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 .
Current Status of 18/603,554
This Office Action is responsive to the amended claims of 11/17/2025.
Claims 1-4, 6-8, and 19-26 have been examined.
Priority
This application is a continuation of now abandoned application 17/668,316, which claims priority to U.S. provisional application 63/147,736, filed 02/09/2021. There is also a PCT family member, PCT/US22/15851, filed 02/09/2022.
The instant claims find support from the provisional application. Therefore, the effective filing date is 02/09/2021.
Information Disclosure Statement
The information disclosure statement (IDS), submitted on 11/17/2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicants’ claim amendments and Remarks of 11/17/2025 are acknowledged and have been considered.
Any rejection and/or objection not specifically addressed or modified below is herein withdrawn.
Claims 41, 44, 47, and 50 are canceled.
In regard to the objection to the drawings, these drawings are of sufficient resolution.
In regard to the obviousness rejection, this rejection is withdrawn. Applicants remarks and Examiner’s reply are summarized below:
The instant base claims (claims 1, 2, and 3) have been narrowed so that the antiseizure medication (ASM) is only Levetiracetam.
Applicants submit unexpected results that the combination of Compound A and levetiracetam results in advantageous increased protection from seizure (page 8 of results).
Examiner reviewed paragraphs [0041], [0215]-[0216], and [0222]-[0224], and figure 14. In each study (shown in figure 14), the combination of Compound A and Levetiracetam resulted in significantly increased protection from seizure compared to either compound alone and compared to the vehicle. The combination of Compound A and Levetiracetam protected 66.7% of animals from seizure (statistically significant from either compound alone and the vehicle). This is persuasive for base claim 1 being surprising/unexpected.
Applicants submit that “Compound A or levetiracetam dosed alone did not result in protection from seizure (plasma and brain concentrations of Compound A were much lower than expected), but combining both compounds protected 3 out of 8 animals from seizing” (from paragraph [0216] and table 17.
Examiner reviewed paragraphs [0215]-[0216], and [0222]-[0224]. Examiner agrees.
Applicant submits
PNG
media_image1.png
219
745
media_image1.png
Greyscale
.
After a review of all the cited paragraphs which Applicants point out their surprising results, Examiner finds them persuasive for base claims 1-3. When Compound A and levetiracetam were administered together, Compound A resulted in more than 10-fold higher concentrations of Compound A in plasma and brain (paragraph [0215], Figure 15, and table 17). Concentrations of Levetiracetam were also higher when the combination was administered (paragraph [0215], Figure 15, and table 17). These are unexpected results for base claims 2 and 3.
However, the combination appears to be still obvious. The prior art strongly suggests the Kerkhoven combination and the art (cited below) supports that at least levetiracetam is known for use in combination therapy, creating a separate rationale of simple substitution of the compound A for another known compound in a combination therapy for treating epilepsy. Applicant’s unexpected result is not sufficient to overcome the preponderance of evidence that the levetiracetam is known largely for a combination therapy. For it to be allowable, it may be that only a very specific dose is unexpected.
Response to Amendment
Claim Rejections - 35 USC § 103
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 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.
Claims 1-4, 6-8, 19-26 are rejected under 35 U.S.C. 103 as being unpatentable over:
BEATCH (US 2019/343823 A1), previously cited
In view of
FANG (Fang et al., “Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types”, Journal of Clinical Neuroscience, January 2014).
BEATCH teaches the compound N-[4-(6-Fluoro-3,4-dihydro-1H-isoquinolin-2-yl)-2,6-dimethylphenyl]-3,3-dimethylbutanamide (paragraph [0004]), which BEATCH refers to as Compound A. This is the same Compound A in base claims 1, 2, 3, and 5.
BEATCH teaches a method of treating a Kv7 potassium channel dysfunction in a human by administering a therapeutically effective amount of Compound A to a human (paragraph [0009]). BEATCH teaches the Kv7 potassium channel dysfunction is a seizure disorder (paragraph [0009]). This helps teach claim 1 (drawn to a method of treating a seizure disorder). This also teaches the seizure disorder is associated with Kv7 potassium channel dysfunction of claim 19.
BEATCH teaches one preferred embodiment, focal onset epilepsy (paragraph [0009]). This teaches Applicant’s elected species of seizure. This also teaches claim 20.
BEATCH teaches that “The mechanism of action of Compound A is different from most known anti-epilepsy agent’s in that it involves enhanced opening of the voltage-gated potassium channels Kv7.2 and Kv7.3 (KCNQ2/3)”, which are types of Kv7 potassium channels (paragraph [0061]). This teaches claim 4. This also teaches claims 6-8.
BEATCH teaches administering Compound A orally to a human (paragraph [0009]). This teaches claim 21.
BEATCH teaches administering compound A for use in reducing a dose of “the compound that is orally administered to a human in need as part of a treatment regimen” (paragraph [0021]). This helps teach claim 2.
BEATCH teaches a method of reducing a dose of Compound A that is orally administered to a human in need thereof as part of a treatment regimen, comprising orally administering a reduced dose of Compound A to the human under fed
Condition. This helps teach claim 3.
BEATCH teaches a dose of Compound A wherein the dose is between 2 to 200 mg (paragraph [0032]). This helps teach claims 23-26.
BEATCH teaches that Compound A is orally administered to a human between 30 minutes prior to consuming food until 2 hours after consuming food (paragraph [0081]). This teaches claim 21.
BEATCH does not teach levetiracetam.
FANG teaches levetiracetam (LEV) as an adjunctive therapy for adults and children suffering from idiopathic and secondary epilepsy of multiple seizure types (abstract). This helps teach claims 1-3.
FANG teaches that all randomized-controlled trials (RCT) had LEV as an adjunctive/combined therapy (section 3.1). FANG teaches that all RCT administered LEV orally (other wise they would have been excluded; Section 2.2). This is an oral dose and teaches claim 22.
The instant claims are prima facie obvious in light of the combination of references BEATCH in view of FANG.
FANG teaches levetiracetam as part as a combination therapy for epilepsy (FANG abstract). Compound A also is a known treatment for epilepsy (BEATCH Paragraphs [0004] and [0009]). The artisan would have found it obvious to substitute the other antiseizure medication (that is part of the combination therapy of FANG) with Compound A, since each of Compound A and levetiracetam, separately, or in combination, are known anti-epileptic agents (BEATCH Paragraphs [0004] and [0009]; FANG abstract). See MPEP 2144.06II. This teaches claims 1, 19, and 20.
BEATCH teaches that “The mechanism of action of Compound A is different from most known anti-epilepsy agent’s in that it involves enhanced opening of the voltage-gated potassium channels Kv7.2 and Kv7.3 (KCNQ2/3)”, which are types of Kv7 potassium channels (paragraph [0061]). This teaches claims 4, 6-8.
BEATCH teaches administering compound A for use in reducing a dose of “the compound that is orally administered to a human in need as part of a treatment regimen” (paragraph [0021]). This helps teach claim 2. BEATCH teaches a method of reducing a dose of Compound A that is orally administered to a human in need thereof as part of a treatment regimen, comprising orally administering a reduced dose of Compound A to the human under fed Condition. This helps teach claim 3.
Furthermore, an artisan would be expected to optimize the doses of Compound A and levetiracetam to increase therapeutic efficacy of treating a seizure disorder in the normal course of dose tailoring. BEATCH teaches a dose of Compound A wherein the dose is between 2 to 200 mg (paragraph [0032]) and teaches Compound A is present in the dosage unit form at a level ranging from about of 0.05 mg/kg to about 2.0 mg/kg (paragraph [0138]). See MPEP 2144.05(II): “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there Is evidence indicating such concentration or temperature is critical”. Neither the specification nor the claims indicate the doses of Compound A and levetiracetam are critical. This teaches claims 2-3, and 23-26.
BEATCH teaches claims 21 (paragraph [0078] and [0081]).
FANG teaches an oral dose (section 2.2) and teaches claim 22.
Conclusion
No claims are presently allowable as written.
Application 17/668,340 (Pub. No. US 2022/0265634 A1) was considered to be a double patent reference but it is not because it treats a different disease (anhedonia) and does not contain a teaching/motivation/suggestion for an additional agent (such as a ASM, levetiracetam).
Application 17/093,183 (Pub. No. US 2021/0161886 A1) was considered to be a double patent reference but it is not because it treats a different disease (depression) and does not contain a teaching/motivation/suggestion for an additional agent (such as a ASM, levetiracetam).
U.S. Patent 11,135,214 B2 was considered to be a double patent reference but it is not because it teaches a different method (of increasing bioavailability of Compound A by administering it under fed conditions) and does not contain a teaching/motivation/suggestion for an additional agent (such as a ASM, levetiracetam).
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 GILLIAN A HUTTER whose telephone number is (571)272-6323. The examiner can normally be reached M-F 7:30-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/G.A.H./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
Prosecution Insights