# US 7,612,050 B2 · Drug for the treatment of osteonecrosis and for the management of patients at risk of developing osteonecrosis

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- Number: US 7,612,050 B2
- Document ID: US7612050B2
- Status: Granted
- Kind: B2
- Application number: 12/191,264
- Filed: 2008-08-13
- Published: 2009-01-01
- Granted: 2009-11-03
- Earliest claimed: 2001-02-06
- Assignees: The Royal Alexandra Hospital for Children
- Inventors: David Graham Little; Nicholas Charles Smith
- Web page: https://patentgrep.com/patent/US7612050B2

## CPC

- A61K 31/663: Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid
- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 38/1825: {Fibroblast growth factor [FGF]}
- A61K 38/1841: {Transforming growth factor [TGF]}
- A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor}
- A61K 38/30: Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 {(insulin-like growth factor binding protein A61K38/1754)}
- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- 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 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 41/00: Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61L 2300/252: Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- A61L 2300/414: Growth factors
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A bisphosphonate for the treatment of osteonecrosis and/or osteonecrosis dissecans. The drug may further he used to prevent the onset of osteonecrosis and/or osetonecrosis dissecans and any complications associated with both diseases.

## Claims

### Claim 1

A method of treating a patient with osteonecrosis, the method comprising:
administering to the patient a drug consisting of at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof.

### Claim 2 (depends on 1)

The method of claim 1 wherein the at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is zoledronic acid or any pharmaceutically acceptable salt or ester thereof.

### Claim 3 (depends on 1)

The method of claim 1 wherein the bisphosphonate is selected from the group consisting of pamidronate, alendronate, etidronate, clodronate, risedronate, tiludronate, ibandronate, incadronate, minodronate, olpadronate, neridronate, EB-1053 or any pharmaceutically acceptable salt, hydrate or ester thereof.

### Claim 4 (depends on 1)

The method of claim 1, wherein said administering is intravenous.

### Claim 5 (depends on 1)

The method of claim 1, wherein said administering is orally, subcutaneously, intramuscularly, transdermally, or topically.

### Claim 6 (depends on 1)

The method of claim 1, wherein said administering is by local administration to a target treatment site.

### Claim 7 (depends on 6)

The method of claim 6, wherein said administering is prior to, at the time of, or after, a core decompression procedure.

### Claim 8 (depends on 6)

The method of claim 6, wherein said administering is administered prior to, at the time of, or after, a bone grafting procedure.

### Claim 9 (depends on 6)

The method of claim 6, wherein said administering is prior to, at the time of, or after, a vascularised bone grafting procedure.

### Claim 10 (depends on 6)

The method of claim 6, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is administered together with a local delivery system.

### Claim 11 (depends on 10)

The method of claim 10, wherein the local delivery system is a bone graft substitute or extender, or autogenous or allogenic bone graft.

### Claim 12 (depends on 2)

The method of claim 2, wherein said administering is parenterally in a dose range of 0.25 mg to 12 mg in an adult patient or 0.005 mg/kg to 0.5 mg/kg in a child up to every three months.

### Claim 13 (depends on 2)

The method of claim 2, wherein said administering is four-weekly, six-weekly or every two months.

### Claim 14 (depends on 2)

The method of claim 2, wherein said administering is every twelve months.

### Claim 15 (depends on 2)

The method of claim 2, wherein said administering is parenterally as a single dose.

### Claim 16 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is pamidronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and wherein administering is parenterally in a dose range of 15 to 90 mg every one to six months in an adult patient or 0.25 mg/kg to 3.0 mg/kg every one to six months in a child.

### Claim 17 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is alendronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and wherein said administering is orally in a dose range from 2.5 mg to 50 mg per day or 10 mg to 300 mg per week for an adult patient and from 0.05 mg/kg to 1.0 mg/kg per day or 0.2 mg/kg to 6.0 mg/kg per week in a child.

### Claim 18 (depends on 3)

The method of claim 3 wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is alendronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and said administering is parenterally in a dose range of 0.25 mg to 30 mg every one to three months, or as a single dose.

### Claim 19 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is risedronate or any pharmaceutically acceptable salt, hydrate or ester thereof administered orally in a dose range of 2.5 mg to 60 mg per day or 10 mg to 300 mg per week in an adult patient or 0.05 mg/kg to 1.0 mg/kg per day or 0.25 mg/kg to 7.0 mg/kg per week in a child.

### Claim 20 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is ibandronate or any pharmaceutically acceptable salt, hydrate or ester thereof administered parenterally in a dose range of 0.25 mg to 30 mg every one to three months, or as a single dose.

### Claim 21 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is ibandronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and said administering is orally in a dose range of 2.5 mg to 30 mg per day, or 15 mg to 210 mg per week in an adult patient or 0.05 mg/kg to 0.5 mg/kg per day or 0.25 mg/kg to 2.5 mg/kg per week for a child.

### Claim 22 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is incadronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and said administering is parenterally in a dose range of 0.25 mg to 30 mg in an adult patient or 0.005 mg/kg to 0.6 mg/kg in a child, wherein said dose is administered every one to three months, or as a single dose.

### Claim 23 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is minodronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and said administering is parentally in a dose range of 0.25 mg to 30 mg every one to three months, or as a single dose.

### Claim 24 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is clodronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and said administering is orally in a dose range of 400 mg to 2400 mg per day or administered intravenously in dose ranges from 150 mg to 300 mg repeated daily for 2 to 5 days.

### Claim 25 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is etidronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and said administering is orally in a dose range of 100 mg to 400 mg per day in an adult or 5 mg to 20 mg/kg per day in a child.

### Claim 26 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is tiludronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and said administering is orally in a dose of 400 mg per day in an adult or 5 mg to 20 mg/kg per day in a child.

### Claim 27 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is olpadronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and wherein said administering is orally in a dose range of 50 mg to 400 mg per day in an adult or 1 mg/kg to 10 mg/kg in a child or administered intravenously every one to three months in dose ranges from 1 mg to 20 mg in an adult or 0.1 mg/kg to 0.5 mg/kg in a child.

### Claim 28 (depends on 3)

The method of claim 3, wherein said at least one bisphosphonate or any pharmaceutically acceptable salt, hydrate or ester thereof is neridronate or any pharmaceutically acceptable salt, hydrate or ester thereof, and said administering is parenterally in a dose range of 10 mg to 100 mg in an adult.