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Heparin-binding protein modified with heparan sulfate sugar chains, process for producing the same and pharmaceutical compositions containing the same

Foreign code F130007236
File No. 2006003228
Posted date Mar 27, 2013
Country United States of America
Application number 54734605
Gazette No. 20080119403
Gazette No. 7741078
Date of filing Mar 31, 2005
Gazette Date May 22, 2008
Gazette Date Jun 22, 2010
International application number JP2005006364
International publication number WO2005095600
Date of international filing Mar 31, 2005
Date of international publication Oct 13, 2005
Priority data
  • P2004-108570 (Mar 31, 2004) JP
  • 2005WO-JP06364 (Mar 31, 2005) WO
Title Heparin-binding protein modified with heparan sulfate sugar chains, process for producing the same and pharmaceutical compositions containing the same
Abstract (US7741078)
A heparin-binding protein having covalently bonded heparan sulfate sugar chains within its molecule is produced by ligating a cDNA encoding a peptide which can be modified with heparan sulfate sugar chains selectively to a cDNA encoding a heparin-binding protein and producing in an animal cell the gene product of the resultant ligated cDNA.
This heparan sulfate sugar chain-modified heparin-binding protein is functionalized by covalently bonding thereto glycosaminoglycan sugar chains containing little chondroitin sulfate.
For example, this heparin-binding protein is excellent in stabilities, such as thermostability, acid resistance, alkali resistance and in vivo stability.
Further, the heparan sulfate sugar chain-modified heparin-binding protein is effective in cell proliferation and tissue regeneration, and has effect of regulating the physiological functions of FGFs.
Thus, this heparin-binding protein is extremely useful as a medicine for preventing or treating various FGF-related diseases.
Scope of claims [claim1]
1. A method of producing a heparin-binding protein having at least one sulfated glycosaminoglycan sugar chain covalently bonded thereto, wherein 90% or more of said at least one sulfated glycosaminoglycan sugar chain being a heparan sulfate sugar chain, wherein the method comprises: (a) a step of ligating a cDNA encoding a peptide consisting of an amino acid sequence shown in SEQ ID NO: 8 which is capable of being modified with at least one heparan sulfate sugar chain to a cDNA encoding a heparin-binding protein;
(b) a step of incorporating the resultant ligated cDNA into an expression vector;
(c) a step of introducing the expression vector into a host cell having a pathway for heparan sulfate sugar chain biosynthesis; and
(d) a step of expressing in the host cell a heparin-binding protein to which at least one heparan sulfate sugar chain is covalently bonded through the peptide consisting of the amino acid sequence shown in SEQ ID NO: 8.
[claim2]
2. The method of claim 1, wherein the cDNA encoding the peptide consists of a nucleotide sequence as shown in SEQ ID NO: 13.
[claim3]
3. The method of claim 1, wherein the heparin-binding protein is a compound belonging to the fibroblast growth factor family.
[claim4]
4. A nucleic acid consisting of the nucleotide sequence as shown in SEQ ID NO: 13 and encoding a peptide which is capable of being modified with at least one heparan sulfate sugar chain.
  • Inventor, and Inventor/Applicant
  • IMAMURA TORU
  • ASADA MASAHIRO
  • SUZUKI MASASHI
  • NATIONAL INSTITUTE OF ADVANCED INDUSTRIAL SCIENCE AND TECHNOLOGY
IPC(International Patent Classification)

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