# US 7,608,281 B2 · Composition and use of RAR antagonists for promoting chondrogenesis

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- Number: US 7,608,281 B2
- Document ID: US7608281B2
- Status: Granted
- Kind: B2
- Application number: 11/652,820
- Filed: 2007-01-12
- Published: 2007-06-14
- Granted: 2009-10-27
- Earliest claimed: 2007-01-12
- Assignees: T. Michael Underhill
- Inventors: Tully Michael Underhill; Andrea Dawn Weston
- Web page: https://patentgrep.com/patent/US7608281B2

## CPC

- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 31/196: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
- A61K 31/202: having three or more double bonds, e.g. linolenic (eicosanoids, e.g. leukotrienes A61K31/557)
- A61K 31/203: Retinoic acids {; Salts thereof}
- A61K 31/235: having an aromatic ring attached to a carboxyl group
- A61K 31/351: not condensed with another ring
- A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)}
- A61K 31/381: having five-membered rings
- A61K 31/382: having six-membered rings, e.g. thioxanthenes (thiothixene A61K31/496)
- A61K 31/655: Azo (—N=N—), diazo (=N2), azoxy (>N—O—N< or N(=O)—N<), azido (—N3) or diazoamino (—N=N—N<) compounds
- A61K 31/665: having oxygen as a ring hetero atom, e.g. fosfomycin
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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

The invention provides compositions comprising a RAR antagonist for promoting chondrogenesis and to methods employing such compositions for treating cartilage and associated bone abnormalities resulting from injury or disease and for ex vivo tissue engineering.

## Claims

### Claim 1

A method for treating degenerative joint disease characterized by cartilage degeneration comprising:
delivering a therapeutically effective amount of an RAR antagonist to the site of disease to stimulate chondrogenesis at said site of disease, wherein said RAR antagonist is provided within a composition comprising a pharmaceutically acceptable carrier and a chondrogenic stimulator.

### Claim 2 (depends on 1)

The method according to claim 1, wherein said chondrogenic stimulator is a protein selected from the group consisting of a bone morphogenetic protein (BMP), an osteogenic protein (OP), and combinations thereof.

### Claim 3 (depends on 2)

The method according to claim 2, wherein said osteogenic protein is OP-1.

### Claim 4 (depends on 1)

The method according to claim 1, wherein said composition is provided as a solution, suspension, gel, matrix, cream, film, paste, capsule, pill or tablet, or is encapsulated within liposomes.

### Claim 5 (depends on 1)

The method according to claim 1, wherein said composition is for intra-articular injection.

### Claim 6 (depends on 1)

The method according to claim 1, wherein said composition is provided within a biodegradable implantable matrix.

### Claim 7 (depends on 1)

The method according to claim 1, wherein said composition is for the treatment of arthritis, abnormal cartilage formation and/or cartilage defects.

### Claim 8 (depends on 1)

The method according to claim 1, wherein said RAR antagonist antagonizes one or more of RARα, RARβ and RARγ.

### Claim 9

A method for treating degenerative joint disease characterized by cartilage degeneration comprising:
delivering a therapeutically effective amount of an RAR antagonist to the site of disease to stimulate chondrogenesis at said site of disease, wherein said method comprises implanting a device comprising:
(a) an implantable biocompatible carrier; and
(b) the RAR antagonist dispersed within or on said carrier,
wherein said carrier comprises demineralized bone, protein-extracted bone, particulate bone, allogenic bone, xenogenic bone or combinations thereof.

### Claim 10 (depends on 9)

The method according to claim 9, wherein said device comprises a biodegradable sponge.

### Claim 11 (depends on 9)

The method according to claim 9, wherein said device is a prosthetic for repairing an orthopaedic defect, injury or anomaly in a vertebrate.

### Claim 12 (depends on 11)

The method according to claim 11, wherein said device has a surface region implantable adjacent or within a target tissue and said RAR antagonist is disposed on said surface region in an amount sufficient to promote enhanced chondrogenesis and associated bone tissue growth into said surface.

### Claim 13 (depends on 9)

The method according to of claim 9, wherein said RAR antagonist is provided within a composition further comprising a pharmaceutically acceptable carrier and a chondrogenic stimulator.

### Claim 14 (depends on 13)

The method according to claim 13, wherein said chondrogenic stimulator is a protein selected from the group consisting of a bone morphogenetic protein (BMP), an osteogenic protein (OP), and combinations thereof.

### Claim 15 (depends on 2)

The method according to claim 2, wherein said BMP is selected from the group consisting of BMP-2, BMP-4 and BMP-5.