Extracellular matrix heparin-binding domains

Patent metadata

Field	Value
Publication number	US-9540428-B2
Application number	US-201313933448-A
Country	US
Kind code	B2
Filing date	Jul 2, 2013
Priority date	Jul 3, 2012
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

Heparin binding peptides derived from a Tenascin (TNC) III1-5 domain or a fibrinogen β15-66 domain have been found that bind certain cytokines with high affinity. Materials and methods for making compositions and devices using these peptides are disclosed.

First claim

The invention claimed is:

1. A biomaterial scaffold comprising a biomaterial matrix that comprises a synthetic polypeptide that comprises SEQ ID NO:8 or SEQ ID NO:9, with the biomaterial scaffold being pharmaceutically acceptable and free of fibrin.

2. The biomaterial scaffold of claim 1 comprising a plurality of said synthetic polypeptides and at least three cytokines being different types of cytokines relative to each other and collectively specifically bound to the plurality of synthetic polypeptides, with each of the three cytokines filling at least about 5% of the synthetic polypeptides present in the scaffold.

3. The biomaterial scaffold of claim 1 wherein the polypeptide further comprises a transglutaminase substrate, with the polypeptide being covalently linked by a transglutaminase-mediated chemical reaction that covalently links the substrate to the scaffold.

4. The biomaterial scaffold of claims 1 further comprising
a cytokine specifically bound to the polypeptide, wherein the cytokine is chosen from the group consisting of fibroblast growth factor-2 (FGF-2), fibroblast growth factor-4 (FGF-4), fibroblast growth factor-6 (FGF-6), fibroblast growth factor-7 (FGF-7), fibroblast growth factor-10 (FGF-10), fibroblast growth factor-17 (FGF-17), fibroblast growth factor-18 (FGF-18), transforming growth factor-β1 (TGF-β1), transforming growth factor-β2 (TGF-β2), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), placental growth factor-2 (PlGF-2), placental growth factor-3 (PlGF-3), bone morphogenetic protein-2 (BMP-2), platelet derived growth factor AA (PDGF-AA), platelet derived growth factor AB (PDGF-AB), platelet derived growth factor BB (PDGF-BB), platelet derived growth factor DD (PDGF-DD), vascular endothelial growth factor-A165 (VEGF-A165), vascular endothelial growth factor-B (VEGF-B), vascular endothelial growth factor-C (VEGF-C), hepatocyte growth factor (HGF), fibroblast growth factor-5 (FGF-5), and bone morphogenetic protein-2/7 (BMP-2/7) or
IGF-1 bound via insulin-like growth factor-binding protein-3 (IGF-BP3) or insulin-like growth factor-binding protein-5 (IGF-BP5), with the IGF-BP3 or IGF-BP5 being specifically bound to the polypeptide.

5. The biomaterial scaffold of claim 1 being a sterile and pharmaceutically acceptable tissue repair matrix.

6. The biomaterial scaffold of claim 1 comprising one or more of VEGF-A165, PDGF-BB, BMP-2, NT-3, and BDNF.

7. The biomaterial scaffold of claim 1 wherein the peptide consists of SEQ ID NO:8 or SEQ ID NO:9.

8. A surface that is free of fibrin and free of fibrinogen comprising one or more immobilized moieties chosen from the group consisting of a synthetic peptide that comprises SEQ ID NO:8 or SEQ ID NO:9
the surface being chosen from the group consisting of a stent, a vascular graft, a cell culture surface, a cell culture vessel, a cell carrier, and tissue culture plastic;
said moieties being immobilized to the surface.

9. The surface of claim 8 being a surface of a medical device.

10. The surface of claim 8 comprising one or more cytokines specifically bound to a domain selected from the group consisting of the TNC III1-5 domain and the β15-66 domain.

11. The surface of claim 8 further comprising at least three different cytokines specifically bound to at least about 5% of the peptides immobilized on the surface.

12. The surface of claim 8 wherein one or more cytokines are specifically bound to the peptide.

13. The surface of claim 8 further comprising
a cytokine specifically bound to the peptide, wherein the cytokine is selected from the group consisting of fibroblast growth factor-2 (FGF-2), fibroblast growth factor-4 (FGF-4), fibroblast growth factor-6 (FGF-6), fibroblast growth factor-7 (FGF-7), fibroblast growth factor-10 (FGF-10), fibroblast growth factor-17 (FGF-17), fibroblast growth factor-18 (FGF-18), transforming growth factor-β1 (TGF-β1), transforming growth factor-β2 (TGF-β2), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), placental growth factor-2 (PlGF-2), placental growth factor-3 (PlGF-3), bone morphogenetic protein-2 (BMP-2), platelet derived growth factor AA (PDGF-AA), platelet derived growth factor AB (PDGF-AB), platelet derived growth factor BB (PDGF-BB), platelet derived growth factor DD (PDGF-DD), vascular endothelial growth factor-A165 (VEGF-A165), vascular endothelial growth factor-B (VEGF-B), and vascular endothelial growth factor-C (VEGF-C), or
one or more cytokine-binding factors are specifically bound to the peptide, the cytokine-binding factors being selected from the group consisting of insulin-like growth factor-binding protein-3 (IGF-BP3) and insulin-like growth factor-binding protein-5 (IGF-BP5).

14. The surface of claim 8 wherein the peptide has identity to SEQ ID NO:8 or SEQ ID NO:9.

Assignees

• Epfl-Tto
• Ecole Polytechnique Fed De Lausanne (Epfl)

Inventors

• Hubbell Jeffrey A
• Martino Mikael
• De Laporte Laura
• Rice Jeffrey J
• Tortelli Federico

Classifications

• C07K14/78

  Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG] · CPC title

• C07K14/75 Primary

  Fibrinogen · CPC title

• C07K14/4718 Primary

  Cytokine-induced proteins · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title