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 with traverse of BW501C67, PSILOCYBIN, and MAJOR DEPRESSIVE DISORDER in the reply filed on 27 July 2026 is acknowledged. Applicant Claims 1, 4-8, 10-12, 17-19, 28, 29, 33, 38, 68, 70-72, and 75 read on the elected species. The Examiner respectfully disagrees. Claims 10-12 are drawn to xylamidine as the peripheral serotonin receptor antagonist. Claim 68 is drawn to two distinct tryptamines. Psilocybin has the structure
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which is not encompassed by either structure of Claim 68. The traversal is on the ground(s) that “all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains”. This is not found persuasive because the election of species requirement was made due to the invention failing to make a contribution over the prior art (See restriction requirement). The prior art of Keating teaches a method as claimed, and thus, an election of species is proper. Furthermore, the Examiner does not find the argument that “all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains” and thus would be expected to have the same properties to be persuasive. For example, a BW501C67 analog wherein variable R2 is H would not be expected to have the same properties as one wherein variable R2 is benzyl as the introduction of this large group introduces changes to the physiochemical properties of the compound (increased molecular weight, increased lipophilicity, etc.), and would be expected to bind to different receptors with different affinities from a variant of the compound wherein R2 is simply hydrogen.
The requirement is still deemed proper and is therefore made FINAL.
A search for the claimed species retrieved prior art (See STN Search, Search Notes). The search was then stopped.
Claims 10-12, 23, 34, 36, 40, 42, 44, 46, 52, 55, 61, 62, 64, 68, and 80 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 27 July 2026.
Claims 1, 4-8, 17-19, 28, 29, 33, 38, 70-72, and 75, submitted on 27 July 2026, represent all claims currently under consideration.
Priority
This application is a 371 of PCT/US2022/041274, filed 23 August 2022, which claims priority to provisional US 63/235,946, filed 23 August 2021. The examined claims are supported in the provisional. However, there is no support for derivatives of xylamidine or BW501C67 in this provisional application. The effective filing date for the claims as examined currently is 23 August 2021.
Information Disclosure Statement
One Information Disclosure Statement (IDS), submitted on 23 February 2024, is acknowledged and has been considered.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because it is fewer than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 33 is objected to because of the following informalities: Each of the compounds such as DMT, LSD, and 2C-B, for example, should be defined before an abbreviation is used to denote them. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 4-7, 28, 29, 33, 38, 70-72, and 75 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Factors to be considered in making the determination as to whether one skilled in the art would recognize that applicant was in possession of the claimed invention as a whole at the time of filing include : (a) Actual reduction to practice; (b) Disclosure of drawings of structural chemical formulas; (c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional characteristics when coupled with a known or disclosed correlation between function and structure; (d) Method of making the claimed invention; (e) Level of skill and knowledge in the art and (f) Predictability in the art. While all of these factors are considered, a sufficient number for a prima facie case are discussed below:
The claims are directed towards a method of treating a psychiatric disorder in a patient in need thereof comprising administering a peripheral serotonin receptor antagonist and a 5-HT2A receptor agonist to the patient. The specification states that “in some embodiments, a peripheral serotonin receptor antagonist is selected from the group consisting of sarpogrelate, temanogrel, xylamidine, BW501C67, BW204C67, a xylamidine analog, a BW501C67 analog, and natidrofuryl” (Page 3). Thus, Applicant is in possession of each of these compounds and derivatives as peripheral serotonin receptor antagonists. However, Applicant is not in possession of each and every possible peripheral serotonin receptor antagonist. Applicant explains the characteristics of these compounds (that they will antagonize peripheral serotonin receptors), but the teachings of the specification do not provide adequate guidance as to the structural metes and bounds of these compounds. There is no descriptor of what these antagonists comprise other than the group of compounds cited above. It is clear that Applicant is in possession of these compounds as peripheral serotonin receptor antagonists as Applicant has demonstrated their use as antagonists (Figures 1-9). The artisan would not know whether a compound could function in this invention without performing a posteriori testing. Thus, Applicant was not in possession of all peripheral serotonin receptor antagonists.
Claims 1, 4-8, 17-19, 28, 71, 72, and 75 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Factors to be considered in making the determination as to whether one skilled in the art would recognize that applicant was in possession of the claimed invention as a whole at the time of filing include : (a) Actual reduction to practice; (b) Disclosure of drawings of structural chemical formulas; (c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional characteristics when coupled with a known or disclosed correlation between function and structure; (d) Method of making the claimed invention; (e) Level of skill and knowledge in the art and (f) Predictability in the art. While all of these factors are considered, a sufficient number for a prima facie case are discussed below:
The claims are directed towards a method of treating a psychiatric disorder in a patient in need thereof comprising administering a peripheral serotonin receptor antagonist and a 5-HT2A receptor agonist to the patient, including 5-HT2A receptor agonists selected from the group consisting of ergoline, tryptamine, phenethylamine, and an amphetamine. The specification states that the 5-HT2A receptor in the central nervous system is activated selectively, and that this agonist can be selected from an ergoline, a tryptamine, a phenethylamine, and an amphetamine (Page 11). The specification further provides several specific 5-HT2A receptor agonists within each of these classifications (Pages 11-12). Thus, Applicant is in possession of these specific compounds as 5-HT2A receptor agonists. However, Applicant is not in possession of all possible 5-HT2A receptor agonists, nor are they in possession of all compounds found within each of these groupings. Applicant explains the characteristics of these compounds (that they will agonize the 5-HT2A receptor), but the teachings of the specification do not provide adequate guidance as to the structural metes and bounds of these compounds. There is no descriptor of what these agonists comprise other than the specific compounds which are cited. The artisan would not know if a specific tryptamine, ergoline, phenethylamine, or amphetamine would be capable of being used in this invention without a posteriori testing. Thus, Applicant was not in possession of all 5-HT2A receptor agonists, nor are they in possession of all ergoline, tryptamine, phenethylamine, or amphetamine 5-HT2A receptor agonists.
Claim Rejections - 35 USC § 112(b)
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.
Claim 4 is 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 4 is indefinite because it is unclear what “substantially attenuate” encompasses. This is not defined within the specification, causing indefiniteness as to exactly what the metes and bounds of the claim are as “substantially attenuate” is not a term of the art.
Claim 4 is 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 4 recites the limitation "the dose of the 5-HT2A receptor agonist" in line 6. There is insufficient antecedent basis for this limitation in the claim as “the dose of the 5-HT2A receptor agonist” has not been previously utilized. The Examiner suggests replacing this language to read “a dose” to overcome the rejection.
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.
Claims 1, 4-8, 17-19, 28, 29, 33, 38, 70-12, and 75 are rejected under 35 U.S.C. 103 as being unpatentable over Blumstock (US 2022/0096504; Publication Date: 31 March 2022; PCT Publication Date: 29 July 2021) in view of The Mayo Clinic (Selective Serotonin Reuptake Inhibitors (SSRIs), https://web.archive.org/web/20210818184607/https://www.mayoclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825, Archived 18 August 2021), Studerus (Journal of Psychopharmacology, 2010, 25, 11), Muttoni (Journal of Affective Disorders, 258, 2019, 11-24), Fuller (European Journal of Pharmacology, 125, 1986, 71-77), and Ansel (Pharmaceutical Dosage Forms and Drug Delivery Systems, 1999, Pgs. 48-53).
Determining the Scope and Contents of the Prior Art:
Blumstock teaches the use of psilocybin in combination with a second therapeutic agent which may be a serotonin receptor antagonist. Blumstock discloses methods and compositions for the treatment of psychological, cognitive, behavioral and/or mood disorders, the composition comprising a 5HT agonist (e.g., psilocybin) (Abstract). Provided herein is a method of managing a neurological condition or one or more symptoms thereof in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of one or more 5HT receptor agonist (e.g., psilocin) or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof (e.g., psilocybin) and a pharmaceutically acceptable excipient (Paragraphs 0008-0010). In some embodiments, the 5HT receptor agonist or a pharmaceutically acceptable salt, solvate, metabolite, derivative or prodrug thereof is present in an amount from about 0.1 mg to bout 50 mg (Paragraph 0016). In some embodiments, the 5HT receptor agonist is psilocybin or a pharmaceutically acceptable salt, solvate, metabolite, derivative, or prodrug thereof (Paragraph 0090). In some embodiments, the pharmaceutical composition further comprises an effective amount of a second agent. In some embodiments, the second agent is a 5HT receptor antagonist (Paragraph 0092). In some embodiments, the neurological condition is depression (Paragraph 0094). Depressive disorders which may involve feelings of extreme sadness, reduced interest in previously enjoyable life activities, including but not limited to depression, severe depression, major depressive disorder, premenstrual dysphoric disorder, and the like (Paragraph 0200). In some embodiments, one or more pharmaceutical compositions are administered simultaneously, sequentially, or at an interval period of time (Paragraph 0225). In some embodiments. Claim 22 claims a method of treating a neurological condition comprising administering psilocybin and a second therapeutic agent, which is a 5HT receptor antagonist.
The Mayo Clinic teaches that SSRIs, which inhibit the uptake of serotonin, resulting in increased levels of serotonin throughout the body, have several unpleasant side effects due to the action of serotonin on different 5HT receptors throughout the body. These side effects include nausea, vomiting, diarrhea, and headache.
Studerus teaches that psilocybin, which is binds to 5-HT receptors throughout the body, can have several unpleasant side effects unrelated to its activity in the brain. Table 2 provides complaints from 24 hours after drug intake, with reports of nausea, headaches, head pressure, face pain, abdominal pain or stomachache, and diarrhea being among the side effects reported by patients.
Muttoni provides a review of the effects of psychedelics such as ayahuasca, psilocybin, and LSD. The authors reported that all psychedelics caused mild increases in heart rate and blood pressure, which reached statistical significance in two studies with psilocybin (3.7, Safety and Tolerability).
Fuller discusses the pharmacology of BW501C67. BW501C67 is a serotonin antagonist that has been reported to not cross the blood-brain barrier compared to other serotonin receptor antagonists such as mainserin, ketanserin, metergoline, and LY53857. All compounds tested were potent inhibitors of the binding of tritiated spiperone to 5HT2 receptors in rat frontal cortex membranes in vitro and were less potent inhibitors of the binding of tritiated serotonin to 5HT1 receptors in rat brain membranes. All were potent antagonists of the 5HT2 receptor-mediated contractile response to serotonin in the rat jugular vein in vitro. At doses of 0.1 and 0.3 mg/kg i.p., BW501C67 antagonized the pressor response to intravenously injected serotonin in pithed rats. In contrast, BW501C67 did not antagonize the elevation of serum corticosterone concentration by quipazine in rats, while the other compounds antagonized this effect with ED50 values between 0.03 and 0.9 mg/kg. These data corroborate the previously reported antiserotonin activity of BW501C67 (Abstract). Since BW501C67 is a potent antagonist of serotonin receptors that block peripheral but not central serotonin receptor in vivo, it is useful for differentiating between central and peripheral serotonin receptors as mediators of functional effects of serotonergic drugs. Compound with this profile of activity may also be useful therapeutic agents for blocking peripheral serotonin receptors such as vascular receptors in the treatment of migraine, hypertension, ischemic trauma, gut receptors in the treatment of serotonin-induced diarrhea, or platelet receptors in the treatment of circulatory disorders associated with excessive platelet aggregation without any propensity for central side effects (Page 76).
Ansel teaches that physicians routinely increase or decrease the dosage of a therapeutic to tailor the treatment to be specific to their patient due to their body mass, underlying conditions, or other considerations such as the specific condition to be treated (Page 48). Ansel does not teach the specific dosages or timings which are claimed.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
Blumstock teaches the use of psilocybin and a second therapeutic agent for the treatment of major depressive disorder, including a serotonin antagonist, but does not explicitly claim the use of BW501C67. The Mayo Clinic, Studerus, and Muttoni demonstrate that increased binding to serotonin receptors by their natural ligand (serotonin) or exogenous ligands such as psilocybin/psilocin can result in unwanted peripheral side effects. Fuller teaches the use of BW501C67 as a sole agent functioning as a peripheral serotonin receptor antagonist, but does not teach its use in combination with psilocybin.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The artisan would likely have a medical degree, and further training in the administration of psychotherapies in the treatment of neurological conditions such as depression. Their training would further include monitoring of side effects from these medications, and how to optimize the dosage of therapeutics to help to mitigate these unwanted effects.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
Blumstock, The Mayo Clinic, Studerus, Muttoni, Fuller and Ansel are considered analogous to the claimed invention as all are involved in the use of pharmacotherapies for the treatment of underlying pathologies. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the method of treating major depressive disorder using psilocybin and a second therapeutic agent which may be a serotonin receptor antagonist by utilizing BW501C67 as the serotonin receptor antagonist. It is known in the art that peripheral activity of serotonin receptor agonism, including with psilocybin, results in unpleasant side effects such as diarrhea, high blood pressure, and headaches. Fuller teaches that BW501C67 acts exclusively on the peripheral serotonin receptors, and states specifically that this compound be useful for mitigating conditions such as headache, high blood pressure, and serotonin-induced diarrhea. Thus, the artisan would be motivated to utilize BW501C67 specifically as it is shown to only act on the periphery, and would not be expected to inhibit the activity of psilocybin in the brain where it will have the most therapeutic effect, but will rather help mitigate unwanted side effects would could make patients less likely to continue treatment. The artisan would have a reasonable expectation of success in choosing BW501C67 as Fuller shows that this compound potently inhibits peripheral receptors, but has no central activity.
Regarding the specific dosages of psilocybin and BW501C67, the artisan would be able to adjust the dosages in view of the teachings of Ansel to ensure the appropriate therapeutic response is achieved in view of their training. Moreover, patent law views differences in concentration (herein, the varying doses of BW5016C7 or psilocybin) as not supporting the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A).
Claims 1, 4-8, 17-19, 28, 29, 33, 38, 70-12, and 75 are rejected under 35 U.S.C. 103 as being unpatentable over Davis (JAMA Psychiatry, 2020, 78, 5, 481-489) in view of The Mayo Clinic (Selective Serotonin Reuptake Inhibitors (SSRIs), https://web.archive.org/web/20210818184607/https://www.mayoclinic.org/diseases-conditions/depression/in-depth/ssris/art-20044825, Archived 18 August 2021), Studerus (Journal of Psychopharmacology, 2010, 25, 11), Muttoni (Journal of Affective Disorders, 258, 2019, 11-24), Fuller (European Journal of Pharmacology, 125, 1986, 71-77), and Ansel (Pharmaceutical Dosage Forms and Drug Delivery Systems, 1999, Pgs. 48-53).
Determining the Scope and Contents of the Prior Art:
Davis teaches the use of psilocybin for the treatment of major depressive disorder. Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in context of supportive psychotherapy. The findings suggest that psilocybin with therapy is an efficacious treatment in MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression (Abstract). There were no serious adverse events in the trial. However, a transient increase in blood pressure that exceeded the protocol criteria for more frequent assessment (ie, diastolic blood pressure >100 mm Hg) occurred during 1 session. Other nonserious adverse events included headache, nausea, and diarrhea (Page 486).
The teachings of The Mayo Clinic, Studerus, Muttoni, Fuller, and Ansel are previously described and are fully incorporated into this rejection.
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
Davis teaches the use of psilocybin for the treatment of major depressive disorder. The Mayo Clinic, Studerus, and Muttoni demonstrate that increased binding to serotonin receptors by their natural ligand (serotonin) or exogenous ligands such as psilocybin/psilocin can result in unwanted peripheral side effects. Fuller teaches the use of BW501C67 as a sole agent functioning as a peripheral serotonin receptor antagonist, but does not teach its use in combination with psilocybin.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The artisan would likely have a medical degree, and further training in the administration of psychotherapies in the treatment of neurological conditions such as depression. Their training would further include monitoring of side effects from these medications, and how to optimize the dosage of therapeutics to help to mitigate these unwanted effects.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
Davis, The Mayo Clinic, Studerus, Muttoni, Fuller and Ansel are considered analogous to the claimed invention as all are involved in the use of pharmacotherapies for the treatment of underlying pathologies. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to modify the method of treating major depressive disorder using psilocybin by combining this method with the serotonin receptor antagonist BW501C67. It is known in the art that peripheral activity of serotonin receptor agonism, including with psilocybin results in unpleasant side effects such as diarrhea, high blood pressure, and headaches, with Davis reporting that patients in this study experienced these side effects. Fuller teaches that BW501C67 acts exclusively on the peripheral serotonin receptors, and states specifically that this compound be useful for mitigating conditions such as headache, high blood pressure, and serotonin-induced diarrhea. Thus, the artisan would be motivated to utilize BW501C67 specifically as it is shown to only act on the periphery, and would not be expected to inhibit the activity of psilocybin in the brain where it will have the most therapeutic effect, but will rather help mitigate unwanted side effects would could make patients less likely to continue treatment. The artisan would have a reasonable expectation of success in choosing BW501C67 as Fuller shows that this compound potently inhibits peripheral receptors, but has no central activity.
Regarding the specific dosages of psilocybin and BW501C67, the artisan would be able to adjust the dosages in view of the teachings of Ansel to ensure the appropriate therapeutic response is achieved in view of their training. Moreover, patent law views differences in concentration (herein, the varying doses of BW5016C7 or psilocybin) as not supporting the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art."). See MPEP 2144.05(II)(A).
Conclusion
Claims 1, 4-8, 17-19, 28, 29, 33, 38, 70-72, and 75 are rejected.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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