Heparin-binding proteins modified with sugar chains, method of producing the same and pharmaceutical compositions containing same

A functionalized heparin-binding protein comprising a heparin-binding protein and at least one sugar chain covalently bonded thereto,

• wherein the at least one sugar chain is selected from the group consisting of a sulfated polysaccharide, a glycosaminoglycan, and an O-linked sugar chain,
• wherein the DNA synthesis promoting activity of the heparin-binding protein is increased by adding the at least one covalently bonded sugar chain,
• wherein the functionalized heparin-binding protein comprises the amino acid sequence of SEQ ID NO:
• 1, 17, 19, 21 or 23 and
• wherein the at least one sugar chain is covalently bonded to a peptide at the N-terminal of SEQ ID NO:
• 1, 17, 19, 21 or 23, wherein the N-terminal consists of residues 1-86 in SEQ ID NO:
• 1, residues 1-65 in SEQ ID NO:
• 17, residues 1-65 in SEQ ID NO:
• 19, residues 1-119 in SEQ ID NO:
• 21, and residues 1-146 in SEQ ID NO:
• 23.

A functionalized heparin-binding protein comprising a heparin-binding protein, comprising the amino acid sequence of SEQ ID NO:

• 1, 17, 19, 21 or 23, and a plurality of sugar chains covalently bonded thereto,
• wherein the sugar chains are selected from the group consisting of a sulfated polysaccharide, a glycosaminoglycan, and an O-linked sugar chain,
• wherein the sugar chains are covalently bonded to a peptide at the N-terminal of said SEQ ID NO., which is covalently bonded to the heparin-binding protein to which the sugar chains are added thereby increasing the DNA synthesis promoting activity of the heparin-binding protein, and
• wherein the N-terminal consists of residues 1-86 in SEQ ID NO:
• 1, residues 1-65 in SEQ ID NO:
• 17, residues 1-65 in SEQ ID NO:
• 19, residues 1-119 in SEQ ID NO:
• 21, and residues 1-146 in SEQ ID NO:
• 23.

A functionalized heparin-binding protein which comprises a heparin-binding protein modified with covalently bonded sugar chains,

• the sugar chain being selected from the group consisting of a sulfated polysaccharide, a glycosaminoglycan, and an O-linked sugar chain,
• wherein the sugar chain is bonded at a Ser-Gly repeat sequence,
• wherein the heparin-binding protein has improved stability over the unmodified proteins, and
• wherein the functionalized heparin-binding protein comprises the amino acid sequence of SEQ ID NO:
• 1, 17, 19, 21 or 23.