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 .
Priority
This application filed on 11/27/2023, is a U.S. national stage application under 35 U.S.C. § 371 of Patent Cooperation Treaty Application No. PCT/US2022/031245, filed on 05/27/2022, which claims the priority benefit of U.S. Provisional Application No. 63/194,586, filed on 05/28/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 01/17/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Status of claims
The preliminary amendment filed on 06/10/2024, that amended claims 9-10, 25, 30 and 50, and canceled Claims 3-4, 6, 8, 13-14, 20, 22, 28-29, 32, 38, 40, 44, 46, 49, 51-52, 56, 59, 62 and 64, is acknowledged.
Claims 1-2, 5, 7, 9-12, 15-19, 21, 23-27, 30-31, 33-37, 39, 41-43, 45, 47-48, 50, 53-55, 57-58, 60-61, 63 and 65-67 are pending.
Election/Restriction
Applicant’s response filed on 04/14/2026 to Restriction/Election Requirement filed on 04/09/2026, is acknowledged. Applicant elected without traverse Group I drawn to a method of treating drug-resistant epilepsy in a subject in need of treatment thereof, comprising intranasally administering a therapeutically effective amount of ketamine, or a pharmaceutically acceptable salt thereof, to the subject. Claims 1-2, 5, 7, 10-12, 15-19, 21, 23-27, 30-31, 33-37, 39, 41-43, 45, 47-48, 50, 53-55, 57-58, 60-61, 63 and 65-67 read on the elected Group. Claim 9 of Group II are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Pursuant to the Election of Species Requirement, Applicant respectively elected without traverse a method of treating epilepsy by administering ketamine wherein the symptoms of the epilepsy are reduced. Claims 1, 11, 15-19, 21, 23-27, 43, 45, 47-48, 50, 63 and 65-67 read on the elected species. Claims 2, 5, 7, 10, 12, 15, 30-31, 33-37, 39, 41-42, 53-55, 57-58 and 60-61 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Thus, claims 1-2, 5, 7, 9-12, 15-19, 21, 23-27, 30-31, 33-37, 39, 41-43, 45, 47-48, 50, 53-55, 57-58, 60-61, 63 and 65-67 are pending with claims 2, 5, 7, 9-10, 12, 15, 30-31, 33-37, 39, 41-42, 53-55, 57-58 and 60-61 are withdrawn, and claims 1, 11, 16-19, 21, 23-27, 43, 45, 47-48, 50, 63 and 65-67 are currently under consideration.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation for “therapeutically effective amount”
Claim 1 recites “…, comprising intranasally administering a therapeutically effective amount of ketamine, …”
The instant specification defined the “therapeutically effective amount” as:
As used herein, a "therapeutically effective amount" of a drug is an amount effective to demonstrate a desired activity of the drug. In some embodiments, a therapeutically effective amount of ketamine is an amount effective to alleviate, i.e., observably reduce, the symptoms of drug-resistant epilepsy. [page 6].
The “therapeutically effective amount” is interpreted consistent with the specification.
Claim interpretation for “substantially no anesthesia”
Claim 16 recites “…, wherein the subject experiences substantially no anesthesia after intra-nasal administration of the ketamine.”
The instant specification described “substantially no anesthesia” as:
For purposes of clarification, "the subject experiences substantially no anesthesia" is understood to mean that the subject exhibits behaviors indicative of minimal to no anesthesia. [page 5].
Thus, “substantially no anesthesia” is interpreted consistent with the specification.
Objection to Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. The embedded hyperlink is on Page 5.
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.
Claims 1, 11, 16-19, 21, 23-27, 43, 45, 47-48, 50, 63, and 65-67 are rejected under 35 U.S.C. 103 as being unpatentable over M. During, et al. (US10765646B2, 09/08/2020 “During” cited in the IDS dated 01/17/2025) in view of Y. Fang et al. Seizure 30 (2015) 14–20 “Fang” cited in the IDS dated 01/17/2025).
During teaches methods of treating a developmental encephalopathy comprises administering to a patient in need thereof an effective amount of ketamine or a derivative thereof, wherein the developmental encephalopathy is Dravet syndrome, infantile spasms, catastrophic epilepsy, Lennox-Gastaut syndrome, West syndrome, early myoclonic encephalopathy, early-onset epileptic encephalopathy, epilepsy with myoclonic-atonic seizures, status epilepticus, and/or nonconvulsive status epilepticus, [col. 2, ln. 17-33], wherein ketamine is formulated for oral, parenteral or intranasal administration [col. 26, li. 11-13]. During teaches that the method is for treating epileptic aphasias, severe epilepsy, status epilepticus [col. 4, ln. 3-5, ln. 39, ln. 58], focal epilepsy and epilepsy [col. 5, ln. 12, ln. 36].
During teaches “a method of treating Lennox-Gastaut syndrome (LGS) comprising intranasally administering to a patient in need thereof a pharmaceutical composition comprising S-ketamine or a pharmaceutically acceptable salt thereof in an amount ranging from about 1 mg to about 100 mg,” wherein the s-ketamine is administered twice weekly. [During’s claim 1].
However, During does not teach that epilepsy is drug resistant epilepsy.
Fang teaches a method of treating multidrug-resistant status epilepticus by administering ketamine [Abstract]. Fang teaches that ketamine was effective and safe for the treatment of Refractory status epilepticus and that administration of ketamine halted seizures. [page 15, col. 1, last para.]. Fang teaches in one study 6 cases with drug-resistance epilepsy, including Lennox–Gastaut syndrome, pseudo-Lennox syndrome, progressive myoclonic epilepsy and myoclonic-astatic epilepsy, wherein all of the seizures remained prolonged despite the use of many anticonvulsants, and with the use of ketamine all of the patients experienced resolution within 24–48 h after the initiation of ketamine, resulting in a clear reduction in epileptiform discharges on EEG and improvement of the mental state of the patients. [page 15, col. 2, 1st para.].
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of instantly claimed invention to intranasally administering a therapeutically effective amount of ketamine for treating drug resistant epilepsy in view of the teaching of Fang. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because Fang teaches that ketamine is effective and safe for treating multidrug-resistant epilepsy in children and adults; Fang teaches that administration of ketamine resolved and halted seizures for 53/60 patients with drug resistant epilepsy [page 15, col. 1, 2nd para.]; Fang teaches that administration of ketamine resulted in a clear reduction in epileptiform discharges on EEG and improvement of the mental state of the patients with drug resistant epilepsy; and use of ketamine is effective with no side effects were recorded during ketamine treatment. [page 15, col. 2, 1st para.]. One of ordinary skill in the art would have been motivated to treat drug resistant epilepsy by administering ketamine intranasally because During teaches treatment of epilepsy by administering ketamine intranasally, and teaches the significant impact of seizure in patient’s life and the limited of treatment options [col. 2, ln. 1-13], and Fang teaches that drug resistant epilepsy cannot be resolved in terms of clinical manifestations or epileptiform discharges following the rational administration of anticonvulsants [page 14, col. 1, 1st para.]. Therefore, the combination of During and Fang teach each and every limitation of claim 1.
Intranasal administration twice weekly reads on claim 19 “multiple intra-nasal doses of ketamine as spaced apart intervals”.
S-ketamine is another name for esketamine, thus, During meets claim 47.
The combination of During and Fang meets each and every structural/method step limitation of claims 11, 48, 50, 63 and 65 recitations of:
Claim 11 “… wherein after intranasally administering the ketamine the frequency, severity, and/or duration of one or more symptoms of the epilepsy is reduced.”
Claim 48 … wherein after intranasally administering the ketamine the frequency of seizures is reduced.
Claim 50 … wherein the reduction in seizure frequency is at least about 10%.
Claim 63 …wherein the Quality of Life in Epilepsy Inventory-10 (QOLIE-10) score of the subject is lower after administering the ketamine.
Claim 65 … wherein the QOLIE -10 score is at least 30% lower after administering the ketamine.
are inherently met by the administration of 32.3 mg ketamine to subjects as taught by During and Fang because they necessarily flow from the administration. MPEP § 2112. Furthermore, claim scope is not limited by claim language that does not limit a claim to a particular structure. MPEP § 2111.04 (citing In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005) (whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited). The above claim 11, 48, 50, 63 and 65 limitations do not limit the method steps in any fashion, but merely reflect the intended result of the claimed administration. Moreover, During teaches that effective treatment is established by showing reduction in the frequency of symptoms after a period of time compared with baseline. [col. 37, ln. 52-63]. During teaches that efficacy of ketamine measures by reduction in symptoms, wherein therapeutically effective amount of ketamine alleviate the symptom of a developmental encephalopathy such as reducing the frequency or severity of seizures, reducing behavior abnormalities, improving behavior, improving movement and balance issues, orthopedic conditions, alleviating delayed language and speech issues, improving growth and nutrition issues, reducing sleeping difficulties, chronic infections, alleviating sensory integration disorders, and disruptions of the autonomic nervous system, or to provide a desired pharmacologic and/or physiologic effect. [col. 24, ln. 55-65, col. 38, ln. 12, ln. 55-56].
With regard to claim 21, During teaches that ketamine is formulated with carrier includes diluents [col. 26, ln. 47].
With regard to claim 23, During teaches that the ketamine formulation can include water-soluble amino acid glycine. [col. 30, ln. 1-2].
With regard to claims 24 and 25, the patient is administered about 0.1 mg/kg to about 10.0 mg/kg, about 0.1 mg/kg to about 5.0 mg/kg of ketamine or a derivative thereof. 32,3 mg calculates to 0.5 mg/kg for human patient with an average weight of 60 kg (32.3mg/60kg = 0.53 mg/kg). Thus, During’s dose of 32.3 meets claim 24 and 25 limitations.
With regard to claim 26, During teaches that ketamine is administered once weekly or twice weekly. [col. 24, ln. 24].
With regard to claim 31, During teaches that ketamine is formulated in suspensions. [col. 26, ln. 19].
With regard to claims 16-18, during teaches internasal administration of 32.3 mg of ketamine for treating an epilepsy [During’s claim 6]. During teaches that for 12-25 minutes of surgical anesthesia a 6.5-13 mg/kg may be given intramuscularly. [col. 1, ln. 39-41]. (6.5-13 mg/kg calculates to 390-780 mg in human with average weight of 60 kg). Thus, one of ordinary skill in the art would reasonably presume that administering 32.3 mg of ketamine would necessarily results in substantially no anesthesia, and that the amount of 32.3 mg is a sub-anesthetic dose of ketamine. During and Fang teaches a substantially identical method as claimed with same amount of ketamine. As such, it is reasonable to presume that the resulting substantially no anesthesia is inherently produced by administering 32.3 mg of ketamine. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112. Claim 18 is met because During teaches that 4.5mg/kg of ketamine is use for induction of 5-10 minutes of surgical anesthesia. [col. 1, ln. 39-40]. 4.5 mg/kg calculates to 270 mg for human with an average weight of 60 mg. 10%-30% of 270 mg is calculates to 27mg-81mg. Thus, During dose of 32.3 mg reads on claim 18.
With regard to claims 27 and 43, During teaches that ketamine is administered twice weekly. [col. 24, ln. 24]. During teaches that in an embodiment ketamine is administered at dosages ranging from about 0.1 mg / kg and about 10 mg / kg of body weight of a patient in need thereof at least once a day. [col. 23, ln. 55-59]. Administering ketamine at least once daily reads on 2 time weekly, three times weekly, four times weekly etc. One of ordinary skill in the art would have been motivated to modify ketamine administration from twice weekly to three times weekly because during teaches that ketamine administered twice weekly or three times weekly, four times weekly etc. The optimization of dosing frequency is taught by During. Moreover, the optimization of dosing frequency for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences. It has been held that the selection of optimal parameters of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05.
With regard to claims 66 and 67, During discloses that in embodiments, methods of treating development encephalopathies include administration of ketamine in combination with one or more other active compounds. The combination therapies can include administration of the active agents together in the same admixture, or in separate admixtures. In embodiments, the pharmaceutical composition includes two, three, or more active agents. In embodiments, the combinations result in a more than additive effect on the treatment of the disease or disorder. Thus, treatment is provided of a developmental encephalopathy with a combination of agents that combined provide a synergistic effect that enhances efficacy. [col. 25, ln. 56 col. 26 ln. 2].
With regard to claim 45, Fang teaches that in one study, ketamine is administered to patient when anti-epileptic drugs had failed and seizures had persisted for 12 days, and the seizures were completely halted in 4 patients. [page 18, col. 1, 1st para.]. Thus, ketamine has been administered during seizures. During and Fand teaches a method of treating drug-resistant epilepsy in a subject in need of treatment thereof, comprising intranasally administering a therapeutically effective amount of ketamine, wherein ketamine administered during seizures. During and Fang are silent on transitioning to a postictal state or a normal state within about 10 minutes after administration of the ketamine, but otherwise teaches a substantially identical method as claimed. As such, it is reasonable to presume that the resulting transitioning to a postictal state or a normal state is inherently within about 10 minutes after administration of the ketamine. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
Conclusion
Claims 1, 11, 16-19, 21, 23-27, 43, 45, 47-48, 50, 63, and 65-67 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm.
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, James H Alstrum-Acevedo can be reached at 571-272-5548. 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.
/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
Prosecution Insights