Chimera humanized vascular endothelial growth factor

Abstract

An object of the present invention is to provide a chimera VEGF-E having a reduced antigenicity while maintaining the activity of VEGF-E. The present invention provides a chimera protein having an activity of growing vascular endothelial cells, which is obtained by substituting a part of the sequence of a VEGF analogous protein having an activity of vascularization that binds to KDR (VEGF rector-2) but does not bind to Flt-1 (VEGF receptor-1) with a corresponding sequence of a human-derived VEGF analogous protein.

1 . DNA encoding a chimera protein which has any of the amino acid sequences shown below:
 (A) the amino acid sequence as shown in SEQ ID NO: 15;   (B) the amino acid sequence which is obtained by deleting 1-20 amino acids of signal peptide at the amino-terminal region and 6 amino acids of histidine-tag at the carboxyl-terminal region from the amino acid sequence as shown in SEQ ID NO: 15; or   (C) the amino acid sequence as shown in (A) or (B), in which one to ten amino acids are deleted, substituted, and/or added, and which has an activity of growing vascular endothelial cells.   
     
     
         2 . An expression vector comprising the DNA according to  claim 1 . 
     
     
         3 . A medicament comprising the expression vector according to  claim 2 . 
     
     
         4 . A transformant having the expression vector according to  claim 2 . 
     
     
         5 . DNA encoding a chimera protein which has any of the amino acid sequences shown below:
 (A) the amino acid sequence which is obtained by deleting 6 amino acids of histidine-tag at the carboxyl-terminal region of the amino acid sequence as shown in SEQ ID NO: 15; or   (B) the amino acid sequence as shown in (A), in which one to ten amino acids are deleted, substituted, and/or added, and which has an activity of growing vascular endothelial cells.   
     
     
         6 . DNA encoding a chimera protein which has any of the amino acid sequences shown below:
 (A) the amino acid sequence which is obtained by deleting 1-20 amino acids of signal peptide at the amino-terminal region from the amino acid sequence as shown in SEQ ID NO: 15; or   (B) the amino acid sequence as shown in (A), in which one to ten amino acids are deleted, substituted, and/or added, and which has an activity of growing vascular endothelial cells.   
     
     
         7 . The DNA according to  claim 1 , wherein the amino acid sequence is obtained by deleting 1-15 amino acids of signal peptide at the amino-terminal region and 6 amino acids of histidine-tag at the carboxyl-terminal region from the amino acid sequence as shown in SEQ ID NO: 15. 
     
     
         8 . The DNA according to  claim 1 , wherein the amino acid sequence is obtained by deleting 1-10 amino acids of signal peptide at the amino-terminal region and 6 amino acids of histidine-tag at the carboxyl-terminal region from the amino acid sequence as shown in SEQ ID NO: 15. 
     
     
         9 . The DNA according to  claim 1 , wherein the amino acid sequence is obtained by deleting 1-5 amino acids of signal peptide at the amino-terminal region and 6 amino acids of histidine-tag at the carboxyl-terminal region from the amino acid sequence as shown in SEQ ID NO: 15. 
     
     
         10 . DNA encoding a chimera protein which has the amino acid sequence as shown in SEQ ID NO: 15.