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 371 of PCT/US2021/031360 (05/07/2021) and has PRO 63/031,346 (05/28/2020).
Status
Claims 1-4, 6-15 as amended are pending.
Rejections not reiterated are withdrawn.
Claim Rejections - 35 USC § 103
Claims 1-4, 6-15 are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (US20160338977) in view of Park et al. (Focus (Am Psychiatr Publ). 2019 Jan 7;17(1):8–12).
Singh teaches in Example 1 a method comprising administering 56 mg esketamine to a patient ([0069]: “All subjects self-administered the intranasal esketamine (28, 56, or 84 mg) or placebo on non-consecutive days.”) where there was an induction phase of 4 weeks ([0035]: “the induction phase is a period of about 3 weeks or a period of about 4 weeks”) wherein esketamine is administered twice weekly ([0036]: “esketamine is administered at least twice weekly to the patient during the induction phase”).
Singh teaches optimization of the dosage by analyzing the effects of the esketamine during the induction phase ([0063]: “Methods for optimizing a dosage of esketamine for a patient having or being predisposed to depression also are provided. These methods can include (a) administering an effective amount of esketamine to the patient during an induction phase at a given frequency of a defined duration, (b) analyzing the effects of the esketamine in the induction phase by rating the depression of the subject, and (c) administering an effective amount of esketamine to the patient during a maintenance phase less frequently of a defined duration.“). Singh teaches monitoring patients for adverse events including hypertension, dissociation, sedation, and nausea ([0079]). Singh teaches monitoring for side effects for less than 90 minutes, i.e. at 40 minutes ([0078]: “The Clinician Administered Dissociative States Scale (CADSS) was measured prior to the start of each dose, at 40 minutes and at 2 hours post dose.”; [0079] side effects).
Although Singh teaches the effects of the NMDA antagonist ketamine (the racemic mixture vs. S-ketamine being esketamine) in patients include elevated blood pressure, Singh does not specifically teach the patients has a systolic blood pressure of < 140 and diastolic blood pressure of < 100 (i.e., BP <140/100) or heart rate increases.
One of ordinary skill in the art following the teaching of Singh regarding “treatment emergent adverse event (TEAE) side effects” ([0079]) would have considered selecting patients that have blood pressures of less than 140/100 due to the potential risk of further increasing BP and a resulting TEAE. Similarly, regarding the claim’s language regarding adverse events, Singh teaches monitoring patients post-dose for TEAEs including hypertension, dissociation, sedation, and nausea which one of ordinary skill in the art would have considered as indicating adverse events as well as heart rate increases following any two consecutive treatment sessions. Futhermore, Park teaches known side effects of ketamine includes heart rate increases (tachycardia) (p. 10: “psychotomimetic symptoms (e.g., dissociative symptoms, hallucinations), sympathomimetic symptoms (e.g., hypertension, tachycardia), and vestibular effects (e.g., dizziness, nausea, and vomiting)”). One of ordinary skill in the art would have considered screening for known adverse events to be routine and would have arrived at the claimed invention with a reasonable expectation of success.
Regarding claims 2-4, Singh teaches monitoring the patient for TEAE post-treatment during the induction phase ([0067]-[0079]) and one of ordinary skill in the art would have been motivated to monitor patients after multiple treatment sessions for appropriate amount of time to ensure therapeutic efficacy, including after eight sessions for 60 minutes.
Regarding claims 6-7, Singh’s description of the subjects does not teach uncontrolled hypertension or not taking medication ([0065]).1 Regarding claim 8, Singh teaches the subjects are less than 65 years old ([0065]). Regarding claim 9, Singh teaches the treatment of MDD ([0025], [0065]). Regarding claim 10, Singh teaches the treatment of depression in suicidal patients ([0025]-[0030]). Regarding claim 11, Singh teaches intranasal maintenance phase of once weekly or every other week ([0085]-[0089]). Regarding claims 12-13, Singh teaches the treatment of MDD includes treatment resistant depression ([0025], [0065], [0068]). Regarding claim 14, Singh teaches adjunctive treatment with an oral antidepressant ([0090]-[0109]). Regarding claim 15, Singh teaches dosing of the oral antidepressant on day 1, but does not specifically teach at least 3 hours after any induction or treatment phase session.
With each of the above claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the optimization of dosing schedules and monitoring for side effects both of which were a concern identified by Singh. Such optimizations are well within the technical grasp of one of ordinary skill in the art and would be expected to be implemented in the course of administering a therapeutic to a patient in order to reduce the risk of side/adverse effects. Thus, one of ordinary skill in the art would have arrived at the invention as claimed with a reasonable expectation of success before the effective filing date of the claimed invention. The claims are prima facie obvious.
Response to Remarks - 35 USC § 103
Applicant also argues that the inventors discovered that the if a patient suffers from adverse events after the first two treatment sessions, then they are more likely to suffer a recurrence after subsequent sessions and that the pattern of adverse events at week 4 is also predictive.
First, it is noted that the instant claims are to a method comprising … intranasally administering … [and] monitoring the patient which is open-ended with respect to additional steps (MPEP 2111.03) and thus allows for additional monitoring of adverse events. In addition, Singh teaches in Example 1 administering 56 mg esketamine to a patient where there was an induction phase and a treatment phase with monitoring for side effects ([0078]-[0079]). One of skill in the art would have considered monitoring a patient after administration of a pharmaceutical such as esketamine as part of routine experimentation, particularly in view of Singh and Park teaching of the known pharmaceutical effects of dissociative effects and anesthesia as well as concerns of side effects ([0012], [0077]-[0080]). Thus, Applicant’s argument is not persuasive.
Applicant amended the claims to “monitoring the patient for a total of less than 90 minutes in a post-treatment session monitoring period” and argues that Singh does not teach such a limitation and the cited art does not suggest monitoring in the same manner. Applicant also argues that there is no discussion in Singh of the occurrence of adverse events following early treatment session is correlated with adverse events in subsequent sessions.
This argument is not persuasive because the prior art suggests administering and monitoring in the same manner as claimed. One of ordinary skill in the art would have considered monitoring a patient after administration of a pharmaceutical such as esketamine as part of routine experimentation, particularly in view of Singh and Park teaching of the known pharmaceutical effects of dissociative effects and anesthesia as well as concerns of side effects ([0012], [0077]-[0080]). In addition, the claim is not limited to correlations of early and subsequent adverse events. Thus, Applicant’s argument is not persuasive.
Double Patenting Rejections
Claims 1-4, 6-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10869844 in view of Singh et al. (US20160338977) and Park et al. (Focus (Am Psychiatr Publ). 2019 Jan 7;17(1):8–12). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims a method of treating depression comprising administering intranasally the same compound as in the instant claims which as detailed in the 35 USC 103 rejection supra and incorporated herein anticipates or renders the claims obvious.
Claims 1-4, 6-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11173134 in view of Singh et al. (US20160338977) and Park et al. (Focus (Am Psychiatr Publ). 2019 Jan 7;17(1):8–12). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims a method of treating depression comprising administering intranasally the same compound as in the instant claims which as detailed in the 35 USC 103 rejection supra and incorporated herein anticipates or renders the claims obvious.
Claims 1-4, 6-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11311500 in view of Singh et al. (US20160338977) and Park et al. (Focus (Am Psychiatr Publ). 2019 Jan 7;17(1):8–12). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims a method of treating depression comprising administering intranasally the same compound as in the instant claims which as detailed in the 35 USC 103 rejection supra and incorporated herein anticipates or renders the claims obvious.
Claims 1-4, 6-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-75 of U.S. Patent No. 11446260 in view of Singh et al. (US20160338977) and Park et al. (Focus (Am Psychiatr Publ). 2019 Jan 7;17(1):8–12). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims a method of treating depression comprising administering intranasally the same compound as in the instant claims which as detailed in the 35 USC 103 rejection supra and incorporated herein anticipates or renders the claims obvious.
Claims 1-4, 6-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 11883526 in view of Singh et al. (US20160338977) and Park et al. (Focus (Am Psychiatr Publ). 2019 Jan 7;17(1):8–12). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims a method of treating depression comprising administering intranasally the same compound as in the instant claims which as detailed in the 35 USC 103 rejection supra and incorporated herein anticipates or renders the claims obvious.
Response to Remarks – Double Patenting Rejection
Applicant argues in the same manner as in the rejections above. Thus, the double patenting rejections are also maintained for the same reasons.
Conclusion
No claims allowed.
THIS ACTION IS MADE FINAL. 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.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
1 Almirall, LLC v. Amneal Pharm., 28 F.4th 265, 273 (Fed. Cir. 2022) (“"[A] reference need not state a feature's absence in order to disclose a negative limitation." AC Techs., S.A. v. Amazon.com, Inc. , 912 F.3d 1358, 1367 (Fed. Cir. 2019).”)
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