DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Pursuant to the preliminary amendment, filed on May 23, 2025, claims 1-283 have been cancelled and claims 284-314 have been added.
Claims 284-314 are pending.
Priority
This application, September 26, 2024, is an application filed under 35 U.S.C. 111(a) which claims priority under 35 U.S.C. 119 or 365 to the benefit of European Application Nos. EP22000083.0, EP22000086.3, filed on March 27, 2022, EP23153939.6, and EP23153995.8 filed on January 30, 2023. The certified copy of the foreign application has been received.
Information Disclosure Statement
There were 47 information disclosure statements (IDSs) filed: 35 were filed on January 16, 2025, the 12 remaining IDSs were filed on February 27, 2025, March 28, 2025, April 30, 2025, May 30, 2025, June 30, 2025, July 31, 2025, August 29, 2025, September 26, 2025, October 31, 2025, December 15, 2025, January 21, 2026, February 23, 2026. All the IDSs have been acknowledged and considered.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 284-287, 291, 293-306, and 309-314 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020169851 (IDS # 22 filed on 1/16/2025, Foreign Patent Document d) (“Terwey”) in view of Ketamine for Treatment-Resistant Bipolar Disorder (KET-BD), Published: February 28, 2022 (“NCT05004896”).
Terwey teaches compositions containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) for treating major depressive disorders and regimens for treating the disorders (Abstract). Terwey teaches a practitioner to administer 5-MeO-DMT to patients suffering from moderate or severe major depressive disorder as indicated by a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or more; or by a Hamilton Depression Rating Scale (HAM-D) score of 17 or more. (p. 1, last ¶; p.2, first ¶). The dosage of 5-MeO-DMT is in a range that causes a patient to experience a peak psychedelic experience and is the range from 1 mg to about 10 mg (p.2, 4th ¶).
Terwey does not teach administering 5-MeO-DMT to a patient suffering from a bipolar II disorder in which the patient is suffering a current major depressive episode.
NCT05004896 teaches administering ketamine for treatment-resistant bipolar disorder (p. 5, Brief Summary). The patient population inclusion criteria includes: 1) bipolar I or II disorder, currently experiencing a major depressive episode without psychotic features; 2) patients with a MADRS score greater than 21; and 3) patients with a depressive episode that have inadequate responses to two or more adequate first-line treatments for bipolar depression (pp. 8-9, Inclusion Criteria).
Terwey and NCT05004896 are considered analogous art because they are both in the same field of administering therapeutics to patients to treat disorders characterized by a MADRS score. Therefore, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA), before the effective filing date of the claimed invention, to administer 5-MeO-DMT at a dosage from 1 mg to about 10 mg, based on the teachings of Terwey, to patients having bipolar II disorder with a major depressive episode, based on the teachings of NCT05004896. This would have been obvious to a PHOSITA because they both teach administration of therapies to patients having a MADRS of at least greater than 20. Thus, a PHOSITA would have had a reasonable expectation of success to substitute 5-MeO-DMT for ketamine, to treat bipolar II disorder, because both bipolar II disorder and major depressive disorder have equivalent ranges of the MADRS score (MPEP §2144.06(II)). The dosage amount taught by Terwey for administration of 5-MeO-DMT overlaps with the range instantly claimed (vide supra) (MPEP §2144.05(I)). Accordingly, claims 284-287, 291, 293-294 are prima facie obvious.
Regarding claims 295-296, 299-301, and 314, Terwey teaches 5-MeO-DMT may be administered in a first dosage for a first administration and then administered in zero to six subsequent administrations. Terwey further teaches the subsequent administrations are at higher dosages than the previous administrations, unless the patient experiences a peak psychedelic experience. The interval time between two administrations is not less than 1 hour and not more than 24 hours, including a range of about 2 to 4 hours (p.2, 6th ¶). The interval time range taught by Terwey overlaps with the range instantly claimed (MPEP §2144.05(I)).
Regarding claims 297-298, Terwey teaches, in Example 3, Table 4, a patient in Part B received up to three administrations of 5-MeO-DMT in a single day wherein the first administration was at a dose of 6 mg, the second administration was at a dose of 12 mg, and the third administration was at a dose of 18 mg. The dosage amounts overlap with ranges instantly claimed (MPEP §2144.05(I)).
Regarding claims 302-304, Terwey teaches after a first administration and subsequent administrations, which were at higher doses than the previous administrations, unless the patient receives a peak psychedelic experience. The peak psychedelic experience is identified through at least 60% of four subscales (mystical, positive mood, transcendence of time and space, and ineffability) of the 30-item revised Mystical Experience Questionnaire (MEQ30). The peak psychedelic experience can also be identified through at least 60% of the maximum possible score of the Oceanic Boundlessness (OBN) dimension of the Altered States of Consciousness (ASC) questionnaire (pp. 90-91, Embodiment 37). Similarly, the peak psychedelic experience can be identified through achievement of a Peak Psychedelic Experience Questionnaire (PPEQ) Total Score of at least 75 (p. 91, Embodiment 38). According to the instant specification the PPEQ and the PES tests are equivalent (Spec., p. 69).
Regarding claims 305-306, Terwey teaches most common routes of administration of 5-MeO-DMT are inhalation of smoke or vapor or intranasal insufflation (p. 14, 3rd ¶). Example 1 also describes administration of 5-MeO-DMT via inhalation (p. 92).
Regarding claims 309-311, Terwey teaches that administration of 5-MeO-DMT leads to a clinical response reflecting at least 50% improvement in the MADRS or HAM-D score compared to the respective score prior treatment, not later than about 2 hours after the last administration of 5-MeO-DMT (p. 88, Embodiment 20). Terwey teaches the same improvement should be observed, compared to the respective score prior to treatment, persists at least 6 days after the last administration of 5-MeO-DMT. The improvement persistence for 6 days overlaps with range claimed in instant claims 310-311 (MPEP §2144.05(I)).
Regarding claim 312, NCT05004896 teaches that a secondary outcome measure includes treatment-emergent mania. Therefore, it would have been prima facie obvious to substitute 5-MeO-DMT for ketamine to treat bipolar II disorder with a major depressive episode, as discussed above, and monitor the outcome of treatment-emergent mania (pp. 5-6, Brief Summary; pp. 7-8, Secondary Outcome Measures).
Regarding claim 313, Terwey teaches that after administration of 5-MeO-DMT, improvements in general psychiatric symptoms, such as anxiety, guilt, improved (p. 99, 3rd ¶).
Claims 288-290 are rejected under 35 U.S.C. 103 as being unpatentable over Terwey in view of NCT05004896 and Malhi et al. (Bipolar Disorders 2007: 9: 571–579) (“Malhi”).
For the purposes of this rejection, Terwey and NCT05004896 are discussed above and are incorporated by reference herein.
Regarding claims 288-290, Terwey and NCT05004896 do not teach administering therapy, like 5-MeO-DMT, to a patient population with Bipolar Depression Rating Scale (BDRS) total scores of greater than or equal to 19, 24, and 37.
Malhi teaches the BDRS scale has strong internal consistency and robust correlation coefficients with the MADRS and HAM-D, and the mixed subscale correlated with the Young Mania Rating Scale (YMRS) (p. 571, Results). Malhi states: “This study provides evidence for the validity of the BDRS for the measurement of depression in bipolar disorder. These results suggest good internal validity, provisional evidence of inter-rater reliability and strong correlations with other depression rating scales.” (p. 571, Conclusions). Malhi provides the BPDRS scale and teaches that higher scores indicate more severe symptoms, there are 20 questions, with each question having a rating from 0 to 3 (pp. 577-579).
Terwey, NCT05004896, and Malhi are analogous art to the claimed invention because they are in the same field of identifying patient population using tests like BDRS and MADRS to diagnose patients with depressive disorders. Therefore, it would have been prima facie obvious to a PHOSITA to administer 5-MeO-DMT to treat bipolar II disorder with a major depressive episode, as discussed above, and include the patient population, to be treated, that have high BDRS scores, based on the teachings of Malhi. Based on the teachings of Malhi, the range of the BDRS score is 0 to 60, therefore a PHOSITA would have had a reasonable expectation of success at arriving at the scores instantly claimed through routine optimization, because Malhi teaches that higher BDRS scores indicate more severe symptoms (MPEP §2144.05(II)). Accordingly, claims 288-290 are prima facie obvious.
Claims 292 is rejected under 35 U.S.C. 103 as being unpatentable over Terwey in view of NCT05004896 and EMDR vs Supportive Therapy in Relapse Prevention in Traumatized Bipolar Patients, Published: August 8, 2016 (“NCT02634372”).
For the purposes of this rejection, Terwey and NCT05004896 are discussed above and are incorporated by reference herein.
Regarding claim 292, Terwey and NCT05004896 do not teach administering therapy, like 5-MeO-DMT, to a patient population with a YMRS score of less than 8.
NCT02634372 teaches a method of treating bipolar disorders through Eye Movement Desensitization and Reprocessing (EMDR) and supportive therapy (pp. 4-5, Study Description). The patients included in this method have a YMRS score of less than 8 (p. 11, Inclusion Criteria).
Terwey, NCT05004896, and NCT02634372 are analogous art to the claimed invention because they are in the same field of identifying a patient population using tests like YMRS to diagnose patients with depressive disorders. Therefore, it would have been prima facie obvious to a PHOSITA to administer 5-MeO-DMT to treat bipolar II disorder with a major depressive episode, as discussed above, and include the patient population, to be treated, that have high YMRS scores <8, based on the teachings of NCT02634372.A PHOSITA would have had a reasonable expectation of success to include this patient population because NCT02634372 teaches the patients being taught have bipolar disorders, therefore substituting the EMDR therapy for 5-MeO-DMT would have been prima facie obvious since the condition being taught between Terwey and NCT02634372 are the same (MPEP §2144.06(II)). Accordingly, claim 292 is prima facie obvious.
Claims 307-308 are rejected under 35 U.S.C. 103 as being unpatentable over Terwey in view of NCT05004896 and Sepeda et al., Journal of Psychedelic Studies 4(2), pp. 114 122 (2020) (“Sepeda”).
For the purposes of this rejection, Terwey and NCT05004896 are discussed above and are incorporated by reference herein.
Regarding claims 307-308, Terwey and NCT05004896 do not teach administering therapy, like 5-MeO-DMT, through sublingual or buccal administration.
Sepeda states: “5-MeO-DMT has been described as producing strong hallucinogenic
effects (e.g., auditory/visual distortions, changes in time perception, and emotional experiences) with a rapid onset and a short duration of action, and has been administered via several routes, including intranasal, sublingual, oral, buccal, intravenous, intramuscular, and inhalation.” (p. 114, Introduction). Sepeda also states, …” recent evidence suggests that 5-MeO-DMT use, reported in cross-sectional surveys and observational prospective studies, is related to self-reported improvement of a variety of mental health symptoms including anxiety, depression, substance use problems, and posttraumatic stress dis order.” (p. 115, 1st col.).
Terwey, NCT05004896, and Sepeda are analogous art to the claimed invention because they are in the same field of administering therapies to treat mental health symptoms. Therefore, it would have been prima facie obvious to a PHOSITA to administer 5-MeO-DMT to treat bipolar II disorder with a major depressive episode, as discussed above, and administer 5-MeO-DMT through sublingual or buccal means. A PHOSITA would have had a reasonable expectation of success to include these routes of administration because Sepeda teaches these routes are the conventional ways to administer 5-MeO-DMT. Accordingly, claims 307-308 are prima facie obvious.
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 284-314 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-90 of copending Application No. 18/850,383 (“‘383”) in view of Terwey. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 284-314 are obvious in view of ‘329 and Terwey. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Claim 1 of ‘383 recites the use of 5-MeO-DMT in treating patients suffering from negative thinking. Claim 4 recites the effects of the administration of 5-MeO-DMT results in reduction in negative thinking is observed 2 hours after the last administration. Claim 6, dependent on claim 1, recites the patient suffering from negative thinking has a mental or nervous system disorder. Claim 7, dependent on claim 6, recites the patient is further suffering from a treatment resistant form of the disorder. Claim 8, dependent on claim 1, recites the patient further suffers from depressive episodes. Claim 9, dependent on claim 8, recites the patient suffers from a treatment resistant disorder. Claim 20, dependent on claim 1, recites the patient suffers from a bipolar disorder associated with negative thinking. Claim 21, dependent on claim 20, recites the bipolar disorder is a bipolar II disorder. Claim 77, dependent on claim 76, recites the use of 5-MeO-DMT results in the patient experiencing a peak psychedelic experience after a dosing regimen. Claim 78, dependent on claim 77, administering 4 mg to about 20 mg of 5-MeO-DMT. Claim 79, dependent on claim 77, recites the dosages are 6 mg, 12 mg, and 18 mg. Claim 82, dependent on claim 81, recites the same dosages in claim 79, are administered from lowest to highest, as a first, second, and third administration, respectively. Claim 84 recites the occurrence of a peak psychedelic experience and is measured through MEQ30, OBN of ASC, and a PES total score of at least 75. Claim 86, dependent on claim 85, recites the administration of 5-MeO-DMT is by way of nasal, buccal, or sublingual routes.
For the purposes of this rejection, the teachings of Terwey are discussed above and are incorporated by reference herein.
It would have been prima facie obvious to treat patients having bipolar II disorder with depressive episodes to achieve a peak psychedelic experience through administration of 5-MeO-DMT, by way of nasal, buccal, or sublingual routes, at a dosage of 6 mg, 12mg, and 18 mg, in a first, second, and third administration, respectively, based on the teachings of ‘383, and include patients that have the appropriate MADRS score, based on Terwey, because they are both in the same field of treating depressive disorders. Including patients that have the characteristics of mental disorders through diagnostic tests like MADRS with scores greater than 20 would have been prima facie obvious to a PHOSITA because they overlap with the ranges instantly claimed (MPEP §2144.05(I)).
Claims 284-314 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33-62 of copending Application No. 18/851,329 (“‘329”) in view of Terwey. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 284-314 are obvious in view of ‘329 and Terwey. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 33 of ‘329 recites a method of treating breastfeeding mothers with mental or nervous system disorders. Claim 54, dependent on claim 33, recites the disorder characterized by depressive episodes. Claim 55, dependent on claim 54, recites the disorder characterized by depressive episodes is bipolar disorder. Claim 56, dependent on claim 33, recites that the bipolar disorder is bipolar II disorder. Claim 62, dependent on claim 33, recites the dosage of 5-MeO-DMT is administered at a dose sufficient to result in the patient having a peak psychedelic experience.
Terwey teaches compositions containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in treating major depressive disorders and regimens for treating the disorder (Abstract). Terwey teaches a licensed medical professional can administer 5-MeO-DMT to patients that may suffer from moderate or severe major depressive disorder as indicated by a Montgomery-Åsberg Depression Rating Scale (MADRS) score of 20 or more, or 35 or more; or by a Hamilton
Depression Rating Scale (HAM-D) score of 17 or more, or 25 or more. (p. 1, last ¶; p.2, first ¶). The dosage of 5-MeO-DMT is in a range that causes a patient to experience a peak psychedelic experience and is the range from 1 mg to about 10 mg (p.2, 4th ¶).
It would have been prima facie obvious to administer 5-MeO-DMT to patients having bipolar II disorder with depressive episodes, based on the teachings of ‘329, and include patients that have the appropriate MADRS scores, based on Terwey, because they are both in the same field of treating depressive disorders. Including patients that have the characteristics of mental disorders through diagnostic tests like MADRS with scores greater than 20, would have been prima facie obvious to a PHOSITA, and the total score overlaps with the ranges instantly claimed (MPEP §2144.05(I)).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHIL CHANDER AGGARWAL whose telephone number is (571)272-7755. The examiner can normally be reached 7am-5pm.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
