DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/26/2026 has been entered.
Status of Claims
Claims 1-2, 4-10, and 12-20 are pending. Claims 7-10 and 15-20 are withdrawn.
Priority
Instant application 17/627,988, filed 01/18/2022 claims priority as follows:
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Response to Amendment/Arguments
The amendment filed 01/26/2026 has been entered. Applicant has amended claims 1-2. Claims 3 and 11 are cancelled.
Claim Rejections - 35 USC § 112 - New
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2, 4-6, and 12-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the closed transitional phrase “consisting of” and limits the composition of claim 1 to only the two “purified” tryptamines or salts thereof. Claims 4 and 12 incorporate the closed composition of claim 1 or claim 2 inside a “comprising” formulation, which is open-ended and permits unlimited additional ingredients. Claims 4 and 12 are indefinite because there are at least two conflicting interpretations of the claim and they result in different claim scope.
Interpretation A is narrower, and requires that a physically discrete sub-combination was prepared that consists of only two purified tryptamines, and that this discrete sub-combination was then incorporated, alongside a pharmaceutically acceptable excipient, into a larger formulation. Under this interpretation, the formulation must contain a discernible sub-unit that is nothing but two purified tryptamines (or salts thereof), and the “comprising” simply allows additional ingredients (excipients, carriers, buffers, additional actives) at the outer formulation level.
Interpretation B is broader, and merely requires that the pharmaceutical formulation of claim 4 or 12 contains, among its components, the two tryptamines from the Markush list plus an excipient. Under this interpretation, any formulation that includes the two named tryptamines satisfies the claim, because one can always abstractly identify any two components within a complex mixture and characterize that subset as a “composition consisting of” those two compounds. The “comprising” at the formulation level means anything else can be present (e.g. toad skin, tree bark, crude venom, other tryptamines, etc). Applying this interpretation, the “consisting of” in claim 1 is effectively meaningless at the claim 4 or 12 level, because the open-ended outer claim encompasses any mixture containing the two named tryptamines.
MPEP 2111.03 and In re Crish, 393 F.3d 1253, 73 USPQ2d 1364 (Fed. Cir. 2004) support broader interpretation B. In In re Crish, the Federal Circuit interpreted claims to “a purified oligonucleotide comprising at least a portion of the nucleotide sequence of SEQ ID NO:1 wherein said portion consists of the nucleotide sequence from … to 2473 of SEQ ID NO:1…” (emphasis added). The court stated that the use of “consists” in the body of the claims did not limit the open-ended "comprising" language in the claim. MPEP 2111.03 establishes that when “consisting of” appears in a clause of the body of a claim (rather than immediately following the preamble), it may not close the claim to unrecited elements at the outer level.
A person of ordinary skill in the art, reading claim 4 or 12 in light of the specification, faces two reasonable and conflicting interpretations of the claim scope. Accordingly, claims 4 and 12 are rejected as indefinite. Claims 5-6 or 13-14 depend from claim 4 or 12 and fail to resolve the issues identified above. Therefore claims 5-6 and 13-14 are also rejected.
Please note that for the purposes of applying prior art, the examiner is applying broader interpretation B (i.e. the formulation requires at least two tryptamines selected from the list, plus an excipient, and may also contain additional unrecited components) to claims 4-6 and 12-14.
Claims 1, 5, and 13 recite “purified” ingredients, and specify that the “purified” ingredients are “independently substantially free from other materials”. Direction provided for the word “purified” in the Specification includes para. [0035], which states: “Within the context of this disclosure, the term ‘purified’ means separated from other materials, such as plant or fungal material, e.g., protein, chitin, cellulose, or water. A purified a compound is substantially free of other materials. For example, a purified a compound is substantially free from a second tryptamine compound; substantially free from histidine; substantially free from a biological material, such as mold, fungus, plant mater, or bacteria; or substantially free from a different unwanted compound…” The specification also describes purified compounds as “80-100% pure, 90-100% pure, or 95-100% pure” in a separate section of para. [0035].
There are multiple issues with the phrase “independently substantially free from other materials” that cause the claims reciting this phrase to be indefinite:
The term “substantially free” in claims 1, 5, and 13 is a relative term which renders the claims indefinite. The term “substantially free” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification lists three purity ranges (80-100% pure, 90-100% pure, or 95-100% pure) in a separate definitional passage, but never ties any of them to the “substantially free” threshold. A person of ordinary skill cannot determine with reasonable certainty whether a tryptamine at 80% purity is “substantially free from other materials.” What about 70%? 50%?
The term “independently” introduces ambiguity into the phrase. The examiner is interpreting the word “independently” as meaning that each tryptamine is evaluated separately for the “substantially free from other materials” condition. The issue is that the claim doesn’t specify when that evaluation occurs.
If evaluated in the final composition, the limitation appears to be nonsensical (in a two-component composition, neither component is “substantially free” of the other by any ordinary understanding). Additionally, for the composition of claim 1 which “consists of” two toad secretion tryptamines, reciting that the two tryptamines are “substantially free from other materials” implies that some other component at a low level is allowed in the composition, which is inconsistent with the closed phrase “consisting of”.
If evaluated before combination, the meaning of the “substantially free” limitation change from a structural description of the composition as claimed to a description of the process by which the composition was prepared (i.e. each tryptamine was separately purified to a substantially-free state before combination). This is a product-by-process interpretation.
A person of ordinary skill in the art, reading claims 1, 5, or 13 in light of the specification, faces multiple reasonable and conflicting interpretations of the claim scope. Accordingly, claims 1, 5, and 13 are rejected as indefinite. Claims 2, 4, 6, 12, and 14 depend from claim 1, 5, or 13 and fail to resolve the issues identified above. Therefore claims 2, 4, 6, 12, and 14 are also rejected.
In view of the issues identified above, the most coherent reading of the “purified” and “substantially free” limitations in the claims is a product-by-process reading (i.e., each element was purified separately, then mixed together into a composition).
Please note that in order to overcome the rejection, the examiner recommends replacing the phrase “substantially free from other materials” with an explicit recitation of purity (e.g., wherein the purified [ingredient] is 80-100% pure, 90-100% pure, or 95-100% pure). Additionally, the examiner recommends amending the claims to plainly recite product-by-process language if that is the intended interpretation of the claims.
Claim Interpretation
The following claim interpretations (identified above but reiterated herein) govern the rejections below.
Claim 1 recites a composition “consisting of” two purified toad secretion tryptamines. Claims 4-6 and 12-14 each recite a formulation “comprising” a composition of claim 1 and an excipient. “Consisting of” is a closed transitional phrase that excludes unrecited ingredients (except impurities ordinarily associated therewith). “Comprising” is an open-ended transitional phrase that permits unlimited additional, unrecited components. See MPEP 2111.03.
Claims 4-6 and 12-14 incorporate claim 1 by reference inside an outer “comprising” formulation. Under BRI consistent with the MPEP 2111.03 and In re Crish, the “consisting of” in claim 1 does not close claims 4-6 or 12-14 to additional, unrecited components at the formulation level. Accordingly, claims 4-6 and 12-14 are being interpreted as requiring a formulation that contains at least two tryptamines from the Markush group of claim 1, plus an excipient, but that may also contain additional components (including additional tryptamines, proteins, lipids, biological materials, or any other substances).
By contrast, claim 1 itself uses “consisting of” as its transitional phrase. Claims 1-2 are therefore being interpreted as closed. The composition of claims 1-2 must only contain the two recited tryptamines or salts thereof.
Claims 1, 5, and 13 recite that the purified tryptamines, purified psilocybin derivatives, purified cannabinoids, or purified terpenes “are independently substantially free from other materials.” As noted above in the rejection under section 112(b), the most consistent interpretation of the “purified” language in the claims is that each tryptamine, psilocybin derivative, cannabinoid, or terpene was independently in a state of high purity prior to combination into the claimed composition. This is a product-by-process limitation. Under MPEP 2113, product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps. “[T]he patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process”. See MPEP 2113 and In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985).
For claims 1-2, 4-6 and 12-14, the “purified” and “substantially free” limitations are being interpreted as product-by-process limitations that do not, by themselves, structurally distinguish the claimed formulation from a prior art formulation containing the same tryptamines obtained by a different process (including extraction from natural sources without individual purification and recombination), provided that the final products are structurally identical or substantially identical.
Claim Rejections - 35 USC § 101 - New
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 4-6 and 12-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 4-6 and 12-14 are directed to a natural product (a composition comprising tryptamine constituents which occur in nature, for example in the toad species Bufo alvarius; and the tree species Piptadenia peregrina). The Examiner has followed the guidance set forth in MPEP 2106 and has concluded that the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
MPEP § 2106 sets forth the Subject Matter Eligibility Test to determine if a claim is directed to patent eligible subject matter.
Eligibility Step 1: The Four Categories of Statutory Subject Matter
As described in MPEP § 2106.03, Step 1 of the eligibility analysis asks: Is the claim to a process, machine, manufacture or composition of matter? The claims recite a composition comprising tryptamine constituents which occur together in nature, and allows for additional unrecited elements. Accordingly, the answer to the question of Step 1 is Yes, because the claims are considered directed to a composition of matter, which is eligible subject matter.
Eligibility Step 2A: Whether a Claim is Directed to a Judicial Exception
Step 2A, Prong One
Step 2A, Prong One asks if the claim recites a natural phenomenon. In the instant case, the elected species composition of instant claim 1 requires the particular tryptamines 5-MeO-DMT and 5-MeO-NMT. The characteristics of this composition are not markedly different from the naturally occurring counterpart in its natural state, for example secretions of the toad species Bufo alvarius; or bark from the tree species Piptadenia peregrina, because as claimed it has the identical chemical structure as it has in nature. This is readily apparent at least in view of Applicant’s own specification and the prior art references Erspramer et al. (Biochemical Pharmacology, vol. 16, no. 7, July 1967, pp. 1149–64; cited in IDS) and Legler et al (Naturwissenschaften, vol. 50, no. 3, Jan. 1963, pp. 94–95). Briefly, Erspramer discloses constituents in the skin of Bufo alvarius and identifies O-methylbufotenine (5-MeO-DMT) and N-methyl-5-methoxytryptamine (5-MeO-NMT) as constituents which are present in the skin (page 1154, Table 1). Legler discloses the isolation of 5-methoxy-N-methyltryptamine (5-MeO-NMT, “compound IIb”) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT, “compound I”) from the bark of Piptadenia peregrina (page 1, Title).
Legler discloses the isolation from bark of a mixture of compounds I, IIa, and IIb comprising 5-MeO-DMT, 5-MeO-NMT, and N-methyltryptamine (page 1, para. 2 to page 2, last para). N-methyltryptamine is a serotonergic drug according to applicant’s own specification (para. [0029]). The isolated mixture comprised approximately 32% of I and 41% of II. II was identified as having roughly equal amounts of IIa (20.5%) and IIb (20.5%). Therefore, the ratio of I (5-MeO-DMT) to IIa (5-MeO-NMT) is approximately
32
20.5
:
20.5
20.5
= 1.56 : 1.
Therefore, with respect to the ratio of 5-MeO-DMT : 5-MeO-NMT in naturally occurring bark material from Piptadenia peregrina plants, ratios reading on the instant claim ratios have been previously identified. Further, the term “excipient” encompasses ingredients such as water, which is present in toad secretions or in tree bark. Therefore, the compositions of claims 4-5 and 12-13 are not markedly different from naturally occurring secretions of the toad species Bufo alvarius; or bark from the tree species Piptadenia peregrina.
With respect to claims 6 and 14, the weight amount of 5-MeO-DMT and 5-MeO-NMT present in toad secretions or in tree bark is dependent upon the amount of the natural material obtained and scales with the amount of material. For example, Erspramer discloses particular amounts of each ingredient in terms of ug or mg per g of dry tissue at page 1157 (see Table 5 and paragraph below Table 5): 5-MeO-NMT (“N-methyl-MT”) is present in an amount of 10-15 ug/g dry tissue; and 5-MeO-DMT (“O-Methylbufotenine”) is present in amounts ranging from 0.4 mg/g to 150 mg/g dry tissue. Thus claims 6 and 14 are not markedly different from naturally occurring secretions of the toad species Bufo alvarius; or bark from the tree species Piptadenia peregrina.
MPEP § 2106.04(b) states that “When a claim recites a nature-based product limitation, examiners should use the markedly different characteristics analysis discussed in MPEP § 2106.04(c) to evaluate the nature-based product limitation and determine the answer to Step 2A.” MPEP 2106.04 (c)(I) states that “if the nature-based product limitation is naturally occurring, there is no need to perform the markedly different characteristics analysis because the limitation is by definition directed to a naturally occurring product and thus falls under the product of nature exception.”
In the instant case, the closest appropriate counterpart(s) are secretions of the toad species Bufo alvarius; or bark from the tree species Piptadenia peregrina which, in view of the above evidence, have been shown to contain the recited constituents in amounts which read on the instant claim limitations. The chemical and physical structure of the claimed composition is not markedly different from the naturally occurring counterpart because the naturally occurring counterpart possesses the claimed constituents in ratios recited by the claim. The applicant has not caused the claimed product to possess at least one characteristic that is different from that of the counterpart.
Therefore, the answer to the question of Step 2A, Prong One is Yes, because the instant claims are considered directed to a product of nature.
Step 2A, Prong Two
Step 2A, Prong Two, asks if the claim recites additional elements that integrate the judicial exception into a practical application. In the instant case, the judicial exception is not integrated into a practical application because the claims merely recite the composition and its constituents without reciting any additional steps or elements that rely on or use the compound for any practical purpose.
Eligibility Step 2B: Whether a Claim Amounts to Significantly More
As described in MPEP 2106.05, Step 2B asks if claims recite additional elements that amount to significantly more than the judicial exception. In the instant case, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception, because there are no “additional elements” required by the present claims since they are directed only to the naturally occurring substance itself.
Thus, the answer to Step 2B is No. Therefore, claims 4-6 and 12-14 are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 102 - New
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 4-5 and 12-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Legler et al (Naturwissenschaften, vol. 50, no. 3, Jan. 1963, pp. 94–95).
Legler discloses the isolation from bark of a mixture of compounds referred to as I, IIa, and IIb comprising 5-MeO-DMT, 5-MeO-NMT, and N-methyltryptamine (page 1, para. 2 to page 2, last para). In particular, Legler states “A small amount of I (5-MeO-DMT) and II was isolated by preparative thin layer chromatography and examined by paper chromatography in the systems tert-butanol/water/formic acid…” (page 1, 2nd para.). Legler subsequently identifies II as a mixture of N-methyltryptamine (IIa) and 5-MeO-NMT (IIb). N-methyltryptamine is a serotonergic drug according to applicant’s own specification (para. [0029]). The isolated mixture of Legler comprised approximately 32% of I and 41% of II (page 1, para. 3). II was identified as having roughly equal amounts of IIa (20.5%) and IIb (20.5%). Therefore, the ratio of I (5-MeO-DMT) to IIa (5-MeO-NMT) is approximately
32
20.5
:
20.5
20.5
= 1.56 : 1.
With respect to claim 4, Legler discloses a composition comprising the two purified toad secretion tryptamines 5-MeO-NMT and 5-MeO-DMT. Legler discloses a composition having 5-MeO-DMT and 5-MeO-NMT in a molar ratio of 1.56 : 1.
With respect to claims 3 and 12, Legler discloses a composition comprising a composition of claim 1 or 2 and an excipient. Legler discloses compositions comprising 5-MeO-NMT, 5-MeO-DMT, and the excipients alumina, silica gel, or water.
With respect to claims 5 and 13, Legler discloses a composition further comprising a therapeutically effective amount of a serotonergic drug. Legler discloses compositions comprising 5-MeO-DMT, 5-MeO-NMT, and the serotonergic drug N-methyltryptamine.
Therefore claims 4-5 and 12-13 are anticipated by Legler.
Claims 4-6 and 12-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Erspamer et al. (Biochemical Pharmacology, vol. 16, no. 7, July 1967, pp. 1149–64; cited in IDS).
Erspramer is drawn to 5-methoxy- and 5-hydroxyindoles in the skin of Bufo alvarius. Erspramer discloses that altogether the skins of 21 specimens of Bufo alvarius were collected and extracted, the bulk extracts pooled to constitute a glandular and non-glandular skin extract (page 1150, 6th para.). In particular, Erspramer discloses constituents from extracts of Bufo alvarius skin and identifies O-methylbufotenine (5-MeO-DMT) and N-methyl-5-methoxytryptamine (5-MeO-NMT) as constituents which are present in the skin extract (page 1154, Table 1). Erspramer discloses particular amounts of each ingredient in terms of ug or mg per g of dry tissue at page 1157 (see Table 5 and paragraph below Table 5): 5-MeO-NMT (“N-methyl-MT”) is present in an amount of 10-15 ug/g dry tissue; and 5-MeO-DMT (“O-Methylbufotenine”) is present in amounts ranging from 0.4 mg/g to 150 mg/g dry tissue.
With respect to claim 4, Erspamer discloses compositions comprising the two toad secretion tryptamines 5-MeO-NMT and 5-MeO-DMT. Erspamer discloses compositions having a molar ratio of 5-MeO-DMT to 5-MeO-NMT reading on the instant claim. For example, 0.4 mg to 10 ug equates to a ratio of 0.4 mg to 0.01 mg or 40:1 of MeO-DMT to 5-MeO-NMT.
With respect to claim 12, Erspamer discloses a composition comprising a composition of claim 1 or 2 and an excipient. Legler discloses compositions comprising 5-MeO-NMT, 5-MeO-DMT, and the excipients alumina, silica gel, methanol, or water.
With respect to claims 5 and 13, Legler discloses a composition further comprising a therapeutically effective amount of a serotonergic drug. Legler discloses compositions comprising 5-MeO-DMT, 5-MeO-NMT, and the serotonergic drug N-methyltryptamine.
With respect to claims 6 and 14, Erspramer discloses that in a typical experiment, 500 ml of the extract corresponds to 15 g of dry tissue. Erpramer’s disclosure is clear that the elution of skin extract on alumina was carried out multiple times, meaning at least 30 g of dry tissue was extracted (page 1153, “Elution of alumina columns loaded with the extract of non-glandular skin was always easy and the result was a good separation and partial purification of the different indole compounds”). Thus, for an extract volume corresponding to 30g of dry skin, the mg amounts of 5-MeO-DMT and 5-MeO-NMT in Erspramer’s extracts are considered to read on the range of “about 0.5 mg – about 200 mg”.
Therefore claims 4-6 and 12-14 are anticipated by Erspamer.
Please note that for product-by-process claims, “Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product.” See MPEP 2113.
Claim Rejections - 35 USC § 103 - Maintained
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.
Claims 1-2, 4-6, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Blumstock et al. (WO 2020157569 A1) in view of Blough et al. (Psychopharmacology, vol. 231, no. 21, Oct. 2014, pp. 4135–44). Blumstock lists a priority date (see page 1, “Priority data”) of 30 January 2019 and therefore has an earlier effective filing date over the instant application.
The instant claims are drawn to a dosage formulation consisting of two purified toad secretion tryptamines or a pharmaceutical formulation comprising said dosage formulation and a pharmaceutically acceptable excipient. Please note that the instant specification does not disclose any particular formulation. No exemplary embodiments are provided. In response to an election of species requirement, a composition comprising the combination of 5-MeO-DMT and 5-MeO-NMT was elected on 02/24/2025.
Blumstock is drawn to methods and compositions for the treatment of psychological, cognitive, behavioral, and/or mood disorders, the composition comprising one or more 5HT receptor agonists and a pharmaceutically acceptable excipient (abstract, claim 1, para. [313]). Blumstock discloses that the 5HT agonist includes compounds such as 5HT2A agonists including bufotenine, LSD, psilocin, psilocybin, DMT, 5-MeO-DMT, etc. (page 9, para. [39]). Blumstock identifies 5HT agonists belonging to the tryptamine family in paras. [47]-[49] and includes bufotenine, n-methylserotonin, serotonin, NMT, psilocin, psilocybin, DET, n-acetylserotonin, 5-MeO-NMT, and 5-MeO-DMT, etc:
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Blumstock therefore teaches that 5HT agonists, such as 5-MeO-DMT and 5-MeO-NMT can be combined in pharmaceutical compositions to be used in the treatment of psychological, cognitive, behavioral, and/or mood disorders. Further, Blumstock teaches (para. [41]) that agonism of 5HT2A facilitates treatment or management of disorders involving cognitive function and social interaction, or the symptoms thereof, as evidenced by the extensive localization of the 5-HT2A receptor in brain areas that mediate cognitive functions and social interaction. In some instances, disorders in which the 5HT2A receptor are involved include, but are not limited to schizophrenia, depression/suicide, anxiety, obsessive compulsive disorders (OCD), bipolar disorders, attention deficit hyperactivity disorder (ADHD), eating disorders such as anorexia nervosa, autism and autism spectrum disorders, Asperger’s, neuropsychiatric diseases and disorders, sexual disorders such as erectile dysfunction, neurodegenerative diseases, inflammatory diseases, autoimmune diseases, metabolic diseases such as obesity and diabetes, central nervous system disorders, peripheral nervous system disorders, Alzheimer’s disease, snoring, sleep apnea (obstructive sleep apnea, central sleep apnea), insomnia, sleep deprivation, restless legs syndrome, parasomnia, nightmares, night terrors, sleepwalking, hypersomnia (daytime sleepiness), narcolepsy and pain.
Blough is relied upon to confirm that both 5-MeO-DMT and 5-MeO-NMT were indeed recognized in the prior art as 5-HT agonists, particularly as potent agonists of 5-HT2A (see page 4139-4140, Tables 1 and 2, entries 17 and 7). The EC50 values disclosed for 5-MeO-DMT and 5-MeO-NMT are 3.87 nM and 3.78 nM, respectively.
Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results.
Moreover, as recognized by MPEP § 2144.06(I):
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
Therefore, applying KSR example rationale (A), it would have been prima facie obvious to combine multiple 5-HT receptor agonists, particularly multiple 5-HT2A receptor agonists into a dosage formulation or pharmaceutical formulation comprising a pharmaceutically acceptable excipient. As noted above, the motivation to combine flows logically from their having been individually taught in the prior art as potent 5-HT2A receptor agonists with a recognized utility for treatment of the same disorder(s). Absent evidence of an unexpected effect (e.g. synergism between two particular compounds) a skilled artisan would have reasonably predicted that the combination would result in a composition having the same or similar utility to the individual components.
With respect to claims 1-2, 4, and 12, please note that differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. In the instant case, the ratio of the first tryptamine to the second tryptamine is considered a result-effective variable that impacts, for example, the occurrence of a desired or undesired effect in a subject. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization. Accordingly, claims 1-2, 4, and 12 are obvious over Blumstock in view of Blough.
With respect to claims 5 and 13, Blumstock teaches (para. [200]) that the 5HT receptor agonist may be psilocybin or a derivative thereof (e.g. psilocin). Therefore, applying KSR example rationale (A), it would have been prima facie obvious to combine multiple 5-HT receptor agonists (such as 5-MeO-DMT, 5-MeO-NMT, and psilocybin) into a dosage formulation or pharmaceutical formulation to prepare a composition having 5-HT agonist activity. As noted above, the motivation to combine flows logically from their having been individually taught in the prior art as 5-HT receptor agonists with a recognized utility for treatment of the same disorder(s). Accordingly, claims 5 and 13 are obvious over Blumstock in view of Blough.
With respect to claims 6 and 14, Blumstock teaches (para. [63]) that the 5HT receptor agonist may be present in the composition in an amount of from about 0.1 mg to about 50 mg, which overlaps with the ranges recited. Please also note that please note that differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization. Accordingly, claims 6 and 14 are obvious over Blumstock in view of Blough.
Response to Arguments
Applicant argues that Blumstock provides no guidance for selecting two purified toad secretion tryptamine compounds according to the present invention.
Applicant’s arguments have been fully considered but are not persuasive. Blumstock teaches that compositions comprising one or more 5HT2A agonists are useful for treating psychological, cognitive, behavioral, and/or mood disorders; and teaches 5HT agonists belonging to the tryptamine family such as 5-MeO-DMT and 5-MeO-NMT. Blumstock therefore provides guidance to select a combination of compounds reading on the instant claims. Absent evidence of an unexpected effect (which has not been presented by applicant and there are no working examples in the application) a skilled artisan would have reasonably predicted that the combination would result in a composition having the same or similar utility to the individual compounds.
Conclusion
Claims 1-2, 4-6, and 12-14 are rejected.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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