Heparan sulphate which binds BMP2

Patent metadata

Field	Value
Publication number	US-10086044-B2
Application number	US-200913062364-A
Country	US
Kind code	B2
Filing date	Sep 11, 2009
Priority date	Sep 11, 2008
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

Abstract

The invention relates to heparan sulphate GAGs obtained by affinity chromatography using the heparin-binding domain of BMP2. The GAGs were obtained from osteoblast extracellular matrix and from a commercially available heparan sulfate (Celsus HS).

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% HS/BMP2 which is capable of specific binding to SEQ ID NO:1 or 6, and to BMP2, wherein the heparan sulphate composition is obtained by a method comprising:
(i) providing a solid support having polypeptide molecules adhered to the support, wherein the polypeptide consists of the amino acid sequence QAKHKQRKRLKSSCKRHP [SEQ ID NO:1]or QAKHKQRKRLKSSCKRH [SEQ ID NO:6];
(ii) contacting the polypeptide molecules with a heparan sulphate fraction obtained from mammalian tissue or extracellular matrix such that polypeptide-heparan sulphate complexes are allowed to form;
(iii) partitioning polypeptide-heparan sulphate complexes from the remainder of the mixture;
(iv) dissociating the heparan sulphate from the polypeptide-heparan sulphate complexes by disrupting the polypeptide-heparan sulphate complexes; and
(v) collecting the dissociated heparan sulphate,

wherein the composition is capable of improving bone fracture repair in a mammal compared to a corresponding untreated fracture.

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

3. The composition of claim 1 , wherein the scaffold is a gel.

4. The composition of claim 1 , wherein the scaffold is a hydrogel.

5. The composition of claim 1 , wherein the scaffold comprises ceramic.

6. The composition of claim 1 , wherein the scaffold comprises β-tricalcium phosphate (TCP).

7. The composition of claim 1 , wherein the scaffold comprises hydroxyapatite (HA).

8. The composition of claim 1 , wherein the scaffold comprises hyaluronic acid.

9. The composition of claim 1 , wherein the scaffold comprises demineralized bone matrix.

10. The composition of claim 1 , wherein the scaffold comprises calcium sulfate.

11. The composition of claim 1 , wherein the scaffold comprises collagen.

12. The composition of claim 1 , wherein the scaffold comprises fibrin.

13. The composition of claim 1 , wherein the scaffold is an allograft.

14. The composition of claim 1 , wherein the scaffold is an autograft.

15. The composition of claim 4 , wherein the hydrogel comprises carboxymethyl cellulose.

16. The composition according to claim 1 which binds to SEQ ID NO:1 with a K D of less than 1 μM.

17. The composition according to claim 1 wherein the HS/BMP2 is N-sulphated.

18. The composition according to claim 1 wherein the HS/BMP2 is 6-O-sulphated.

19. The composition according to claim 1 additionally comprising BMP2 protein.

Assignees

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

Inventors

• Cool Simon Mckenzie
• Nurcombe Victor
• Dombrowski Christian

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61L27/54

  Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)} · CPC title