# US 10,245,281 B2 · Glycosaminoglycans

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- Number: US 10,245,281 B2
- Document ID: US10245281B2
- Status: Granted
- Kind: B2
- Application number: 14/814,680
- Filed: 2015-07-31
- Published: 2015-11-19
- Granted: 2019-04-02
- Earliest claimed: 2011-09-16
- Assignees: Agency for Science, Technology and Research
- Applicants: Agency for Science, Technology and Research
- Inventors: Simon Cool; Victor Nurcombe
- Web page: https://patentgrep.com/patent/US10245281B2

## CPC

- A61K 31/727: Heparin; Heparan
- A61K 31/737: Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate (A61K31/727 takes precedence)
- A61K 38/1866: {Vascular endothelial growth factor [VEGF]}
- A61L 27/34: Macromolecular materials
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C08B 37/0078: {Degradation products}
- A61L 2300/412: Tissue-regenerating or healing or proliferative agents
- 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
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)

## Abstract

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

## Claims

### 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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

### Claim 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.

### Claim 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.

### Claim 6 (depends on 5)

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.

### Claim 7 (depends on 1)

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

### Claim 8 (depends on 1)

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) collecting the dissociated glycosaminoglycans.

### Claim 9 (depends on 8)

The method of claim 8, wherein the mixture comprising glycosaminoglycans is a heparan sulphate preparation obtained from porcine mucosa.

### Claim 10 (depends on 4)

The method of claim 4 wherein the HS7 is capable of binding SEQ ID NO:1 or 2.

### Claim 11 (depends on 4)

The method of claim 4 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) collecting the dissociated glycosaminoglycans.

### Claim 12 (depends on 11)

The method of claim 11, wherein the mixture comprising glycosaminoglycans is a heparan sulphate preparation obtained from porcine mucosa.

### Claim 13 (depends on 5)

The method of claim 5 wherein the HS7 is capable of binding SEQ ID NO:1 or 2.

### Claim 14 (depends on 5)

The method of claim 5 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) collecting the dissociated glycosaminoglycans.

### Claim 15 (depends on 14)

The method of claim 14, wherein the mixture comprising glycosaminoglycans is a heparan sulphate preparation obtained from porcine mucosa.