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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/30/26 has been entered.
Maintained rejections
Rejections set forth in the final office action mailed on 4/1/25 are maintained. The rejections have been modified to address new claims 14 and 15 submitted on 4/30/26. Rejections have also been modified to incorporate additional teachings of Johnson directed to the relationship between concentration of NaV1.6 channel inhibitor and inhibition of NaV1.6 channel.
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) 1-8 and 10-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Griffin et al (WO 2019/232209, published 05/12/19) in view of Johnson et al (eLife, 2022, 11, e72468, 1-26; published 3/2/22).
Scope of prior art
Griffin teaches a method of treating a condition relating to aberrant function of a sodium ion channel comprising administering the subject in need an effective amount of a therapeutic compound (paragraph [0026]). The conditions to be treated include the currently claimed generalized epilepsy and focal epilepsy (paragraph [00190], [00191]).
With regards to the structure of the compound, Griffin teaches compound 3 which has the same structure as the currently claimed compound it’s synthesis and biological activity as inhibitor of NaV1.6 sodium channel (compound paragraph [00138], synthesis paragraphs [00251]-[00252], testing paragraphs [00468], [00475], [00476]).
Regarding amount to be administered, Griffin teaches 1mg to 2g oral unit dose [00182]. In paragraphs [0091] and [0092], art teaches that the effective amount is an amount required to elicit the desired biological response and therapeutically effective amount is the amount required to provide a therapeutic benefit of a given disease or condition.
Regarding subject population, Griffin teaches that the subjects in need encompass pediatric and adult subjects (paragraph [0088]).
Ascertaining the difference
The currently claimed invention is entirely with the scope of Griffin. While Griffin teaches the currently claimed active agent, the subject population, the condition to be treated and a dose range that encompasses the claimed dose, Griffin does not explicitly teach a 15mg or a 45mg daily dose administered to adult or child subject with generalized epilepsy or focal epilepsy.
Griffin is also silent with regards to suppression of photoparoxysmal response.
Secondary reference
Johnson et al teach and demonstrate that NBI-921352, an inhibitor that targets NaV1.6 channels prevents seizures in various animal models. Johnson describes focal onset seizures (page 14, last paragraph) and generalized seizures (page 9, second paragraph).
Obviousness
A person of ordinary skill in the art would have found it obvious to try treating focal and generalized epilepsy in a subject in need of such treatment by administering to the subject a therapeutically effective amount of compound 3 as taught by Griffin.
Griffin teaches a family of compounds, including compound 3 for treatment of epileptic conditions including generalized and focal epilepsy. Griffin teaches a broad dose range and states that exact dose for each patient would need to be determined by a practitioner. Griffin provides a NaV1.6 channel inhibition activity of compounds where compound 3 is in the most active group. The teachings of Griffin provide teaching, suggestion and motivation to treat epilepsy by administration of therapeutically effective amount of compound 3.
Johnson teaches that compounds having activity as NaV1.6 channel inhibitors prevent seizures in animal models with epilepsy causing mutations. Since the compound of Johnson and Compound 3 of Griffin are inhibitors of NaV1.6 channels, a person of ordinary skill would expect compound 3 to also be useful in preventing epileptic seizures that result from gain of function mutations in NaV1.6 channels. Johnson therefore provides reasonable expectation of success that compound 3 of Griffin would be active in treatment of epilepsy. Based on the teachings and suggestion of Griffin and in view of the results reported by Johnson, a POSA would have fount it obvious to try treatment of focal and generalized epilepsy by administering to a subject in need compound 3.
"[A] person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103."KSR, 550 U.S. at, 82 USPQ2d at 1397.
Regarding dose:
While Griffin does not recite 15mg or 45mg dose, the claimed dose is within the range provided by Griffin. Additionally, Griffin teaches that a practitioner would determine the optimal dose for given subject depending on the condition and physical characteristics. In order to practice the invention of Griffin, a skilled practitioner would have found it necessary to determine the optimal safe and effective dose to administer. Determining the optimal dose is within the scope of routine optimization and one would expect that higher plasma concertation of sodium ion channel inhibitor would result in higher efficacy of inhibition. On page 3, figure 1, Johnson demonstrates that concentration of NBI-921352 is directly in relation to degree of NaV1.6 channel inhibition. This indicates that the amount of NaV1.6 channel inhibitor is a result effective variable and optimization of a result effective variable is with the realm of routine optimization.
Regarding suppression of photoparoxysmal response:
Suppression of photoparoxysmal response is an property inherently present when compound 3 of Griffin is administered. Since compound 3 of Griffin is the same as Compound 1 of the current claims, it is inherent that if administration of Compound 1 results in suppression of photoparoxysmal response, then the activity occurs when compound 3 is administered.
Regarding claim 14, directed to no ataxia, lethargy or vomiting upon administration of compound 1:
Since Griffen teaches administration of the claimed compound for treatment of the claimed disease to the claimed subject population at a dose that is effective at treating said disease, it is inherent that the method does not result in ataxia, lethargy or vomiting.
Regarding administration of the agent as a monotherapy (claim 15):
In claims 96 and 98 Griffin teaches treatment of condition relating to aberrant function of a sodium channel (cl 96) specifically epilepsy (cl 98-99) by administering to a subject an effective amount of the compound. Since claims recite administration of only one active agent, examiner is interpreting it as being directed to monotherapy.
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 1-8 and 10-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,731,976. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims of the ‘976 patent are directed to a method for modulating sodium ion channel activity in a subject in need thereof comprising administering to the subject a therapeutically effective amount of compound 1 (claims 1 and 16). Subject in need thereof is a subject with focal epilepsy (claim 22) or a subject with generalized epilepsy (claim 21). The subject is human (claim 30).
Regarding age of the subject:
It would have been obvious to practice the method of ‘976 patent on any human subject, which includes both adults and children. ‘976 comprises claims where the compound if administered to children with childhood epilepsy (claims 6 and 9).
Regarding dose:
Claims of the ‘976 patent are directed to administering therapeutically effective amount of compound 1. While specific doses are not recited in the claims, it would have been necessary for a skilled artisan to determine the proper therapeutically effective dose in order to practice the method.
Regarding suppression of photoparoxysmal response:
Suppression of photoparoxysmal response is a property inherently present when compound 1 is administered. It is inherent that administration of Compound 1, while practicing the method of the ‘976 patent, results in suppression of photoparoxysmal response.
Claims 1-8 and 10-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
Claims 1-4 of U.S. Patent No. 11,731,978 in view of Griffin et al (WO 2019/232209)
Claims 1-18 of U.S. Patent No. 11,014,931 in view of Griffin et al (WO 2019/232209)
Claims 1-14 of U.S. Patent No. 11,866,439 in view of Griffin et al (WO 2019/232209)
Claims of US patents 11,731,978, 11,014,931 and 11,866,439 are directed to compound of formula 1 and pharmaceutical composition comprising compound of formula 1. While these patents do not comprise claim limitations directed to a method of treating generalized or focal epilepsy, a person of ordinary skill would have found it obvious to utilize the compound in the currently claimed method in view of Griffin et al. Griffin teaches a method of treating a condition relating to aberrant function of a sodium ion channel comprising administering the subject in need an effective amount of a therapeutic compound (paragraph [0026]). The conditions to be treated include the currently claimed generalized epilepsy and focal epilepsy (paragraph [00190], [00191]). Compound 3 of Griffin, which displays higher NaV1.6 channel inhibition activity is the same as Compound 1 in the referenced patents.
A person of ordinary skill in the art would have found it obvious to try using the compound 1 of the referenced patents in a method of treating generalized epilepsy or focal epilepsy. Suggestion for such utility is provided by Griffin.
Reply to applicant’s remarks
Remarks filed on 4/30/26 have been fully considered and found to be unpersuasive.
Compound 1 of the current claims and compound 3 of Griffin are the same compound. From here on Examiner will refer to it as compound 1 as recited in the claims.
The first argument is directed to applicants’ discovery that compound 1 is more potent and is active at lower doses compared to standard of care antiepileptic drugs. This argument is not persuasive because a person of ordinary skill would have found it obvious to determine the optimal effective and safe dose for treatment of epilepsy by administering compound 1. Since compounds 1 has not previously been used to treat epilepsy a skilled artisan would not have no expectation as what amount would constitute an effective dose. Given that Griffin teaches compound 1, its activity as NaV1.6 channel inhibitor and suggests treatment of epilepsy, a skilled artisan would determine the effective dose through routine optimization, and by doing so would arrive at currently claimed dose. Additionally, Johnson demonstrates in figure 1 that concertation of NaV1.6 channel inhibitor determines efficacy of inhibition making the dose administered to a subject a result effective variable which can be optimized for efficacy and safety.
The second argument is directed to increased tolerability of compound 1 due to its preference for inhibiting persistent INa relative to peak INa. This argument is not persuasive. Griffin already teaches treatment of epilepsy by administration of compound 1. Applicants’ discovery that compound 1 is better tolerated than standard of care medications is an additional benefit to practicing the method suggested by Griffin. The fact that applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.1985). It is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable. In re Woodruff. 16 USPQ2d 1934, 1936 (Fed. Cir. 1990).
Lastly, applicant argues that the unique properties of compound 1, characterized by increased potency, tolerability, and associated effective dose could not have been predicted from teaching of Griffin and Johnson. Applicant is correct, there was no way to predict what amount would constitute a safe and effective dose. Neither applicant’s claimed dose or any other dose could have been predicted based on the teachings of Griffin and Johnson. However, determining an effective and safe dose is considered to be routine because it involves optimization of a result effective variable, and the dose claimed by the applicants is within the dose range taught by Griffin. Griffin teaches administration of an effective dose, which would motivate to a skilled artisan to determine what the effective dose is.
Conclusion
Claim(s) 1-8 and 10-15 are pending
Claim(s) 1-8 and 10-15 are rejected
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YEVGENY VALENROD whose telephone number is (571)272-9049. The examiner can normally be reached Mon-Fri 9am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 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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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628
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