Glycosaminoglycans

Patent metadata

Field	Value
Publication number	US-9498494-B2
Application number	US-201213603569-A
Country	US
Kind code	B2
Filing date	Sep 5, 2012
Priority date	Sep 11, 2008
Publication date	Nov 22, 2016
Grant date	Nov 22, 2016

Abstract

Heparan sulphate HS/BMP2 is disclosed, together with the use of HS/BMP2 in the repair and regeneration of bone tissue.

First claim

The invention claimed is:

1. A composition comprising a solid or solidified scaffold coated or impregnated with a therapeutically effective amount of an isolated or substantially purified heparan sulphate composition comprising a heparan sulphate component, wherein the heparan sulphate component is at least 97% isolated or substantially purified heparan sulphate HS/BMP2, wherein following digestion with heparin lyases I, II and III and then subjecting the resulting disaccharide fragments to capillary electrophoresis analysis the heparan sulphate HS/BMP2 has a disaccharide composition comprising:

Normalised weight

Disaccharide
percentage

ΔHexUA,2SGlcNS,6S
14.8 ± 3.0

ΔHexUA,2S-GlcNS
 4.9 ± 2.0

ΔHexUA-GlcNS,6S
11.1 ± 3.0

ΔHexUA,2SGlcNAc,6S
 4.8 ± 2.0

ΔHexUA-GlcNS
22.2 ± 3.0

ΔHexUA,2S-GlcNAc
 1.1 ± 0.5

ΔHexUA-GlcNAc,6S
10.1 ± 3.0

ΔHexUA-GlcNAc
31.1 ± 3.0.

2. The composition of claim 1 wherein following digestion with heparin lyases I, II and III and then subjecting the resulting disaccharide fragments to capillary electrophoresis analysis the heparan sulphate HS/BMP2 has a disaccharide composition comprising:

Normalised weight

Disaccharide
percentage

ΔHexUA,2SGlcNS,6S
14.8 ± 1.0

ΔHexUA,2S-GlcNS
 4.9 ± 0.4

ΔHexUA-GlcNS,6S
11.1 ± 1.0

ΔHexUA,2SGlcNAc,6S
 4.8 ± 0.6

ΔHexUA-GlcNS
22.2 ± 3.0

ΔHexUA,2S-GlcNAc
 1.1 ± 0.4

ΔHexUA-GlcNAc,6S
10.1 ± 1.0

ΔHexUA-GlcNAc
31.1 ± 1.6.

3. The composition of claim 1 wherein the HS/BMP2 is capable of binding SEQ ID NO:1 or 6.

4. The composition of claim 1 wherein the solid or solidified scaffold is further coated or impregnated with BMP2 protein, mesenchymal stem cells, or a combination thereof.

5. The composition of claim 1 , wherein the solid or solidified scaffold is a gel.

6. The composition of claim 1 , wherein the solid or solidified scaffold is a hydrogel.

7. The composition of claim 1 , wherein the solid or solidified scaffold comprises ceramic.

8. The composition of claim 1 , wherein the solid or solidified scaffold comprises β-tricalcium phosphate (TCP).

9. The composition of claim 1 , wherein the solid or solidified scaffold comprises hydroxyapatite (HA).

10. The composition of claim 1 , wherein the solid or solidified scaffold comprises hyaluronic acid.

11. The composition of claim 1 , wherein the solid or solidified scaffold comprises demineralized bone matrix.

12. The composition of claim 1 , wherein the solid or solidified scaffold comprises calcium sulfate.

13. The composition of claim 1 , wherein the solid or solidified scaffold comprises collagen.

14. The composition of claim 1 , wherein the solid or solidified scaffold comprises fibrin.

15. The composition of claim 1 , wherein the solid or solidified scaffold is an allograft.

16. The composition of claim 1 , wherein the solid or solidified scaffold is an auto graft.

17. The composition of claim 6 wherein the hydrogel comprises carboxymethyl cellulose.

18. A method of treating a bone fracture in a patient, the method comprising administration of a therapeutically effective amount of HS/BMP2 according to claim 13 to the patient, thereby treating the bone fracture.

19. The method of claim 18 wherein the method comprises administering said HS/BMP2 to the tissue surrounding the fracture.

20. The method of claim 18 wherein the HS/BMP2 is formulated as a pharmaceutical composition or medicament comprising HS/BMP2 and a pharmaceutically acceptable carrier, adjuvant or diluent.

21. The method of claim 18 wherein the method further comprises administering BMP2 protein to the patient.

Assignees

• Cool Simon Mckenzie
• Nurcombe Victor
• Dombrowski Christian
• Agency Science Tech & Res

Inventors

• Cool Simon Mckenzie
• Nurcombe Victor
• Dombrowski Christian

Classifications

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61K31/726

  Glycosaminoglycans, i.e. mucopolysaccharides (chondroitin sulfate, dermatan sulfate A61K31/737) · CPC title

• A61L27/20

  Polysaccharides · CPC title

• A61K31/727 Primary

  Heparin; Heparan · CPC title

• A61K38/1875

  Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor · CPC title