# US 2019/0169619 A1 · Use of mir101 or mir128 in the treatment of seizure disorders

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- Number: US 2019/0169619 A1
- Document ID: US20190169619A1
- Status: Published application
- Kind: A1
- Application number: 16/211,309
- Filed: 2018-12-06
- Published: 2019-06-06
- Earliest claimed: 2017-12-06
- Assignees: Ovid Therapeutics Inc.
- Applicants: Ovid Therapeutics Inc.
- Inventors: Matthew DURING
- Web page: https://patentgrep.com/patent/US20190169619A1

## CPC

- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- A61K 9/0085: {Brain, e.g. brain implants; Spinal cord}
- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K 35/761: Adenovirus
- A61P 25/08: Antiepileptics; Anticonvulsants
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- C12N 2310/141: MicroRNAs, miRNAs
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12N 2330/51: Specially adapted vectors
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods of treating a seizure disorder in a patient in need thereof are provided which include delivering to the patient an effective amount of a composition that increases the level of microRNA-101 molecules in brain cells of the patient. Methods of treating a seizure disorder in a patient in need thereof are provided which include delivering to the patient an effective amount of a composition that increases the level of microRNA-128 molecules in brain cells of the patient. Methods of treating a seizure disorder in a patient in need thereof are provided which include administering a vector encoding microRNA-101, pri-miR101 or pre-miR101 to the patient. Methods of treating a seizure disorder in a patient in need thereof are provided which include administering a vector encoding microRNA-128, pri-miR128 or pre-miR128 to the patient. In embodiments, increased levels of microRNA-101 and/or microRNA-128 cause improvement in one or more symptoms of the seizure disorder.

## Claims

### Claim 1

A method of treating a seizure disorder in a patient in need thereof comprising administering to the patient an effective amount of a pharmaceutical composition that increases the level of microRNA-101 molecules in the patient's brain,

### Claim 2 (depends on 1)

The method according to claim 1, wherein the composition includes microRNA-101, pri-miR101 or pre-miR101.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the composition includes a vector including nucleic acid encoding microRNA-101, pri-miR101 or pre-miR101.

### Claim 4 (depends on 3)

The method according to claim 3, wherein after the administering, microRNA-101, pri-miR101 or pre-miR101 is expressed, and expression of microRNA-101, pri-miR101 or pre-miR101, in the patient is associated with reduced symptoms of the seizure disorder.

### Claim 5 (depends on 3)

The method according to claim 3, wherein the nucleic acid encoding microRNA-101, pri-miR101 or pre-miR101, is operably linked to a promoter selected from the group consisting of CAG promoter, CMV promoter, human synapsin 1 gene promoter (hSyn), dynorphin promoter, encephalin promoter and CaMKII promoter.

### Claim 6 (depends on 3)

The method according to claim 3 wherein the vector includes a woodchuck post-transcriptional regulatory element (WPRE).

### Claim 7 (depends on 3)

The method according to claim 3, wherein the vector includes a bovine growth hormone polyadenylation sequence (BGHpA).

### Claim 8 (depends on 3)

The method according to claim 3, wherein the vector includes a fluorescence reporter cassette.

### Claim 9 (depends on 3)

The method according to claim 3, wherein the vector is an adeno-associated virus (AAV).

### Claim 10 (depends on 9)

The method according to claim 9, wherein the adeno-associated virus is AAV1, AAV2, AAV4, AAV5, AAV7, AAV8, AAV9 or AAVRec3.

### Claim 11 (depends on 3)

The method according to claim 3, wherein the vector is a lentivirus.

### Claim 12 (depends on 3)

The method according to claim 3, wherein the vector is pAM/CBA-miR101-1-WPRE-BGHpA.

### Claim 13 (depends on 1)

The method according to claim 1, wherein the composition is delivered to a target location in the patient's brain.

### Claim 14 (depends on 1)

The method according to claim 1, wherein the composition is administered via a route selected from the group consisting of oral, buccal, sublingual, rectal, topical, intranasal, vaginal and parenteral.

### Claim 15 (depends on 1)

The method according to claim 1, wherein the seizure disorder is selected from the group consisting of epilepsy, epilepsy with generalized tonic-clonic seizures, epilepsy with myoclonic absences, frontal lobe epilepsy, temporal lobe epilepsy, occipital lobe epilepsy, parietal lobe epilepsy, Landau-Kleffner Syndrome, Rasmussen's syndrome, Dravet syndrome, Doose syndrome, CDKL5 disorder, infantile spasms (West syndrome), juvenile myoclonic epilepsy (JME), vaccine-related encephalopathy, intractable childhood epilepsy (ICE), Lennox-Gastaut syndrome (LGS), Rett syndrome, Ohtahara syndrome, CDKL5 disorder, childhood absence epilepsy, essential tremor, acute repetitive seizures, benign rolandic epilepsy, status epilepticus, refractory status epilepticus, super-refractory status epilepticus (SRSE), PCDH19 pediatric epilepsy, brain tumor induced seizures, hamartoma induced seizures, drug withdrawal induced seizures, alcohol withdrawal induced seizures, increased seizure activity and breakthrough seizures.

### Claim 16 (depends on 1)

The method according to claim 1, wherein the seizure disorder is characterized by focal seizures.

### Claim 17 (depends on 1)

The method according to claim 1, wherein the seizure disorder is focal cortical dysplasia.

### Claim 18 (depends on 1)

The method according to claim 1, wherein the method provides improvement in at least one symptom selected from the group consisting of ataxia, gait impairment, speech impairment, vocalization, involuntary laughter, impaired cognition, abnormal motor activity, clinical seizure, subclinical seizure, hypotonia, hypertonia, drooling, mouthing behavior, aura, convulsions, repetitive movements, unusual sensations, frequency of seizures and severity of seizures.

### Claim 19 (depends on 1)

The method according to claim 1, further comprising applying ultrasound to a target location in the patient's brain to enhance permeability of the patient's blood brain barrier at the target location, wherein the vector is delivered to the target location.

### Claim 20 (depends on 1)

The method of claim 1, wherein the composition includes a vector that is a non-viral vector.

### Claim 21 (depends on 1)

The method of claim 1, wherein the non-viral vector is a liposome mediated delivery vector.

### Claim 22 (depends on 1)

The method according to claim 1, further comprising applying ultrasound to a target location in the patient's brain to enhance permeability of the patient's blood brain barrier at the target location, wherein the composition is delivered to the target location.

### Claim 23

A vector comprising nucleic acid encoding microRNA-101, pri-miR101 or pre-miR101, under regulatory control of a CAG promoter, a woodchuck post-transcriptional regulatory element (WPRE) and a bovine growth hormone polyadenylation sequence (BGHpA).