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 .
Current Status
This action is responsive to the amended claims of 08/03/2026. Claims 1-5,12-15, 28, and 47-58 are pending. Claims 33 and 38 have been canceled. Claims 55-58 are new.
Claims 1-5,12-15, 28, 47-58 have been examined on the merits.
Priority
The effective filing date remains 04/09/2021.
Response to Arguments
Examiner acknowledges receipt of and has reviewed the amendments and remarks of 08/03/2026; no new matter is found.
The objection to the specification is maintained. The substitute table does not improve the resolution of the existing table on Pg. 9 of the specification.
The objections to claims 4 and 47 are both withdrawn since Applicant has amended in line with Examiner’s suggestions.
The 112(b) rejection of claim 4 is withdrawn since the amendment clearly recites claim 4 depends from claim 1.
The 102(a)(1) rejection of claims 1-5, 12-15, 38, and 47-54 over SULLIVAN is withdrawn due to amendment. The amendment requires the subject treated is a human. SULLIVAN does not anticipate human treatment.
This amendment to claim 1 is from original claim 33 which was previously rejected under USC 103 by SULLIVAN, HANADA, and EISAI. Note, while the imported limitation is from an existing claim, claim 1 has also been broadened in scope to treatment of behavioral, sleep, and myoclonic or reflex seizure disorders rather than just SYNGAP1 neurodevelopment disorders. Thus, the rejections made over claim 1 and its dependent claims, below, can properly be made final.
The 102(a)(1) rejection of claim 38 over FDA is withdrawn since claim 38 has been canceled.
The 102(a)(1) rejection of claims 5 and 38 over ROCAMORA is withdrawn due to amendment. The embodiment 2 of claim 5 has been struck and claim 5 now requires SYNGAP1 involvement, which is not taught by ROCAMORA. Claim 38 is canceled.
Note, ROCAMORA may be properly applied to claim 1 and its dependents since claim 1 has been broadened to the scope of the struck embodiments 2-4 from claim 5 (i.e., treatment of behavioral, sleep, and myoclonic or reflex seizure disorders rather than just SYNGAP1 neurodevelopment disorders).
The 102(a)(1) rejection of claims 5 and 38 over HANADA is withdrawn due to amendment. The embodiment 4 of claim 5 has been struck and claim 5 now requires SYNGAP1 involvement, which is not taught by HANADA. Claim 38 is canceled.
Note, HANADA may be properly applied to claim 1 and its dependents like ROCAMORA.
The 102(a)(1) rejection of claims 5 and 38 over NISHI evidenced by KHAN is withdrawn due to amendment. The embodiment 3 of claim 5 has been struck and claim 5 now requires SYNGAP1 involvement, which is not taught by NISHI. Claim 38 is canceled.
Note, NISHI may be properly applied to claim 1 and its dependents like ROCAMORA.
The 103 rejection of claims 1, 28, and 33 over SULLIVAN, in view of HANADA, and in view of EISAI is maintained over claims 1 and 28 and modified to account for amendments to the claims. The limitations of claims 2-4 and 33 have been incorporated into claim 1. Claim 33 is also canceled.
Applicant argues these amendments to claim 1 overcome this obviousness rejection. Examiner disagrees because the claims 2-4 were already anticipated under USC 102(a)(1) by SULLIVAN. Note, none of the claims depending from claim 1 (other than 28 and 33) previously required the subject be human – by amendment these claims require such limitation. Independent claim 5 also did not previously require the subject be human. Further, Applicant has struck the original limitation of SYNGAP1 neurodevelopmental disorder effectively broadening the scope of the disease population which is treated in claim 1 compared to that of the originally presented claims 1-4. Moreover, Applicant has not addressed any of the merits of the reasoning underlying the rejection.
Thus, the rejection is properly modified below to account for the amendments to the claims and the addition of new claims 55-58.
The 103 rejection of claim 38 over HANADA in view of EISAI is withdrawn since claim 38 is canceled.
Response to Amendments
Specification - Maintained
The disclosure is objected to because of the following informalities: The table on Pg. 9 in Example 4 is of low resolution and is unreadable. The replacement table provided 08/03/2026 is still difficult to read:
PNG
media_image1.png
366
576
media_image1.png
Greyscale
. Please provide a higher resolution table.
Appropriate correction is required.
Claim Objections – Necessitated by Amendment
Claim 47 is objected to because of the following informalities: the second instance of human is misspelled “huma subject”. Please correct this typo. Appropriate correction is required.
Claim Rejections - 35 USC § 102 –
Necessitated by Amendment
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 15, and 49-50 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ROCAMORA (Rocamora, R. et al., Seizure, published 10 Feb. 2020, 76, 137-142; provided in IDS of 10/09/2023).
ROCAMORA teaches human patients with refractory epilepsy received perampanel starting at 2 mg/day (Pg. 137 Abstract methods) wherein treatment significantly improved sleep parameters including total sleep time, latency, efficiency, and duration (Pg. 137 Abstract results). ROCAMORA teaches the patients had abnormal sleepiness and pathological sleep quality (Pg. 139 Fig. 1), i.e., identified as suffering from a sleep disorder. Note, treatment of the subject necessarily includes identifying a subject and selecting the identified subject for treatment.
Thus, ROCAMORA teaches treatment of a subject identified as having a sleep disorder with perampanel (instant claims 1-2 and 49) with a dose up to 2 mg/day (instant claims 15 and 50).
Claims 1, 4, 13-15, 28, and 53-54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by HANADA (WO 2014/034756; provided in IDS of 10/09/2023; translation provided 02/02/2026).
HANADA teaches perampanel is administered to a patient in need thereof for treating status epilepticus (Pg. 15 ¶3) wherein status epilepticus is myoclonic seizures (Pg. 18 ¶2) and the patient is preferably a human including both adults and children (Pg. 9 ¶3 and Pg. 29 ¶1). The daily dose of perampanel is preferably 1 mg/day or 2 mg/day (Pg. 31 ¶1). Since HANADA teaches administration to a patient for treatment of status epilepticus with myoclonic seizures Examiner understands HANADA to teach identification of a subject suffering from/susceptible to myoclonic seizures. Note, treatment of the subject necessarily includes identifying a subject and selecting the identified subject for treatment.
Thus, HANADA teaches treatment of a human adult or child identified as having a myoclonic seizure with perampanel (instant claims 1, 4, 28, and 53) with a dose up to 1 mg/day, 1.5 mg/day, and 2 mg/day (instant claims 13-15 and 54). The phrase “up to” is considered, under the broadest reasonable interpretation (BRI), to include all doses below the recited dose, e.g., “up to 1.5 mg/day” is equivalent to a dose of ≤1.5 mg/day inclusive of 1 mg/day.
Claims 1, 3, 28, and 51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NISHI (WO 2019/045121; provided 02/02/2026) evidenced by KHAN (Khan, Epilepsy Research and Treatment, pub. 2012, 2012, 1-8; provided 02/02/2026).
NISHI teaches a method of treating epileptic encephalopathy in a mammal (Pg. 32 claim 1) comprising administering an anti-epileptic drug perampanel (Pg. 35 claim 25) wherein the mammal is a human adult, juvenile, child, or infant (Pg. 32 claims 11-12). KHAN discloses epileptic encephalopathy manifests with cognitive, behavioral, and neurological deficits (Pg. 7 Conclusions ¶1). Thus, as evidenced by KHAN, NISHI teaches treatment of a human adult/child having or susceptible to a behavioral problem. Note, treatment of the subject necessarily includes identifying a subject and selecting the identified subject for treatment.
Claim Rejections - 35 USC § 103 –
Necessitated by Amendment
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.
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 1-5, 12-15, 28, and 47-58 are rejected under 35 U.S.C. 103 as being unpatentable over HANADA (WO 2014/034756; provided in IDS of 10/09/2023; translation provided 02/02/2026) as applied to claims 1, 4, 13-15, 28, and 53-54, above, further in view of SULLIVAN (Sullivan et al., Biological Psychiatry, 2020, 86, 829-842; provided in IDS of 10/09/2023) and in view of EISAI (Eisai, FYCOMPA (perampanel) Full Prescribing Information, Revised 10/2012, pg. 1-26, retrieved from www.accessdata.fda.gov on 01/16/2026; provided 02/02/2026).
The instant claims are drawn to treatment of a human subject, pediatric (claim 28), having/susceptible to sleep, behavioral, or myoclonic seizure disorders by administering perampanel (claim 1-4, 49, 51, & 53) wherein the subject has a SYNGAP1 disorder (claims 5 & 47-48). The perampanel is dosed at up to 0.5 mg/day (claims 12 & 55), up to 1.0 mg/day (claims 13 & 56), up to 1.5 mg/day (claims 14 & 57), and up to 2.0 mg/day (claims 15, 50, 52, 54, & 58).
Determining the Scope and Contents of the Prior Art:
HANADA teaches the method of instant claims 1, 4, 13-15, 28, and 53-54, above, ¶21. HANADA further teaches the particular treatment regimen for a patient will depend on a variety of factors including age, weight, sex, time of administration, and severity of the condition being treated (Pg. 11 ¶1).
SULLIVAN teaches administration of perampanel to mice with Syngap1 epileptogenesis phenotype (i.e., SYNGAP1 neurodevelopmental disorder) wherein the perampanel dosing significantly rescued cortical gamma homeostasis (i.e., the subject was treated) (Pg. 829 Abstract). A dose of 2 mg/kg was administered twice a day (Pg. 833 Left Col. ¶1).
SULLIVAN teaches sleep dysfunction is common feature of neurodevelopment disorders and is reported in patients with SYNGAP1 (Pg. 832 Left Col. ¶2). Syngap1 phenotype mice spent more time asleep than wild type mice (Pg. 832 Left Col. ¶2); i.e., identified as suffering from and susceptible to sleep disorder. Syngap1 mice treated with perampanel showed significant rescue to gamma dysregulation during wake and non-REM sleep similar to wild type (Pg. 834 Left Col. ¶2).
SULLIVAN teaches Syngap1 mutation results in haploinsufficiency and causes mental retardation type 5 with severe behavioral problems (Pg. 829 Left col. ¶1). Further, Syngap1 mice showed hyperactivity (Pg. 833 Left Col. ¶2); i.e., identified as suffering from and susceptible to a behavioral problem. Perampanel treatment significantly rescued cortical gamma homeostasis (i.e., the subject was treated) (Pg. 829 Abstract).
SULLIVAN teaches myoclonic seizures occurred in Syngap1 mice (Pg. 829 Abstract Results); i.e., identified as suffering from such. Perampanel treatment prevented seizures in the mice (Pg. 833 Left Col. ¶1). SULLIVAN further teaches uncontrolled epilepsy in children is at least partially responsible for cognitive regression (Pg. 832 Right col. ¶2). Further, while the treatment was carried out in mice, the seizure states of the SYNGAP1 mice were compared to those of a child with a SYNGAP1 disorder (Pg. 829 Abstract).
EISAI teaches dosage and administration of perampanel approved by the FDA for treatment of seizures in human patients (Pg. 1). EISAI teaches the safety and efficacy of perampanel in pediatric patients 12-16 years old (Pg. 10 sect. 8.4). EISAI teaches pediatric patients can be dosed similarly to adults (Pg. 14 last ¶).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
SULLIVAN does not teach the subject is a human nor a pediatric patient.
HANADA and EISAI do not teach the subject has a SYNGAP1 disorder.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of a sleep, behavior, and seizure disorders associated with SYNGAP1 disorder and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the treatment. Said artisan has also reviewed the problems in the art regarding SYNGAP1, sleep, behavior, and seizure disorders and uses of perampanel and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references HANADA, in view of SULLIVAN, and in view of EISAI.
Regarding claims 1, 4, 13-15, 28, and 53-54, HANADA teaches the method of such claims but is silent as to SYNGAP1 status.
Regarding claims 1, 4, 5, 28, 47, and 53, the artisan would be motivated to treat subjects with SYNGAP1 disorder with the method of HANADA since SULLIVAN teaches an overlap in symptoms (i.e., myoclonic seizure – Pg. 829 Abstract Results) and overlap in treatment drug – perampanel (Pg. 829 Abstract). Since the mice in SULLIVAN are utilized as a model for childhood SYNGAP1 disorder and myoclonic seizure (Pg. 829 Abstract) and since the method of HANADA is utilized to treat myoclonic seizure in children (Pg. 9 ¶3 and Pg. 29 ¶1), the artisan would have an expectation of success in combining the teachings of SULLIVAN and HANADA to arrive at a method of treating SYNGAP1 disorder and concomitant myoclonic seizure in a human child by administering perampanel.
Regarding claims 2-3, 5, 28, 47, 49, and 51, further, since SULLIVAN teaches SYNGAP1 disorder associated sleep dysfunction (Pg. 834 Left Col. ¶2) and behavioral problems (Pg. 833 Left Col. ¶2) are also treated by the perampanel, the artisan would have an expectation of success in also treating children subjects suffering from/susceptible to such disorders.
Regarding claims 13-15, 48, 50, 52, 54, and 56-58, since treatment of each of the instant disorders is taught above and since HANADA teaches perampanel is preferably dosed at 1 mg/day or 2 mg/day (Pg. 31 ¶1), the artisan would be motivated, with a reasonable expectation of success, to utilize HANADA as a clear starting point for human dosing of such disorders. Further, the artisan would have an expectation of success in using such dosing for children since perampanel is safe and effective in such populations, as recognized by EISAI (all teachings above). Thus, the instant doses of “up to” 1.0, 1.5, and 2.0 mg/day are obvious; see BRI discussion (¶21).
Regarding claims 12 and 55, the artisan would be motivated to optimize the dosage of perampanel per patient using the teachings of HANADA as a starting point.
MPEP 2144.05(II)(A) provides guidance about the routine optimization of prior art conditions: "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. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.").”
Furthermore, MPEP 2144.05(I) provides guidance about overlapping ranges: “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.”
In the instant case, HANADA teaches doses up to 1 mg/day and 2 mg/day (Pg. 31 ¶1). These dosages are considered to approach the instantly claimed up to 0.5 mg/day. Since HANADA teaches the treatment regimen (i.e., dosing) will depend on a variety of patient factors (Pg. 11 ¶1), the artisan would recognize the dosage amount of perampanel as a result-effective variable, i.e., a variable that achieves a recognized result. Thus, the dosage is analogous to the “concentration or temperature” recited in the MPEP and may be optimized by routine experimentation. Absent any evidence demonstrating the contrary, the determination of the optimum or workable dosage of perampanel would have been well within the practice of the artisan given the guidance of the prior art.
Note, similar logic can be applied to claims 13-15, 48, 50, 52, 54, and 56-58 regarding dosing for SYNGAP1-related disorders. While HANADA does not teach SYNGAP1, the artisan would have the same motivation/expectation of success to optimize the dose of perampanel as discussed above. In this case, the starting dosages of HANADA directly match the dosages of instant claims 13-15, 48, 50, 52, 54, and 56-58.
Conclusion
Claims 1-5, 12-15, 28, and 47-58 are rejected.
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 SARA ELIZABETH BELL whose telephone number is (703)756-5372. The examiner can normally be reached Monday-Friday 9:00-5:30.
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.
/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
Prosecution Insights