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 .
DETAILED ACTION
Applicant’s amendment filed on 06/27/2025, wherein claims 1, 3, 4, 14, 15 have been amended, and claims 2, 5-10 have been cancelled.
Election/Restrictions
Note: Claims 5-12 have been withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species. See Non-Final Rejection dated 12/30/2024. Also, previous claims 14-15 are now renumbered as 13-14.
Claims 1, 3-4, 13-14 (previous claims 14-15) are examined herein on the merits so far as they read on the elected species.
Any rejection from the previous office action which is not restated herein, is withdrawn.
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 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.
1) Claim(s) 1, 3, 4, 13-14 are rejected under 35 U.S.C. 103 as being unpatentable over MARVIN et al. (WO 2017160813, PTO-892), in view of Davis et al. (US 20050096396 A1, PTO-892), and further in view of Javitt (WO 2014/011590, PTO-1449).
MARVIN et al. teaches a method of treating obsessive compulsive disorder comprising administering therapeutically effective amount of a positive allosteric α4β2 nicotinic acetylcholine receptor modulator, and one or more additional agents known to treat symptoms of compulsive-like behavior and/or an obsessive-compulsive related disorder or disease. See claims 1, 9. It is taught that one or more additional agents are D-cycloserine, mirtazapine (contains S-mirtazapine and R-mirtazapine). See claim 10.
MARVIN et al. does not explicitly teach administration of a combination of D-cycloserine and mirtazapine;
MARVIN et al. does not teach administration of 500 mg/day of D-cycloserine.
Davis et al. teaches that D-cycloserine is used to treat obsessive compulsive disorder. See claim 29. Administration of a dose on 400-500 mg to treat obsessive compulsive disorder is taught. See claims 29, 34.
Javitt discloses a composition comprising NMDA receptor agonist D-cycloserine in an amount of 500 mg/day or greater (instant amount as in instant claim 3), and an antidepressant mirtazapine (racemic mixture contains S and R mirtazapine). See claims 1, 5, 9; para [0060], mirtazapine; paras [0063]-[0064], D-cycloserine; TABLE 1, page 30; paras [00125]-[00127], page 33; a composition comprising mirtazapine and D-cycloserine in a vehicle is also taught i.e meets single composition as in instant claim 14, see para [00127], Table 1; see para [00112], wherein it is taught that the medications are dissolved in a vehicle. It is taught that D-cycloserine is administered at a dose that produces serum levels in excess of 25 microgram/mL. See para [0064]. It is taught that the composition is in the form of oral or parenteral dosage. See claim 11. The dosage can be sustained release dosage. See claim 17.
It would have been obvious to a person of ordinary skill in the art to administer D-cycloserine and mirtazapine (contains S-mirtazapine and R-mirtazapine; instant claim 1 recites the method comprising administering a composition comprising i.e the composition can contain R-mirtazapine) to a subject suffering from obsessive compulsive disorder (OCD) because 1) MARVIN et al. teaches treating obsessive compulsive disorder comprising administering therapeutically effective amount of a positive allosteric α4β2 nicotinic acetylcholine receptor modulator, and one or more additional agents known to treat symptoms of compulsive-like behavior and/or an obsessive-compulsive related disorder or disease (see claims 1, 9), and MARVIN teaches that one or more additional agents known to treat symptoms of compulsive-like behavior and/or an obsessive-compulsive related disorder or disease are D-cycloserine, mirtazapine (contains S-mirtazapine and R-mirtazapine; instant claim 1 recites composition comprising i.e the composition can contain R-mirtazapine) (see claim 10); and further 2) Davis et al. also teaches that D-cycloserine is used for treating OCD. One of ordinary skill in the art would have been motivated to administer D-cycloserine and mirtazapine (contains S-mirtazapine and R-mirtazapine; instant claim 1 recites the method comprising administering a composition comprising i.e the composition can contain R-mirtazapine) to a subject suffering from obsessive compulsive disorder with reasonable expectation of success of treating obsessive compulsive disorder with at least additive therapeutic effect.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to obtain a composition comprising D-cycloserine, and mirtazapine (racemic mixture contains S-mirtazapine and R-mirtazapine; instant claim 1 recites composition comprising i.e the composition can contain R-mirtazapine) because Javitt discloses a composition comprising NMDA receptor agonist D-cycloserine in an amount of 500 mg/day or greater (instant amount as in instant claim 3; meets the recitation D-cycloserine provided at a net NMDA receptor antagonistic dose as in instant claim 2), and mirtazapine (racemic mixture contains S and R mirtazapine). One ordinary skill in the art would have been motivated to obtain a composition comprising D-cycloserine, and mirtazapine (contains S-mirtazapine and R-mirtazapine; instant claim 1 recites composition comprising i.e the composition can contain R-mirtazapine) with reasonable expectation of success of administering the composition to a subject suffering from OCD and with reasonable expectation of success of treating OCD.
Further, it would have been obvious to a person of ordinary skill in the art to formulate D-cycloserine to produce an average plasma level in the subject of greater than 25 microgram/mL because Javitt teaches that D-cycloserine is administered at a dose that produces serum levels in excess of 25 microgram/mL. One ordinary skill in the art would have been motivated to formulate D-cycloserine to produce an average plasma level in the subject of greater than 25 microgram/mL with reasonable expectation of success of administering the composition to a subject suffering from OCD and with reasonable expectation of success of treating OCD.
It would have been obvious to a person of ordinary skill in the art to administer D-cycloserine at a dose of 7.5 mg-12.5 mg/kg/day.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize parameters such as amounts of D-cycloserine to administer to a subject suffering from OCD. The optimization of result effect parameters such as amounts of therapeutic agent to be administered is obvious as being within the skill of the artisan. The optimization of effective amounts of known active agents to be administered, is considered well in the competence level of an ordinary skilled artisan in pharmaceutical science, involving merely routine skill in the art.
The determination of the optimum ranges for the presently claimed active agent(s) would have been a matter well within the purview of one of ordinary skill in the art.
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to obtain a sustained release composition comprising D-cycloserine at a dose of 500 mg/day or greater (instant amount as in instant claim 3; meets the recitation D-cycloserine provided at a net NMDA receptor antagonistic dose), and mirtazapine (racemic mixture contains S and R mirtazapine) because Javitt teaches that the compounds can be administered in a sustained release dosage form.
Response to Arguments
Applicant’s arguments have been considered, but not found persuasive as discussed above and those found below.
Applicant’s surprising results for the combination of S-mirtazapine and DCS which showed a significantly greater effect than R-isomer in a model of anxiety disorder have been considered. The effect of S-mirtazapine and R-mirtazapine depends on the amount of S-mirtazapine and R-mirtazapine employed, and the amount of DCS. It is pointed out that any unexpected results have to be commensurate in scope with instant claims. The unexpected results are provided employing particular amounts of DCS in combination with particular amounts of S-mirtazapine or R-mirtazapine. Instant claims recite any amount of D-cycloserine (claims 1, 13, 14), and any amount of S-mirtazapine. Thus, the unexpected results are not commensurate in scope with instant claims and do not demonstrate criticality of a claimed range of the compounds in the claimed method. See MPEP 716.02. Therefore, the evidence presented in specification herein is not seen to be clear and convincing in support of non-obviousness of the instant claimed invention over prior art.
Prior Art Made of Record:
US 20100216805 A1, OCD para [0049], para [0179], combination
WO 2009018368 A1…claim 30 OCD; teaches D-cycloserine can be used as an NMDA enhancer; and teaches additional agents such as mirtazapine can be used.
US 20050096396 A1; Milnacipran, D-cycloserine; Davis et al. teaches that D-cysloserine is administered at a dose on 400-500 mg to treat obsessive compulsive disorder. See claims 29, 34.
WO 2017160813 A1, claim 10 includes D-cycloserine for treating OCD; used above.
Conclusion
No claims are 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 SHOBHA KANTAMNENI, Ph.D whose telephone number is (571)272-2930. The examiner can normally be reached on Monday to Friday; 8.00 am-4.30 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel, Ph.D can be reached on 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHOBHA KANTAMNENI/Primary Examiner, Art Unit 1627