DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Amendments
Applicant’s amendments to the claims of October 1, 2025, in response to the Office Action of April 1, 2025, are acknowledged.
Response to Arguments
Applicant’s arguments and declaration of Dr. Javitt provided to the Office on October 1, 2025, have been fully considered. While the examiner notes that the declaration and arguments are sufficient to overcome the prior art, they have not established unexpected results. They have established that the dosage of DEX claimed must be higher than that taught by the cited prior art for DEX to qualify as an NMDAR antagonist. There is no comparison to the closest prior art.
As such, the examiner applies Meyerson et al., (US2005/0209218 A1) as necessitated by the Amendment to the claims. In particular, Applicant has amended the claims to require a dose of dextromethorphan to be an NMDAR antagonistic dose. According to Applicant, a POSA understand that the dose must be different for DEX to function as an NMDAR antagonist.
Meyerson teaches treating psychiatric conditions such as depression, major depression, refractory depression, and bipolar depression, among others. See par. 5. CNS-related disorders that can be treated also include GAD, mania, and manic depressive illness. See par. 18. An NMDA receptor antagonist can be used, which may be memantine. Further, it can also include dextromethorphan (DEX). See par. 36 and 37. The amount of DEX can include from 100-800 mg per day and 200 to 500 mg per day. See par. 36 and 37. The combination comprises an NMDAR antagonist and a second agent. See prior art claim 1. Further, the second agent is duloxetine of only 7 potential agents. Claim 10 is limited to duloxetine alone as the second agent. Thus, duloxetine is preferred. While the dosage of DEX includes high dosages up to 5000 mg daily, it is also established that DEX is used as an NMDA receptor antagonist. The first and second agents can be in a single formulation. See par.’s 50, 51, 69, Example 5, and prior art claim 14.
Overall, the amendments to the claims to require DEX be used as an NMDAR antagonist and the declaration indicating that DEX was not used as such by the previously cited prior art. In response to that amendment, the examiner cites art below that teaches treating a claimed subject population with an NMDAR antagonist, including DEX, in combination with duloxetine. New claim 21 merely requires a “previous” administration of ketamine. This can mean that ketamine was administered much earlier and ketamine is shown below to have many uses. Further, if an AE associated with treatment were to occur, it would be logical to switch to another API- this is the case for treating depression or any other condition. As such, a rejection is set forth below.
Status of the Claims
Claims 1-3, 5, 6, and 16-21 are pending and examined.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 5, 6, and 16-20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Meyerson et al., (US2005/0209218 A1), in view of Serafini et al., “Duloxetine versus venlafaxine in the treatment of unipolar and bipolar depression,” Clin Ter. 2010;161(4):321-7, and in view of Goldstein, “Duloxetine in the treatment of major depressive disorder,” Neuropsychiatric Disease and Treatment,” 2007:3(2) 193-209.
Meyerson teaches treating psychiatric conditions such as depression, major depression, refractory depression, and bipolar depression. See par. 5. CNS-related disorders including GAD, mania, manic depressive illness. See par. 18. An NMDA receptor antagonist can be used, which may be memantine. Further, it can also include dextromethorphan. See par. 36 and 37. The amount of DEX can include from 100-800 mg per day and 200 to 500 mg per day. See par. 36 and 37. The combination comprises an NMDAR antagonist and a second agent. See prior art claim 1. Further, the second agent is duloxetine of only 7 potential agents. Claim 10 is limited to only duloxetine. Thus, duloxetine is preferred. While the dosage of DEX includes high dosages up to 5000 mg daily, it is established that DEX is used as a NMDA receptor antagonist. The first and second agents can be in a single formulation. See par.’s 50, 51, 69, Example 5, and prior art claim 14.
Serafini teaches duloxetine to be safe for reducing suicidal ideation and can be used to treat unipolar and bipolar depression.
Goldstein teaches duloxetine treated MDD including those with melancholic and non-melancholic features. See p203, 2nd full par. A manic episode can result if a major depressive episode if the initial presentation of bipolar disorder. See p205, last par. Efficacy of duloxetine in MDD was established in multiple studies. See p196, 4th par.
It would have been prima facie obvious to a person of ordinary skill in the art to arrive at the claimed invention in view of Meyerson, Serafini, and Goldstein. One would be motivated to do so because Meyerson teaches treating the claimed subject population with a combination of an NMDAR antagonist, including DEX, and a second agent, including duloxetine. Subjects to be treated include those with depression, major depression, refractory depression, and bipolar depression. Formulations can include combinations and they can be in the form of a coated tablet. Further, duloxetine is known to treat unipolar and bipolar depression, major depressive disorder, melancholic and non-melancholic symptoms. There is a reasonable and predictable expectation of success in treating the claimed conditions with DEX and duloxetine. The examiner notes that the results of administering a same combination to a same subject population would expected to be similar, absent evidence to the contrary. Thus, a lower incidence of side effects would be expected.
Claims 1-3, 5, 6, and 16-21 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Meyerson et al., (US2005/0209218 A1), in view of Serafini et al., “Duloxetine versus venlafaxine in the treatment of unipolar and bipolar depression,” Clin Ter. 2010;161(4):321-7, and in view of Goldstein, “Duloxetine in the treatment of major depressive disorder,” Neuropsychiatric Disease and Treatment,” 2007:3(2) 193-209, and in view of
Meyerson teaches treating psychiatric conditions such as depression, major depression, refractory depression, and bipolar depression. See par. 5. CNS-related disorders including GAD, mania, manic depressive illness. See par. 18. An NMDA receptor antagonist can be used, which may be memantine. Further, it can also include dextromethorphan. See par. 36 and 37. The amount of DEX can include from 100-800 mg per day and 200 to 500 mg per day. See par. 36 and 37. The combination comprises an NMDAR antagonist and a second agent. See prior art claim 1. Further, the second agent is duloxetine of only 7 potential agents. Claim 10 is limited to only duloxetine. Thus, duloxetine is preferred. While the dosage of DEX includes high dosages up to 5000 mg daily, it is established that DEX is used as a NMDA receptor antagonist. The first and second agents can be in a single formulation. See par.’s 50, 51, 69, Example 5, and prior art claim 14. An enteric coating is taught. See par.’s 65 and 72, Example 5.
Serafini teaches duloxetine to be safe for reducing suicidal ideation and can be used to treat unipolar and bipolar depression.
Goldstein teaches duloxetine treated MDD including those with melancholic and non-melancholic features. See p203, 2nd full par. A manic episode can result if a major depressive episode if the initial presentation of bipolar disorder. See p205, last par. Efficacy of duloxetine in MDD was established in multiple studies. See p196, 4th par.
It would have been prima facie obvious to a person of ordinary skill in the art to arrive at the claimed invention in view of Meyerson, Serafini, and Goldstein. One would be motivated to do so because Meyerson teaches treating the claimed subject population with a combination of an NMDAR antagonist, including DEX, and a second agent, including duloxetine. Subjects to be treated include those with depression, major depression, refractory depression, and bipolar depression. Formulations can include combinations and they can be in the form of a coated tablet. Further, duloxetine is known to treat unipolar and bipolar depression, major depressive disorder, melancholic and non-melancholic symptoms. There is a reasonable and predictable expectation of success in treating the claimed conditions with DEX and duloxetine. The examiner notes that the results of administering a same combination to a same subject population would expected to be similar, absent evidence to the contrary. Thus, a lower incidence of side effects would be expected.
With regard to claim 21, the examiner interprets “was previously treated with ketamine” to include those subjects that do not have ketamine in their system and the phrase includes any time previously. In other words, if a subject was treated for another condition at another time, it would be inclusive of previous treatment with ketamine. This also includes subjects being treated with ketamine for any condition and can even include receiving ketamine for anesthesia. As evidenced by the following, ketamine is taught to treat a variety of conditions. See Nose et al., (US2013/0046225); Papalos (US2012/0225949); and Mayer et al., (U.S. Pat. No. 5,352,683). As such, there is no reason that a subject treated “previously” for another condition or if a subject experienced an adverse event associated with ketamine that they would not be put on another API.
As such, no claim is allowed.
Conclusion
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 extension fee 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 JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628