DETAILED ACTION
This office action is in response to applicant’s filing dated November 6, 2025.
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 8, 9, 23-25, 44, 45, and 60-66 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed November 6, 2025. Acknowledgement is made of Applicant's amendment of claim 8, 23-25, and 63-66. Claims 1-7, 10-22, 26-43, and 46-59 were previously canceled.
Applicants elected without traverse (i) ketamine as the agent species, (ii) PMS as the menstrually related disorder species, and (iii) irritability as the menstrually related symptom in the reply filed on October 28, 2021. Examination was expanded to the following species: premenstrual dysphoric disorder (PMDD) and anxiety in the Office Action dated February 14, 2022.
In order to accelerate prosecution, examination has been expanded to the following species: mood swings, because mood swings was identified during the prior art search.
New claims 63 and 65 are directed to the elected species, irritability. New claims 64 and 66 are directed to the expanded species, mood swings. Thus, claims 63-66 are presently under examination.
Claims 8, 9, 23-25, 44, 45, and 60-66 are presently under examination as they relate to the elected species: (i) ketamine, (ii) PMS, and (iii) irritability, and expanded species PMDD, and mood swings.
Priority
The present application is a 371 of PCT/US17/63836 filed on November 30, 2017, which claims benefit of US Provisional Application Nos 62/427,814 and 62/568,488 filed on November 30, 2016 and October 5, 2017, respectively. The effective filing date of the instant application is November 30, 2016.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 6, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
New Objections and/or Rejections
Necessitated by Claim Amendment
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 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 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 8, 9, 23-25, 44, and 60-66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weg (US 2014/0057988 A1, cited in a previous Office Action) in view of Freeman (Psychoneuroendocrinology, 2003; 28(Suppl 3):25-37, cited in a previous Office Action), Irwin et al (J Palliat Med, 2010; 13(7):903-8); Lara et al (Int J Neuropsychopharm, 2013; 16:2111–2117); and Erickson et al (US 2015/0196501 A1, cited in a previous Office Action).
Regarding claims 8, 9, 60, and 63-66, Weg teaches a method for treating the development of anxiety in a subject comprising administering an NMDA receptor antagonist (claim 1) wherein the NMDA receptor antagonist comprises ketamine (claim 2). Weg further teaches "anxiety" refers to an emotional state of apprehension or other unease that is distressing or otherwise unpleasant to a person; anxiety may also occur comorbidly with other mental disorders or may be a symptom of them, such as in premenstrual dysphoric syndrome [0005]. Weg further teaches the method comprises the administration of the anxiolytic agent by a variety of routes including transmucosal [0023]. Thus, Weg teaches a method of treating premenstrual dysphoric syndrome wherein the symptom is anxiety comprising administering ketamine, including via transmucosal administration. A subject suffering from premenstrual dysphoric disorder reads on a subject experiencing menstrually related symptoms. Regarding the elected menstrually related disorder species, PMS, PMDD is a form of PMS as evidenced by Freeman (Psychoneuroendocrinology, 2003; 28(Suppl 3):25-37). Freeman teaches premenstrual dysphoric disorder is a severe dysphoric form of PMS (abstract). Thus, PMDD reads on PMS.
Weg does not explicitly teach the subject is experiencing menstrually related symptoms including irritability or mood swings.
However, Freeman teaches symptoms required to diagnose PMDD include anxiety, mood swings, and irritability (Table 3); PMS clearly involves emotional symptoms such as irritability, mood swings, tension and depression; and irritability may be the cardinal symptom of the syndrome (page 28. 2nd paragraph). Thus, a subject suffering from PMDD reads on a subject in need of treatment of anxiety, irritability and/or mood swings.
Irwin teaches ketamine has many properties that make it a good candidate for treating depression and anxiety (page 903, right, 2nd paragraph). Irwin teaches S.B. had severe anxiety symptoms related to shortness of breath; she reported one to three panic attacks per day; she was noticeably anxious during the initial interview; she also reported feeling irritable, which was confirmed by her caregiver/roommate; she would shout and appear extremely irritated when the phone rang or the dog would bark (page 904, left, 2nd paragraph); by 120 minutes after ketamine dosing, she no longer had suicidal thoughts and noted a significant improvement in her depression and anxiety; S.B. expressed hope for the future and no longer felt irritable; the overt signs of anxiety and irritability she displayed prior to ketamine dosing were absent (page 904, right, 2nd paragraph).
Lara teaches ketamine administered to one subject every 7 days, 20 doses the clinical outcome included a clear reduction of irritability and to another subject every 7 days continuous treatment for ~4 months the clinical outcome included less mood swings and irritability (page 2114, Table 1).
As such, since Weg teaches a method of treating premenstrual dysphoric syndrome wherein the symptom is anxiety comprising administering ketamine, including via transmucosal administration and that PMDD is a form of PMS; since Freeman teaches symptoms required to diagnose PMDD include anxiety, mood swings, and irritability and irritability may be the cardinal symptom of the syndrome of PMS; since Irwin teaches a method of treating anxiety comprising administering ketamine wherein the subject is experiencing irritability wherein the irritability is treated; and since Lara teaches ketamine treatment resulted in reduction of mood swings and irritability, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of treating premenstrual dysphoric syndrome wherein the symptom is anxiety comprising administering ketamine, including via transmucosal administration taught by Weg to treat a subject suffering from premenstrual dysphoric syndrome wherein the symptom is anxiety experiencing irritability and/or mood swings with an expectation of success, since the prior art establishes that ketamine is useful for treating irritability in a subject experiencing anxiety and for reducing irritability and mood swings.
Regarding claims 23 and 24, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to initiate the method of treating premenstrual dysphoric syndrome wherein the symptom is anxiety experiencing irritability and/or mood swings comprising administering ketamine, including via transmucosal administration following or just prior to the appearance of irritability and/or mood swings in view of the cited art since the art establishes that ketamine is useful for treating irritability in a subject experiencing anxiety and for reducing irritability and mood swings.
Regarding claim 44, Weg does not explicitly teach the ketamine is enantiomerically pure S-(+)-ketamine.
However, Erickson teaches emerging evidence supports the use of ketamine for treatment of mood, anxiety, and expressive symptoms in children with bipolar disorder [0022] and that the composition may comprise racemic ketamine, the composition may comprise S-ketamine, or the composition may comprise greater than 99% of the S enantiomer of ketamine [0032]. Thus, Erikson establishes that S-ketamine is useful for treating anxiety and is safe for use in children.
Weg does not explicitly teach the ketamine is administered daily or intermittently or that there is at least one week during which no ketamine is administered (instant claims 8 and 25). However, Weg does teach administration of 2 to 3 teaches administration of active agent prior to undergoing procedure and experiences relieve from anxiety (see Examples I-VI) and night before flight and day of flight to relieve anxiety (Example VII). Moreover, Erickson teaches a randomized double-blind, placebo-controlled parallel group pilot study of four ascending doses of intranasal ketamine with open-label extension [0085], all visits were at least 4 days apart, with maximum of 8+/-2 days between visits [0087], subjects are age ≥12 and <31 years old [0062], ketamine will be compounded into a mucosal atomization device which delivers 10 mg of atomized ketamine per 0.1 cc spray, in Phase 1, participants will self-administer 2 sprays at visit 1, 4 sprays at visit 2, 6 sprays at visit 3, and 8 sprays at visit 4, unless subject reaches treatment response, prior to Phase 2, all subjects will undergo a 2 week wash-out period, in Phase 2, all patients will receive active drug in ascending doses of 20 mg at week 1, 40 mg week 2, 60 mg week 3, 80 mg week 4, unless subject reaches treatment response [0088], and outcome measures include Anxiety Depression and Mood Scale [0092]. It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to treat utilize the treatment regimen and doses of ketamine taught by Weg and Erickson as a starting point for optimizing the amount of ketamine for use in a method of treating premenstrual dysphoric disorder or symptom thereof wherein the symptom is anxiety with an expectation of success, since the prior art establishes that these doses are known to be safe to administer to humans and to measure Anxiety Depression and Mood Scale outcomes and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Regarding the amounts of ketamine of instant claims 8, 44, and 62, Erickson teaches emerging evidence supports the use of ketamine for treatment of mood, anxiety, and expressive symptoms in children with bipolar disorder [0022], ketamine is compounded into a mucosal atomization device which delivers 20 mg of atomized ketamine per 0.1 cc spray; the subject will self-administer (or administer with the help of a caregiver) ketamine every four to seven days; on the first administration, 2 sprays are administered; on subsequent administration days, one spray will be added to the dosage, unless the subject reaches treatment response as described herein [0040] and subject measures include Anxiety Depression and Mood Scale [0041]. Moreover, Erickson teaches a composition comprising ketamine [0031], wherein the composition is administered weekly, every two to seven days or on a daily basis [0034], the composition may be administered in an escalating dose [0034], wherein the dose administered comprises 20 to 120 mg ketamine, such dosage may be administered at regular intervals, for example daily, weekly, or every 1 to 7 days, every 2 to 6 days, every 3 to 5 days, or any combination thereof, the dosage may vary among individuals and may generally be a weekly dose with a supplemental dosage as needed [0035]. Moreover, Erickson teaches ketamine doses ranging from 30-120 mg per dose in 12 youth ages 6 to 19 years in open-label study resulted in improved symptoms in bipolar disorder.
As such, since Weg teaches a method for treating premenstrual dysphoric disorder or symptom thereof, wherein the symptom is anxiety comprising administering ketamine; since Freeman teaches anxiety, irritability and mood swings are required symptoms for diagnosing PMDD; and since Erickson teaches ketamine is known in the art to treat mood, anxiety, and expressive symptoms, that doses of 30-120 mg are known to be safe to administer to children, and that outcomes in Anxiety Depression and Mood Scale are measured as a treatment outcome at these doses, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to treat utilize the doses of ketamine taught by Erickson as a starting point for optimizing the amount of ketamine for use in a the method of treating premenstrual dysphoric syndrome wherein the symptom is anxiety having irritability and/or mood swings comprising administering ketamine, including via transmucosal administration with an expectation of success, since the prior art establishes that these doses are known to be safe to administer to children.
Regarding claims 23 and 24, Weg teaches a method of treating, ameliorating or preventing the onset of anxiety in a subject comprises administering to such subject an NMDA receptor antagonist; the NMDA receptor antagonist may comprise ketamine and its pharmaceutically acceptable salts, and is administered as a premedication; instances of use in this manner include administration prior to an anxiety causing event (abstract). It would have been prima facie obvious to treat premenstrual dysphoric syndrome wherein the symptom is anxiety, irritability, and mood swings to initiate treatment with ketamine just prior to the appearance of anxiety, irritability, and mood swings or following the appearance of anxiety, irritability, and mood swings, since the prior art establishes that anxiety, irritability and mood swings are required symptoms for diagnosing PMDD; that ketamine is useful for treating anxiety that is a symptom of PMDD and for treating, ameliorating or preventing the onset of anxiety; and that ketamine is known in the art to treat mood, anxiety, and expressive symptoms.
Regarding claim 61, Weg administration of active agent night before flight and day of flight to relieve anxiety (Example VII) for treating anxiety. It would have been prima facie obvious to one of ordinary skill in the art to administer the ketamine in the evening to treat premenstrual dysphoric syndrome wherein the symptom is anxiety since the prior art teaches it is suitable to administer ketamine in the evening or during the day to treat anxiety.
Taken together, all this would result in the practice of the method of claims 8, 9, 23-25, 44, and 60-66 with a reasonable expectation of success.
Claim 45 is/are rejected under 35 U.S.C. 103 as being unpatentable over Weg (US 2014/0057988 A1, cited in a previous Office Action) in view of Freeman (Psychoneuroendocrinology, 2003; 28(Suppl 3):25-37, cited in a previous Office Action), Irwin et al (J Palliat Med, 2010; 13(7):903-8); Lara et al (Int J Neuropsychopharm, 2013; 16:2111–2117); and Erickson et al (US 2015/0196501 A1, cited in a previous Office Action) as applied to claims 8, 9, 23-25, 44, and 60-66 above, and further in view of Hashimoto et al (WO 2015/037248 A1, cited in a previous Office Action).
Regarding claim 45, as set forth above, the combined teachings of Weg, Freeman, Irwin, Lara, and Erickson suggest a method of treating premenstrual dysphoric syndrome wherein the symptom is anxiety experiencing irritability and/or mood swings comprising administering ketamine, including via transmucosal administration in a dose and treatment regimen that renders the instantly claimed dose and treatment regimen obvious (see above 103 rejection). The cited art does not explicitly teach the ketamine is pure R-(-)-ketamine.
However, Hashimoto teaches R(-)-ketamine or a pharmacologically acceptable salt thereof may be used as an agent to be used for treatment and/or prevention of depressive symptoms such as anxiety [0041]; R(-)-ketamine or a pharmaceutically acceptable salt thereof can be safely used because of having less side effects found in S( + )-ketamine and RS( +/-)-ketamine; its dosage per day varies depending on the condition and body weight of a patient, the kind of a compound, an administration route, and the like; in terms of the amount of an active ingredient, it is desired that the dosage in the case of parenteral administration be from about 0.01 to 1,000 mg/person/day, preferably from 0.1 to 500 mg/person/day, and the dosage in the case of oral administration be from about 0.01 to 500 mg/person/day, preferably from 0.1 to 100 mg/person/day [0051].
As such, since Weg, Freeman, Irwin, Lara, and Erickson suggest a method of treating premenstrual dysphoric syndrome wherein the symptom is anxiety experiencing irritability and/or mood swings comprising administering ketamine, including via transmucosal administration in a dose and treatment regimen that renders the instantly claimed dose and treatment regimen obvious; and since Hashimoto teaches R(-)-ketamine is useful for treating symptoms including anxiety, ketamine is known in the art to treat mood, anxiety, and expressive symptoms and R(-)-ketamine or a pharmaceutically acceptable salt thereof can be safely used because of having less side effects found in S-(+)-ketamine and RS-(+/-)-ketamine, it would have been prima facie obvious to one of ordinary skill in the art to utilize R(-)-ketamine as the ketamine in the method of treating premenstrual dysphoric syndrome wherein the symptom is anxiety experiencing irritability and/or mood swings, since the prior art teaches R(-)-ketamine has less side effects than S( + )-ketamine or racemic ketamine. Moreover, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to treat utilize the doses of R(-)-ketamine taught by Hashimoto as a starting point for optimizing the amount of R(-)-ketamine for use in a method of treating premenstrual dysphoric disorder or symptom thereof; wherein the symptom is anxiety with an expectation of success, since the prior art establishes that these doses are useful for treating symptoms such as anxiety and because dosage and treatment regimen are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Taken together, all this would result in the practice of the method of claim 45 with a reasonable expectation of success.
Response to Arguments
Since a new rejection was issued (see above), it is the Examiner’s belief that most of the arguments presented by Applicant have been considered/answered in the rejection itself.
Conclusion
Claims 8, 9, 23-25, 44, and 60-66 are rejected.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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 L 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.
/Rayna Rodriguez/ Primary Examiner, Art Unit 1628