The Final rejection mailed on 07/02/2026 is herewith WITHDRAWN and replaced with the following OFFICE ACTION.
DETAILED ACTION
The Office Action is in response to the Applicant's reply filed June 11, 2026 to the office action made on March 11, 2026.
Claims 133-135, 137-152 are currently pending and Claims 133-135, 137-152 are examined on the merits herein.
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 filed on 03/28/2025 is a continuation of 19/008,882 filed on 01/03/2025, which is a continuation of 18/648,049 filed on 04/26/2024, which is a continuation of 17/449,785 filed on 10/01/2021 which is a continuation of PAT 11135214 filed on 05/13/2019 , which has a PRO 62/670,253 filed on 05/11/2018.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 6/11/26 is in compliance with the provisions of S7 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
Response to Arguments
The arguments over the rejection of claims 117-146 under 35 U.S.C. 103 over Vernier et al. ( US20110003850 A1) in view of Johannessen et al. (Management of Focal-Onset Seizures. Qrugs, 2006, Volume 66, Number 13, Page 1704) is not persuasive. The rejection is herewith maintained. Applicant argues
For example, in a Phase 2b randomized clinical trial including 325 patients with a seizure disorder, treatment with 20 mg or 25 mg of azetukalner was associated with statistically significant decrease in monthly seizure frequency. French, J.A. et al., JAMA Neurology, 2023, 80(11), 1145, 1145 (hereinafter "French 2023," and provided herewith as Exhibit A). This study further demonstrated that seizure freedom for patients receiving consecutive durations of azetukalner for 6 months or more was achieved in 17.5% of the patients, and for 12 months or more, 10.5% of the patients. Id., 1151. These results are particularly impressive and unexpected given that this study was carried out in a highly treatment-resistant patient population, characterized by patients having previously tried and stopped a median of six antiseizure medications. Id., 1151. In addition, this study reported that azetukalner at these doses was generally well tolerated. Id., 1146.
Applicant also continues that French 2023 discusses an unmet need for “new antiseizure treatment options that are well tolerated and have the potential to confer seizure freedom for individuals who continue to experience seizures despite treatment with available antiseizure medications.” The March 2026 Phase 3 results showed “ azetukalner was generally well-tolerated and demonstrated a safety and tolerability profile consistent with prior studies.”
The Examiner states a teaching of treatment of a disease, disorder, or condition such as a seizure disorder in a patient comprising administering compound A:
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in an amount of from about 10 mg to about 2000 mg per day to a patient. [0337], reads on the claimed concentration range. The Examiner’s contention is that Applicant has not provided data for the dosages that were “previously tried and stopped” when those amounts relate to azetukalner. Furthermore, Applicant has not provided any evidence regarding azetukalner dosages that are, i.e. not “well-tolerated,” as argued.
The nonstatutory double patenting over U.S. Applic. No. 18679045 is maintained as both the copending claims and claims herein teach the same active Compound A, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (claim 1), in the same amounts, 10 to 30 mg (claim 125), useful in treatment of the same condition, seizure disorder (claim 1). The rejection is maintained.
The nonstatutory double patenting over U.S. Applic. No. 17093183 (US Pat US12178811B2) is maintained as both the copending claims and claims herein teach the same active, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (claim 1), in the same amounts, 2 to 200 mg (claim 10), useful in treatment of the same condition, enhancing the opening of a Kv7 potassium channel in the human (claim 4). The rejection is maintained.
The nonstatutory double patenting rejection over U.S. Applic. No. 18921788 and U.S. Applic. No. 18958937 are maintained. Applicant argues the copending applications have a later patent term filing date and therefore the ODP should be withdrawn. The Examiner states the only remaining issue is not the ODP and therefore the rejections must be maintained.
The nonstatutory double patenting over U.S. Applic. No. 19008882– is maintained as both the copending claims and claims herein teach the same active in the same amounts useful in treatment of the same conditions. The Examiner points out that the newly added claims recite the same limitations and therefore the ODP still applies.
With respect to the arguments regarding U.S. PAT. No. 11957675, the Examiner points out that the current MPEP guidelines do not yet reflect the PTAB decision. The rejection is maintained.
The nonstatutory double patenting over U.S. Patent No. 11135214 is maintained as both the copending claims and claims herein teach the same active Compound A, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (claim 6), in the same amounts, 2 to 200 mg (claim 16), useful in treatment of the same conditions, seizure disorder in the human(claim 6).
With respect to the arguments regarding U.S. Patent No. 11091441B2, the Examiner points out that the current MPEP guidelines do not yet reflect the PTAB decision. The rejection is maintained.
The nonstatutory double patenting over U.S. Applic. No. 18/648,049 is maintained as both the copending claims and claims herein teach the same active, Compound A, N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (claim 117) in the same amounts, 5 to 50 mg (claim 127), useful in treatment of the same conditions, conditions associated with Kv7 potassium channel dysfunction in the human(claim 117).
The rejections are as below:
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.
Claims 133-135, 137-152 are rejected under 35 U.S.C. 103 as being unpatentable over Vernier et al. ( US20110003850 A1) in view of Johannessen et al. (Management of Focal-Onset Seizures. Qrugs, 2006, Volume 66, Number 13, Page 1704}
Vernier et al. teaches a method of treating or preventing a disease, disorder, or condition that is affected by modulation of at least one potassium ion channel selected from KCNQ2/3, KCNQ4, and KCNQ5, such as treating or preventing a seizure disorder in a patient comprising administering compound A:
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in an amount of from about 10 mg to about 2000 mg per day to a patient. [0337] Tests examples show oral administration of the compound. [0529]. A syrup formulation [0330] is taught by the reference (reads on an immediate release formulation). The reference teaches [0527] “for a compound testing, time-to-peak effect studies are initially performed using 0.5, 1, 2, 4, 8 and 24 hr time points, typically using a single 5 or 25 mg/kg dose.” The amount of active is from about 10 mg to about 2000 mg per day to a patient (see claim 1).
Vernier et al. does not specify seizure focal onset nor a specific 15, 20, 25 mg daily dose.
Johannessen et al. teaches focal onset seizures are manifestations of abnormal epileptic firing of brain cells in a localized area or areas of the brain.
It would have been obvious to one of ordinary skill in the art at the time of filing to treat focal onset seizures. The motivation to treat focal onset seizures is because the compound A is generally useful in treatment of seizure disorders. Hence, a skilled artisan would have had reasonable expectation of successfully achieving similar results. Additionally, it would have been obvious to one having ordinary skill in the art at the time the invention was made to modify the dosage, since it has been held that where the general conditions, 10 mg to about 2000 mg per day, of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USP 233.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 117, 124-135, and 143-146 of U.S. Applic. No. 18679045. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of administering Compound A to a human in need thereof; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6-dimethylpheny1]-3,3- dimethylbutanamide; the improvement comprising administering Compound A to the human without dose titration while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26-32, 35-46 of U.S. Applic. No. 17093183 (US Pat US12178811B2). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of treating a depressive disorder in a human in need thereof, comprising administering a therapeutically effective amount of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2.6- dimethylphenyl]-3,3-dimethylbutanamide; wherein Compound A is orally administered to the human under fed conditions while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8-21, 24, 35 of U.S. Applic. No. 18921788 – claims filed on 2/28/25; IDS filed 1/23/25. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of enhancing the opening of a Kv7 potassium channel in a human, comprising administering an effective amount of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide; and wherein the human is suffering from anhedonia while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of U.S. Applic. No. 18958937 – claims filed on 11/25/24; IDS filed 1/23/25. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of treating one or more somatic symptoms of a depressive disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of azetukalneror a pharmaceutically acceptable salt thereofwhile the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 117-136 of U.S. Applic. No. 19008882– claims filed on 1/3/25; IDS filed 1/23/25. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of enhancing opening of a Kv7 potassium channel in a human in need
thereof, comprising orally administering an effective amount of Compound A to the human under fed conditions; wherein Compound A is V-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide, the human suffering from a seizure disorder; while the claims herein are drawn to in a method of orally administering Compound A to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 19-34 of U.S. PAT. No. 11957675. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a Method of treating anhedonia, comprising administering a therapeutically effective amount of Compound A to a human in need thereof; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide, wherein Compound A is orally administered to the human from between about 30 minutes before to about 2 hours after eating a meal and Compound A is administered at a dose of 5-150 mg per day to the human , while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11135214. Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patented claims are drawn to a method of orally administering Compound A to a human in need thereof, wherein Compound A is N-[4-(6-fluoro-3,4-dihydro-1H- isoquinolin-2-yl)-2,6-dimethylphenyl]-3 ,3-dimethyloutanamide; wherein the improvement comprises orally administering an amount of Compound A to the human from between 30 minutes prior to consuming food until 2 hours after consuming food while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20-22 of U.S. Patent No. 11091441B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the US Patented claims are drawn to method of preparing the pharmaceutical composition of claim 7, the method comprising combining the crystalline form of Compound A with the pharmaceutical excipient, carrier, and/or diluent to form the pharmaceutical composition wherein the crystalline form is administered to the human from between 30 minutes before to 2 hours after eating a meal while the claims herein are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Claims 133-135, 137-152 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 117, 119-123, 126-135,139-151 of U.S. Applic. No. 18/648,049 – claims filed on 1/3/25; IDS filed 1/23/25. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering a therapeutically effective amount of Compound A to the human under fed conditions; wherein Compound A is V N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylphenyl]-3,3-dimethylbutanamide while the claims herein are drawn to in a method of orally administering Compound A to a method of treating a disease, disorder, or condition associated with Kv7 potassium channel dysfunction in a human in need thereof, comprising orally administering 10-50 mg of Compound A to the human; wherein Compound A is N-[4-(6-fluoro-3,4-dihydro- 1 H-isoquinolin-2-yl)-2,6- dimethylpheny1]-3,3-dimethylbutanamide. The claims are rendered obvious.
Conclusion
No claims are allowed.
Correspondence
The arguments are not persuasive and the rejection is made FINAL.
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 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.
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