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 .1
Status of Claims
Claims 1-19 are pending and examined.
Election/Restrictions
Applicant’s election of the below species in the reply filed on Jan 9 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant elected the following species:
CDKL5 deficiency disorder as the epileptic disorder,
oral as the route of administration, and
suspension
Claims 1-4, and 6-19 read on the elected species. Note upon further search, examination and consideration of the claims, the species of disorder has been expanded to include seizures, and related epileptic disorders, where the route of administration has been expanded to include oral capsules and injections as per the cited art below. Accordingly, withdrawn claim 5 (species of oral capsule) has been rejoined and is under examination.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted Nov 8 2023 and Jan 9 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 9 is objected to because of the following informalities:
In line 4, claim 9 recites infantile spasms (or West syndrome). As these terms are synonymous, use of the word “or” is to be deleted to avoid recitation of the same condition in the alternative.
In lines 8-9, claim 9 recites “a” breakthrough seizures and “an” infantile spasms. Correction is required to reconcile the singular modifier terms “a” and “an” with the plural “seizures” and “spasms.” As the balance of diseases/conditions of claim 9 are recited in the singular, these terms should also be recited in the singular also.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (4th paragraph)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10 and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 10 depends from claim 1 and recites “the frequency” of seizure. “Frequency” is recited for the first time in the claims in claim 10. It is not recited in claim 1 from which claim 10 depends. Therefore, claim 10 should be amended to recite “a” frequency of seizures, rather than “the” frequency of seizures; or delete the term “the” altogether in claim 10.
Claim 16 depends from claim 1. Claim 1 recites the limitation of “a ganaxolone plasma concentration,” where claim 16, which depends from claim 1, also recites “a ganaxolone plasma concentration,” rather than “the” ganaxolone plasma concentration in claim 16.
Applicant may cancel the claims, amend the claims to place them in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Claim Rejections - 35 USC § 102
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 and 6-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2016/0228454 A1 (US Pub 454). US Pub 454 is cited on the IDS submitted on Nov 8 2023 (US Ref. No. 12).
Claim 1 is a method for treating seizure or an epilepsy disorder comprising administering to a subject in need thereof ganaxolone (GNX) in a therapeutically effective amount that produces a GNX plasma concentration of at least about 100 ng/ml or greater for approximately about 70% or more of a 24 day.
US Pub 454 teaches a method for comprising administering to a subject in need (seizure) thereof GNX administering an effective amount of the injectable GNX (formulation comprising GNX) in a therapeutically effective amount that produces a GNX plasma concentration of at least about 100 ng/ml or greater for approximately about 70% or more of a 24 day. See paragraphs 7 and 86.
Regarding claim 2 discloses where GNX is administered 3 times per day, US Pub 454 teaches GNX intervals administered of 1 to 24 hours per day, where B-cyclodextrin GNX is injected every 8 hrs. See paragraph 75.
Claims 6-8 are directed to a dose of GNX administered up to 63 mg/kg/day, up to 1800 mg per day or up to 1500 mg per day. US Pub 454 discloses ganaxolone doses of 15 mg/kg. See paragraphs 12-13. See also paragraph 75 doses of from about from about 1 mg/kg to about 20 mg/kg, from about 2 mg/kg to about 15 mg/kg, from about 2 mg/kg to about 10 mg/kg, or about 2 mg/kg to about 8 mg/kg, where the doses are administered at schedules every 8 hours (including 1hrs, 2 hrs, 4hrs, 6 hrs, 8hrs, 12hrs, or 24hrs), from 1 to 10 days. See also paragraphs 80 and 85 noting a dose of about 1 mg/kg to about 200 mg/kg and about 1 mg/kg to about 20 mg/kg ganaxolone, where US Pub 454 teaches administration of doses given at intervals of up 24 hours.
Regarding claim 9, US Pub 454 discloses treatment of various seizures disorders including the following claimed by applicant, status epilepticus, refractory status epilepticus, super-refractory status epilepticus. See paragraph 5.
Claims 10-11 are directed to wherein administering ganaxolone reduces the frequency of seizure or major motor frequency in the subject relative to baseline.
Claims 12-13 are directed to the claimed method wherein a reduction in seizure frequency of about 20% or 35% or greater relative to baseline seizure frequency, or greater or of at least about 35%.
Regarding claims 10-13, US Pub 454 teaches under its Results section, starting at paragraph 136, Tables 6-7 summarizes the treatment effects for ganaxolone administered 15 minutes or 60 minutes post seizure.
US Pub 454 teaches “When dosed 15 minutes after SE-onset, GNX reduced EEG power across all frequency ranges to levels at or below baseline for at up to 5 h.” See paragraph 140. Note that such levels of reduction of EEG power below baseline encompasses about 20% or about 35% baseline as claimed.
Claims 14-15 are directed to wherein the subject and/or seizure activity in the subject is monitored by electroencephalogram (EEG). Pub 454 teaches monitoring of subjects via EEG. See Example 8 starting at paragraph 121 and specifically paragraph 122 reciting EEG monitoring. See also EEG analysis and Results starting at paragraphs 132 and 136, Table 6.
Claim 16 claims where the ganaxolone amount is sufficient to produce a ganaxolone plasma concentration of at least about 100 ng/ml or greater for approximately 75% or more of a 24 hour day. US Pub 454 teaches certain embodiments the interval between bolus doses is from about 10 to about 24 hours and once an initial Cmax is reached the plasma concentration of ganaxolone is not below 100 ng/mL at any time between bolus doses. See paragraph 86.
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.
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 1-2 and 6-18 are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0228454 A1, as evidenced by Walpole et al. The weight of nations: an estimation of adult human biomass BMC Public Health 2012, 12:439.
US Pub 454 is cited on the IDS submitted on Nov 8 2023 (US Ref. No. 12). Walpole is cited by the Examiner on the PTO-892 form.
Note that claims 1-2 and 6-16, are taught by US Pub 454, where the particular species of an injectable formulation/administration of GNX is taught to treat the claimed subject in need, suffering from epileptic seizures.
As detailed above, claims 1-2, directed to the claimed method of treating seizures/epilepsy with GNX administered 3 times a day, are taught by US Pub 454 at paragraphs 7 and 85; and paragraph 75 (GNX administered every 8 hours per day).
Claims 6-8’s ranges of doses are known, where US Pub 454 teaches overlapping doses of GNX at paragraphs 12-13, 75 and 80.
Claim 9 is taught by US Pub 454, where it discloses status epilepticus, refractory status epilepticus, super-refractory status epilepticus. See paragraph 5.
With regard to claims 10-13 and the limitations of reduction of seizures/major motor frequency from baseline (of about 20% or 35% or greater), US Pub 454 teaches reductions of status epilepticus from baseline. See Results section starting at paragraph 136, Tables 6-7 and paragraph 140.
US Pub 454 teaches the EEG monitoring limitations of claims 14-15 at Example 8, paragraphs 121-122, 132 and 136; and Table 6.
It is noted that US Pub 454, while teaching a dose of mg/kg as detailed above, does not necessarily teach the species of a dose of 500 or 600 mg administered three times a day to a subject as per claims 17-18. To address this species, GNX administered 3 times per day at the doses claimed, US Pub 454 teaches GNX intervals administered of 1 to 24 hours per day, where B-cyclodextrin GNX is injected every 8 hrs. See paragraph 75.
The dose of the single injection may be from about 1 mg/kg to about 20 mg/kg, from about 2 mg/kg to about 15 mg/kg, from about 2 mg/kg to about 10 mg/kg, or about 2 mg/kg to about 8 mg/kg. See paragraph 75. Given an adult patient can weigh/body mass, anywhere from about 60 to about 80 kg, as evidenced by Walpole et al. 2012, Table 3) a person having ordinary skill in the art (PHOSITA) would routinely optimize doses with these taught ranges of US Pub 454, based on weight, to arrive at doses of 500 mg or 500 mg, dosed every 8 hours (i.e. 3 times a day). Prior to the filing the present application, it would have been prima facie obvious to a PHOSITA following the dosing ranges of US Pub 454 in terms of mg/kg, 3 times a day, as detailed above to modify as evidenced by Walpole in terms of the average weight of human adult subject in order to arrive at the claimed method of treatment of claims 17-18.
The PHOSITA would have had a reasonable expectation of success because of the known doses of mg/kg of GNX to treat seizures three times a day as per US Pub 454, where average weights of humans are known, as per Walpole.
Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over US 2019/0160078 A1, as evidenced by Walpole et al. The weight of nations: an estimation of adult human biomass BMC Public Health 2012, 12:439. Walpole and US Pub 078 are cited on the PTO-892 form.
Regarding claims 1-4, US Pub 078 discloses a method for treating seizure or an epilepsy disorder, where a pregnenolone steroid (example GNX) is administered 3 times a day, a liquid oral formulation. See paragraph 23. See also paragraph 19, where plasma levels of GNX are from 240 ng/ml to 400 ng/ml in a day at least about 6, 7, 8, 9, 10 or 12 hours. The “at least” about limitation encompasses the 70% or more of a 24 hour a day limitation of claim 1.
Per claims 3-4, US Pub 078 teaches administration of an oral suspension of GNX administered three times a day. See paragraph 401.
Regarding claim 5, US Pub 078 teaches the use of an oral capsule. See paragraph 434.
Note that US Pub 078 does not explicitly recite the limitation of 70% of a 24 hour day as required by claim 1. However, prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings paragraph 23 with those teachings of paragraph 19 to ensure that GNX plasma concentration is at least 100 ng/ml (240ng/ml as per paragraph 19) for at least 6-10 or 12 hour a day, where the at least number hours of paragraph 19, encompasses the claimed range limitation of 70% of a 24 hour day of claim 1.
The PHOSITA would have had a reasonable expectation of success because US Pub 078 teaches that such GNX plasma concentration level is “at least” its taught hours of 6-10 or 12 hours a day, encompassing the 70% of a 24 hour day limitation of claim 1.
Regarding claims 6-8 and the limitations of dose up 63 mg/kg/day, 1800 mg/day, 1500 mg/day, US Pub 078 discloses
initially administering a dose of ganaxolone to the patient in an amount from about 0.5 mg/kg/day to about 15 mg/kg/day; and
progressively increasing the dose of ganaxolone over the course of 4 weeks to an amount from about 18 mg/kg/day to about 60 mg/kg/day, wherein the total dose of ganaxolone is up to about 1800 mg/day. See claim 17.
Regarding claim 9 and diseases treated, US Pub 078 teaches treatment of Lennox-Gastaut syndrome (LGS) and Dravet Syndrome. See paragraph 18.
Regarding claims 10-13 and the limitations of reduction of seizures/major motor frequency from baseline (of about 20% or 35% or greater), US Pub 078 teaches an efficacy outcome includes the administration of GNX, where a proportion of subjects with ≥25%, 50% or 75% reduction in 28-day seizure frequency (individual seizures and seizures in clusters) compared with baseline. See paragraph 520.
Claims 14-15 are directed to the method wherein the subject and/or seizure activity in the subject is monitored by electroencephalogram (EEG). Regarding claims 14-15, US Pub 078 teaches such monitoring of seizures by EEG. See paragraph 269.
Regarding claim 16, US Pub 078 discloses a method for treating seizure or an epilepsy disorder, where a pregnenolone steroid (example GNX) is administered 3 times a day, as a liquid oral formulation. See paragraph 23. See also paragraph 19, where plasma levels of GNX are from 240 ng/ml to 400 ng/ml in a day at least about 6, 7, 8, 9, 10 or 12 hours. The “at least” about limitation encompasses the 75% or more of a 24 hour a day limitation of claim 16.
Note that US Pub 078 does not explicitly recite the limitation of 75% of a 24 hour day as required by claim 16. However, prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings paragraph 23 with those teachings of paragraph 19 to ensure that GNX plasma concentration is at least 100 ng/ml (240ng/ml as per paragraph 19) for at least 6-10 or 12 hour a day, where the at least number hours of paragraph 19, encompasses the claimed range limitation of 75% of a 24 hour day of claim 16.
The PHOSITA would have had a reasonable expectation of success because US Pub 078 teaches that such GNX plasma concentration level is “at least” its taught hours of 6-10 or 12 hours a day, encompassing the 75% of a 24 hour day limitation of claim 16.
Regarding claims 17-18, US Pub 078 teaches ranges that compass the claimed 500 mg or 600 mg of GNX administered 3 times a day. See paragraph 399 where it teaches GNX administered from about 450 mg/day to about 1800 mg/day, in three divided doses.
Claim 19 is directed to wherein about 200 mg to about 600 mg, about 300 mg to about 600 mg, about 400 mg to about 600 mg or about 500 mg to about 600 mg of ganaxolone is administered orally to the subject three times a day.
Regarding claim 19, US Pub 078 teaches GNX administered from about 200 mg/day to about 1800 mg/day, 450 mg/day to about 1800 mg/day, in three divided doses. See paragraph 399.
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 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 and 19-25 of U.S. Patent No. 11701367. See PTO-892 form for listing of reference patent.
The disclosure of claims 1-19 are discussed and incorporated herein.
The reference patent discloses the claimed method, where it teaches a method for treating tuberous sclerosis-related epilepsy comprising administering GNX to a subject in need (orally), three times a day, with a plasma concentration of at least about 100 ng/ml over a period of at least about 70% of a day. See claims 1, 5 and 12-13 The reference patent claims 2-5 and 14-17 disclose oral suspensions, tablets and capsules of GNX. Reference claims 6-11 and 19-24 disclose the claimed limitations of doses of 1800 mg per day; 1500 mg per day (500 mg 3 times a day); no more than about 63 mg/kg per day, or 21 mg/kg three times a day. Reference patent claim 25 teaches the claimed species of epilepsy, including an infantile spasm, a focal impaired awareness seizure, a focal seizure, or a generalized seizure. See claim 25.
Claims 1-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-60 of copending Application No. 18/591,515.
This is a provisional nonstatutory double patenting rejection.
The disclosure of claims 1-19 are discussed and incorporated herein.
The reference application discloses the claimed method, where it teaches a method for treating tuberous sclerosis-related epilepsy comprising administering GNX (or analogs thereof) to a subject in need (orally), three times a day, with a plasma concentration of at least about 100 ng/ml over a period of at least about 70% of a day; formulations of oral suspensions, tablets and capsules of GNX; the claimed limitations of doses of 1800 mg per day; 1500 mg per day (500 mg 3 times a day); no more than about 63 mg/kg per day, or 21 mg/kg three times a day; monitoring of subject and seizures by EEG; reductions in seizure frequency about 20% or 35% or greater relative to baseline; and seizure species such as infantile spasm, focal seizure and focal impaired awareness seizure and generalized seizure. See claims 1-60.
Conclusion and Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a CON of PCT/US21/61937 12/06/2021
PCT/US21/61937 has PRO 63/122,378 12/07/2020
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