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 .
Priority
This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/US22/53428, filed 12/19/2022, which claims the priority benefit of PRO Application No. 63/291,210, filed 12/17/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/16/2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Application
Claims 1-2, 4-5, 7-10, 13, 16-17, 20, 22, 24-28, 30, and 59 are currently pending and under examination. Claim1-2, 5, 7, 10, 13, 16-17, 24-26, 28, 30, and 59 have been amended. Claims 3, 6, 11-12, 14-15, 18-19, 21, 23, 29, 31-58, and 60-64 have been canceled by applicant without prejudice or disclaimer.
Claim Interpretation
The limitations of “c.” and “d.” of instant claim 1 are being interpreted as requiring one or both “c.” or “d.” limitations which is the broadest interpretation of the claim. See MPEP 2111.
Claim Objections
Claim 1 is objected to because of the following informalities: the semi-colon “;” should be replaced with a comma between the words “injection” and the word “and” in lines 7-8 of instant claim 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-2, 4-5, 7-10, 13, 16-17, 20, 22, 24-28, 30, and 59 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 a method of treating a substance use disorder, does not reasonably provide enablement for prevention of said disease or disorder. 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.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." In In re Wands, 8 USPQ2d 1400 (1988), the factors to be considered in determining whether a disclosure meets the enablement requirement are as follows:
1. The nature of the invention
2. The state of the prior art
3. The predictability or lack thereof in the art
4. The amount of direction or guidance present
5. The presence or absence of working examples
6. The breadth of the claims
7. The quantity of experimentation needed, and
8. The level of skill in the art
The Nature of the Invention and Breadth of the Claims
The instant claims are drawn to a method of treating a substance use disorder in a subject in need thereof comprising;
a. identifying the subject, wherein the subject has reduced substance consumption for
at least 1 day prior to the administration of step (b ); and
b. administering to the subject a pharmaceutical composition comprising
5-MeO-DMT or a salt thereof wherein the administering is performed
sublingually buccally by intramuscular injection or by intravenous injection;
and providing the subject with one or both of:
c. a treatment holiday of 1 week to 12 months after the administering of step (b); and
d. a therapy session between 1 week and 10 weeks after the administering of step (b ).
The nature of the invention is therefore drawn to the pharmaceutical art. These claims cover diseases that are known to exist and those that may be discovered in the future, for which there is no enablement provided.
The State of the Prior Art and the Predictability or lack thereof in the art
“Substance use disorders (SUDs) affect almost 20 million adults and over 440,000 adolescents in the United States. Annually, it is estimated that more than 70,000 Americans die from drug overdoses, and that SUDs cost American society more than $740 billion annually in lost
workplace productivity, healthcare expenses, and crime-related costs. Drug-related deaths in the
United States have more than tripled since 2000, and there are more deaths, illness, and disabilities from substance use than from any other preventable health condition to the extent that one in four deaths in the United States is currently attributable to alcohol, tobacco, and illicit or prescription drug use. To date there are only three FDA approved drugs for the treatment of alcohol use disorder-disulfiram, naltrexone, and acamprosate-and only three approved drugs for the treatment of Opioid Use Disorder-buprenorphine, methadone, and naltrexone-and none for
many other SUDs, highlighting the need for new and effective treatments for SUDs.” (Specification, [03])
However, the prior art compound of 5-MeO-DMT is not reported to completely prevent the onset of any or every substance use disorder by sublingually buccally by intramuscular injection or by intravenous injection. Barsuglia et al. (A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder), discloses “5-MeO-DMT similarly lacks documentation of its clinical effects in humans with addiction. Therefore, we documented the clinical effects and pre- and post-treatment changes on cerebral blood flow via single-photon emission computed tomography (SPECT) in an individual with alcohol use disorder who was seeking a combination protocol of ibogaine and 5-MeO-DMT for addiction treatment.” (Section 1.3, pg. 127)
It is noted that pharmacological activity in general is a very unpredictable area. In cases involving physiological activity, such as the instant case, “the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.” See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The Amount of Guidance Present and Presence/Absence of Working Examples
The only guidance disclosed by the specification regarding prevention of preventions of the substance use disorder is found in the specification [35], on pages 8-9:
The specification describes “treatment” and “treating” in [35] as “The term "treatment" or "treating" refers to an approach for obtaining beneficial or desired results with respect to a disease, disorder, or medical condition including a therapeutic benefit and/or a prophylactic benefit. In embodiments, treatment or treating involves administering a disclosed compound or composition to a subject. A therapeutic benefit may include the eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit may be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder, such as observing an improvement in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. In embodiments, for prophylactic benefit, a composition is administered to a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease, even though a diagnosis of this disease may not have been made. Treating can include, for example, reducing, delaying or alleviating the severity of one or more symptoms of the disease or condition, or it can include reducing the frequency with which symptoms of a disease, defect, disorder, or adverse condition, and the like, are experienced. Treating can refer to a method that results in some level of treatment or amelioration of the disease or condition, and can contemplate a range of results directed to that end, including prevention of the condition entirely” (emphasis added)
The specification does not provide any guidance for determining which particular patient population would be susceptible to developing substance use disorder or who would respond to treatment. Also, lacking are data showing that the compound of 5-MeO-DMT is capable of treating all or every substance use disorder. For example, Kanayama et al. Pages 121-158 (Treatment of anabolic–androgenic steroid dependence: Emerging evidence and its implications), discloses anabolic–androgenic steroids (AAS) as a substance of abuse whereas the current disclosure does not address patients with an anabolic steroid dependency.
The quantity of experimentation needed, and level of skill in the art
In order to treat every or all substance use disorder types, one would need to precisely identify those subjects with the disease or disorder who are likely to respond to treatment, administer the claimed invention, and demonstrate that administration directly resulted in the subject overcoming the disease or disorder. One skilled in the art would conclude that the guidance in the specification would not have taught one skilled in the art how to treat every or all substance use disorder types using the compound of 5-MeO-DMT, because there is no guidance for how to select a patient population and no evidence that the claimed compounds can broadly treat every substance use disorder type. Given the lack of guidance in the specification and the lack of success in the prior art, one skilled in the art would find that preventing the claimed diseases or disorders would require experimentation that is unduly burdensome. Claims 2, 4-5, 7-10, 13, 16-17, 20, 22, 24-28, 30, and 59 are all dependent on claim 1 and are therefore also encompassed by this rejection.
This rejection may be overcome by amending the claim language of claim 1 to indicate the method of claim 1 is a method of treating not preventing.
Claim Rejections - 35 USC § 112
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 and 16 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 limitation “b.” line 8 recites the broad recitation providing the subject with one or both of: limitations c. or d., and the claim also recites limitation d. is required after limitation c. by the use of the term “and” at the end of limitation c. which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
This rejection may be overcome by amending claim language to clearly indicate whether the limitations “c.” and “d.” are both required as indicated by limitation “c.” or one or the other is required as indicated by limitation “b.” of instant claim 1.
The term “legal” in claim 16, line 2is a relative term which renders the claim indefinite. The term “legal” 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 legal status of an opioid does not change the identity or mechanism of action and examiner note that a legal prescription opioid may easily become an illegal prescription opioid if used by an unauthorized individual who was not prescribed the medication. Furthermore, the legal status of a compound may change over time or by location (i.e. country). For example, Levine et al. (An Intoxication Involving BRONTM and Verapamil*), disclose controlled opioids as ingredients in an over the counter medication which would require a prescription in the United States, “[t]he first three drugs listed appear together In an over-the-counter cold medication In Japan, under the trade name BRON. Blood quantitations (in mg/L) were as follows: chlorpheniramine, 2.6; dihydrocodeine, 4.7; methylephedrine, 5.6; salicylate, 150; and verapamil, 6.0.” (Abstract).
This rejection may be overcome by cancelling the claim or by amending claim language to clearly specify which opioid compound applicant intends.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 4-5, 7-10, 13, 16-17, 20, 22, 24-28, 30, and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Barsuglia et al. (A case report SPECT study and theoretical rationale for the sequential administration of ibogaine and 5-MeO-DMT in the treatment of alcohol use disorder) in view of Terwey (WO2020/169851A1).
The instant claims are directed to a method of treating a substance use disorder in a subject in need thereof comprising
a. identifying the subject, wherein the subject has reduced substance consumption (abstaining from moderate to heavy substance consumption) for at least 1 day to 1 week prior to the administration of step (b ); and
b. administering to the subject a pharmaceutical composition comprising 6-80 mg
5-MeO-DMT (99% purity) or a salt thereof wherein the administering is performed
sublingually buccally by intramuscular injection(s) (within 1-8 hours) or by intravenous injection; and providing the subject with one or both of:
c. a treatment holiday of 1 week to 12 months after the administering of step (b); and
d. a therapy session between 1 week and 10 weeks after the administering of step (b ).
Barsuglia et al. teach 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring psychedelic (bufotoxin source) which demonstrates anti-addictive properties and has potential therapeutic effects in treating alcohol use disorder. (Abstract). Barsuglia also teaches selection of a patient “We present the case of a 31-year-old male military veteran with moderate alcohol use disorder who sought treatment at an inpatient clinic in Mexico that utilized a sequential protocol with ibogaine hydrochloride (1550 mg, 17.9 mg/kg) on day 1, followed by vaporized 5-MeO-DMT (bufotoxin source 50 mg, estimated 5-MeO-DMT content, 5-7 mg) on day 3. The patient received SPECT neuroimaging that included a resting-state protocol before, and 3 days after completion of the program.” (Abstract). Barsuglia discloses the patient was required to refrain from drinking alcohol for 1 week prior to admission (section 3.1,1st para., pg. 129). Barsuglia discloses a telephonic follow-up therapy session at 1 month wherein the patient had abstained from alcohol use and at 3-month follow-up, he reported at approximately 10 weeks post-treatment he had returned to drinking one to two alcoholic beverages (Boochcraft, ~7% alcohol content) per week, which was relatively less compared to his prior baseline daily drinking habits (5-6 drinks per day). (4.2, pg. 136). Barsuglia discloses group therapy “[b]efore ibogaine treatment, he received group therapy in an outpatient program at the local VA hospital for 2 years, as well as weekly psychotherapy for 6 months for alcohol use and PTSD.” (pg. 128, 4th para.). Barsuglia also teaches 5-MeO-DMT found naturally in the bufotoxin of the Colorado river toad and also synthetically produced and that users of synthetic 5-MeO-DMT in uncontrolled settings reported therapeutic effects attributed to their use (pg. 125, section 1.2, para. 1-2). Barsuglia also discloses “the bufotoxin which contains 5-MeO-DMT after combustion/vaporization may contain some trace amounts of bufotenine (pg. 145, 2nd para.). Barsuglia discloses Table 1 “Imaging, Treatment Course, and Follow-up Timeline”, wherein telemedicine follow-ups are performed at 30 and 90 days following the start of therapy in which 5-MeO-DMT is administered on day 3(Table 1, pr. 131).
However, Barsuglia et al. fail to disclose administering of 5-MeO-DMT is performed sublingually, buccally by intramuscular injection or by intravenous injection.
Terwey et al. teach 5-MeO-DMT is administered via the intravenous, intramuscular
or subcutaneous route. (Abstract) Terwey teaches improved methods for the treatment of mental disorders, in particular psychoactive substance abuse, comprising administering to a patient in need thereof a therapeutically effective amount of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) (pg. 1, 1st para.). Terwey also teaches an intramuscular dosage of 1-10 mg 5-MeO-DMT of a first dose followed by 0-6 subsequent administrations wherein each subsequent administration uses a dosage higher than the previous administration in an interval between administrations of 1 to 24 hours with a preferable interval disclosed as 2-4 hours (pg. 2, para. 3-6). Terwey discloses intramuscular administration assures rapid onset of action (pg. 22, 3rd para.) Terwey also discloses “The treatment of patients with substance abuse includes, but is not limited to, patients with alcohol related disorders, opioid related disorders, sedative, hypnotic, or anxiolytic related disorders, cocaine related disorders, other stimulant related disorders and nicotine dependence.” (pg. 18, 2nd para.). Terwey discloses “It is contemplated that pharmaceutically acceptable salts of 5-MeO-DMT will typically be used. An example for such a salt is the hydrochloride.” (definitions, pg. 15) Terwey discloses example 2 (pg. 96) and example 3 (pg. 102) wherein 5-MeO-DMT is administered at a purity of over 99%. Terwey teaches example 6 wherein a patient has follow-up visits to evaluate safety and efficacy at days 7, 14, and 28 days in an evaluation phase followed by a follow-up phase wherein efficacy and safety evaluations occur monthly wherein “Patients who had achieved at least a 50% reduction from baseline in MADRS total score at the primary endpoint will be eligible for three-monthly re-treatment with 5-MeO-DMT using the highest dose given in the blinded phase, with the first re-treatment on day 28.” (pg. 113, para. 2-3)
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to administer a method of treating a substance use disorder in a subject by using the disclosures of selecting an individual with an alcohol use disorder who has abstained from use for a period of 1 week prior to treatment and administering a high purity (over 99%) 5-MeO-DMT which can be derived from natural or synthetic sources, and periodic follow-up therapy sessions to evaluate effectiveness of the treatment from Barsuglia with the teachings of Terwey of a hydrochloric salt version of 5-MeO-DMT to improve solubility in a total amount of 1-49 mg (up to 6 total subsequent increasing dosing’s of 4+ 5+ 6+ 7+ 8+ 9+ 10 mg = 49 mg) within 8 hours, administered intramuscularly for rapid onset of action because a skilled artisan would have found short controlled exposures to 5-MeO-DMT to be an effective form of treating a substance use disorder. See MPEP 2144.05 (I and II), and MPEP 2144.09.
A person of ordinary skill in the art would have been motivated to improve the methods of Barsuglia of a single administration of an inhaled dose of 5-MeO-DMT with Terwey’s disclosure of intramuscular and oral administration which provided better bioavailability of 5-MeO-DMT to the patient while affording improved safety to medical care givers from exposure to 5-MeO-DMT using inhaled methods of administration and providing follow-up evaluation/administration of 5-MeO-DMT when determined by a medical professional after a period of time after treatment to give one of ordinary skill a reasonable expectation of success in attenuating substance use by over 20%.
Conclusion
All claims are rejected, no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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/E.V./Examiner, Art Unit 1623
/SAMANTHA L SHTERENGARTS/Primary Examiner, Art Unit 1623
