# US 10,245,301 B2 · Glycosaminoglycans

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- Number: US 10,245,301 B2
- Document ID: US10245301B2
- Status: Granted
- Kind: B2
- Application number: 15/262,895
- Filed: 2016-09-12
- Published: 2016-12-29
- Granted: 2019-04-02
- Earliest claimed: 2008-09-11
- Assignees: Agency for Science, Technology and Research
- Applicants: Agency for Science, Technology and Research
- Inventors: Simon McKenzie Cool; Victor Nurcombe; Christian Dombrowski
- Web page: https://patentgrep.com/patent/US10245301B2

## CPC

- A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor}
- A61K 31/727: Heparin; Heparan
- A61K 31/737: Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate (A61K31/727 takes precedence)
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61L 27/26: Mixtures of macromolecular compounds
- A61L 27/365: {Bones}
- A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells}
- A61L 27/3847: {Bones}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- B01D 15/3823: {of other types, e.g. avidin, streptavidin or biotin}
- C07K 14/51: Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
- C08B 37/0003: {General processes for their isolation or fractionation, e.g. purification or extraction from biomass}
- C08B 37/0075: {Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof}
- C12N 5/0663: {Bone marrow mesenchymal stem cells (BM-MSC)}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61L 2300/236: Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
- A61L 2300/252: Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- A61L 2300/414: Growth factors
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- C12N 2501/155: Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
- C12N 2501/90: Polysaccharides
- 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
- B01D: SEPARATION (separating solids from solids by wet methods B03B, B03D; by pneumatic jigs or tables B03B; by other dry methods B07; magnetic or electrostatic separation of solid materials from solid materials or fluids, separation by high-voltage electric fields B03C; centrifuges, vortex apparatus B04; presses per se for squeezing-out liquid from liquid-containing material B30B9/02; treatment of water C02F, e.g. softening by ion-exchange C02F1/42; {arrangements of air intake cleaners in gas turbine plants F02C7/05} ; arrangements or mounting of filters in air-conditioning, air-humidification or ventilation F24F13/28)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

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

## Claims

### Claim 1

A method of treatment of injury or disease, the method comprising administering, to an individual in need thereof, 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, and which 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 method comprises the repair and/or regeneration of bone.

### Claim 2 (depends on 1)

The method of claim 1 wherein the method is for the treatment of bone defect or bone fracture.

### Claim 3 (depends on 2)

The method of claim 2 wherein the method is a treatment of a fracture of a long bone, short bone, flat bone, irregular bone or sesamoid bone.

### Claim 4 (depends on 2)

The method of claim 2 wherein the method is a treatment of a fracture or defect of a skeletal bone, bone of the cranio-facial region, bone of the axial skeleton, appendicular bone or bone of the pelvic skeleton.

### Claim 5 (depends on 4)

The method of claim 4 wherein the method is a treatment of a fracture or defect of a bone of the head, neck, face, jaw, nose or cheek.

### Claim 6 (depends on 1)

The method of claim 1 wherein the method is for the repair or regeneration of bone during dental or facial or cranial surgery, or a spinal disc fusion treatment.

### Claim 7 (depends on 2)

The method of claim 2 wherein the bone defect or bone fracture is a critical or non-union bone defect regeneration, compression fracture, compacted fracture, spiral fracture, complete and incomplete fractures, transverse, linear and oblique fractures or comminuted fractures.

### Claim 8 (depends on 1)

The method of claim 1 wherein the method is for the treatment of osteoporosis or osteoarthritis.

### Claim 9 (depends on 1)

The method of claim 1, wherein the method involves administering the HS/BMP2 directly to the site of injury or disease in order to stimulate the growth, proliferation and/or differentiation of new tissue to effect a repair of the injury or to cure or alleviate the disease condition.

### Claim 10 (depends on 2)

The method of claim 2, wherein the method involves injecting HS/BMP2 to the tissue surrounding the fracture.

### Claim 11 (depends on 1)

The method of claim 1 wherein the method involves surgically implanting a biocompatible implant or prosthesis comprising HS/BMP2.

### Claim 12 (depends on 1)

The method of claim 1, wherein the method further comprises administering mesenchymal stem cells to the patient.

### Claim 13 (depends on 1)

The method of claim 1, wherein the method further comprises administering BMP2 to the patient.

### Claim 14 (depends on 1)

The method according to claim 1 wherein the HS/BMP2 binds to SEQ ID NO:1 with a KD of less than 1 μM.
