Heparan sulphates

Patent metadata

Field	Value
Publication number	US-10596296-B2
Application number	US-201515307407-A
Country	US
Kind code	B2
Filing date	Apr 30, 2015
Priority date	Apr 30, 2014
Publication date	Mar 24, 2020
Grant date	Mar 24, 2020

Abstract

A heparan sulphate that binds TGPβ1 is disclosed.

First claim

The invention claimed is:

1. A method of treating a disease, condition or injury to tissue in a patient, the method comprising administration of a therapeutically effective amount of heparan sulphate HS16 to the patient leading to repair or regeneration of the tissue, wherein the heparan sulphate HS16 consists of heparan sulfate chains isolated from their core protein, which binds to a peptide or polypeptide consisting of the amino acid sequence RKDLGWKWIHEPKGYH (SEQ ID NO:1), wherein
the disease, condition or injury to tissue is treatable by the growth, proliferation, or differentiation of new tissue; and
the disaccharide composition of heparan sulphate HS16, following digestion with heparin lyases I, II and III and then subjecting the resulting disaccharide fragments to HPLC analysis, comprises:

Disaccharide
Normalised weight percentage

ΔUA,2S-GlcNS,6S
14.75 ± 3.0

ΔUA,2S-GlcNS
 4.58 ± 2.0

ΔUA-GlcNS,6S
12.98 ± 3.0

ΔUA-GlcNS
22.24 ± 3.0

ΔUA,2S-GlcNAc
 0.56 ± 0.5

ΔUA-GlcNAc,6S
12.63 ± 3.0

ΔUA-GlcNAc
32.26 ± 3.0.

2. The method of claim 1 , wherein the heparan sulphate HS16is administered to tissue at or surrounding a wound or at a location on the patient's body at which regeneration or repair of tissue is required.

3. The method of claim 1 , wherein the method further comprises administering TGβ1protein to the patient.

4. A method of treating a disease, condition or injury to tissue in a patient, the method comprising surgically implanting a biocompatible implant or prosthesis, which implant or prosthesis comprises a biomaterial and heparan sulphate HS16, into tissue of the patient at or surrounding the site of the disease, condition or injury leading to repair or regeneration of the tissue, wherein the heparan sulphate HS16consists of heparan sulfate chains isolated from their core protein, which binds to a peptide or polypeptide consisting of the amino acid sequence RKDLGWKWIHEPKGYH (SEQ ID NO:1), wherein
the disease, condition, or injury to tissue is treatable by growth, proliferation, or differentiation of new tissue; and
the disaccharide composition of heparan sulphate HS16, following digestion with heparin lyases I, II and III and then subjecting the resulting disaccharide fragments to HPLC analysis, comprises:

Normalised

Disaccharide
weight percentage

ΔUA,2S-GlcNS,6S
14.75 ± 3.0 

ΔUA,2S-GlcNS
4.58 ± 2.0 

ΔUA-GlcNS,6S
12.98 ± 3.0 

ΔUA-GlcNS
22.24 ± 3.0 

ΔUA,2S-GlcNAc
0.56 ± 0.5 

ΔUA-GlcNAc,6S
12.63 ± 3.0 

ΔUA-GlcNAc
 32.26 ± 3.0. 

5. The method of claim 1 , wherein the disaccharide composition of heparan sulphate HS16, following digestion with heparin lyases I, II and III and then subjecting the resulting disaccharide fragments to HPLC analysis, comprises:

Disaccharide
Normalised weight percentage

ΔUA,2S-GlcNS,6S
14.75 ± 1.0

ΔUA,2S-GlcNS
 4.58 ± 0.4

ΔUA-GlcNS,6S
12.98 ± 1.0

ΔUA-GlcNS
22.24 ± 1.6

ΔUA,2S-GlcNAc
 0.56 ± 0.4

ΔUA-GlcNAc,6S
12.63 ± 1.0

ΔUA-GlcNAc
32.26 ± 1.6.

6. The method of claim 1 , wherein the heparan sulphate HS16is obtained by a method comprising:
(i) providing a solid support having polypeptide molecules adhered to the support, wherein the polypeptide comprises a heparin-binding domain having the amino acid sequence RKDLGWKWIHEPKGYH (SEQ ID NO:1);
(ii) contacting the solid support with a mixture comprising glycosaminoglycan such that polypeptide-glycosaminoglycan complexes are allowed to form;
(iii) partitioning polypeptide-glycosaminoglycan complexes from the remainder of the mixture;
(iv) dissociating glycosaminoglycans from the polypeptide-glycosaminoglycan complexes; and
(v) collecting the dissociated glycosaminoglycans.

7. The method of claim 1 , wherein administration is by injection.

8. The method of claim 1 , wherein the heparan sulphate HS16is formulated for administration by injection.

9. The method of claim 1 , wherein the heparan sulphate HS16is formulated with a pharmaceutically acceptable carrier, adjuvant, excipient or diluent.

10. The method of claim 1 , wherein the tissue is a connective tissue selected from cartilage, bone, tendon, ligament, skin, and corneal tissue.

11. The method of claim 1 , wherein the tissue is ca

Assignees

• Agency Science Tech & Res

Inventors

• Cool Simon
• Nurcombe Victor
• Lee Jonathan

Classifications

• A61K31/727

  Heparin; Heparan · CPC title

• A61L15/44

  Medicaments · CPC title

• A61L15/60

  Liquid-swellable gel-forming materials, e.g. super-absorbents · CPC title

• A61L27/52

  Hydrogels or hydrocolloids · CPC title

• A61L27/54

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