# US 12,109,216 B2 · Methods for treating subjects with Prader-Willi syndrome or Smith-Magenis syndrome

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- Number: US 12,109,216 B2
- Document ID: US12109216B2
- Status: Granted
- Kind: B2
- Application number: 18/421,914
- Filed: 2024-01-24
- Published: 2024-06-27
- Granted: 2024-10-08
- Earliest claimed: 2014-11-14
- Assignees: Essentials, Inc.
- Applicants: Essentialis, Inc.
- Inventors: Neil M. Cowen
- Web page: https://patentgrep.com/patent/US12109216B2

## 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 increasing by at least 3% the lean body mass or the lean body mass/fat mass ratio in a subject having Prader-Willi Syndrome (PWS) or Smith-Magenis syndrome (SMS), said method comprising administering once daily to said subject effective amount of a KATP channel opener, or a pharmaceutically acceptable salt thereof;
wherein said KATP channel opener is diazoxide or a pharmaceutically acceptable salt thereof;
wherein said KATP channel opener, or a pharmaceutically acceptable salt thereof is formulated as an oral controlled release pharmaceutical composition;
wherein the administration of the KATP channel opener is sufficient to increase the lean body mass or lean body mass/fat mass ratio of the subject by at least 3% compared to the lean body mass or lean body mass/fat mass ratio of the subject prior to the start of the administration; and
wherein the subject's circulating ghrelin level is reduced by at least 15% after at least 10 weeks of administering the diazoxide, or a pharmaceutically acceptable salt thereof.

### Claim 2

A method of increasing by at least 3% the lean body mass or the lean body mass/fat mass ratio in a subject having Prader-Willi Syndrome (PWS) or Smith-Magenis syndrome (SMS), said method comprising administering once daily to said subject effective amount of a KATP channel opener, or a pharmaceutically acceptable salt thereof;
wherein said KATP channel opener is diazoxide or a pharmaceutically acceptable salt thereof;
wherein said KATP channel opener, or a pharmaceutically acceptable salt thereof is formulated as an oral controlled release pharmaceutical composition;
wherein the administration of the KATP channel opener is sufficient to increase the lean body mass or lean body mass/fat mass ratio of the subject by at least 3% compared to the lean body mass or lean body mass/fat mass ratio of the subject prior to the start of the administration; and
wherein the subject's circulating total cholesterol level is reduced by at least 4% after at least 10 weeks of administering the diazoxide, or a pharmaceutically acceptable salt thereof.

### Claim 3 (depends on 2)

The method of claim 2, wherein the subject's circulating total cholesterol level comprises circulating high-density lipoprotein cholesterol (HDL-C) and wherein the subject's circulating HDL-C level is increased by at least 25% after at least 10 weeks of administering the diazoxide, or a pharmaceutically acceptable salt thereof.

### Claim 4 (depends on 2)

The method of claim 2, wherein the subject's circulating total cholesterol level comprises circulating low-density lipoprotein cholesterol (LDL-C) and wherein the subject's circulating LDL-C level is reduced by at least 7% after at least 10 weeks of administering the diazoxide, or a pharmaceutically acceptable salt thereof.

### Claim 5 (depends on 2)

The method of claim 2, wherein the subject's circulating total cholesterol level comprises circulating non-high-density lipoprotein cholesterol (non-HDL-C) and wherein the subject's circulating non-HDL-C level is reduced by at least 13% after at least 10 weeks of administering the diazoxide, or a pharmaceutically acceptable salt thereof.