Glycosaminoglycans

Patent metadata

Field	Value
Publication number	US-10245281-B2
Application number	US-201514814680-A
Country	US
Kind code	B2
Filing date	Jul 31, 2015
Priority date	Sep 16, 2011
Publication date	Apr 2, 2019
Grant date	Apr 2, 2019

Abstract

Heparan sulphate HS7 is disclosed, together with the use of HS7 in the growth and/or development and/or regeneration of tissue.

First claim

We claim:

1. A method of treating vascular disease, cardiovascular disease, heart disease, ischemia, ischemic disease, stroke, ischemic vascular disease, myocardial infarction, or a disease or condition characterised by decreased blood flow to tissues or organs due to blocked or partially blocked arteries in a patient, the method comprising administration of a therapeutically effective amount of isolated or substantially purified heparan sulphate HS7 to the patient, thereby stimulating or promoting growth of blood vessels in the patient;
wherein
HS7 is heparan sulphate having the disaccharide composition:

Disaccharide
Normalised weight percentage

ΔUA,2S-GlcNS,6S
11.08 ± 3.0

ΔUA,2S-GlcNS
 4.46 ± 2.0

ΔUA-GlcNS,6S
15.84 ± 3.0

ΔUA,2S-GlcNAc,6S
 4.76 ± 2.0

ΔUA-GlcNS
20.27 ± 3.0

ΔUA,2S-GlcNAc
 1.01 ± 0.5

ΔUA-GlcNAc,6S
10.63 ± 3.0

ΔUA-GlcNAc
31.95 ± 3.0

following digestion with heparin lyases I, II and III and then subjecting the resulting disaccharide fragments to capillary electrophoresis analysis; and
HS7 is heparin-free and provides high activating affinity for VEGF.

2. The method of claim 1 wherein the method comprises administering the HS7 to tissue at or surrounding a wound or location on the patient's body at which blood vessel growth is required.

3. The method of claim 1 wherein the method further comprises administering VEGF protein to the patient.

4. A method of treating a vascular disease, cardiovascular disease, heart disease, ischemia, ischemic disease, stroke, ischemic vascular disease, myocardial infarction, or a disease or condition characterised by decreased blood flow to tissues or organs due to blocked or partially blocked arteries in a patient, the method comprising surgically implanting a biocompatible implant or prosthesis, which implant or prosthesis comprises a biomaterial and HS7, into tissue of the patient at or surrounding the wound or location at which blood vessel growth is required,
wherein
HS7 is heparan sulphate having the disaccharide composition:

Disaccharide
Normalised weight percentage

ΔUA,2S-GlcNS,6S
11.08 ± 3.0

ΔUA,2S-GlcNS
 4.46 ± 2.0

ΔUA-GlcNS,6S
15.84 ± 3.0

ΔUA,2S-GlcNAc,6S
 4.76 ± 2.0

ΔUA-GlcNS
20.27 ± 3.0

ΔUA,2S-GlcNAc
 1.01 ± 0.5

ΔUA-GlcNAc,6S
10.63 ± 3.0

ΔUA-GlcNAc
31.95 ± 3.0

following digestion with heparin lyases I, II and III and then subjecting the resulting disaccharide fragments to capillary electrophoresis analysis; and
HS7 is heparin-free and provides high activating affinity for VEGF.

5. A method comprising administering isolated or substantially purified HS7 to vascular cells or vascular tissue in vivo, wherein growth of blood vessels is promoted.

6. The method of claim 5 wherein the HS7 has the disaccharide composition:

Disaccharide
Normalised weight percentage

ΔUA,2S-GlcNS,6S
11.08 ± 3.0

ΔUA,2S-GlcNS
 4.46 ± 2.0

ΔUA-GlcNS,6S
15.84 ± 3.0

ΔUA,2S-GlcNAc,6S
 4.76 ± 2.0

ΔUA-GlcNS
20.27 ± 3.0

ΔUA,2S-GlcNAc
 1.01 ± 0.5

ΔUA-GlcNAc,6S
10.63 ± 3.0

ΔUA-GlcNAc
31.95 ± 3.0

following digestion with heparin lyases, I, II and III and then subjecting the resulting disaccharide fragments to capillary electrophoresis analysis.

7. The method of claim 1 wherein the HS7 is capable of binding SEQ ID NO:1 or 2.

8. The method of claim 1 wherein the HS7 is 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 of SEQ ID NO:1;
(ii) contacting the polypeptide molecules with a mixture comprising glycosaminoglycans 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) co

Assignees

• Agency Science Tech & Res

Inventors

• Cool Simon
• Nurcombe Victor

Classifications

• A61K38/1866

  Vascular endothelial growth factor [VEGF] · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K31/727 Primary

  Heparin; Heparan · CPC title

• A61K31/737

  Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate (A61K31/727 takes precedence) · CPC title

• A61L27/54

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