species for a remission of depressive symptoms shown as follows:
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are maintained.
Claims 16-21, 23, and 25-30 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Newly added claim 31 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to the claims filed on July 21, 2026, wherein claims 1-4, 6, 16, 20-21 and 23 are unchanged; claims 5, 7-14, 18 and 25-27 are canceled; and claim 31 is newly added.
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 1-4, 6, 15-17, 19-24, and 28-31 are pending.
Claims 16-17, 19-21, 23, and 28-30 remain withdrawn. Claim 31 is withdrawn.
Claims 1-4, 6, 15, 22 and 24 are under examination in accordance with the elected species.
Priority
The instant application 18/675,614 filed on May 28, 2024 is a continuation of U.S. Application No. 17/431,626 filed on August 21, 2021, which is a 371 of PCT/EP2020/054803 filed on February 24, 2020, which claims priority to and the benefits of Foreign Application No. EP19158774.0 filed on February 22, 2019.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 17/431,626, filed on August 17, 2021.
Receipt is acknowledged of a certified copy of foreign application EP19158774.0, however the present application does not properly claim priority to the submitted foreign application. It is noted that the foreign application fails to discloses the followings:
the major depressive disorder is moderate or severe major depressive disorder as indicated by Montgomery-Asberg Depression Rating Scale (MADRS) score of 20 or more or by a 17-item Hamilton Depression Rating Scale (HAM-D) score of 17 or more; the major depressive disorder is severe major depressive disorder as indicated by a MADRS score of 35 or more or by a HAM-D score of 25 or more;
the patient is suffering from suicidal ideation with intent to act or wherein the patient is at imminent risk for suicide;
wherein a clinical response, as assessed by at least 50% improvement of a MADRS or HAM-D score, compared to a respective score prior to the administration of the 5-MeODMT or a pharmaceutically acceptable salt thereof, is observed on the 6th day or later after the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof;
the patient is in remission of depressive symptoms, as assessed by a MA DRS score equal to or less than 10, or a HAM-D score equal to or less than 7, on day 7 or later after the administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof; and
the Peak Psychedelic Experience Questionnaire as part of the elected criteria species to identify the occurrence of a peak psychedelic experience.
Therefore, each of these findings demonstrate that instant claims 3-4, 15, 22, 24, drawn to a method of major depressive disorder that includes one of the limitations noted above, are not entitled to the benefit of the foreign application, and will receive an effective filing date of February 24, 2020, which is the filing date of 371 of PCT/EP2020/054803.
If this copy is being filed to obtain priority to the foreign filing date under 35 U.S.C. 119(a)-(d) or (f), 365(a) or (b), or 386(a), applicant must also file a claim for such priority as required by 35 U.S.C. 119(b) or 365(b), and 37 CFR 1.55. If the application was filed before September 16, 2012, the priority claim must be made in either the oath or declaration or in an application data sheet; if the application was filed on or after September 16, 2012, the claim for foreign priority must be presented in an application data sheet.
If the application being examined is an original application filed under 35 U.S.C. 111(a) (other than a design application), the claim for priority must be presented during the pendency of the application, and within the later of four months from the actual filing date of the application or sixteen months from the filing date of the prior foreign application. See 37 CFR 1.55(d)(1). If the application being examined is a national stage application under 35 U.S.C. 371, the claim for priority must be made within the time limit set forth in the PCT and Regulations under the PCT. See 37 CFR 1.55(d)(2). Any claim for priority under 35 U.S.C. 119(a)-(d) or (f), 365(a) or (b), or 386(a) not presented within the time period set forth in 37 CFR 1.55 is considered to have been waived. If a claim for foreign priority is presented after the time period set forth in 37 CFR 1.55, the claim may be accepted if the claim properly identifies the prior foreign application and is accompanied by a grantable petition under 37 CFR 1.55(e) to accept an unintentionally delayed claim for priority and the applicable petition fee under 37 CFR 1.17(m)(1) or (m)(2).
Terminal Disclaimer
The terminal disclaimer filed on July 21, 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of any patent granted on Application Number 17/801,389 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Action Summary
All rejection(s) pertaining to claim 7 are moot because the claim was canceled in view of the amendments filed on July 21, 2026.
Claims 1, 3-4, 15, 22 and 24 rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792) are maintained.
Claims 1-4, 15, 22, and 24 remain rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792) as applied to claims 1, 3-4, 15, 22 and 24 above, and further in view of Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are maintained.
Claims 1, 3-4, 6-7, 15, 22, and 24 rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792) as applied to claims 1, 3-4, 15, 22 and 24 above, and further in view of Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043) are maintained but revisited and modified in view of the claim amendments.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 34-38, and 46-47 of copending Application No. 18/679,917 (reference application) in view of Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792), and Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043) are withdrawn in view of the abandonment of the reference application.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 9 of copending Application No. 18/373,904 (referred to herein as “’904”); and over claims 1-5, 9 and 32-35 of copending Application No. 18/373,903 (referred to herein as “’903”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are maintained, but revisited and modified in view of the amendments.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 49, 50-51, and 81-84 of copending Application No. 18/373,906 (referred to herein as “’906”); over claims 1 and 49-51 of copending Application No. 18/373,914 (referred to herein as “’914”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are maintained, but revisited and modified in view of the amendments.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 24 and 35-36 of copending Application No. 17/801,389 (reference application), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are withdrawn in view of the terminal disclaimer filed on July 21, 2026.
Claims 1-4, 6, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 120, 126-127, 131 and 147 of copending Application No. 18/850,376 (referred to herein as “‘376”); claims 70, 76-77, 81, 97 of copending Application No. 18/850,362 (referred to herein as “’362”); claims 33, 35, 58 and 60-61 of copending Application No. 18/850,394 (referred to herein as “’394”); claims 115-121, 125 and 141 of copending Application No. 18/850,348 (referred to herein as “’348”); claims 114-120, 124 and 135 of copending Application No. 18/851,294 (referred to herein as “’294”); claims 97, 106-112 and 123 of copending Application No. 18/851,301 (referred to herein as “’301”); claims 98, 107-111, 112 and 125 of copending Application No. 18/850,370 (referred to herein as “’370”; and claims 119, 121-126, 130 and 141 of copending Application No. 18/851,362 (referred to herein as “’362”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are maintained, but revisited and modified in view of the amendments.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 48-55, 70 and 76 of copending Application No. 18/851,322, in view of Stamets (US 2019/0105313 A1), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are withdrawn in view of the abandonment of the reference application.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 78-85, 100 and 106 of copending Application No. 18/851,356, in view of Stamets (US 2019/0105313 A1), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are withdrawn in view of the amendments.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9-16, and 109-112 of copending Application No. 18/851,346; claims 1, 9-12, 56-59, 61, 62, and 66-67 of copending Application No. 18/851,311; and claims 1, 13-16, 100-103, 105, and 110-111 of copending Application No. 18/851,349 are withdrawn in view of the amendments.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33, 35 and 54-55 of copending Application No. 18/851,329 (reference application), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are withdrawn in view of the abandonment of the reference application.
Claims 1-4, 6-7, 15, 22 and 24 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,172,960 B2 in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are maintained, but revisited and modified in view of the amendments.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/920,063 (reference application), in view Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are maintained, but revisited and modified in view of the amendments.
Claims 1-4, 6-7, 15, 22 and 24 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-30 of copending Application No. 19/573,936 (reference application), in view Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) are withdrawn in view of the amendments.
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, 3-4, 15, 22 and 24 remain rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627; cited in the IDS filed on June 26, 2024), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited in the IDS filed on June 26, 2024).
Carhart-Harris et al. teaches patients with moderate-to-severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (a low oral dose of psilocybin 10 mg on a first dosing day and a high oral dose of psilocybin 25 mg on a second dosing day, separated by 1 week), and the depressive symptoms relative to baseline were markedly reduced 1 week and 3 after high-dose treatment (see e.g., p. 621, right column, last paragraph; abstract, “methods”). Carhart-Harris et al. further teaches the inclusion criteria were major depression of a moderate to severe degree (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]), and no improvement despite two adequate courses of antidepressant treatment of different pharmacological classes lasting at least 6 weeks within the current depressive episode (see e.g., p. 620, left column, last two lines to right column, line 5). Carhart-Harris et al. further teaches the baseline and demographic characteristics of the patients, including patient 2 shown below:
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487
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(see e.g., Table 1). Carhart-Harris et al. further the clinician-administered ratings, including MADRS, were completed at baseline and 1 week after the high-dose session shown below:
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291
175
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(see e.g., Table 3).
Carhart-Harris et al. does not teach 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT).
Stamets teaches a method for treating or improving neurological or mental health conditions comprising administration of an effective amount of a composition comprising psilocybin or psilocin to a subject in need thereof, where the neurological or mental health conditions comprise, inter alia, depression (see e.g., claims 1 and 4-5). Stamets further teaches psilocybin dephosphorylates into psilocin in the liver (see e.g., [0030]):
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.
Stamets further teaches psilocybin and psilocin prodrugs and analogs that may similarly prove useful include those where the hydroxyl group is modified or the methyl groups of the terminal amine nitrogen have been modified (see e.g., p. 3, right column, line 9-12). Stamets further teaches preferred analogs include: analogs substituted at other positions such as, inter alia, 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT); In general, equimolar amounts of an analog may be used in place of psilocybin and/or psilocin in the formulas above, or amounts producing equivalent functional effects may be utilized (see e.g., p. 3, right column, last 3 lines to p. 4, left column, line 2 and line 11-14). Stamets further teaches formulating a composition into a dosage form comprising, inter alia, inhalers (see e.g., [0021]).
Davis et al. teaches in a 5-MeO-DMT survey study, which includes respondents that used 5-MeO-DMT at least once in their lifetime (see e.g., p. 780, “procedure” section), 81% of survey respondents had consumed 5-MeO-DMT through a smoking/vaporizing route of administration (see e.g., p. 783, left column, 1st paragraph under Table 2; Table 3). Davis et al. further teaches current unpublished reports of 5-MeO-DMT use describe inhalation (e.g., smoking or vaporizing) as a common means of consumption (see e.g., p. 780, left column, 3rd paragraph). Davis et al. further teaches the incidence of self-reported lifetime psychiatric disorders in this sample included depression (61%), wherein 77% of the survey respondents with depression reported improvement of their psychiatric conditions (see e.g., p. 784, right column, 1st paragraph; Table 6). Davis et al. further teaches the typical dose of 5-MeO-DMT used by the survey respondents shown as follows (see e.g., Table 3):
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916
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.
In short, Carhart-Harris et al. teaches the administration of two oral doses of psilocybin (10 mg and 25 mg, 7 days apart) for treating treatment-resistant major depression. The difference between the method of Carhart-Harris et al. and the claimed method is that the prior art method administers a therapeutically effective amount of psilocybin rather than the claimed 5-MeO-DMT to a subject with treatment-resistant major depression. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Carhart-Harris et al. by replacing the psilocybin with its analog as taught by Stamets et al., and selectively choose the 5-MeO-DMT taught by Davis et al. as the analog to arrive at the claimed invention. One would have been motivated to do so, because Stamets teaches psilocybin and psilocin prodrugs and analogs, including 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), may similarly prove useful for treating or improving neurological or mental health conditions comprising depression; and Davis et al. teaches the 5-MeO-DMT survey respondents with depression reported improvement of their psychiatric conditions after the administration of 5-MeO-DMT. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT , as taught by Stamets et al. and Davis et al., would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully treat treatment-resistant major depression.
Regarding the limitation of “wherein the major depressive disorder is moderate or severe major depressive disorder as indicated by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 20 or more or by a 17-item Hamilton Depression Rating Scale (HAM-D) score of 17 or more” in claim 3, and the limitation of “wherein the major depressive disorder is severe major depressive disorder as indicated by a MADRS score of 35 or more or by a HAM-D score of 25 or more” in claim 4, each of these limitations is drawn to the severity of major depressive disorder. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the method of Carhart-Harris et al., Stamets et al. and Davis et al. set forth above for treating moderate to severe major depressive disorder with 17+ on the HAM-D scale. One would have been motivated to do so, because Carhart-Harris et al. teaches psilocybin treats moderate-to-severe treatment-resistant major depression (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]), including HADM score of 28. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT, as taught by Stamets et al. and Davis et al., would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully treat moderate to severe treatment-resistant major depression with 17+ on the HAM-D scale; and that renders obvious the limitation of “a HAM-D score of 25 or more”.
Regarding the limitation of “wherein the 5-MeO-DMT or a pharmaceutically acceptable salt thereof is administered via inhalation” in claim 15, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the method of Carhart-Harris et al., Stamets et al. and Davis et al. set forth above for set forth above for administering the 5-MeO-DMT via inhalation. One would have been motivated to do so, because Davis et al. teaches 81% of the 5-MeO-DMT survey respondents through a smoking/vaporizing route of administration, and inhalation (e.g., smoking or vaporizing) is a common means of 5-MeO-DMT consumption. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that inhalation is the most common route of administering 5-MeO-DMT; and therefore, one would have reasonably expected by administering the 5-MeO-DMT via inhalation would have successfully deliver said compound to the patient.
Regarding the limitation of “wherein a clinical response, as assessed by at least 50% improvement of a MADRS… compared to a respective score prior to the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof, is observed on the 6th day or later after the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 22, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of Carhart-Harris et al., Stamets et al. and Davis et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a baseline MADRS of 31.0 and MADRS of 9.7 at 1 week after the last dose of psilocybin. Please note the percentage improvement can be calculated using the MADRS score observed 1 week after the administration of psilocybin and the baseline MADRS score, which when calculated by
100
%
-
9.7
31.0
×
100
%
=
68.71
%
, gives 68.1% improvement of the MADRS score on day 7; and that lies within the claimed range of “at least 50% improvement”. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT, as taught by Stamets et al. and Davis et al., would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
With respect to “wherein the patient is in remission of depressive symptoms, as assessed by a MADRS score equal to or less than 10…, on day 7 or later after the administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 24, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of Carhart-Harris et al., Stamets et al. and Davis et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a MADRS of 9.7 at 1 week after the last dose of psilocybin. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT, as taught by Stamets et al. and Davis et al., would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
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.
Claims 1-4, 15, 22, and 24 remain rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792) as applied to claims 1, 3-4, 15, 22 and 24 above, and further in view of Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450).
The teachings of Carhart-Harris et al., Stamets and Davis et al. are set forth above and applied as before.
Carhart-Harris et al., Stamets and Davis et al. does not teach the major depressive disorder is diagnosed in accordance with a Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) published by the American Psychiatric Association in claim 2; However, Carhart-Harris et al. teaches the patient’s general practitioner or psychiatrist provided written documentation of the patient’s diagnosis and mental health background in every case (see e.g., p. 622, right column, line 24-27).
Tolentino et al. teaches depression diagnosis requires five or more symptoms (Diagnostic and Statistical Manual of Mental Disorders-DSM-5) (see e.g., abstract). Tolentino et al. further teaches according to the DSM-5 criteria, the symptoms are summed to determine the presence or the absence of a major depression episode by citing the Diagnostic and Statistical Manual of Mental Disorders, 5th edition published by American Psychiatric Association (see e.g., p. 2, left column, 2nd paragraph; p. 7, reference 4).
It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Carhart-Harris et al., Stamets and Davis et al. set forth above to treat major depressive disorder diagnosed by general practitioner using the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) published by the American Psychiatric Association as taught by Tolentino et al. to arrive at the claimed invention. One would have been motivated to do so, because Carhart-Harris et al. teaches each and every patients with the major depression are diagnosed by general practitioner; and Tolentino et al. teaches depression diagnosis requires five or more symptoms to determine the presence or the absence of a major depression episode according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) published by American Psychiatric Association. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the patient with major depression diagnosed by a general practitioner using the DSM-5 published by American Psychiatric Association would reasonably be treated by administering the 5-MeO-DMT set forth in the method of Carhart-Harris et al., Stamets and Davis et al. above.
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.
Claims 1, 3-4, 6, 15, 22, and 24 remain rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024) as applied to claims 1, 3-4, 15, 22 and 24 above, and further in view of Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043).
The teachings of Carhart-Harris et al., Stamets and Davis et al. are set forth above and applied as before.
Carhart-Harris et al., Stamets and Davis et al. does not teach the patient is suffering from suicidal ideation in claim 6. However, Carhart-Harris et al. teaches data obtained from large-scale population studies have recently challenged the view that psychedelics negatively affect mental health, with one study’s findings showing lower rates of psychological distress and suicidality among people who had used psychedelics within their lifetime than among those who used no psychedelics but an equivalent amount of other drugs (see e.g., p. 619, right column, line 12 to p. 20, left column, line 3).
Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt in the United States adult population (see e.g., p. 1, line1-7 and line 16-20; Table 1). Hendricks et al. further teaches psilocybin in particular may thus hold promise as an innovative mental health intervention and suicide prophylaxis (see e.g., p. 3, line 25-26).
Regarding claim 6, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of Carhart-Harris et al., Stamets and Davis et al. set forth above to treat the patient with suicidal thinking to arrive at the claimed invention. One would have been motivated to do so, because Carhart-Harris et al. teaches the lifetime use of psychedelics lower rates of psychological distress and suicidality; and Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past year suicidal thinking, past year suicidal planning, and past year suicide attempt, which hold promise as an innovative mental health intervention and suicide prophylaxis. One would have reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT, as taught by Stamets et al. and Davis et al., would have exerted the same or substantially similar suicide prophylaxis effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully treat the patient suffering from suicidal ideation; and that renders obvious the limitation of “suicidal ideation”.
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's arguments filed on July 21, 2026 with respect to the rejection of claims 1, 3-4, 15, 22 and 24 under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792) have been fully considered but they are not persuasive for the reasons set forth below.
Applicant's arguments filed on July 21, 2026 with respect to the rejection of claims 1-4, 15, 22, and 24 remain rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792) as applied to claims 1, 3-4, 15, 22 and 24 above, and further in view of Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) have been fully considered but they are not persuasive for the reasons set forth below.
Applicant’s arguments filed on July 21, 2026 with respect to the rejection of claims 1, 3-4, 6-7, 15, 22, and 24 rejected under 35 U.S.C. 103 as being unpatentable over Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), in view of Stamets (US 2019/0105313 A1) and Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792) as applied to claims 1, 3-4, 15, 22 and 24 above, and further in view of Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043) have been fully considered but they are not persuasive for the reasons set forth below.
The claim amendments submitted on July 21, 2026 canceled claim 7; thus, the rejection of record has been revisited and modified in view of claim amendment. All rejection(s) pertaining to claim 7 are moot because the claim was canceled in view of the amendments.
In Summary, applicant argues Carhart-Harris et al. does not teach administration of psilocybin alone, but rather combination therapy with psychotherapy before, during, and after administration; and therefore, the reference does not isolate the antidepressant effect of psilocybin in treatment-resistant major depressive disorder. Applicant further argues compounds similar in structure will not have similar properties, because psilocybin binds to the 5-HT2A receptor whereas 5-MeO-DMT has 300-fold high selectivity for the 5-HT1A receptor over the 5-HT2A receptor by directing attention to Table 1 of Halberstadt et al. (Psychopharmacology, 2012. Vol. 221(4): 709-718, Table 1; cited in the IDS filed on June 26, 2024 as Reference 146); and Tale 1 of Liechi et al. (Neuropsychopharmacology, 2017. Vol. 42(11): 2114-2127; cited in the IDS filed on June 25, 2024 as Reference 484). Applicant further argues Stamets only mentioned 5-MeO-DMT once, see paragraph [0018], line 72, and that is buried in a laundry list of tryptamine analog as the 26th compound; and does not teach depression or major depressive disorder by directing attention to the Office Action mailed on March 19, 2021 in U.S. Application No. 16/211,281; thus, there is no reason to select 5-MeO-DMT. Applicant further argues Davis et al. does not provide any data on whether 5-MeO-DMT would have any effective in any depressive disorder nor disclose any survey respondent were diagnosed with major depressive disorder; and therefore, the gap between self-reported changes of unknown magnitude in self-reported "depression" of anonymous survey respondents tainted with selection bias is vast, and Davis does not bridge it.
In response, applicant’s argument are not found persuasive for the reasons set forth below:
First, in response to applicant’s argument that Carhart-Harris teaches a combination therapy rather than monotherapy, said argument is not found persuasive. It is respectfully noted that the instant claim(s) recite the transitional term "comprising" (see e.g., “the method comprising administering to a patient who is diagnosed with major depressive disorder…”, line 2-3 of claim 1) that is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004). In other words, the transition “comprising” in the instant method claim(s) indicates that the claim allows for additional steps, and does not exclude psychotherapy or other therapies before, during, and after the administration of 5-MeO-DMT. Therefore, the mere fact that Carhart-Harris et al. teaches psychological support was provided before, during, and after each session (see e.g., abstract), it does not constitute a teachings way from administering a therapeutically effective amount of psilocybin for treating treatment-resistant major depression because it does not criticize, discredit, or otherwise discourage the use of psilocybin for the treatment of treatment-resistant major depression.
In response to applicant’s argument that the psilocybin of Carhart-Harris et al. and the 5-MeO-DMT taught by Stamets and Davis et al. do not have similar properties (i.e., psilocybin primary binds to the 5-HT2A receptor whereas 5-MeO-DMT is more selective for the 5-HT1A receptor), said argument is not found persuasive. It is respectfully noted that Halberstadt et al. and Liechti et al. presented by applicant are not used to form the basis of rejection of record; However, Halberstadt et al. and Liechti et al., which are cited in the IDS filed on June 26, 2024 have been fully considered by the Examiner. Solely to rebut applicant’s argument, both 5-MeO-DMT and psilocbin bind to 5-HT1A and 5-HT2A receptors. While 5-MeO-DMT has greater binding affinity to 5-HT1A receptor, the binding affinity data provide by applicant clearly demonstrates 5-MeO-DMT is also capable of binding to 5-HT2A. Specifically, based upon the Table 1 of Halberstadt et al. presented by applicant, which discloses the receptor binding data for 5-MeO-DMT, the 5-MeO-DMT binds to 5-HT2A receptor at a Ki value of 907±170 nM, and binds to 5-HT1A receptor at Ki value of 3.0±0.2 nM shown below:
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; and based upon the Table 1 of Liechti et al. presented by applicant, which discloses the receptor interaction profiles for psilocin, the psilocin binds to 5-HT2A receptor at a Ki value of 0.049±0.01 μM, and binds to 5-HT1A receptor at Ki value of 0.123±0.02 μM shown below:
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. It is noted that the receptor binding data disclosed by Liechti et al. is drawn to psilocin rather than psilocybin instantly claimed, and psilocybin is taught by Liechti et al. as a prodrug for psilocin (see e.g., p. 2115, left column, last paragraph). In view of the foregoing, 5-MeO-DMT clearly binds to 5-HT2A receptor at a Ki value of 907±170 nM, and that cannot be used to provide basis to support that 5-MeO-DMT does not act on 5-HT2A receptor.
Second, 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 this case, applicant improperly evaluate each reference individually rather than considering the combined teachings of the reference as a whole. It is respectfully noted that applicant presents arguments specifically against Carhart-Harris et al., Stamets and Davis et al. individually rather than all the cited prior arts together. For instance, applicant argues Stamets fails to teach the motivation to select 5-MeO-DMT for depression or major depressive disorder when the rejection of record also relies on Davis et al. to provide nexus between 5-MeO-DMT and depression; and applicant argues Davis et al. fails to teach major depressive disorder or treatment-resistant form of major depressive disorder when the rejection of record relies on Carhart-Harris et al. to established psilocybin is useful for treating treatment-resistant form of major depressive disorder, and relies on Stamets to teach the structural similarity between psilocybin and its analog 5-MeO-DMT are expected to be similarity useful to established relevance of data. It is respectfully noted that the obviousness-type rejection under 35 U.S.C. 103 does not require that each and every claimed limitation be disclosed within a single reference no require that each and every claimed limitation be disclosed within each and every reference. Rather, the issue is whether the collective teachings of the prior art(s) would have suggested the claimed invention to one of ordinary skill in the art with a reasonable expectation of success. Therefore, applicant’s arguments are against the references individually rather than considering the collective teachings as a whole.
Specifically, the rejection of record uses Carhart-Harris et al. to teach the administration of psilocybin for treating treatment-resistant major depression; and further relies on Stamets to established psilocybin and its analogs, including methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (see e.g., p. 4, left column, line 2), may similarly prove useful (see e.g., p. 3, right column, line 9-12); and equimolar amounts of an analog may be used in place of psilocybin and/or psilocin, or amounts producing equivalent functional effects may be utilized (see e.g., p. 3, right column, last 3 lines to p. 4, left column, line 2 and line 11-14); and relies on Davis et al. to teach the 5-MeO-DMT survey respondents with depression reported improvement of their psychiatric conditions after the administration of 5-MeO-DMT (see e.g., p. 784, right column, 1st paragraph; Table 6) (see rejection above for details). In other words, one would have reasonably expected to be successful for interchanging psilocybin of Carhart-Harris et al. with a known psilocin analog, methoxy-N,N-dimethyltryptamine (5-MeO-DMT), in the method of treating treatment-resistant major depression, because Stamets clearly teaches methoxy-N,N-dimethyltryptamine is one of the analogs that may be similarly useful as psilocybin, and Davis et al. clearly teaches 5-MeO-DMT survey respondents with depression demonstrate improvement of their psychiatric conditions. It is respectfully noted that according to MPEP 2143.02, I, “[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)”. In other words, absolute predictability is not a necessary prerequisite to a case of obviousness. Rather, a degree of predictability that one of ordinary skill would have found to be reasonable is sufficient. Therefore, the Examiner is not required to produce evidence to demonstrate absolute predictability of success for treating treatment-resistant major depression; instead, the issues lies whether the collective teachings as a whole would have suggest one of ordinary skill in the art to interchange psilocybin with its analog 5-MeO-DMT for treating treatment-resistant major depression with a reasonable expectation of success. As such, applicant’s arguments are not found persuasive.
In response to applicant’s arguments with respect to the disclosure of Staments (“Stamets first introduced "depression" upon its filing on December 6, 2018, and did so only to newly added claims, and only with respect to the specific claimed combinations of compounds that do not include 5-MeO-DMT”), said arguments are not found persuasive. The patentability of each case is evaluated on a case-by-case basis, rather than in view of the Office Actions of other U.S. Patent Application (i.e., U.S. Application No. 16/211,281); therefore, the Examiner cannot comment on the Office Action mailed on March 19, 2021 in the U.S. Application No. 16/211,281. It is respectfully noted that applicant clearly indicate Stamets discloses depression on the filing date of December 6, 2018, and that is clearly before the effective filing date of the instant application. Solely to rebut applicant’s arguments that depression is only applicable to combinations of compound that exclude 5-MeO-DMT, Staments clearly teaches the neurological or mental health conditions, comprise depression (see e.g., claim 5), that can be treated with the administration of an effective amount of the composition comprising, inter alia, psilocybin, or psilocybin (see e.g., claim 1); and further teaches psilocybin and psilocin prodrugs and analogs, including 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (p. 3, right column, last 3 lines to p. 4, left column, line 2 and line 11-14), may similarly prove useful (see e.g., p. 3, right column, line 9-12). According to MPEP 2141.02, VI, “[a] prior art reference must be considered in its entirety, i.e., as a whole, including portions that would lead away from the claimed invention. W.L. Gore & Assoc., Inc. v. Garlock, Inc., 721 F.2d 1540, 220 USPQ 303 (Fed. Cir. 1983), cert. denied, 469 U.S. 851 (1984)”. Same logic is applicable to instant case, the fact that Statements teaches psilocybin and analog 5-MeO-DMT are expected to be similarly useful, one would have reasonably expected 5-MeO-DMT is also contemplated for use in the method of treating depression as the neurological or mental health condition. According to MPEP 2121, I, “[w]hen the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07. See also In re Antor Media Corp., 689 F.3d 1282, 103 USPQ2d 1555 (Fed. Cir. 2012)”. In other words, if applicant contends the method of Staments is inoperable, e.g., in capable of treating depression, said objective evidence is respectfully requested.
Furthermore, in response to applicant’s arguments that the disclosure of Davis et al. fails to provide data on whether 5-MeO-DMT would have any effect in any depressive disorder, because self-reported changes of unknown magnitude in self-reported depression of anonymous survey respondents tainted with selection bias, said arguments are not found persuasive. It is respectfully noted that Davis et al. clearly teaches in the 5-MeO-DMT survey, “a series of question about respondent’s history of being diagnosed with several medical or psychiatric (e.g., depression, anxiety) conditions and whether their symptoms associated with each condition had improved, stayed the same, or worsen following 5-MeO-DMT use” (see e.g., p. 781, left column, 2nd paragraph). The mere fact that Davis et al. teaches depression diagnoses are self-reported, and 77% of the survey respondents with depression reported improvement of their psychiatric conditions (see e.g., p. 784, right column, 1st paragraph; Table 6), it does not make the teachings of Davis et al. as a whole inoperable nor discourage one of ordinary skill in the art to use 5-MeO-DMT for the treatment for depression. Again, according to MPEP 2121, I, “[w]hen the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07. See also In re Antor Media Corp., 689 F.3d 1282, 103 USPQ2d 1555 (Fed. Cir. 2012)”. In this case, applicant fails to provides any factual support, such as experimental data, technical analysis, scientific reasoning, literature evidence, or an explanation showing why a person of ordinary skill in the art would have conclude the prior art(s), including the 5-MeO-DMT taught by Davis et al., could not work for its intended purpose, rebuttal evidence of nonenablement supporting such assertion is respectively requested.
Lastly, please note arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). Objective 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)
Since the Examiner has provide prior arts to established a reasonable expectation of success to arrive at the claimed invention, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case. In view of the foregoing, the arguments presents by applicant are not found persuasive, the rejection of record has been maintained but revisited and modified in view of the claim amendments.
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.
Claims 1-4, 6, 15, 22 and 24 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 9 of copending Application No. 18/373,904 (referred to herein as “’904”); and over claims 1-5, 9 and 32-35 of copending Application No. 18/373,903 (referred to herein as “’903”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450).
The claims of each reference application are drawn to a method that administers the same compound (an effective amount of 5-MeO-DMT or a pharmaceutically acceptable salt thereof) to the patient that overlaps in scope with the instant application (a patient suffers from postpartum depression and moderate or severe depression and from compromised or severely comprised maternal functioning); wherein the patients is in remission of depressive symptoms on day 7. Please note the claimed term “postpartum depression (PPD)” refers to a major depressive disorder with peripartum onset according to the definition set forth in the reference application(s); therefore, the patient of the reference application is a patient who is diagnosed with major depressive disorder. Please see the reference claims indicated in the statement above.
The difference between each of these reference application is that the ‘904 application teaches the administration via intravenous, intramuscular, or subcutaneous route; and the ‘903 application teaches the administration via inhalation.
The difference between the method of reference application and the claimed method is that the claims of reference application does not teach the patient is suffering from a treatment-resistant form of major depressive disorder. The claims of reference application also does not teach the patient is diagnosed in accordance with DSM-5 as claimed in claim 2. The reference application also does not teach the patient is suffering from suicidal ideation in claim 6. The claims of ‘903 application does not teach the 5-MeO-DMT is administered via inhalation as claimed in claim 15.
Carhart-Harris et al. teaches patients with moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]), unipolar, treatment-resistant major depression received two oral doses of psilocybin (a low oral dose of psilocybin 10 mg on a first dosing day and a high oral dose of psilocybin 25 mg on a second dosing day, separated by 1 week), and the depressive symptoms relative to baseline were markedly reduced 1 week and 3 after high-dose treatment (see e.g., p. 621, right column, last paragraph; abstract, “methods”; p.620, left column, last two lines to right column, line 5). Carhart-Harris further teaches the mean MADRS score decreased from a baseline of 31.0 to 9.7 at 1 week post-treatment (see e.g., Table 3).
Stamets further teaches a method for treating or improving neurological or mental health conditions comprising administration of an effective amount of a composition comprising psilocybin or psilocin to a subject in need thereof, where the neurological or mental health conditions comprise, inter alia, depression (see e.g., claims 1 and 4-5). Stamets further teaches psilocybin and psilocin prodrugs and analogs (compounds having a structure similar to another, but differing from it in respect of a certain substituent in which one or more atoms or functional groups which are replaced with other atoms or groups or substituents) that may similarly prove useful, including 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (see e.g., [0018]). Stamets further teaches formulating a composition into a dosage form comprising, inter alia, inhalers (see e.g., [0021]).
Davis et al. teaches 81% of survey respondents had consumed 5-MeO-DMT through a smoking/vaporizing route of administration, and 3% using other route (e.g., injected, sublingual, rectal)(see e.g., p. 783, left column, 1st paragraph under Table 2; Table 3); and current unpublished reports of 5-MeO-DMT use describe inhalation (e.g., smoking or vaporizing) as a common means of consumption (see e.g., p. 780, left column, 3rd paragraph).
Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt in the United States adult population (see e.g., p. 1, line1-7 and line 16-20; Table 1). Hendricks et al. further teaches psilocybin in particular may thus hold promise as an innovative mental health intervention and suicide prophylaxis (see e.g., p. 3, line 25-26).
Tolentino et al. teaches depression diagnosis requires five or more symptoms (Diagnostic and Statistical Manual of Mental Disorders-DSM-5) (see e.g., abstract). Tolentino et al. further teaches according to the DSM-5 criteria, the symptoms are summed to determine the presence or the absence of a major depression episode by citing the Diagnostic and Statistical Manual of Mental Disorders, 5th edition published by American Psychiatric Association (see e.g., p. 2, left column, 2nd paragraph; p. 7, reference 4).
In the instant case, the difference between the method of each reference application and the claimed invention is that the reference application does not teach treatment-resistant form of major depressive disorder. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method set forth in the claims of each reference application to incorporate the patient suffering from a treatment-resistant form of major depressive disorder as the postpartum depression (a major depressive disorder with peripartum onset), as taught by Carhart-Harris et al. and Stamets, to arrive at the claimed invention. One would have been motivated to do so, because Carhart-Harris et al. teaches psilocybin treats moderate-to-severe treatment-resistant major depression (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]); and Stamets teaches psilocybin and psilocin prodrugs and analogs, including 5-MeO-DMT, may be similarly useful for treating or improving neurological or mental health conditions comprising depression. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that administering 5-MeO-DMT at a therapeutically effective amount would have successfully exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al. for treating moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]) treatment-resistant form of major depressive disorder as the postpartum depression; and thar renders obvious the limitation(s) in claim 3-4.
Regarding claim 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of each reference application, Carhart-Harris and Stamets set forth above to incorporate the major depressive disorder diagnosed by general practitioner using the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) published by the American Psychiatric Association as taught by Tolentino et al. to arrive at the claimed invention. One would have been motivated to do so, because Tolentino et al. teaches depression diagnosis requires five or more symptoms to determine the presence or the absence of a major depression episode according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) published by American Psychiatric Association. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the patient with postpartum depression (a major depressive disorder with peripartum onset), in which the major depressive disorder is diagnosed by a general practitioner using the DSM-5 published by American Psychiatric Association, would reasonably be treated by administering the 5-MeO-DMT set forth in the above.
Regarding claim 6, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of each reference application, Carhart-Harris and Stamets set forth above to treat the patient suffering from suicidal ideation to arrive at the claimed invention. One would have been motivated to do so, because Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past year suicidal thinking and past year suicidal planning thus hold promise as an innovative mental health intervention and suicide prophylaxis. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the 5-MeO-DMT, which is a psilocybin analog, would have exerted the same or substantially similar suicide prophylaxis effect as the psilocybin taught by Hendricks et al. for treating a patient suffering from suicidal ideation.
Regarding claim 15, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the method of ‘904 application, Carhart-Harris and Stamets set forth above by replacing the intravenous, intramuscular, or subcutaneous route with inhalation to arrive at the claimed invention. One would have been motivated to do so, because Davis et al. teaches 81% of the 5-MeO-DMT survey respondents consumed 5-MeO-DMT through a smoking/vaporizing route of administration whereas 3% consumed it via other routes (e.g., injected); and further teaches inhalation (e.g., smoking or vaporizing) is a common means of 5-MeO-DMT consumption. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that inhalation is the most common route of administering 5-MeO-DMT over injection; and therefore, one would have reasonably expected by replacing the intravenous, intramuscular, or subcutaneous route with inhalation would have successfully deliver 5-MeO-DMT to the patient.
Regarding the limitation of “wherein a clinical response, as assessed by at least 50% improvement of a MADRS… compared to a respective score prior to the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof, is observed on the 6th day or later after the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 22, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of each reference application, Carhart-Harris et al., and Stamets et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a baseline MADRS of 31.0 and MADRS of 9.7 at 1 week after the last dose of psilocybin. Please note the percentage improvement can be calculated using the MADRS score observed 1 week after the administration of psilocybin and the baseline MADRS score, which when calculated by
100
%
-
9.7
31.0
×
100
%
=
68.71
%
, gives 68.1% improvement of the MADRS score on day 7; and that lies within the claimed range of “at least 50% improvement”. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT of the reference application would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
With respect to “wherein the patient is in remission of depressive symptoms, as assessed by a MADRS score equal to or less than 10…, on day 7 or later after the administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 24, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of each reference application, Carhart-Harris et al., and Stamets et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a MADRS of 9.7 at 1 week after the last dose of psilocybin. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT of the reference application would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed on July 21, 2026 with respect to the provisional rejection of claims 1-4, 6-7, 15, 22 and 24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 9 of copending Application No. 18/373,904 (referred to herein as “’904”); and over claims 1-5, 9 and 32-35 of copending Application No. 18/373,903 (referred to herein as “’903”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) have been fully considered but they are not persuasive.
In Summary, applicant presents the same arguments (“Stamets does not make the connection between analogs and Depression”), which has been addressed in the response to applicant's arguments with respect to the rejection under 35 U.S.C. 103 set forth above.
In response, Applicant’s argument is not found persuasive for the same reasons set forth above. Given that applicant did not put forth any new arguments specifically against this provisional double patenting rejection, the rejection has been maintained but revisited and modified in view of the amendments.
Claims 1-4, 6, 15, 22 and 24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 86-92 of copending Application No. 18/373,906 (referred to herein as “’906”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450)(newly reapplied as necessitated by amendment); and claims 1-4, 6, 15, 22 and 24 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/373,914 (referred to herein as “’914”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450).
The claims of each of these reference applications are drawn to a method of administering the same compound (an effective amount of 5-MeO-DMT or a pharmaceutically acceptable salt thereof) to a patient producing breast milk.
The difference between each of these reference application is that the ‘914 application teaches the administration via intravenous, intramuscular, or subcutaneous route; and the ‘906 application teaches the administration via inhalation.
The claims of reference application do not teach the patient is suffering from a treatment-resistant form of major depressive disorder. The claims of reference application also do not teach the patient is diagnosed in accordance with DSM-5 in claim 2. The claims of reference application also do not teach the patient is suffer from the moderate or severe major depressive disorder in claims 3-4. The reference application also does not teach the patient is suffering from suicidal ideation in claim 6. The claims of ‘914 application does not teach the 5-MeO-DMT is administered via inhalation in claim 15.
Carhart-Harris et al. teaches patients with moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]), unipolar, treatment-resistant major depression received two oral doses of psilocybin (a low oral dose of psilocybin 10 mg on a first dosing day and a high oral dose of psilocybin 25 mg on a second dosing day, separated by 1 week), and the depressive symptoms relative to baseline were markedly reduced 1 week and 3 after high-dose treatment (see e.g., p. 621, right column, last paragraph; abstract, “methods”; p.620, left column, last two lines to right column, line 5). Carhart-Harris further teaches the mean MADRS score decreased from a baseline of 31.0 to 9.7 at 1 week post-treatment (see e.g., Table 3).
Stamets further teaches a method for treating or improving neurological or mental health conditions comprising administration of an effective amount of a composition comprising psilocybin or psilocin to a subject in need thereof, where the neurological or mental health conditions comprise, inter alia, depression (see e.g., claims 1 and 4-5). Stamets further teaches psilocybin and psilocin prodrugs and analogs (compounds having a structure similar to another, but differing from it in respect of a certain substituent in which one or more atoms or functional groups which are replaced with other atoms or groups or substituents) that may similarly prove useful, including 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (see e.g., [0018]). Stamets further teaches formulating a composition into a dosage form comprising, inter alia, inhalers (see e.g., [0021]).
Davis et al. teaches 81% of survey respondents had consumed 5-MeO-DMT through a smoking/vaporizing route of administration, and 3% using other route (e.g., injected, sublingual, rectal)(see e.g., p. 783, left column, 1st paragraph under Table 2; Table 3); and current unpublished reports of 5-MeO-DMT use describe inhalation (e.g., smoking or vaporizing) as a common means of consumption (see e.g., p. 780, left column, 3rd paragraph).
Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt in the United States adult population (see e.g., p. 1, line1-7 and line 16-20; Table 1). Hendricks et al. further teaches psilocybin in particular may thus hold promise as an innovative mental health intervention and suicide prophylaxis (see e.g., p. 3, line 25-26).
Tolentino et al. teaches depression diagnosis requires five or more symptoms (Diagnostic and Statistical Manual of Mental Disorders-DSM-5) (see e.g., abstract). Tolentino et al. further teaches according to the DSM-5 criteria, the symptoms are summed to determine the presence or the absence of a major depression episode by citing the Diagnostic and Statistical Manual of Mental Disorders, 5th edition published by American Psychiatric Association (see e.g., p. 2, left column, 2nd paragraph; p. 7, reference 4).
In the instant case, the difference between the method of each reference application and the claimed invention is that the reference application does not teach treatment-resistant form of major depressive disorder, and moderate or severe major depressive disorder. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method set forth in the claims of each reference application to incorporate the patient suffering from a treatment-resistant form of major depressive disorder as taught by Carhart-Harris et al. and Stamets to arrive at the claimed invention. One would have been motivated to do so, because Carhart-Harris et al. teaches psilocybin treats moderate-to-severe treatment-resistant major depression (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]); and Stamets teaches psilocybin and psilocin prodrugs and analogs, including 5-MeO-DMT, may be similarly useful for treating or improving neurological or mental health conditions comprising depression. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that administering 5-MeO-DMT at a therapeutically effective amount would have successfully exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al. for treating moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]) treatment-resistant form of major depressive disorder as the postpartum depression; and thar renders obvious the limitation(s) in claim 3-4.
Regarding claim 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of each reference application, Carhart-Harris and Stamets set forth above to incorporate the major depressive disorder diagnosed by general practitioner using the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) published by the American Psychiatric Association as taught by Tolentino et al. to arrive at the claimed invention. One would have been motivated to do so, because Tolentino et al. teaches depression diagnosis requires five or more symptoms to determine the presence or the absence of a major depression episode according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) published by American Psychiatric Association. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the patient with postpartum depression (a major depressive disorder with peripartum onset), in which the major depressive disorder is diagnosed by a general practitioner using the DSM-5 published by American Psychiatric Association, would reasonably be treated by administering the 5-MeO-DMT set forth above.
Regarding claims 6, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of each reference application, Carhart-Harris and Stamets set forth above to treat the patient suffering from suicidal ideation to arrive at the claimed invention. One would have been motivated to do so, because Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past year suicidal thinking and past year suicidal planning thus hold promise as an innovative mental health intervention and suicide prophylaxis. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the 5-MeO-DMT, which is a psilocybin analog, would have exerted the same or substantially similar suicide prophylaxis effect as the psilocybin taught by Hendricks et al. for treating a patient suffering from suicidal ideation.
Regarding claim 15, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the method of ‘914 application, Carhart-Harris and Stamets set forth above by replacing the intravenous, intramuscular, or subcutaneous route with inhalation to arrive at the claimed invention. One would have been motivated to do so, because Davis et al. teaches 81% of the 5-MeO-DMT survey respondents consumed 5-MeO-DMT through a smoking/vaporizing route of administration whereas 3% consumed it via other routes (e.g., injected); and further teaches inhalation (e.g., smoking or vaporizing) is a common means of 5-MeO-DMT consumption. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that inhalation is the most common route of administering 5-MeO-DMT over injection; and therefore, one would have reasonably expected by replacing the intravenous, intramuscular, or subcutaneous route with inhalation would have successfully deliver 5-MeO-DMT to the patient.
Regarding the limitation of “wherein a clinical response, as assessed by at least 50% improvement of a MADRS… compared to a respective score prior to the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof, is observed on the 6th day or later after the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 22, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of each reference application, Carhart-Harris et al., and Stamets et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a baseline MADRS of 31.0 and MADRS of 9.7 at 1 week after the last dose of psilocybin. Please note the percentage improvement can be calculated using the MADRS score observed 1 week after the administration of psilocybin and the baseline MADRS score, which when calculated by
100
%
-
9.7
31.0
×
100
%
=
68.71
%
, gives 68.1% improvement of the MADRS score on day 7; and that lies within the claimed range of “at least 50% improvement”. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT of the reference application would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
With respect to “wherein the patient is in remission of depressive symptoms, as assessed by a MADRS score equal to or less than 10…, on day 7 or later after the administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 24, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of each reference application, Carhart-Harris et al., and Stamets et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a MADRS of 9.7 at 1 week after the last dose of psilocybin. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT of the reference application would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering the therapeutically effective amount of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed on July 21, 2026 with respect to the provisional rejection of claims 1-4, 6, 15, 22 and 24 on the ground of nonstatutory double patenting as being unpatentable over claims 86-92 of copending Application No. 18/373,906 (referred to herein as “’906”); over claim 1 of copending Application No. 18/373,914 (referred to herein as “’914”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) have been fully considered but they are not persuasive.
In Summary, applicant presents the same arguments (“Stamets does not make the connection between analogs and Depression”), which has been addressed in the response to applicant's arguments with respect to the rejection under 35 U.S.C. 103 set forth above.
In response, Applicant’s argument is not found persuasive for the same reasons set forth above and are applied as before. It is respectfully noted that the claims of copending applications have been amended, but they still contains claims drawn to a method of administering 5-MeO-DMT or a pharmaceutically acceptable salt thereof. Given that applicant did not put forth any new arguments specifically against this provisional double patenting rejection, the rejection has been maintained, but revisited and modified in view of the amendment.
Claims 1-4, 6, 15, 22 and 24 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 120, 126-127, 131 and 147 of copending Application No. 18/850,376 (referred to herein as “‘376”); claims 70, 76-77, 81, 97 of copending Application No. 18/850,362 (referred to herein as “’362”); claims 33, 35, 58 and 60-61 of copending Application No. 18/850,394 (referred to herein as “’394”); claims 115-121, 125 and 141 of copending Application No. 18/850,348 (referred to herein as “’348”); claims 114-120, 124 and 135 of copending Application No. 18/851,294 (referred to herein as “’294”); claims 97, 106-112 and 123 of copending Application No. 18/851,301 (referred to herein as “’301”); claims 98, 107-111, 112 and 125 of copending Application No. 18/850,370 (referred to herein as “’370”; and claims 119, 121-126, 130 and 141 of copending Application No. 18/851,362 (referred to herein as “’362”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450).
The claims of each of these reference application are drawn to a method comprising administering the same compound (an effective amount of 5-MeO-DMT or a pharmaceutically acceptable salt thereof to the patient that overlaps in scope with the instant application (a patient is also suffering from major depressive disorder, and the patient suffers from a treatment resistant form of the disorder), wherein the treatments leads to an improvement in the disorder in a patient. Please see the reference claims indicated in the statement above.
The difference between each of these reference application is that the ‘294, ‘301, and ‘141 applications teach the administration via intravenous injection; and the ‘376, ‘362, ‘394, ‘348 and ‘370 applications teach the administration via inhalation.
The claims of reference application do not teach the patient is diagnosed in accordance with DSM-5 in claim 2. The claims of reference application also do not teach the patient is suffer from the moderate or severe major depressive disorder in claims 3-4. The reference application also does not teach the patient is suffering from suicidal ideation in claim 6. The claims of ‘294, ‘301, and ‘141 application does not teach the 5-MeO-DMT is administered via inhalation in claim 15.
Carhart-Harris et al. teaches patients with moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]), unipolar, treatment-resistant major depression received two oral doses of psilocybin (a low oral dose of psilocybin 10 mg on a first dosing day and a high oral dose of psilocybin 25 mg on a second dosing day, separated by 1 week), and the depressive symptoms relative to baseline were markedly reduced 1 week and 3 after high-dose treatment (see e.g., p. 621, right column, last paragraph; abstract, “methods”; p.620, left column, last two lines to right column, line 5). Carhart-Harris further teaches the mean MADRS score decreased from a baseline of 31.0 to 9.7 at 1 week post-treatment (see e.g., Table 3).
Stamets further teaches a method for treating or improving neurological or mental health conditions comprising administration of an effective amount of a composition comprising psilocybin or psilocin to a subject in need thereof, where the neurological or mental health conditions comprise, inter alia, depression (see e.g., claims 1 and 4-5). Stamets further teaches psilocybin and psilocin prodrugs and analogs (compounds having a structure similar to another, but differing from it in respect of a certain substituent in which one or more atoms or functional groups which are replaced with other atoms or groups or substituents) that may similarly prove useful, including 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (see e.g., [0018]). Stamets further teaches formulating a composition into a dosage form comprising, inter alia, inhalers (see e.g., [0021]).
Davis et al. teaches 81% of survey respondents had consumed 5-MeO-DMT through a smoking/vaporizing route of administration, and 3% using other route (e.g., injected, sublingual, rectal)(see e.g., p. 783, left column, 1st paragraph under Table 2; Table 3); and current unpublished reports of 5-MeO-DMT use describe inhalation (e.g., smoking or vaporizing) as a common means of consumption (see e.g., p. 780, left column, 3rd paragraph).
Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt in the United States adult population (see e.g., p. 1, line1-7 and line 16-20; Table 1). Hendricks et al. further teaches psilocybin in particular may thus hold promise as an innovative mental health intervention and suicide prophylaxis (see e.g., p. 3, line 25-26).
Tolentino et al. teaches depression diagnosis requires five or more symptoms (Diagnostic and Statistical Manual of Mental Disorders-DSM-5) (see e.g., abstract). Tolentino et al. further teaches according to the DSM-5 criteria, the symptoms are summed to determine the presence or the absence of a major depression episode by citing the Diagnostic and Statistical Manual of Mental Disorders, 5th edition published by American Psychiatric Association (see e.g., p. 2, left column, 2nd paragraph; p. 7, reference 4).
In the instant case, the difference between the method of each of these reference applications and the claimed invention is that the reference application does not teach moderate or severe major depressive disorder. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method set forth in the claims of reference application to incorporate moderate or severe major depressive disorder as the major depressive disorder. One would have been motivated to do so, because Carhart-Harris et al. teaches psilocybin treats moderate-to-severe treatment-resistant major depression (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]); and Stamets teaches psilocybin and psilocin prodrugs and analogs, including 5-MeO-DMT, may be similarly useful for treating or improving neurological or mental health conditions comprising depression. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the administration of psilocybin analog 5-MeO-DMT at a therapeutically effective amount would have successfully exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al. for treating moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]) treatment-resistant form of major depressive disorder as the major depressive disorder; and thar renders obvious the limitation(s) in claim 3-4.
Regarding claim 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference application, Carhart-Harris and Stamets set forth above to incorporate the major depressive disorder diagnosed by general practitioner using the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) published by the American Psychiatric Association as taught by Tolentino et al. to arrive at the claimed invention. One would have been motivated to do so, because Tolentino et al. teaches depression diagnosis requires five or more symptoms to determine the presence or the absence of a major depression episode according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) published by American Psychiatric Association. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the patient with major depressive disorder diagnosed by a general practitioner using the DSM-5 published by American Psychiatric Association would reasonably be treated by administering the 5-MeO-DMT set forth above.
Regarding claims 6, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference application, Carhart-Harris and Stamets set forth above to treat the patient suffering from suicidal ideation to arrive at the claimed invention. One would have been motivated to do so, because Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past year suicidal thinking and past year suicidal planning thus hold promise as an innovative mental health intervention and suicide prophylaxis. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT would have exerted the same or substantially similar suicide prophylaxis effect as the psilocybin taught by Hendricks et al. for treating a patient suffering from suicidal ideation, including the patient suffering from suicidal ideation with intent to act.
Regarding claim 15, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the method of each of the 294, ‘301, and ‘141 applications, Carhart-Harris and Stamets set forth above by replacing the intravenous injection with inhalation to arrive at the claimed invention. One would have been motivated to do so, because Davis et al. teaches 81% of the 5-MeO-DMT survey respondents consumed 5-MeO-DMT through a smoking/vaporizing route of administration whereas 3% consumed it via other routes (e.g., injected); and further teaches inhalation (e.g., smoking or vaporizing) is a common means of 5-MeO-DMT consumption. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that inhalation is the most common route of administering 5-MeO-DMT over injection; and therefore, one would have reasonably expected by replacing the intravenous injection with inhalation would have successfully deliver 5-MeO-DMT to the patient.
Regarding the limitation of “wherein a clinical response, as assessed by at least 50% improvement of a MADRS… compared to a respective score prior to the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof, is observed on the 6th day or later after the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 22, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of reference application, Carhart-Harris et al., and Stamets et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a baseline MADRS of 31.0 and MADRS of 9.7 at 1 week after the last dose of psilocybin. Please note the percentage improvement can be calculated using the MADRS score observed 1 week after the administration of psilocybin and the baseline MADRS score, which when calculated by
100
%
-
9.7
31.0
×
100
%
=
68.71
%
, gives 68.1% improvement of the MADRS score on day 7; and that lies within the claimed range of “at least 50% improvement”. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that a therapeutically effective amount of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
With respect to “wherein the patient is in remission of depressive symptoms, as assessed by a MADRS score equal to or less than 10…, on day 7 or later after the administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 24, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of reference application, Carhart-Harris et al., and Stamets et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a MADRS of 9.7 at 1 week after the last dose of psilocybin. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog 5-MeO-DMT would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering a therapeutically effective amount of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed on July 21, 2026 with respect to the rejection of claims 1-4, 6, 15, 22 and 24 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 120, 126-127, 131 and 147 of copending Application No. 18/850,376 (referred to herein as “‘376”); claims 70, 76-77, 81, 97 of copending Application No. 18/850,362 (referred to herein as “’362”); claims 33, 35, 58 and 60-61 of copending Application No. 18/850,394 (referred to herein as “’394”); claims 115-121, 125 and 141 of copending Application No. 18/850,348 (referred to herein as “’348”); claims 114-120, 124 and 135 of copending Application No. 18/851,294 (referred to herein as “’294”); claims 97, 106-112 and 123 of copending Application No. 18/851,301 (referred to herein as “’301”); claims 98, 107-111, 112 and 125 of copending Application No. 18/850,370 (referred to herein as “’370”; and claims 119, 121-126, 130 and 141 of copending Application No. 18/851,362 (referred to herein as “’362”), in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) have been fully considered but they are not persuasive.
In Summary, applicant presents the same arguments (“Stamets does not make the connection between analogs and Depression”), which has been addressed in the response to applicant's arguments with respect to the rejection under 35 U.S.C. 103 set forth above.
In response, Applicant’s argument is not found persuasive for the same reasons set forth above. Given that applicant did not put forth any new arguments specifically against this provisional double patenting rejection, the rejection has been maintained but revisited and modified in view of the amendments.
Claims 1-4, 6, 15, 22 and 24 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,172,960 B2 in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450).
The claims of the reference patent is drawn to a hydrobromide salt of 5-MeO-DMT in crystalline form; and a pharmaceutical composition comprising said salt.
The claims of reference application do not teach administering a therapeutically effective amount of the salt to a patient suffering from a treatment-resistant form of major depressive disorder. The claims of reference application also do not teach the patient is diagnosed in accordance with DSM-5 in claim 2. The claims of reference application also do not teach the patient is suffer from the moderate or severe major depressive disorder in claims 3-4. The reference application also does not teach the patient is suffering from suicidal ideation in claim 6. The claims of ‘914 application does not teach the 5-MeO-DMT is administered via inhalation in claim 15.
Carhart-Harris et al. teaches patients with moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]), unipolar, treatment-resistant major depression received two oral doses of psilocybin (a low oral dose of psilocybin 10 mg on a first dosing day and a high oral dose of psilocybin 25 mg on a second dosing day, separated by 1 week), and the depressive symptoms relative to baseline were markedly reduced 1 week and 3 after high-dose treatment (see e.g., p. 621, right column, last paragraph; abstract, “methods”; p.620, left column, last two lines to right column, line 5). Carhart-Harris further teaches the mean MADRS score decreased from a baseline of 31.0 to 9.7 at 1 week post-treatment (see e.g., Table 3).
Stamets further teaches a method for treating or improving neurological or mental health conditions comprising administration of an effective amount of a composition comprising psilocybin or psilocin to a subject in need thereof, where the neurological or mental health conditions comprise, inter alia, depression (see e.g., claims 1 and 4-5). Stamets further teaches psilocybin and psilocin prodrugs and analogs (compounds having a structure similar to another, but differing from it in respect of a certain substituent in which one or more atoms or functional groups which are replaced with other atoms or groups or substituents) that may similarly prove useful, including 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (see e.g., [0018]). Stamets further teaches also preferred, where possible, are the salts of the tryptamine compounds, for example hydrochloride, fumarate, maleate, picrate, oxalate, tartrate and sulfate salts, which are typically more stable (see e.g., [0018]). Stamets further teaches formulating a composition into a dosage form comprising, inter alia, inhalers (see e.g., [0021]).
Davis et al. teaches 81% of survey respondents had consumed 5-MeO-DMT through a smoking/vaporizing route of administration, and 3% using other route (e.g., injected, sublingual, rectal)(see e.g., p. 783, left column, 1st paragraph under Table 2; Table 3); and current unpublished reports of 5-MeO-DMT use describe inhalation (e.g., smoking or vaporizing) as a common means of consumption (see e.g., p. 780, left column, 3rd paragraph).
Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt in the United States adult population (see e.g., p. 1, line1-7 and line 16-20; Table 1). Hendricks et al. further teaches psilocybin in particular may thus hold promise as an innovative mental health intervention and suicide prophylaxis (see e.g., p. 3, line 25-26).
Tolentino et al. teaches depression diagnosis requires five or more symptoms (Diagnostic and Statistical Manual of Mental Disorders-DSM-5) (see e.g., abstract). Tolentino et al. further teaches according to the DSM-5 criteria, the symptoms are summed to determine the presence or the absence of a major depression episode by citing the Diagnostic and Statistical Manual of Mental Disorders, 5th edition published by American Psychiatric Association (see e.g., p. 2, left column, 2nd paragraph; p. 7, reference 4).
In the instant case, the difference between the reference patent and the claimed invention is that the reference application is drawn to a hydrobromide salt of 5-MeO-DMT whereas the instant application is drawn to a method of use. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to administer the hydrobromide salt of 5-MeO-DMT of reference patent at a therapeutically effective amount for treating treatment-resistant form of major depressive disorder, including moderate or severe major depressive disorder, to arrive at the claimed invention. One would have been motivated to do so, because Carhart-Harris et al. teaches psilocybin treats moderate-to-severe treatment-resistant major depression (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]); Stamets teaches psilocybin and psilocin prodrugs and analogs, including 5-MeO-DMT and salts of the tryptamine compounds, may be similarly useful for treating or improving neurological or mental health conditions comprising depression; and Davis et al. teaches the 5-MeO-DMT survey respondents with depression reported improvement of their psychiatric conditions after the administration of 5-MeO-DMT. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that administering the hydrobromide salt of 5-MeO-DMT at a therapeutically effective amount would have successfully exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al. for treating moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]) treatment-resistant form of major depressive disorder; and thar renders obvious the limitation(s) in claim 3-4.
Regarding claim 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference patent, Carhart-Harris, Stamets and Davis et al. set forth above to incorporate the major depressive disorder diagnosed by general practitioner using the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) published by the American Psychiatric Association as taught by Tolentino et al. to arrive at the claimed invention. One would have been motivated to do so, because Tolentino et al. teaches depression diagnosis requires five or more symptoms to determine the presence or the absence of a major depression episode according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) published by American Psychiatric Association. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the patient with major depressive disorder diagnosed by a general practitioner using the DSM-5 published by American Psychiatric Association would reasonably be treated by administering the 5-MeO-DMT set forth above.
Regarding claims 6, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference patent, Carhart-Harris, Stamets and Davis et al. set forth above to treat the patient suffering from suicidal ideation to arrive at the claimed invention. One would have been motivated to do so, because Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past year suicidal thinking and past year suicidal planning thus hold promise as an innovative mental health intervention and suicide prophylaxis. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog, hydrobromide salt of 5-MeO-DMT, would have exerted the same or substantially similar suicide prophylaxis effect as the psilocybin taught by Hendricks et al. for treating a patient suffering from suicidal ideation.
Regarding claim 15, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the method of reference patent, Carhart-Harris, Stamets and Davis et al. set forth above to administer the 5-MeO-DMT via inhalation to arrive at the claimed invention. One would have been motivated to do so, because Davis et al. teaches 81% of the 5-MeO-DMT survey respondents consumed 5-MeO-DMT through a smoking/vaporizing route of administration whereas 3% consumed it via other routes (e.g., injected); and further teaches inhalation (e.g., smoking or vaporizing) is a common means of 5-MeO-DMT consumption. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that inhalation is the most common route of administering the 5-MeO-DMT; and therefore, one would have reasonably expected by administering the hydrobromide salt of 5-MeO-DMT via inhalation would have successfully deliver 5-MeO-DMT to the patient.
Regarding the limitation of “wherein a clinical response, as assessed by at least 50% improvement of a MADRS… compared to a respective score prior to the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof, is observed on the 6th day or later after the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 22, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of reference patent, Carhart-Harris et al., Stamets et al. and Davis et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a baseline MADRS of 31.0 and MADRS of 9.7 at 1 week after the last dose of psilocybin. Please note the percentage improvement can be calculated using the MADRS score observed 1 week after the administration of psilocybin and the baseline MADRS score, which when calculated by
100
%
-
9.7
31.0
×
100
%
=
68.71
%
, gives 68.1% improvement of the MADRS score on day 7; and that lies within the claimed range of “at least 50% improvement”. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog, hydrobromide salt of 5-MeO-DMT, would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering a therapeutically effective amount of a hydrobromide salt of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
With respect to “wherein the patient is in remission of depressive symptoms, as assessed by a MADRS score equal to or less than 10…, on day 7 or later after the administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 24, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of reference patent, Carhart-Harris et al., Stamets et al. and Davis et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a MADRS of 9.7 at 1 week after the last dose of psilocybin. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog, hydrobromide salt of 5-MeO-DMT, would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering a therapeutically effective amount of hydrobromide salt of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed on July 21, 2026 with respect to the rejection of claims 1-4, 6-7, 15, 22 and 24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,172,960 B2 in view of Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) have been fully considered but they are not persuasive.
In Summary, applicant argues the claims of reference patent is drawn to a product rather than a method comprising administering a therapeutically effective amount of the hydrobromide salt to a patient suffering from treatment-resistant major depressive disorder. Applicant argues the nonstatutory double patenting rejection of record transform crystalline salt and composition claims into a method of treatment claim is not being consistent with the instructions of MPEP, because no part of the reference patent may be used as it were prior art, and subject matter disclosed outside the scope of a reference claim cannot be used to support the rejection.
In response, applicant’s arguments are not found persuasive for the reasons set forth below:
It may well be true the reference patent recites a product (“hydrobromide salt of 5-MeO-DMT in crystalline form and pharmaceutical compositions comprising that salt”) whereas the claimed invention recites a method of treating; However, it is clear that the crystalline form of a hydrobromide salt of 5-MeO-DMT has the same chemical structure as the hydrobromide salt of 5-MeO-DMT, which is a pharmaceutically acceptable salt of 5-MeO-DMT. In other words, the difference between the claims of reference patent and the claimed invention lies on the fact that the claims of reference patent do not teach administering a therapeutically effective amount of the salt (“hydrobromide salt of 5-MeO-DMT in crystalline form and pharmaceutical compositions comprising that salt”) to a patient suffering from a treatment-resistant form of major depressive disorder, in addition to the limitation(s) recites in the dependent claims as indicated in the rejection of record (see rejection above).
It is respectfully noted that there is nowhere in the MPEP that states the obviousness-type double patenting rejection cannot be made using the product claim(s) from a reference patent or application to render the method claim(s) of instant application obvious; Rather, the analysis of obviousness-type nonstatutory double patenting rejection centers on whether the claimed invention would have been an obvious variation of a claim in a reference patent from the perspective of a person of ordinary skill in the art. In this case, the obviousness-type double patenting rejection of record clearly established the nexus between treatment-resistant major depressive disorder with the salt of 5-MeO-DMT. Specifically, as noted in the obviousness-type double patenting rejection set forth above, Carhart-Harris et al. demonstrate psilocybin can treats moderate-to-severe treatment-resistant major depression (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]); Stamets teaches psilocybin and psilocin prodrugs and analogs, including 5-MeO-DMT and salts of the tryptamine compounds, may be similarly useful for treating or improving neurological or mental health conditions comprising depression; and Davis et al. teaches the 5-MeO-DMT survey respondents with depression reported improvement of their psychiatric conditions after the administration of 5-MeO-DMT. In other words, one would have reasonably expected to be successful, because one would have reasonably understood that the hydrobromide salt of 5-MeO-DMT, is a salt of 5-MEO-DMT; and would have expected that the hydrobromide salt of 5-MeO-DMT is an analog that is expected to be similarly useful as psilocybin. Accordingly, one would have reasonably expected that administering the product of reference patent at a therapeutically effective amount would have successfully exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al. for treating moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]) treatment-resistant form of major depressive disorder, in the absence of evidence to the contrary.
Therefore, the obviousness-type double patenting rejection of record has been maintained, but revisited and modified in view of the amendments.
Claims 1-4, 6, 15, 22 and 24 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/920,063 (reference application), in view Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450).
The claims of the reference application is drawn to a hydrobromide salt of 5-MeO-DMT in crystalline form; and a pharmaceutical composition comprising said salt.
The claims of reference application do not teach administering a therapeutically effective amount of the salt to a patient suffering from a treatment-resistant form of major depressive disorder. The claims of reference application also do not teach the patient is diagnosed in accordance with DSM-5 in claim 2. The claims of reference application also do not teach the patient is suffer from the moderate or severe major depressive disorder in claims 3-4. The reference application also does not teach the patient is suffering from suicidal ideation in claim 6. The claims of ‘914 application does not teach the 5-MeO-DMT is administered via inhalation in claim 15.
Carhart-Harris et al. teaches patients with moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]), unipolar, treatment-resistant major depression received two oral doses of psilocybin (a low oral dose of psilocybin 10 mg on a first dosing day and a high oral dose of psilocybin 25 mg on a second dosing day, separated by 1 week), and the depressive symptoms relative to baseline were markedly reduced 1 week and 3 after high-dose treatment (see e.g., p. 621, right column, last paragraph; abstract, “methods”; p.620, left column, last two lines to right column, line 5). Carhart-Harris further teaches the mean MADRS score decreased from a baseline of 31.0 to 9.7 at 1 week post-treatment (see e.g., Table 3).
Stamets further teaches a method for treating or improving neurological or mental health conditions comprising administration of an effective amount of a composition comprising psilocybin or psilocin to a subject in need thereof, where the neurological or mental health conditions comprise, inter alia, depression (see e.g., claims 1 and 4-5). Stamets further teaches psilocybin and psilocin prodrugs and analogs (compounds having a structure similar to another, but differing from it in respect of a certain substituent in which one or more atoms or functional groups which are replaced with other atoms or groups or substituents) that may similarly prove useful, including 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (see e.g., [0018]). Stamets further teaches also preferred, where possible, are the salts of the tryptamine compounds, for example hydrochloride, fumarate, maleate, picrate, oxalate, tartrate and sulfate salts, which are typically more stable (see e.g., [0018]). Stamets further teaches formulating a composition into a dosage form comprising, inter alia, inhalers (see e.g., [0021]).
Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt in the United States adult population (see e.g., p. 1, line1-7 and line 16-20; Table 1). Hendricks et al. further teaches psilocybin in particular may thus hold promise as an innovative mental health intervention and suicide prophylaxis (see e.g., p. 3, line 25-26).
Davis et al. teaches 81% of survey respondents had consumed 5-MeO-DMT through a smoking/vaporizing route of administration, and 3% using other route (e.g., injected, sublingual, rectal)(see e.g., p. 783, left column, 1st paragraph under Table 2; Table 3); and current unpublished reports of 5-MeO-DMT use describe inhalation (e.g., smoking or vaporizing) as a common means of consumption (see e.g., p. 780, left column, 3rd paragraph).
Tolentino et al. teaches depression diagnosis requires five or more symptoms (Diagnostic and Statistical Manual of Mental Disorders-DSM-5) (see e.g., abstract). Tolentino et al. further teaches according to the DSM-5 criteria, the symptoms are summed to determine the presence or the absence of a major depression episode by citing the Diagnostic and Statistical Manual of Mental Disorders, 5th edition published by American Psychiatric Association (see e.g., p. 2, left column, 2nd paragraph; p. 7, reference 4).
In the instant case, the difference between the reference application and the claimed invention is that the reference application is drawn to a hydrobromide salt of 5-MeO-DMT whereas the instant application is drawn to a method of use. It would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to administer the hydrobromide salt of 5-MeO-DMT of reference application at a therapeutically effective amount for treating treatment-resistant form of major depressive disorder, including moderate or severe major depressive disorder, to arrive at the claimed invention. One would have been motivated to do so, because Carhart-Harris et al. teaches psilocybin treats moderate-to-severe treatment-resistant major depression (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]); Stamets teaches psilocybin and psilocin prodrugs and analogs, including 5-MeO-DMT and salts of the tryptamine compounds, may be similarly useful for treating or improving neurological or mental health conditions comprising depression; and Davis et al. teaches the 5-MeO-DMT survey respondents with depression reported improvement of their psychiatric conditions after the administration of 5-MeO-DMT. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that administering the hydrobromide salt of 5-MeO-DMT at a therapeutically effective amount would have successfully exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al. for treating moderate-to-severe (17+ on the 21-item Hamilton Depression Rating scale [HAM-D]) treatment-resistant form of major depressive disorder; and thar renders obvious the limitation(s) in claim 3-4.
Regarding claim 2, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference application, Carhart-Harris, Stamets and Davis et al. set forth above to incorporate the major depressive disorder diagnosed by general practitioner using the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) published by the American Psychiatric Association as taught by Tolentino et al. to arrive at the claimed invention. One would have been motivated to do so, because Tolentino et al. teaches depression diagnosis requires five or more symptoms to determine the presence or the absence of a major depression episode according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) published by American Psychiatric Association. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the patient with major depressive disorder diagnosed by a general practitioner using the DSM-5 published by American Psychiatric Association would reasonably be treated by administering the 5-MeO-DMT set forth above.
Regarding claims 6, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to modify the method of reference application, Carhart-Harris, Stamets and Davis et al. set forth above to treat the patient suffering from suicidal ideation to arrive at the claimed invention. One would have been motivated to do so, because Hendricks et al. teaches lifetime psilocybin use reduces likelihood of past year suicidal thinking and past year suicidal planning thus hold promise as an innovative mental health intervention and suicide prophylaxis. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog, hydrobromide salt of 5-MeO-DMT, would have exerted the same or substantially similar suicide prophylaxis effect as the psilocybin taught by Hendricks et al. for treating a patient suffering from suicidal ideation.
Regarding claim 15, it would have been prima facie obvious to one of ordinary skill in the art at the time the application was filed to arrive at the claimed invention by modifying the method of reference application, Carhart-Harris, Stamets and Davis et al. set forth above to administer the 5-MeO-DMT via inhalation to arrive at the claimed invention. One would have been motivated to do so, because Davis et al. teaches 81% of the 5-MeO-DMT survey respondents consumed 5-MeO-DMT through a smoking/vaporizing route of administration whereas 3% consumed it via other routes (e.g., injected); and further teaches inhalation (e.g., smoking or vaporizing) is a common means of 5-MeO-DMT consumption. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that inhalation is the most common route of administering 5-MeO-DMT; and therefore, one would have reasonably expected by administering the hydrobromide salt of 5-MeO-DMT via inhalation would have successfully deliver 5-MeO-DMT to the patient.
Regarding the limitation of “wherein a clinical response, as assessed by at least 50% improvement of a MADRS… compared to a respective score prior to the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof, is observed on the 6th day or later after the administration of the 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 22, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of reference application, Carhart-Harris et al., Stamets et al. and Davis et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a baseline MADRS of 31.0 and MADRS of 9.7 at 1 week after the last dose of psilocybin. Please note the percentage improvement can be calculated using the MADRS score observed 1 week after the administration of psilocybin and the baseline MADRS score, which when calculated by
100
%
-
9.7
31.0
×
100
%
=
68.71
%
, gives 68.1% improvement of the MADRS score on day 7; and that lies within the claimed range of “at least 50% improvement”. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog, hydrobromide salt of 5-MeO-DMT, would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering a therapeutically effective amount of a hydrobromide salt of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
With respect to “wherein the patient is in remission of depressive symptoms, as assessed by a MADRS score equal to or less than 10…, on day 7 or later after the administration of 5-MeO-DMT or a pharmaceutically acceptable salt thereof” in claim 24, the claimed limitation is drawn to the intended result or outcome of the method steps positively recited. According to MPEP 2144.05 I, “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”. The method of reference application, Carhart-Harris et al., Stamets et al. and Davis et al. set forth above renders obvious the claimed limitation, because Carhart-Harris et al. teaches the patients with treatment-resistant major depression treated with two oral doses of psilocybin has a MADRS of 9.7 at 1 week after the last dose of psilocybin. One would have a reasonable expectation of success to arrive at the claimed invention, because one would have reasonably expected that the psilocybin analog, hydrobromide salt of 5-MeO-DMT, would have exerted the same or substantially similar antidepressant effect as the psilocybin taught by Carhart-Harris et al.; and therefore, one would have reasonably expected that administering a therapeutically effective amount of hydrobromide salt of 5-MeO-DMT can successfully improves a clinical response assessed by MADRS score similar to the psilocybin.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed on July 11, 2026 with respect to the provisional rejection of claims 1-4, 6, 15, 22 and 24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/920,063 (reference application), in view Carhart-Harris et al. (The Lancet Psychiatry, 2016. Vol. 3: 619-627), Stamets (US 2019/0105313 A1), Davis et al. (J Psychopharmacol, 2018. Vol. 32(7): 779-792; cited under “other documents”, cite no. 69 in the IDS filed on June 26, 2024), Hendricks et al. (J Psychopharmacol. 2015;29(9):1041-1043), and Tolentino et al. (Front Psychiatry, 2018. Vol. 9: 450) have been fully considered but they are not persuasive.
In Summary, applicant argues the same arguments present in the nonstatutory double patenting rejection over claims of U.S. Patent No. 12,172,960 B2 are applicable to this particular provisional nonstatutory double patenting rejection.
In response, Applicant’s arguments against the nonstatutory double patenting rejection over claims of U.S. Patent No. 12,172,960 B2 are not found persuasive for the same reasons set forth above and are applied as before. Given that applicant did not put forth any new arguments specifically against this provisional double patenting rejection, the rejection has been maintained but revisited and modified in view of the amendments.
Conclusion
No claims are allowed.
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.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
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