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 .
Application Status
Applicant's amendment and response filed on March 11, 2026 has been reviewed by the examiner and entered of record in the file.
Claims 31 and 34-36 are amended, claims 19 and 21-30 are canceled, and claims 37-45 are newly added.
4. Claims 31-45 are under examination and are the subject of this office action.
Information Disclosure Statement
5. Applicant’s information disclosure statement (IDS) submitted March 11, 2026 is in compliance with the provisions of 37 CFR 1.97 and has been considered by the examiner. Please refer to the signed copy of Applicant’s PTO-1449 form, submitted herewith.
Previous Claim Rejections - 35 USC § 112(a)
6. Claims 19 and 21-30 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, regarding the limitation wherein the non-hallucinogenic amount “is insufficient to record a hallucinogenic experience upon administration of the psilocybin or psilocin to the subject, wherein the assessment of the subject for a hallucinogenic experience comprises a Five Dimensions of Altered States of Consciousness (5D-ASC) assessment of the subject.”
7. In view of the cancellation of claims 19 and 21-30, the previous 35 USC § 112(a)
rejection for lack of written description is withdrawn.
8. Claims 19, 21-25, and 28-36 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating depression and anxiety comprising administering a pharmaceutical composition comprising psilocybin to a subject in need thereof, does not reasonably provide enablement for a method of treating the other disorders embraced by “a disorder involving a lack of motivation or cognitive engagement in a subject.”
9. In view of the cancellation of claims 19, 21-25 and 28-30, and the amendment to claims 31-36 to limit the disorder to be treated to depression or anxiety, the previous 35 USC § 112(a) rejection for lack of enablement is withdrawn.
Previous Claim Rejections – 35 USC § 103
10. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
11. Claims 31-35 were previously rejected under 35 U.S.C. 103 as being unpatentable over Griffiths et al., Journal of Psychopharmacology (2016), as evidenced by Nall, Rachel, webpage printout of https://www.medicalnewstoday.com/articles/315862 (2019) and as evidenced by Folk, Jim, webpage printout of https://www.anxietycentre.com/anxiety-disorders/symptoms/lack-of-motivation/ (2025) and as evidenced by Ferhava et al., ScienceDirect (2016), and further in view of Studerus et al., Journal of Psychopharmacology (2011) (cited on Applicant’s IDS of September 23, 2025).
12. In view of Applicant’s amendatory changes to the claims, the previous obviousness rejection is withdrawn.
13. Claim 28 was previously rejected under 35 U.S.C. 103 as being unpatentable over Griffiths et al., Journal of Psychopharmacology (2016), as evidenced by Nall, Rachel, webpage printout of https://www.medicalnewstoday.com/articles/315862 (2019) and as evidenced by Folk, Jim, webpage printout of https://www.anxietycentre.com/anxiety-disorders/symptoms/lack-of-motivation/ (2025) and as evidenced by Ferhava et al., ScienceDirect (2016), and further in view of Studerus et al., Journal of Psychopharmacology (2011), and further in view of Chadeayne, Andrew, U.S. 20180221396 A1 as evidenced by Volkow et al., Mol Psychiatry (2011).
14. In view of the cancellation of claim 28, the previous obviousness rejection is withdrawn.
15. Claim 36 was previously rejected under 35 U.S.C. 103 as being unpatentable over Griffiths et al., Journal of Psychopharmacology (2016),
as evidenced by Nall, Rachel, webpage printout of https://www.medicalnewstoday.com/articles/315862 (2019) and as evidenced by Folk, Jim, webpage printout of https://www.anxietycentre.com/anxiety-disorders/symptoms/lack-of-motivation/ (2025) and as evidenced by Ferhava et al., ScienceDirect (2016), in view of Studerus et al., Journal of Psychopharmacology (2011), and further in view of Catlow et al., Exp Brain Res (2013), as evidenced by Howlett and Stein, Chapter 16: Post-Traumatic Stress Disorder (Translational Research in Traumatic Brain Injury 2016).
16. In view of Applicant’s amendatory changes to the claims, the previous obviousness rejection is withdrawn.
New Claim Rejections – 35 USC § 103
17. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
18. Claims 31-35, 37 and 39-44 are rejected under 35 U.S.C. 103 as being unpatentable over Griffiths et al., Journal of Psychopharmacology (2016), as evidenced by Nall, Rachel, webpage printout of https://www.medicalnewstoday.com/articles/315862 (2019) and as evidenced by Folk, Jim, webpage printout of https://www.anxietycentre.com/anxiety-disorders/symptoms/lack-of-motivation/ (2025) and as evidenced by Ferhava et al., ScienceDirect (2016),
Claim 31, as amended is directed to a method of treating depression or anxiety involving a lack of motivation or cognitive engagement in a subject in need thereof, (more specifically depression (claim 34) or anxiety (claim 35) wherein the anxiety can by generalized anxiety disorder (claim 37)), comprising orally administering (claim 33) to the subject a pharmaceutical composition consisting essentially of:
(a) a therapeutically effective of psilocybin or psilocin, wherein the psilocybin or psilocin is in an amount of about 0.1 mg to about 4.5 mg; and
(b) a pharmaceutically acceptable excipient;
wherein administration of the pharmaceutical composition treats the subject having a disorder involving a lack of motivation or cognitive engagement, and
wherein any prior administration of psilocybin or psilocin comprises no more than 4.5 mg psilocybin or psilocin (claim 32).
Claim 39 is drawn to a method of treating depression or anxiety involving a lack of motivation or cognitive engagement in a subject in need thereof, (more specifically depression (claim 42) or anxiety (claim 43), wherein the anxiety can by generalized anxiety disorder (claim 44)), comprising orally administering (claim 41) to the subject a pharmaceutical composition, wherein the pharmaceutical composition comprises:
(a) a therapeutically effective amount of psilocybin or psilocin, wherein the psilocybin or psilocin is in an amount between 0.1 mg and 4.5 mg; and
(b) a pharmaceutically acceptable excipient;
wherein the psilocybin or psilocin is the only active agent; and wherein administration of the pharmaceutical composition treats the subject having depression or anxiety involving a lack of motivation or cognitive engagement.
19. Griffiths et al. teach the effects of administering low dose psilocybin on depression and anxiety in a subject in need thereof (wherein said subject had a DSM-IV diagnosis of chronic adjustment disorder with anxiety (11 participants), chronic adjustment disorder with mixed anxiety and depressed mood (11), dysthymic disorder (5), generalized anxiety disorder (GAD) (5), major depressive disorder (MDD) (14), or a dual diagnosis of GAD and MDD (4), or GAD and dysthymic disorder (1)), comprising administering a pharmaceutical composition consisting essentially of psilocybin to said subject at a single “low-dose” of 3 mg/ 70 kg, orally in the form of a gelatin capsule with lactose as the inactive filler/excipient (see Abstract, Methods at page 1182, left column, and page 1183, left column, first full sentence). The capsule consisting essentially of psilocybin meets the limitation of “wherein the psilocybin or psilocin is the only active ingredient.” Griffiths et al. go on to teach that “data from the same dose-effect study showed significant psilocybin effects at 5 mg/70 kg, which raised concerns that 3 mg/70 kg might not serve as an inactive placebo.” (Page 1184, right column, first paragraph).
20. Griffiths et al. teach that even at the low dose of 1 mg/70 kg, “some pharmacological activity of this dose cannot be ruled out entirely. Thus, it might have been preferable to use an even lower dose of psilocybin (e.g. 0.01/70 kg) to assure pharmacological inactivity while maintaining the benefit of the instruction that psilocybin would be administered in each session.” (Page 1195, left column, last paragraph). As such, one skilled in the art having awareness that Griffiths et al. reported significant psilocybin effects at 5 mg/70 kg, would have been motivated to administer psilocybin in an amount close to 4.5 mg as required by claims 31 and 39, which is reasonably suggested by the “5 mg/70 kg” taught by Griffiths et al. And, dose regimen optimization is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize given the guidance of the prior art. Moreover, the determination of known effective amounts of known active agents to be administered to treat the same disease is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. As Griffiths et al. teach a dosage range for psilocybin that is used to treat depression and/or anxiety, and how to decrease that dosage based on hallucinogenic effects, the optimization of dosage based on said hallucinogenic effects is considered a result effective variable.
21. Following the initial low-dose administration of 1 mg or 3 mg/kg, wherein the subject(s) had not received prior administration of psilocybin (which meets the limitation of “wherein any prior administration of psilocybin or psilocin comprises no more than 4.5 mg of psilocybin or psilocin,” required by claims 32 and 40), said subject(s) demonstrate a marked reduction in depression and anxiety as measured by the GRID-HAMD-17 depression scale, the Beck Depression Inventory scale, the HADS depression scale, the HAM-A anxiety scale, and the STAI-Trait Anxiety scale (See Table 4, Post-session 1 assessment time-point, wherein outcomes were measured 5 weeks after the Low-Dose session).
22. Griffiths et al. do not explicitly teach that the disorder involves a lack of motivation or cognitive engagement.
23. Yet, it is clear as evidenced by Nall, Rachel, that “a persistent lack of motivation is a characteristic symptom of depression,” (page 1, first paragraph) and Fervaha et al. evidence that “[many] individuals with major depressive disorder present with prominent motivational deficits” (page 32, left column, lines 8-9). As evidenced by Folk, “[l]ow or lack of motivation is a common anxiety symptom,” (page 1, first paragraph).
24. As such, a subject suffering from anxiety, depression, or a combination thereof, meets the limitation of a subject having depression or anxiety “involving a lack of motivation or cognitive engagement.”
25. It would have been obvious to one of skill in the art before the effective filing date of the claimed invention to administer a pharmaceutical composition consisting essentially of a therapeutically effective low non-hallucinogenic dose of psilocybin of around 3 mg/kg to a subject suffering from depression or anxiety with a reasonable expectation of success.
As such, claims 31-35, 37 and 39-44 are prima facie obvious.
26. Claim 36 is newly rejected under 35 U.S.C. 103 as being unpatentable over Griffiths et al., Journal of Psychopharmacology (2016),
as evidenced by Nall, Rachel, webpage printout of https://www.medicalnewstoday.com/articles/315862 (2019) and as evidenced by Folk, Jim, webpage printout of https://www.anxietycentre.com/anxiety-disorders/symptoms/lack-of-motivation/ (2025) and as evidenced by Ferhava et al., ScienceDirect (2016), as applied to claims 31-35, 37 and 39-44 above, and further in view of Catlow et al., Exp Brain Res (2013), as evidenced by Howlett and Stein, Chapter 16: Post-Traumatic Stress Disorder (Translational Research in Traumatic Brain Injury 2016).
This rejection is newly applied as necessitated by Applicant’s amendments to the claims.
Claim 31 is addressed in detail, above.
Claim 36 is drawn to claim 31, and further limits wherein the disorder is a trauma or a stressor-related disorder.
27. Griffiths et al. as evidenced by Nall, Rachel and Folk, Jim, and Ferhava et al., suggest the administration of a pharmaceutical composition consisting essentially of a therapeutically effective non-hallucinogenic dose of psilocybin at about 3 mg to a subject having depression and/or anxiety that is a characterized by a lack of motivation or cognitive engagement in said subject, but do not teach wherein the disorder trauma or a stressor-related.
28. Yet, Catlow et al. teach that the administration of a single low dose of psilocybin (PSOP) facilitates extinction of the conditioned fear response, and suggest its administration as treatment for PTSD:
“low-dose PSOP which acts primarily on the 5-HT2A receptor facilitates extinction of a conditioned fear response and raises the possibility of targeting the 5-HT2A receptor to treat conditions where a previously neutral set of stimuli are associated with noxious, or life-threatening events, such as post-traumatic stress disorder.”
(Page 489, right column, last sentence).
29. And, it is clear as evidenced by Howlett that “depression is often comorbid with both TBI and PTSD, and can result in concentration problems, memory problems, irritability, reduced motivation, and fatigue.24” [emphasis added] (Page 3, second paragraph under “Diagnosis of PTSD and TBI).
30. Thus, one skilled in the art before the effective filing date of the claimed invention would have been motivated to administer a pharmaceutical composition consisting essentially of a therapeutically effective low dose of psilocybin in the amount of 3 mg as taught by Griffiths et al., to a patient diagnosed with depression and/or anxiety wherein the disorder is post-traumatic stress disorder as specifically named by Catlow et al., and evidenced by Howeltt, and would have a reasonable expectation of success.
As such, claim 36 is prima facie obvious.
Response to Arguments
31. Applicant traverses the previous obviousness rejections. While the previous obviousness rejections are withdrawn and new 35 U.S.C. 103 rejections are applied, each of the new rejections rely on the same references that were employed previously, with the exception of Studerus et al., in all of the pending rejections. Applicant argues the following points:
(i) Applicant alleges that the effective filing date of January 30, 2019, for at least claims 31-36 disqualifies the use of both Folk (published in 2025) and Nall (published August 12, 2019) as prior art references. For this reason alone, Applicant respectfully submits that there is no prima facie case of obviousness that can be maintained because the Office relies on these references for a missing explicit element of the claims.
32. Applicant's arguments have been fully considered but they are not persuasive. Regarding the effective filing date of the claimed invention and the use of the Folk reference and the Nall reference, it is noted that both Folk and Nall are employed as evidentiary references. The publication date of evidentiary references need not antedate the effective filing date of the claimed invention, i.e., references cited to show a universal fact need not be available as prior art before the effective filing date of applicant’s claimed invention. In re Wilson, 311 F.2d 266, 135 USPQ 442 (CCPA 1962). Such facts include the characteristics and properties of a material or a scientific truism. See MPEP 2124. In this case, Folk and Nall are each relied upon to show characteristics of depression and/or anxiety.
(ii) Applicant amended claim 31 to remove the term "about" from the range limitation of "0.1 mg to 4.5 mg" and argues that the difference between the presently claimed range and this newly alleged disclosure of Griffiths is significant and unexpected, especially in light of the teachings of Griffiths with regards to the "5 mg/70 kg" amounts having "significant psilocybin effects." Applicant notes that the passage that the Office cites to in Griffiths cites to an earlier reference by the Griffiths laboratory (Griffiths et al. "Psilocybin occasioned mystical- type experiences: Immediate and persisting dose-related effects", Psychopharmacol. 218:649- 665 (2011) ("Griffiths 2011"; Exhibit A), which conducted psilocybin studies in normal, healthy subjects: The low dose of psilocybin was decreased from 3 to 1 mg/70 kg after 12 participants because data from the same dose-effect study showed significant Psilocybin effects at 5 mg/70 kg, which raised concern that 3 mg/70 kg might not serve as an inactive placebo. Griffiths (2016) at 1184 (emphasis added), citing to Griffiths et al. (2011).
Applicant contends that the passage in Griffiths does not indicate that the "5 mg/70 kg" dose showed significant therapeutic psilocybin effects (comparing Office Action at 45 (2nd paragraph) with Griffiths (2016) at 1184). Notably, the Griffiths 2011 study was conducted in "healthy participants" (see Griffiths (2016) at 1184) and therefore its results could not have reflected a therapeutic effect. Accordingly, Applicant alleges that the citation to "5 mg/70 kg" dosage amount in Griffiths by the Office is not relevant to the presently claimed therapeutic range of "0.1 mg to 4.5 mg".
Applicant argues that Griffiths 2011 documented a significant increase in "Anxiety or Fearfulness", at the 5 mg/70 kg dose that the ordinarily skilled artisan would have recognized could be associated with anxiety or depression, see Griffiths 2011 at Table 1, and is a known side effect of psilocybin and psilocin. Applicant submits that the ordinarily skilled artisan in view of Griffiths 2011's results would not have recognized a "5 mg/70 kg" dose in healthy subjects as being directed to or useful in the treatment of anxiety or depression involving a lack of motivation or cognitive engagement as claimed.
Applicant contends that Griffiths itself recognized that there was a difference between a 5 mg dose in healthy subjects and the 3 mg very low placebo dose used in its study. Griffiths did lower the dose to 1 mg/70 kg as indicated by the Office because of the "significant psilocybin effect" results in Griffiths 2011, see Office Action at 45 and Griffiths at 1184, and at the end of the study Griffiths combined the results from the 1 mg and 3 mg placebo patients because statistical analysis demonstrated that "neither of the [results] were significantly different" from each other. See Griffiths at 1186 ("Statistical Analysis"). Applicant alleges that Griffiths recognized that at least both lower doses of 1 mg/70 kg and 3 mg/70 kg were placebos (i.e., lacking hallucinogenic effects) in the treatment of anxiety and depression in cancer patients, in contrast to the Office's contentions.
Applicant respectfully submits that the "5 mg/70 kg" dose disclosure in Griffiths would have discouraged the ordinarily skilled artisan because this dose provoked symptoms associated with anxiety and depression, as seen in Griffiths 2011, and known adverse side effects of psilocybin treatment. (Griffiths 2011 at Table 1).
33. Applicant's arguments have been fully considered but they are not persuasive. Griffiths et al. teach a method of treating disorders including depression or anxiety comprising administering a pharmaceutical composition consisting essentially of psilocybin to said subject at a single “low-dose” of 3 mg/ 70 kg (Abstract, Methods at page 1182, left column, and page 1183, left column, first full sentence). Griffiths et al. go on to teach that “data from the same dose-effect study showed significant psilocybin effects at 5 mg/70 kg, which raised concerns that 3 mg/70 kg might not serve as an inactive placebo.” (Page 1184, right column, first paragraph).
Griffiths et al. teach that even at the low dose of 1 mg/70 kg, “some pharmacological activity of this dose cannot be ruled out entirely. Thus, it might have been preferable to use an even lower dose of psilocybin (e.g. 0.01/70 kg) to assure pharmacological inactivity while maintaining the benefit of the instruction that psilocybin would be administered in each session.” (Page 1195, left column, last paragraph).
34. As Griffiths et al. suggest dose amounts ranging from 0.01 mg up to 5 mg psilocybin and how to optimize that dosage based on hallucinogenic effects, the optimization of dosage is considered a result-effective variable. And, dose regimen optimization is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize given the guidance of the prior art. Moreover, the determination of known effective amounts of known active agents to be administered to treat the same disease is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art. Thus nothing unobvious is seen one of skill in the art starting with a dose amount of 0.01 mg, 1 mg, 3 mg, or 5 mg, as disclosed by Griffiths et al, and optimizing said amount for a method of treating depression or anxiety in a subject in need thereof, with a reasonable expectation of success.
35. It is noted that while Applicant alleges that Griffiths et al. teach the 5 mg/70 kg dose of psilocybin is discouraged because it “provoked symptoms associated with anxiety and depression” in normal, healthy subjects, these side effects are not documented at this dosage in a subject in need thereof, i.e., a subject suffering from depression and/or anxiety. And, even if one agreed that the Griffiths et al. taught away from the 5 mg/70 kg dose of psilocybin, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have "relatively acceptable dimensional stability" and "some degree of flexibility," but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since "Gurley asserted no discovery beyond what was known in the art." 27 F.3d at 554, 31 USPQ2d at 1132.). Furthermore, "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
36. Therefore one skilled in art before the effective filing date of the claimed invention would have considered administering any dose amount of psilocybin ranging from 0.01 mg up to 5 mg, with a reasonable expectation of success.
Claim Objections
37. Claims 38 and 45 are objected to as being dependent upon a base claim (rejected under 35 U.S.C. § 103).
Conclusion
38. Claims 31-45 are present in the application. Claims 31-37 and 39-44 are rejected. Claims 38 and 45 are objected to. No claim is presently allowed.
39. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
40. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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