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 .
Maintained rejections
The sole rejection of the claims under 35 USC 103 over Chen et al., is maintained. Reply to applicant’s remarks filed on 10/16/25 are addressed following the repeated text of the rejection of record. Rejection has been altered to include teachings in Chen directed to prucalopride because the claims have been amended to limit 5HT4R agonist to prucalopride. Rejection has also been altered to address the limitation of newly added claim 25 directed monohydrochloride salt of prucalopride.
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 (i.e., changing from AIA to pre-AIA ) 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1 and 10-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (Neuropsychopharmacology, 2020, 45, 542-552; published on 10/10/2019).
Scope of prior art
Chen is directed to prophylactic efficacy of 5-HT4R agonists against stress. Specifically, Chen teaches RS-67,333, prucalopride and PF-o4995274 as 5-HT4R agonists. Chen teaches that chronic administration of RS-67,333, in mice models, is prophylactic against stress (page 543, Results, 1st paragraph) and against a wide range of CORT induced behavioral abnormalities (page 543, Results, 4th paragraph). Chen further teaches that a single injection of RS-67,333 attenuates learned fear and protects against stress induced hypophagia (page 545, column 1). Chen also teaches prucalopride attenuated learned fear and decreased depressive-like behavior (page 548, column 1, paragraph 2)
Regarding ketamine, Chen teaches that ketamine is prophylactic against stress-induced depressive-like behavior and like RS-67,333 also attenuates learned fear (page 545, column 1). Ketamine meets the limitations of claims 3 and 5 directed to antagonist of NMDAR (claim 3) and agonist of AMPAR (claim 5). On page 548, Chen teaches that ketamine is known to inhibit NMDAR and activate AMPAR (page 548, second column, first paragraph).
Ascertaining the difference
Chen only performs studies using mice and does not treat actual human subjects.
While Chen teaches anti-stress prophylactic activity of RS-67,333 and of Ketamine, art does not teach administration of the both agents as a combination treatment.
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application would have found it obvious to try to prophylactically treat stress induced disorders by administration to a subject in need a combination of ketamine and prucalopride. Chen teaches both agents as prophylactic agents for reducing stress induced behavior. Prucalopride and ketamine are taught to be effective in reducing stress induced fear and depressive and anxiety-like behavior (abstract). Chen also teaches that stress exposure is a significant risk factor for MDD and PTSD and that ketamine is known as a resilience enhancing drug against stress and has potential to prevent PTSD. Given that both prucalopride and ketamine are taught to be used for the same purpose, a skilled artisan would have found it obvious to use them together in a combination therapy against stress induced pathologies. Ketamine is a known agent with a well-known safety profile, and RS-67,333 is taught to not result in adverse side effects even after chronic administration (page 548, column 2, third paragraph). Since both agents are effective against stress-induced pathologies and both are taught to be safe, or not result in adverse effects, a skilled artisan would have found it obvious to try administering the combination to a subject in need of reduction of stressed induced pathologies. With regards to timing of administration, a skilled practitioner would have found to obvious to determine through routine practice, the optimal time periods for administering the combination treatment prior to the onset of stress-induced disorders.
With regards to new claim 25, Chen teaches prucalopride as a monohydrochloride salt (paragraph bridging pages 542 and 543).
Reply to applicant’s remarks
Applicants have traversed the rejection of record in the reply filed on 10/16/25. Arguments presented by the applicant have been fully considered and found to be unconvincing.
Applicants are arguing that the combination of ketamine and prucalopride is patentable over Chen because the administration of both agents results in an unexpected result. The unexpected result is one of synergy wherein the combination provides greater effect than additive effect of each individual agent. This argument is not persuasive. To support the claim to unexpected results applicants rely on the disclosure of the specification on page 50, lines 21. Said disclosure is directed to decreased immobility time when 10mg + 10mg of prucalopride + ketamine is compared to 10mg of each agent. This data is presented in Figure 1E which is reproduced below (see spec. page 50, line 19):
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Figure 1E fails to demonstrate more than additive effect of the claimed combination. The error bars of the 10+10 administration overlap with the error bars for administration of prucalopride. Additionally, when other amounts are compared, there is an unexpected lack of efficacy from the combined treatment. For example, 30 + 1.5 results in greater immobility than each agent alone at the specified dose.
In view of the data presented in Figure 1E, applicant’s assertion of unexpected results is found to be unsupported.
Conclusion
Claims 1 and 10-25 are pending
Claims 1 and 10-25 are rejected
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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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628