DETAILED ACTION
This office action is in response to applicant’s filing dated April 8, 2026.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-4, 7-13, and 16-21 are pending in the instant application. Acknowledgement is made of applicant’s remarks filed April 8, 2026. Claims 5-6 and 14-15 were previously cancelled.
Election/Restrictions
Applicant’s election without traverse of a pharmaceutical combination of naltrexone and the 5HT3 receptor agonist serotonin hydrochloride and the cognitive or neurological disorder of depression in the reply filed on April 8, 2026 is acknowledged.
Claims 1-4, 7-13, and 16-21 are read on the elected species and are presently under examination as they relate to the elected species of naltrexone and serotonin hydrochloride and depression.
Claim Objections
Claims 1-4, 8, and 18 are objected to because of the following informalities:
Claim 1, line 5, reads “comprisinq administering a composition comprising an agonist of a 5- hydroxytryptamine (5-HT)” the phrase should read “comprisinq administering a composition further comprising an agonist of a 5- hydroxytryptamine (5-HT)”.
Claim 2, line 4, reads “the method comprising administering a composition comprising” the phrase should read “the method comprising administering a composition further comprising”
Claim 3 reads “the method of claim 2, wherein the composition comprising naltrexone, or a metabolite thereof, or an analogue selected from the group consisting of methylnaltrexone, nalmefene and nalorphine is administered separate, simultaneous or sequentially with the agonist of a 5-hydroxytryptamine receptor subtype 3” the claim should read “the method of claim 2, wherein the composition comprising naltrexone, or the metabolite thereof, or the analogue selected from the group consisting of methylnaltrexone, nalmefene and nalorphine is administered separately, simultaneously or sequentially with the agonist of a 5-hydroxytryptamine receptor subtype 3”.
Claim 4, lines 2-3, read “wherein naltrexone, or metabolite or analogue thereof” the phrase should read “wherein the naltrexone, or the metabolite or the analogue thereof”
Claim 8, line 7, reads “ibogaine, varenicline, YM-31636”. The phrase should read “ibogaine, varenicline, and YM-31636”.
Claim 18, line 6, reads “ibogaine, varenicline, YM-31636”. The phrase should read “ibogaine, varenicline, and YM-31636”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Scope of Enablement
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, 7-13, and 16-21 are 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 treating migraine, anxiety, depression, psychosis and paranoia in a subject in need thereof comprising an effective amount of naltrexone, methylnaltrexone, nalmefene, or nalorphine and either as psilocybin, psilocin, mescaline, lysergic acid diethylamide (LSD), ketamine, salvinorin A, ibotenic acid, muscimol, N,N- dimethyltryptamine (DMT), 3,4-methylenedioxymethamphetamine (MDMA), methyldiethanolamine, also known as N-methyl diethanolamine (MDEA), 3,4- methylenedioxy amphetamine (MDA), 4-Bromo-2,5 dimethoxyphenethylamine (2C-B); 1-(8-Bromo-2,3,6,7-tetrahydrobenzo-[1,2-b;4,5-b']difuran-4-yl)2-amino- ethane (2C-B-fly); 4-Ethyl-2,5-dimeth-oxyphenethylamine (2C-E); 4-Ethyl-thio-20 2,dimethoxyphenethylamine (2C-T-2); 4-Ethylthio-2,5-dimethoxy-amphetamine (ALEPH-2); 4-Ethylthio-2,5-dimethoxyphenylbutylamine (4C-T-2); 2,5- Dimethoxy-4-ethoxyamphetamine (MEM); 2,4,5-Trimethox-amphetamine (TMA- 2); 3,4,5-Trimethoxamphetamine (TMA); 2,5-Dimethoxy-4-bromo-amphetamine (DOB); 2,5-Dimethoxy-4-iodo-amphetamine (DOI); 2,5-Dimethoxy-4- methylamphetamine (DOM); 2,5-Dimethoxy-4-ethylamphet-amine (DOET); 5- Methoxy-N,N-dimethyl-tryptamine (5-MeO-DMT); N,N-Dipropyltryptamine (DPT); 5-Methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MIPT); N,N- Diisopropyltryptamine (DIPT); 5-Methoxy-N,N-diiso-propyltryptamine (5-MeO-DIPT); 6-Fluoro-N,N-dimethyltryptamine (6-fluoro-DMT); lisuride; ibogaine; cis- 2a; RR-2b; SS-2c; 2-Ethyl-5-methoxy-N,N-dimethyltryptamine (EMDT), serotonin hydrochloride, or metabolites or combinations thereof, does not reasonably provide enablement for treating all types of cognitive or neurological disorders by administering naltrexone, methylnaltrexone, nalmefene, and nalorphine in combination with any type of 5HT3 agonist. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention relates to a method of treating a cognitive or neurological disorder in a subject comprising administering naltrexone, methylnaltrexone, nalmefene, or nalorphine and a 5HT3 agonist to the subject.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art of treating any cognitive or neurological disorder, the examiner cites Cleveland Clinic Staff (U1, Cleveland Clinic Staff. “Neurological Disorders” Cleveland Clinic, (2024) pp. 1-3).
Cleveland Clinic staff, cited for evidentiary purposes, teaches that neurological disorders encompass n hundreds of different types of complex and multifaceted diseases with varying subcategories and unique characteristics such as Alzheimer’s disease, muscular dystrophy, migraine, stroke, and brain and spine injuries (pp. 1, paragraph 6). Cleveland Clinic Staff also teach that potential treatments for such diseases vary wildly and that there is currently no “one-size-fits-all” approach to neurological disorder treatment (pp. 3, paragraph 2). As such, due to different etiologies, pathologies, and patient populations of the various varieties of cancer, developing cancer treatment combinations is generally unpredictable.
As illustrative of the state of the art of targeting pain, the examiner cites Cortes-Altamirano et al. (V, Cortes-Altamirano, J. L. et al. “Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 Receptors and their Role in the Modulation of Pain Response in the Central Nervous System” Current Neuropharmacology, (2018) pp. 210-215) for evidentiary purposes.
Cortes-Altamirano teaches that pain is a ubiquitous symptom present in normal cell activity and in the vast majority of diseases and disorders (pp 210, paragraph 4). The molecular mechanism of action of the pain response is incredibly complex, involving numerous neurotransmitter systems implicated in the transmission, processing, and control of pain (pp 211, paragraph 2). Even the effects of particular receptors on pain are complex and contextual, with Cortes-Altamirano teaching that in certain circumstances the activation of pain-like states is caused via the activation of 5HT3 receptors (pp 215, paragraph 6). As such, the treatment of pain and chronic pain is generally unpredictable.
As illustrative of the state of the art of DNA damaging agents and anticancer drugs, the examiner cites Dukat (Dukat, M. “5-HT3 Serotonin Receptor Agonists: A Pharmacophoric Journey”, Current Medicinal Chemistry – Central Nervous System Agents (2004) pp. 1-3, cited in the IDS submitted on December 20, 2023) and Lapoint (W, Lapoint, L. “What Is Combination Drug Therapy”, (2022) pp. 2-4) for evidentiary purposes.
Dukat teaches that there are numerous types of 5HT3 agonists spread over three different structural classes (pp. 78 paragraph 3). Even amongst members of the same structural class of 5HT3 agonists, there are major differences between the pharmacological, physical, and chemical qualities of the different agonists. For instance, despite fluoro pyrroloquinoxalines and quipazine both being arylpiperazines, fluoro pyrroloquinoxaline is capable of crossing the blood brain barrier and has a significant 5HT3 selectivity while quipazine is generally unselective (pp 79, paragraph 2; pp 81, paragraph 2). As such due to differences in potency, selectivity, and mechanisms of actions, it is not predictable that any such 5HT3 agonist is compatible with naltrexone, methylnaltrexone, nalmefene, or nalorphine and will induce a therapeutic response against a generic cognitive or neurological disorder.
Lapoint, teaches that pharmaceuticals used in combination will act differently than those in isolation, as such additional experimentation is needed to determine suitable combination therapeutics (pp. 4, paragraph 1). As such, categories of 5HT3 agonists would require additional testing with naltrexone, methylnaltrexone, nalmefene, or nalorphine to see if the compounds are biologically compatible and therapeutically effective against neurological and cognitive disorders. Thus, one cannot predict if a generic 5HT3 agonist will be chemically compatible with naltrexone, methylnaltrexone, nalmefene, or nalorphine, especially given the sheer variety of available anti-cancer drugs with vastly different chemical, physical, pharmacological, and mechanism of action properties. As such, specification is not enabling for all types of 5HT3 agonists.
2. The breadth of the claims
Claims 1-4, 7-13, and 16-21 are very broad in terms of the type of disorders being treated and/or the 5HT3 agonist being used. Although some dependent claims recite aspects (particular disorders and 5HT3 agonists) which in isolation may be enabled, they incorporate aspects from the independent claim which make the dependent claim overly broad (e.g. claim 9 recites a method of treatment for pain, chronic pain, migraine, treatment-resistant depression, anxiety, depression, psychosis and paranoia with a combination comprising naltrexone, methylnaltrexone, nalmefene, or nalorphine and a generic 5HT3 agonist, without limit).
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification demonstrates that naltrexone is able of upregulating 5HT3 receptor expression in CD3+ lymphocytes. The specifications envision that the increased expression of 5HT3 by naltrexone would be able to increase the efficacy of 5HT3 agonists such as psilocybin, psilocin, mescaline, lysergic acid diethylamide (LSD), ketamine, salvinorin A, ibotenic acid, muscimol, N,N- dimethyltryptamine (DMT), 3,4-methylenedioxymethamphetamine (MDMA), methyldiethanolamine, also known as N-methyl diethanolamine (MDEA), 3,4- methylenedioxy amphetamine (MDA), 4-Bromo-2,5 dimethoxyphenethylamine (2C-B); 1-(8-Bromo-2,3,6,7-tetrahydrobenzo-[1,2-b;4,5-b']difuran-4-yl)2-amino- ethane (2C-B-fly); 4-Ethyl-2,5-dimeth-oxyphenethylamine (2C-E); 4-Ethyl-thio-20 2,dimethoxyphenethylamine (2C-T-2); 4-Ethylthio-2,5-dimethoxy-amphetamine (ALEPH-2); 4-Ethylthio-2,5-dimethoxyphenylbutylamine (4C-T-2); 2,5- Dimethoxy-4-ethoxyamphetamine (MEM); 2,4,5-Trimethox-amphetamine (TMA- 2); 3,4,5-Trimethoxamphetamine (TMA); 2,5-Dimethoxy-4-bromo-amphetamine (DOB); 2,5-Dimethoxy-4-iodo-amphetamine (DOI); 2,5-Dimethoxy-4- methylamphetamine (DOM); 2,5-Dimethoxy-4-ethylamphet-amine (DOET); 5- Methoxy-N,N-dimethyl-tryptamine (5-MeO-DMT); N,N-Dipropyltryptamine (DPT); 5-Methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MIPT); N,N- Diisopropyltryptamine (DIPT); 5-Methoxy-N,N-diiso-propyltryptamine (5-MeO-DIPT); 6-Fluoro-N,N-dimethyltryptamine (6-fluoro-DMT); lisuride; ibogaine; cis- 2a; RR-2b; SS-2c; 2-Ethyl-5-methoxy-N,N-dimethyltryptamine (EMDT), serotonin hydrochloride, or metabolites and combinations thereof.
However, the specification does not provide any in vitro data demonstrating both naltrexone and a 5HT3 agonist being used in combination or any in vivo data. Given the breadth of 5HT3 agonists and potential cognitive and neurological disorders, the applicant is not enabled for the treatment of any neurological or cognitive disorder with a combination of naltrexone, methylnaltrexone, nalmefene, or nalorphine and any generic 5HT3 agonist.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that naltrexone, methylnaltrexone, nalmefene, or nalorphine could be predictably used to treat all cognitive and neurological disorders in combination with any 5HT3 agonist. Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (42 USPQ 2d 1001, Fed. Circuit 1997).
As noted above, the specification does not provide experimental support for any combination of naltrexone, methylnaltrexone, nalmefene, or nalorphine and 5HT3 agonist being biologically compatible and effective against any cognitive or neurological disorder. Determining if any particular claimed combination would treat any particular cognitive or neurological disorder disease state would require formulating different combinations, determining an acceptable dosage, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicants. As noted supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
Accordingly, claims 1-4, 7-13, and 16-21 do not comply with the enablement requirement of 35 U.S.C. 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Written Description
Claims 1-4, 7-13, and 16-21 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 claims contain 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. This is a written description rejection.
The Written Description Guidelines for examination of patent applications indicates, "the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical characteristics and/or other chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show applicant was in possession of the claimed genus." (Federal register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see especially page 1106 column 3) and (see MPEP 2164).
Claims 1-4, 7-13, and 16-21 are drawn to a method of treating a subject having a cognitive or neurological disorder, comprising administering an effective amount of naltrexone, an analogue of naltrexone selected from methylnaltrexone, nalmefene, or nalorphine, or any metabolite naltrexone of prior to treatment with any 5-HT subtype 3 agonist. Claims 7 and 13 further exemplify that the 5-HT3 agonist is selected from psilocybin, psilocin, mescaline, lysergic acid diethylamide (LSD), ketamine, salvinorin A, ibotenic acid, muscimol, N,N- dimethyltryptamine (DMT), 3,4-methylenedioxymethamphetamine (MDMA), methyldiethanolamine, also known as N-methyl diethanolamine (MDEA), 3,4- methylenedioxy amphetamine (MDA), 4-Bromo-2,5-dimethoxyphenethylamine (2C- B); 1-(8-Bromo-2,3,6,7-tetrahydrobenzo-[1,2-b;4,5-b']difuran-4-yl)2-amino-ethane (2C-B-fly); 4-Ethyl-2,5-dimeth-oxyphenethylamine (2C-E); 4-Ethyl-thio-2,5- dimethoxyphenethylamine (2C-T-2); 4-Ethylthio-2,5-dimethoxy-amphetamine (ALEPH-2); 4-Ethylthio-2,5-dimethoxyphenylbutylamine (4C-T-2); 2,5-Dimethoxy-4- ethoxyamphetamine (MEM); 2,4,5-Trimethox-amphetamine (TMA-2); 3,4,5- Trimethoxamphetamine (TMA); 2,5-Dimethoxy-4-bromo-amphetamine (DOB); 2,5- Dimethoxy-4-iodo-amphetamine (DOI); 2,5-Dimethoxy-4-methylamphetamine (DOM); 2,5-Dimethoxy-4-ethylamphet-amine (DOET); 5-Methoxy-N,N-dimethyl- tryptamine (5-MeO-DMT); N,N-Dipropyltryptamine (DPT); 5-Methoxy-N-methyl-N- isopropyltryptamine (5-MeO-MIPT); N,N-Diisopropyltryptamine (DIPT); 5-Methoxy- N,N-diiso-propyltryptamine (5-MeO-DIPT); 6-Fluoro-N,N-dimethyltryptamine (6- fluoro-DMT); lisuride; ibogaine; cis-2a; RR-2b; SS-2c; 2-Ethyl-5-methoxy-N,N- dimethyltryptamine (EMDT), serotonin hydrochloride, or any metabolite thereof. 5HT3 agonists, naltrexone metabolites, and metabolites of all species exemplified in claims 7 and 17 encompass a broad chemical genuses, including current therapeutics, native chemical compounds, and an innumerable number of uninvented compounds. The claims encompass multiple genuses of molecules which function as a 5HT3 agonist, a metabolite of naltrexone, or a metabolite of the compounds listed as 5-HT3 agonists in claims 7 or 17 with no other defined structural components.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." MPEP § 2163. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618.
In the instant case, the claims are drawn to a method of treating a subject having a cognitive or neurological disorder, comprising administering an effective amount of naltrexone, an analogue selected from methylnaltrexone, nalmefene, or nalorphine, or a metabolite of naltrexone and a 5HT3 agonist.
The claims are generic, broadly reciting genus of “5HT3 agonist,” “naltrexone metabolite,” or a metabolite of any compound exemplified in claims 7 and 17. As stated supra, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claims 1-4, 7-13, and 16-21 are broad and generic, with respect to all possible compounds encompassed by the claims.
Applicant has failed to show that they were in possession of all the diverse compounds encompassed by “5HT3 agonist,” “naltrexone metabolite,” or a metabolite of any compound exemplified in claims 7 and 17. In the specifications, the applicant only exemplifies a composition containing psilocybin, psilocin, mescaline, lysergic acid diethylamide (LSD), ketamine, salvinorin A, ibotenic acid, muscimol, N,N- dimethyltryptamine (DMT), 3,4-methylenedioxymethamphetamine (MDMA), methyldiethanolamine, also known as N-methyl diethanolamine (MDEA), 3,4- methylenedioxy amphetamine (MDA), 4-Bromo-2,5 dimethoxyphenethylamine (2C-B); 1-(8-Bromo-2,3,6,7-tetrahydrobenzo-[1,2-b;4,5-b']difuran-4-yl)2-amino- ethane (2C-B-fly); 4-Ethyl-2,5-dimeth-oxyphenethylamine (2C-E); 4-Ethyl-thio-20 2,dimethoxyphenethylamine (2C-T-2); 4-Ethylthio-2,5-dimethoxy-amphetamine (ALEPH-2); 4-Ethylthio-2,5-dimethoxyphenylbutylamine (4C-T-2); 2,5- Dimethoxy-4-ethoxyamphetamine (MEM); 2,4,5-Trimethox-amphetamine (TMA- 2); 3,4,5-Trimethoxamphetamine (TMA); 2,5-Dimethoxy-4-bromo-amphetamine (DOB); 2,5-Dimethoxy-4-iodo-amphetamine (DOI); 2,5-Dimethoxy-4- methylamphetamine (DOM); 2,5-Dimethoxy-4-ethylamphet-amine (DOET); 5- Methoxy-N,N-dimethyl-tryptamine (5-MeO-DMT); N,N-Dipropyltryptamine (DPT); 5-Methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MIPT); N,N- Diisopropyltryptamine (DIPT); 5-Methoxy-N,N-diiso-propyltryptamine (5-MeO-DIPT); 6-Fluoro-N,N-dimethyltryptamine (6-fluoro-DMT); lisuride; ibogaine; cis- 2a; RR-2b; SS-2c; 2-Ethyl-5-methoxy-N,N-dimethyltryptamine (EMDT), and serotonin hydrochloride maybe used in combination with either naltrexone, an analogue selected from methylnaltrexone, nalmefene, or nalorphine or a metabolite of naltrexone for treating cognitive and neurological disorders. As there are an innumerably large number of potential 5HT3 agonists, naltrexone metabolites, and metabolites of compounds exemplified in claims 7 and 17, it would require extensive manpower to make and test each compound to determine which compound would possess the recited properties (i.e., to treat a cognitive or neurological disease in a subject when used in a combination as recited in the claims) and be useful in the instantly claimed compositions.
Given the broad scope of the claimed subject matter, Applicant has not provided sufficient written description that would allow the skilled in the art to recognize a method of treating a patient with a cognitive or neurological disorder, comprising naltrexone, an anologue selected from methylnaltrexone, nalmefene, or nalorphine, or a generic metabolite and a generic 5HT3 agonist or a generic metabolite of chemical species recited in claims 7 and 17 claimed in claims 1-4, 7-13, and 16-21.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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 1, 4, 7, and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yoon et al. (X1, Yoon, G. et al “Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder” JAMA Psychiatry (2019) pp. 1-5).
Regarding claims 1, 7, and 9-11, Yoon et al. teaches a treatment method for depression (e.g. a cognitive and neurological disorder, exemplified in claims 9) comprising administering infusion of ketamine (which is inherently in a composition as to infuse a drug one must dissolve it into a liquid carrier; e.g. which reads on 5-HT3 agonist and which is exemplified in claims 7) and naltrexone, where a subject was treated with naltrexone 2 days prior (e.g. which reads on the prior and sequential treatment of claims 3 and 10 and within the range of 1-4 days prior to 5HT3 agonist treatment of claim 11) to ketamine treatment (pp. 2, paragraph 2).
Thus, Yoon anticipates the method of claims 1, 7, and 9-11.
Regarding claims 4 Yoon mentions an alternative study where subjects suffering from depression were treated with 25 mg of naltrexone (e.g. which falls within the claimed range of 0.01 mg – 50 mg of claims 4) prior to ketamine treatment (pp. 5, paragraph 1).
Thus, Yoon anticipates the method of claims 4.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 7, 9-13, 16-17, and 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Yoon et al. (X1, Yoon, G. et al “Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder” JAMA Psychiatry (2019) pp. 1-5) in view of NIDA Staff (U2, NIDA Staff. “Naltrexone.” ATTC (2012) pp. 1).
The teachings of Yoon are set forth above and applied as before.
Yoon does not teach that naltrexone is administered in a composition or that naltrexone is administered orally in the form of a tablet or capsule.
However, NIDA Staff teaches that there are multiple prescription formulations (i.e. compositions) comprising Naltrexone including as a pill or capsule or an intramuscular injection where Naltrexone is in a composition (pp. 1, paragraph 5).
Since Yoon teaches a treatment method for depression (e.g. a cognitive and neurological disorder, exemplified in claims 9 and 19) comprising administering infusion of ketamine (e.g. which reads on 5-HT3 agonist and which is exemplified in claims 7 and 17) and naltrexone, where a subject was treated with naltrexone 2 days prior (e.g. which reads on the prior and sequential treatment of claims 3, 10, 20 and within the range of 1-4 days prior to 5HT3 agonist treatment of claims 11 and 21) to ketamine, and since NIDA Staff teach that Naltrexone can be administered either through FDA approved formulations (i.e. compositions) of an intramuscular injection or orally through a pill or capsule (which reads on the limitations of claims of 12 and 13), at the time of the invention it would have been prima facie obvious for a person of ordinary skill in the art to substitute one functional equivalence (an intramuscular injection of naltrexone) for another (an oral administration of a composition comprising naltrexone via a pill or capsule) with an expectation of success, since the prior art establishes that both function in similar manner, thus resulting in the practice of claims 1-4, 7, 9-13, 16-17, and 19-21, with a reasonable expectation of success.
Claims 1, 4, and 7-11 are rejected under 35 U.S.C. 103 as being unpatentable over Yoon et al. (X1, Yoon, G. et al “Association of Combined Naltrexone and Ketamine With Depressive Symptoms in a Case series of Patients With Depression and Alcohol Use Disorder” JAMA Psychiatry (2019) pp. 1-5) in view of Desert Biologicals Staff (V2, Desert Biologicals Staff. “Cerebromax”, Desert Biologicals (2018) pp. 1-2).
The teachings of Yoon are set forth above and applied as before.
Yoon does not expressly teach that the 5-HT3 agonist is m-chlorophenylbiguanide hydrochloride, N-methylquipazine dimaleate, PSEM 895, quipazine dimaleate, RS56812 hydrochloride, serotonin hydrochloride, SR7227 hydrochloride, 1-phenylbiguanide hydrochloride, cereulide, 2-methyl-5-HT, alpha-methyltryptamine, bufotenin, chlorophenylbiguanide, ibogaine, varenicline, or YM-31636.
However, Desert Biologicals teaches that Cerebromax solution comprising serotonin hydrochloride which is capable of treating cognitive and neurological disorders with symptoms relating to sleep, memory, and emotional issues (pp. 1, paragraph 3-4).
Since Yoon teaches a method of treating a cognitive or neurological condition with the 5-HT3 agonist ketamine, and since Desert Biologicals teach that a solution comprising serotonin hydrochloride can treat symptoms of cognitive and neurological disorders such as sleep, memory, and emotional issues, at the time of the invention it would have been prima facie obvious for a person of ordinary skill in the art to substitute one functional equivalence (ketamine) for another (serotonin hydrochloride) with an expectation of success, since the prior art establishes that both function in similar manner, thus resulting in the practice of claims 1, 4, and 7-11 with a reasonable expectation of success.
Claims 2-3, 12-13, and 16-21 are rejected under 35 U.S.C. 103 as being unpatentable over Yoon et al. and Desert Biologicals as applied to claims 1, 4, 7-8, and 10-11 above, and further in view of NIDA Staff (U2, NIDA Staff. “Naltrexone.” ATTC (2012) pp. 1).
Yoon and Desert Biologicals teach all the limitations of claims 2-3, 16-17, 18, and 20-21 (see 103 above), except where the naltrexone is administered as a composition or administered orally in the form of a tablet or capsule.
However, NIDA Staff teaches that there are multiple prescription formulations (i.e. compositions) comprising Naltrexone including as a pill or capsule or an intramuscular injection where Naltrexone is in a composition (pp. 1, paragraph 5).
Since Yoon teaches a treatment method for depression (e.g. a cognitive and neurological disorder, exemplified in claims 9 and 19) comprising administering infusion of ketamine (e.g. which reads on 5-HT3 agonist and which is exemplified in claims 7 and 17) and naltrexone, where a subject was treated with naltrexone 2 days prior (e.g. which reads on the prior and sequential treatment of claims 3, 10, 20 and within the range of 1-4 days prior to 5HT3 agonist treatment of claims 11 and 21) to ketamine, Desert Biologicals teaches that a solution comprising serotonin hydrochloride can treat symptoms of cognitive and neurological disorders such as sleep, memory, and emotional issues, and NIDA Staff teach that Naltrexone can be administered either through FDA approved formulations (i.e. compositions) of an intramuscular injection or orally through a pill or capsule (which reads on the limitations of claims of 12 and 13), at the time of the invention it would have been prima facie obvious for a person of ordinary skill in the art to substitute one functional equivalence (an intramuscular injection of naltrexone) for another (an oral administration of a composition comprising naltrexone via a pill or capsule) with an expectation of success, since the prior art establishes that both function in similar manner, thus resulting in the practice of claims 2-3, 12-13, and 16-21 with a reasonable expectation of success.
Conclusion
Claims 1-4, 7-13, and 16-21 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AARON RAFANAN ULLMAN whose telephone number is (571)272-6623. The examiner can normally be reached 7:30 am to 5:00 pm M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.R.U./Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
Prosecution Insights