# US 12,178,823 B1 · Methods for treating subjects with Prader-Willi syndrome or Smith-Magenis syndrome

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- Number: US 12,178,823 B1
- Document ID: US12178823B1
- Status: Granted
- Kind: B1
- Application number: 18/824,811
- Filed: 2024-09-04
- Published: 2024-12-26
- Granted: 2024-12-31
- Earliest claimed: 2014-11-14
- Assignees: Essentialis, Inc.
- Applicants: Essentialis, Inc.
- Inventors: Neil M. Cowen
- Web page: https://patentgrep.com/patent/US12178823B1

## CPC

- A61K 31/549: having two or more nitrogen atoms in the same ring, e.g. hydrochlorothiazide
- A61K 9/00: Medicinal preparations characterised by special physical form {(nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12)}
- A61K 9/0004: {Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas}
- A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose}
- A61K 9/5026: {obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates}
- A61K 9/5042: {Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose}
- A61K 9/5047: {Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose}
- A61K 31/137: Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine {or methadone}
- A61K 31/155: Amidines ([IMAGE cpc-sch-A61K-1029.gif]), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A61K 31/551: having two nitrogen atoms, e.g. dilazep
- A61K 38/27: Growth hormone [GH], i.e. somatotropin
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/08: for glucose homeostasis (pancreatic hormones A61P5/48)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 285/18: 1,2,4-Thiadiazines; Hydrogenated 1,2,4-thiadiazines
- C07D 285/22: condensed with one six-membered ring
- A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
- 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Provided are immediate or prolonged administration of certain potassium ATP (KATP) channel openers, optionally in combination with growth hormone, to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving KATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of KATP channel openers that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are methods of co-administering KATP channel openers with other drugs (e.g., in combination with growth hormone) to treat diseases of humans and animals (e.g., Prader-Willi Syndrome (PWS), Smith-Magenis syndrome (SMS), and the like.

## Claims

### Claim 1

A method of treating a subject having Prader-Willi Syndrome (PWS), the method comprising administering to said subject for at least 10 weeks a pharmaceutical formulation comprising an effective amount of diazoxide, or a pharmaceutically acceptable salt thereof, wherein administration reduces one or more aggressive behaviors in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt is diazoxide choline.

### Claim 3 (depends on 1)

The method of claim 1, wherein said pharmaceutical formulation is administered orally.

### Claim 4 (depends on 1)

The method of claim 1, wherein the pharmaceutical formulation is an oral controlled release pharmaceutical formulation.

### Claim 5 (depends on 1)

The method of claim 1, further comprising administering human growth hormone to the subject.

### Claim 6 (depends on 1)

The method of claim 1, wherein said administering is carried out for one or more years.

### Claim 7 (depends on 1)

The method of claim 1, wherein the pharmaceutical formulation is administered once per day.

### Claim 8 (depends on 7)

The method of claim 7, wherein the pharmaceutically acceptable salt is diazoxide choline.

### Claim 9 (depends on 1)

The method of claim 1, wherein the administration of diazoxide, or a pharmaceutically acceptable salt thereof, is in an amount from about 0.1 mg/kg/day to about 20 mg/kg/day.

### Claim 10 (depends on 1)

The method of claim 1, wherein the administration of diazoxide, or a pharmaceutically acceptable salt thereof, is in an amount from about 1.5 mg/kg/day to about 5.1 mg/kg/day.

### Claim 11 (depends on 1)

The method of claim 1, wherein the administration of diazoxide, or a pharmaceutically acceptable salt thereof, is in an amount of about 2.4 mg/kg/day.

### Claim 12 (depends on 1)

The method of claim 1, wherein the administration of diazoxide, or a pharmaceutically acceptable salt thereof, is in an amount of about 3.3 mg/kg/day.

### Claim 13 (depends on 1)

The method of claim 1, wherein the administration of diazoxide, or a pharmaceutically acceptable salt thereof, is in an amount of about 4.2 mg/kg/day.

### Claim 14 (depends on 1)

The method of claim 1, wherein the administration of diazoxide, or a pharmaceutically acceptable salt thereof, is in an amount from about 5 mg/kg/day to about 10 mg/kg/day.

### Claim 15 (depends on 1)

The method of claim 1, wherein the subject is a pediatric patient.

### Claim 16 (depends on 1)

The method of claim 1, wherein hyperphagia of the subject is reduced by at least 10% after at least 10 weeks of administering the diazoxide, or a pharmaceutically acceptable salt thereof.

### Claim 17 (depends on 1)

The method of claim 1, wherein hyperphagia of the subject is reduced by at least 20% after at least 10 weeks of administering the diazoxide, or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 1)

The method of claim 1, wherein hyperphagia of the subject is reduced by at least 30% after at least 10 weeks of administering the diazoxide, or a pharmaceutically acceptable salt thereof.

### Claim 19 (depends on 8)

The method of claim 8, wherein the once-daily administration of diazoxide choline is in an amount from about 25 mg to about 100 mg.

### Claim 20 (depends on 8)

The method of claim 8, wherein the once-daily administration of diazoxide choline is in an amount from about 50 mg to about 180 mg.

### Claim 21 (depends on 8)

The method of claim 8, wherein the once-daily administration of diazoxide choline is in an amount from about 50 mg to about 275 mg.

### Claim 22 (depends on 8)

The method of claim 8, wherein the once-daily administration of diazoxide choline is in an amount from about 300 mg to about 500 mg.

### Claim 23 (depends on 8)

The method of claim 8, wherein the once-daily administration of diazoxide choline is in an amount from about 500 mg to about 2000 mg.

### Claim 24 (depends on 8)

The method of claim 8, wherein the once-daily administration of diazoxide choline is in an amount from about 25 mg to about 500 mg.