# US 10,500,203 B2 · Compositions and methods for treating bone diseases

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- Number: US 10,500,203 B2
- Document ID: US10500203B2
- Status: Granted
- Kind: B2
- Application number: 15/758,083
- Filed: 2016-08-23
- Published: 2018-08-30
- Granted: 2019-12-10
- Earliest claimed: 2015-09-09
- Assignees: Rush University Medical Center
- Applicants: Rush University Medical Center
- Inventors: Di Chen; Rong Xie
- Web page: https://patentgrep.com/patent/US10500203B2

## CPC

- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A01K 67/0276: Knock-out vertebrates
- A61K 9/0034: {Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants}
- A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465)
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 31/52: Purines, e.g. adenine
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A01K 2217/075: inducing loss of function, i.e. knock out
- A01K 2217/077: heterozygous knock out animals displaying phenotype
- A01K 2227/105: Murine
- A01K 2267/0306: Animal model for genetic diseases
- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A61K 2123/00: Preparations for testing in vivo
- 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)
- A01K: ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Certain aspects of the present invention generally relate to compositions and methods for treating a bone disease, for example a genetic bone disease. In one embodiment the bone disease is fibular hemimelia, proximal femoral focal deficiency, tarsal coalition or humeroradial synostosis.

## Claims

### Claim 1

A method for treating an orthopedic disease, comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an inhibitor of beta-catenin signaling, wherein the orthopedic disease is fibular hemimelia.

### Claim 2 (depends on 1)

The method of claim 1, wherein the composition is administered in-utero.

### Claim 3 (depends on 2)

The method of claim 2, wherein the composition is administered in the third trimester of pregnancy.

### Claim 4 (depends on 1)

The method of claim 1, wherein the composition is administered after birth of the subject.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject is a subject having an elevated level of beta-catenin signaling.

### Claim 6 (depends on 1)

The method of claim 1, wherein the inhibitor of beta-catenin signaling is selected from the group consisting of LGK-974, IWP-2, iCRT 3, iCRT 14, ICG 001, XAV-939, KY02111, and a combination of at least two thereof.

### Claim 7 (depends on 6)

The method of claim 6, wherein the inhibitor of β-catenin signaling is iCRT 14.

### Claim 8 (depends on 6)

The method of claim 6, wherein the inhibitor of β-catenin signaling is XAV-939.

### Claim 9 (depends on 6)

The method of claim 6, wherein the inhibitor of β-catenin signaling is LGK-974.

### Claim 10 (depends on 6)

The method of claim 6, wherein the inhibitor of β-catenin signaling is iCRT 3.

### Claim 11 (depends on 6)

The method of claim 6, wherein the inhibitor of β-catenin signaling is IWP-2.

### Claim 12 (depends on 6)

The method of claim 6, wherein the inhibitor of β-catenin signaling is ICG 001.

### Claim 13 (depends on 6)

The method of claim 6, wherein the inhibitor of β-catenin signaling is KY02111.