Polypeptides containing β-tricalcium phosphate linkages and their use

Abstract

To provide a composition that significantly improves bone healing and accelerates tissue regrowth.SOLUTION: The present invention provides a chimeric polypeptide that comprises (i) one or more β-tricalcium phosphate (β-TCP)-binding sequence(s), wherein at least one of the one or more β-TCP-binding sequence(s) is selected from the group consisting of specific sequences and (ii) a mammalian growth factor. The present invention also provides a composition containing the chimeric polypeptide.SELECTED DRAWING: Figure 1A

Claims

1. It is a chimeric polypeptide, A β-tricalcium phosphate (β-TCP) bound peptide containing Sequence ID No. 22, which is conjugated to mammalian growth factor. A chimeric polypeptide containing...

2. The aforementioned mammalian growth factors include bone morphogenetic protein 2 (BMP-2), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), insulin-like growth factor (IGF-1), fibroblast growth factor (FGF), fibroblast growth factor 2 (FGF2), fibroblast growth factor 18 (FGF18), transforming growth factor α (TGF-α), transforming growth factor β (TGF-β), transforming growth factor β1 (TGF-β1), transforming growth factor β3 (TGF-β3), bone morphogenetic protein 1 (OP-1), bone morphogenetic protein 2 (OP-2), bone morphogenetic protein 3 (OP-3), Osteogenesis imperfecta 3 (BMP-3), Osteogenesis imperfecta 4 (BMP-4), Osteogenesis imperfecta 5 (BMP-5), Osteogenesis imperfecta 6 (BMP-6), Osteogenesis imperfecta 7 (BMP-7), Osteogenesis imperfecta 9 (BMP-9), Osteogenesis imperfecta 10 (BMP-10), Osteogenesis imperfecta 11 (BMP-11), Osteogenesis imperfecta 12 (BMP-12), Osteogenesis imperfecta 13 (BMP-13), Osteogenesis imperfecta 15 (BMP-15), Dentin Phosphoprotein (DPP), Plant-Related Growth Factor (Vgr), Growth and Differentiation Factor 1 (GDF-1), Growth and Differentiation Factor 3 (GDF-3), Growth and Differentiation Factor 5 (GDF-5), Growth and Differentiation Factor 6 (GDF-6), Growth and Differentiation Factor 7 (GDF-7), Growth and Differentiation Factor 8 (GDF-8), Growth and Differentiation Factor 11 (GDF-11), Growth and Differentiation Factor 15 (GDF-15), Angiovascular Epithelial Growth Factor (VEGF), Hyaluronic Acid-Binding Protein (HABP), Collagen-Binding Protein (CBP), Keratinocyte Growth Factor (KGF), Tumor Necrosis Factor α (TNFα), Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL), WNT Family Member 1 (WNT1), WNT Family Member Bar 2 (WNT2), wnt family member 2B (WNT2B), wnt family member 3 (WNT3), wnt family member 3A (WNT3A), wnt family member 4 (WNT4), wnt family member 5A (WNT5A), wnt family member 5B (WNT5B), wnt family member 6 (WNT6), wnt family member 7A (WNT7A), wnt family member 7B (WNT7B), wnt family member 8A (WNT8A), wnt family member 8B (WNT8B),A chimeric polypeptide according to claim 1, selected from the group consisting of WNT family member 9A (WNT9A), WNT family member 9B (WNT9B), WNT family member 10A (WNT10A), WNT family member 10B (WNT10B), WNT family member 11 (WNT11), and WNT family member 16 (WNT16).

3. The chimeric polypeptide according to claim 2, wherein the mammalian growth factor is BMP-2.

4. A composition comprising a chimeric polypeptide according to any one of claims 1 to 3, and β-TCP.

5. The composition according to claim 4, wherein the β-TCP is formulated as granules, powder, putty, or paste.

6. The composition according to claim 4, wherein the β-TCP is disposed on or inside a scaffold, mesh, or sponge.

7. The composition according to any one of claims 4 to 6, wherein the composition is a pharmaceutical composition.

8. A composition according to any one of claims 4 to 7 for use in a method of delivering a therapeutic agent to a subject, wherein the method comprises the step of administering a therapeutically effective amount of the composition to the subject.

9. A composition according to any one of claims 4 to 7 for use in a method for promoting the formation of bone or cartilage in a subject, wherein the method comprises the step of administering a therapeutically effective amount of the composition to the subject.

10. A composition according to any one of claims 4 to 7 for use in a method of replacing and / or repairing the bone or cartilage of a subject, wherein the method comprises the step of administering a therapeutically effective amount of the composition to the subject.

11. A composition according to any one of claims 4 to 7 for use in a method for treating a fracture or osteopenia in a subject, wherein the method comprises the step of administering a therapeutically effective amount of the composition to the subject.

12. The composition according to any one of claims 8 to 11, wherein the subject is suffering from a fracture.

13. The composition according to any one of claims 8 to 11, wherein the subject suffers from a bone defect.

14. The composition according to claim 9 or 10, wherein the subject suffers from cartilage laceration or cartilage defect.

15. The composition according to claim 9 or 10, wherein the subject is suffering from cartilage loss.

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