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 10/09/2023. Claims 1-5, 12-15, 28, 33, 38, and 47-54 are pending. Claims 1-5, 12-15, 28, 33, 38, and 47-54 have been examined on the merits.
Note, no restriction/election requirement has been put in place.
Priority
The effective filing date is 04/09/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/09/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
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:
PNG
media_image1.png
315
492
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Greyscale
. Please provide a higher resolution table.
Appropriate correction is required.
Claim Objections
Claims 4 and 47 are objected to because of the following informalities. Appropriate correction is required.
Claim 4 recites, in line 2, “or susceptible a myoclonic”. The word “to” is missing. Claim 4 should read “susceptible to a myoclonic”.
Claim 47 begins with “A method of claim 1”, please replace “A method” with “The method”.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 recites “The method 1 through 3”. The dependency of this claim is unclear since the preamble does not clearly recite a claim from which the claim 4 depends, but the claim is also not written in clearly independent form. Thus, the metes and bounds of the claim are undefined rendering the claim indefinite.
Note: The current amendments read “The method
Claim Rejections - 35 USC § 102
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 1-5, 12-15, 38, and 47-54 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by SULLIVAN (Sullivan et al., Biological Psychiatry, 2020, 86, 829-842; provided in IDS of 10/09/2023). SULLIVAN was available online 10 January 2020; this is before the grace period.
Regarding claims 1 and 47, 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). Thus, a subject suffering from SYNGAP1 neurodevelopmental disorder was identified and administered an effective amount of perampanel. Note, treatment of the subject with perampanel necessarily includes “selecting the identified subject for treatment”.
Regarding claims 2 and 49, 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). Note, treatment of the subject with perampanel necessarily includes “selecting the identified subject for treatment”.
Regarding claims 3 and 51, SULLIVAN teaches Syngap1 mutation result in haploinsufficiency and cause mental retardation type 5 with severe behavioral problems (Pg. 829 Left col. ¶1). Further, SULLIVAN identified hyperactivity in Syngap1 mice (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). Note, treatment of the subject with perampanel necessarily includes “selecting the identified subject for treatment”.
Regarding claims 4 and 53, 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). Note, treatment of the subject with perampanel necessarily includes “selecting the identified subject for treatment”.
Regarding claim 5, since SULLIVAN teaches each of the claims 1-4 (above) wherein the subject is identified as suffering from SYNGAP1 neurodevelopmental disorder, sleep disorder, behavioral problem, and myoclonic seizures and further treatment with perampanel (i.e., administration of an effective amount), all 4 embodiments of instant claim 5 are anticipated. Note, treatment of the subject with perampanel necessarily includes “selecting the identified subject for treatment”.
Regarding claims 12-15, SULLIVAN teaches 2 mg/kg was administered at 10AM and 6PM (Pg. 833 Left Col. ¶1). Using a reference weight of 20 g for a mouse, the dosages come out to 0.04 mg given 2x a day or 0.08 mg/day. Thus, SULLIVAN teaches up to 0.5 mg, 1.0 mg, 1.5 mg, and 2.0 mg is administered to the subject per day since the dosage per day does not exceed these amounts.
Regarding claim 38, since SULLIVAN teaches administration of perampanel (Pg. 829 Abstract, Pg. 833 Left Col. ¶1), SULLIVAN anticipates each of the four kit embodiments of the instant claim. The kit embodiments require (a) perampanel and (b) instructions for use. The instructions are viewed as non-functional printer matter, see MPEP 2112.01(III): “Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004)… explaining "[i]f we were to adopt [applicant’s] position, anyone could continue patenting a product indefinitely provided that they add a new instruction sheet to the product.”
In the instant case, the instructions are not functionally related to the product, i.e., perampanel functions independent of the instructions. Thus, the instructions will not distinguish the claimed compound from the prior art. Since SULLIVAN teaches (a) perampanel and (b) instructions do not distinguish the claim from the prior art, the prior art teaches the structural limitations of the instant claim.
Regarding claims 48, 50, 52, and 54, since SULLIVAN teaches the practice of instant claims 47, 49, 51, and 53 (above) and since SULLIVAN teaches perampanel is administered at 0.08 mg/day to the Syngap1 mice (i.e., the identified subject) (Pg. 833 Left Col. ¶1), the instant claims are anticipated.
Claim 38 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by FDA (FDA, CIPRO (ciprofloxacin hydrochloride) Full Prescribing Information, Revised 07/2016, pg. 1-53, retrieved from www.fda.gov/drugsatfda on 01/16/2026).
FDA teaches a tablet and suspension for oral use as an antibacterial (Pg. 1 Left Col. Line 4-5 & sect. Indications and Usage) comprising 250 or 500 mg of ciprofloxacin hydrochloride (Pg. 10 Sect. 3). The tablet/suspension (i.e., a pharmaceutical composition and unit dosage oral form) does not comprise any perampanel (see whole document). The instant claim is drawn to a unit dosage oral form (e.g., an oral tablet or suspension) comprising perampanel in an amount of less than 2 mg. Since no lower limit is given, the broadest reasonable interpretation includes a pharmaceutical oral tablet/suspension comprising 0 mg of perampanel. Thus, FDA anticipates the instant claim.
Claims 5 and 38 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).
Regarding claim 5 embodiment 2, ROCAMORA teaches 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 selecting the identified subject for treatment. Thus, ROCAMORA teaches the instant claim.
Regarding claim 38, ROCAMORA teaches administration of perampanel starting at 2 mg/day (Pg. 137 Abstract methods). The instructions are viewed as non-functional printer matter, see MPEP 2112.01(III).
Claims 5 and 38 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). A machine translation of HANADA is referenced here and is provided attached to this action.
Regarding claim 5 embodiment 4, HANADA teaches a pharmaceutical composition of perampanel for the treatment of status epilepticus (Pg. 40 claim 1) wherein the perampanel is administered to a patient in need thereof for treating status epilepticus (Pg. 15 ¶3). HANADA further teaches status epilepticus includes myoclonic seizures (Pg. 18 ¶2). Since HANADA teaches administration to a patient for treatment of status epilepticus, which includes myoclonic seizures, Examiner understands HANADA to teach identification of a subject suffering from myoclonic seizures. Note, treatment of the subject necessarily includes selecting the identified subject for treatment. Thus, HANADA teaches the instant claim.
Regarding claim 38, HANADA teaches a pharmaceutical composition of perampanel (Pg. 40 claim 1). The instructions are viewed as non-functional printer matter, see MPEP 2112.01(III).
Claims 5 and 38 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NISHI (WO 2019/045121) evidenced by KHAN (Khan, Epilepsy Research and Treatment, pub. 2012, 2012, 1-8).
Regarding claim 5 embodiment 3, 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). 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 mammal having epileptic encephalopathy and therefore having behavioral deficits (i.e., identified as suffering from a behavioral problem). Note, treatment of the subject necessarily includes selecting the identified subject for treatment. Thus, NISHI teaches the instant claim.
Regarding claim 38, NISHI teaches perampanel (Pg. 35 claim 25). The instructions are viewed as non-functional printer matter, see MPEP 2112.01(III).
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.
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.
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.
Claims 1, 28, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over SULLIVAN (Sullivan et al., Biological Psychiatry, 2020, 86, 829-842; provided in IDS of 10/09/2023) as applied to claim 1 above (¶15), and further in view of HANADA (WO 2014/034756; provided in IDS of 10/09/2023) and EISAI (Eisai, FYCOMPA (perampanel) Full Prescribing Information, Revised 10/2012, pg. 1-26, retrieved from www.accessdata.fda.gov on 01/16/2026). A machine translation of HANADA is referenced here and is provided attached to this action.
Determining the Scope and Contents of the Prior Art:
SULLIVAN teaches the method of claim 1, see ¶15 above for the relevant teachings. SULLIVAN further teaches uncontrolled epilepsy in children is at least partially responsible for cognitive regression (Pg. 832 Right col. ¶2).
HANADA teaches a pharmaceutical composition of perampanel for the treatment of status epilepticus (Pg. 40 claim 1) and administration to a patient in need thereof (Pg. 15 ¶3) wherein status epilepticus includes myoclonic seizures (Pg. 18 ¶2). HANADA teaches the patient is more preferably a human (Pg. 9 ¶3).
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 SYNGAP1 disorder and possesses the technical knowledge necessary to make adjustments to the method to optimize/enhance the method outcomes. Said artisan has also reviewed the problems in the art regarding SYNGAP1 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 SULLIVAN, HANADA, and EISAI.
The artisan would find it obvious to treat a human pediatric patient with the method of SULLIVAN in view of the teachings of HANADA and EISAI. Since HANADA (Pg. 18 ¶2) and SULLIVAN (Pg. 829 Abstract Results) are both drawn to treatment of myoclonic seizures by perampanel and since HANADA teaches the preferred patient is human (Pg. 9 ¶3), the artisan would be motivated to treat a human by SULLIVAN’s method. The artisan would have an expectation of success since EISAI teaches FDA approved dosage and administration of perampanel (Pg. 1) and the efficacy/safety in pediatric patients (Pg. 10 sect. 8.4). Thus, the artisan would recognize the utility and safety of perampanel in humans/pediatric patients and, further, would find children an important patient population since SULLIVAN teaches uncontrolled epilepsy in children contributes to cognitive regression (Pg. 832 Right col. ¶2).
Thus, the combined references teach the instant claims.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over HANADA (WO 2014/034756; provided in IDS of 10/09/2023) and EISAI (Eisai, FYCOMPA (perampanel) Full Prescribing Information, Revised 10/2012, pg. 1-26, retrieved from www.accessdata.fda.gov on 01/16/2026). A machine translation of HANADA is referenced here and is provided attached to this action.
Determining the Scope and Contents of the Prior Art:
HANADA teaches a pharmaceutical composition of perampanel for the treatment of status epilepticus (Pg. 40 claim 1) and administration to a patient in need thereof (Pg. 15 ¶3). The daily oral dose of perampanel is 0.1 mg to 100 mg/day, preferably 2, 4, 6, 8 10, 12 mg/day (Pg. 31 ¶1). HANADA teaches the dose of the drug in the pharmaceutical composition will vary depending on the patient’s disease state or symptoms, age, sex, weight and sensitivity, mode of administration, administration period and interval, and formulation and type of composition (Pg. 26 last ¶).
EISAI teaches FDA approved oral tablets of containing 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg of perampanel (Pg. 1 Dosage Forms and Strengths) for once daily use (Pg. 2 Sect. 2.1 ¶1-2) for treatment of seizures in epileptic patients (Pg. 1 Indications and Usage). EISAI teaches the recommended starting dose is 2 mg/day (Pg. 2 sect. 2.1 ¶1).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
HANADA does not teach the unit oral dosage form comprises less than 2 mg perampanel.
EISAI does not teach the unit oral dosage form comprises less than 2 mg perampanel.
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 unit dosage oral form of perampanel useful for treating epilepsy and possesses the technical knowledge necessary to make adjustments to the dosage form to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding perampanel dosing 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 and EISAI.
The artisan would be motivated to optimize the dosage of perampanel in the unit dosage oral form of HANADA, based on the additional teachings of HANADA and EISAI.
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: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists…Similarly, 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 a daily oral dose of perampanel of 0.1 mg to 100 mg/day, preferably 2 mg/day (Pg. 31 ¶1) and EISAI teaches a dose of 2-12 mg/day (Pg. 1 Dosage Forms and Strengths). These dosages are considered to overlap with the instantly claimed “less than 2 mg”. Since HANADA the dose of the drug in the pharmaceutical composition will vary depending on the patient’s disease state or symptoms, age, sex, weight and sensitivity, mode of administration, administration period and interval, and formulation and type of composition (Pg. 26 last ¶), the artisan would recognize the dosage 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. Therefore, the determination of the optimum or workable dosage of perampanel would have been well within the practice of the artisan. Furthermore, absent any evidence demonstrating a patentable difference between the instant and prior art compositions and the criticality of the claimed dosage regimen, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the artisan.
Further, the artisan would have a reasonable expectation of success since the references HANADA (Pg. 40 claim 1) and EISAI (Pg. 1 Indications and Usage) are both directed to treatment of epileptic seizures. Moreover, since EISAI teaches FDA approved dosages of 2-12 mg/day (Pg. 2 Sect. 2.1 ¶1-2) wherein the recommended starting dose is 2 mg/day (Pg. 2 sect. 2.1 ¶1), the artisan would recognize dosages up to 12 mg/day as safe (i.e., anywhere between 0 and 12 mg/day is safe). Thus, the artisan would recognize 0-2 mg/day as a safe dosage range which could be exploited for a patient that has less severe symptoms, lower weight, or high sensitivity to perampanel, in view of HANADA (Pg. 26 last ¶).
Thus, the combined references teach the instant claim.
Conclusion
Claims 1-5, 12-15, 28, 33, 38, and 47-54 are rejected.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625