Polypeptides as apelin inhibitors and uses thereof

Abstract

The present invention relates to polypeptides and their uses as apelin inhibitors. More particularly, the present invention relates to a polypeptide comprising the sequence as set forth in SEQ ID NO:1 wherein at least one arginine residue at position 18, 19, 22 or 23 has been substituted or deleted.

1 . A polypeptide comprising the sequence as set forth in SEQ ID NO:1 or a function conservative variant thereof wherein at least one arginine residue at position 18, 19, 22 or 23 has been substituted or deleted. 
     
     
         2 . The polypeptide according to  claim 1  which comprises a sequence as set forth in SEQ ID NO:2 or a function conservative variant wherein at least one arginine residue at position 59,60, 63, or 64 has been substituted or deleted. 
     
     
         3 . The polypeptide according to  claim 1  wherein 1, 2, 3, or 4 arginine residues are substituted or deleted. 
     
     
         4 . The polypeptide according to  claim 1  wherein the arginine residue(s) are substituted independently by a neutral amino acid selected from the group consisting of asparagine, glutamine, serine, threonine, tyrosine, glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine and tryptophane. 
     
     
         5 . The polypeptide according to  claim 1  wherein the arginine residues are independently substituted by a serine residue. 
     
     
         6 . The polypeptide according to  claim 1  wherein the arginine residues are all substituted by a serine residue. 
     
     
         7 . (canceled) 
     
     
         8 . A method of treating an angiogenic disease in a subject in need thereof comprising
 administering to the subject a therapeutic amount of a polypeptide comprising a sequence as set forth in SEQ ID NO:1 or a function conservative variant thereof wherein at least one arginine residue at position 18, 19, 22 or 23 has been substituted or deleted.   
     
     
         9 - 12 . (canceled) 
     
     
         13 . A method of producing a polypeptide comprising the steps of:
 (i) culturing a transformed host cell comprising I) a nucleic acid comprising a sequence encoding a polypeptide comprising a sequence as set forth in SEQ ID NO:1 or a function conservative variant thereof wherein at least one arginine residue at position 18, 19, 22 or 23 has been substituted or deleted, or II) a vector comprising the nucleic acid, said step of culturing being carrier out under conditions suitable to allow expression of said polypeptide; and   (ii) recovering the expressed polypeptide.   
     
     
         14 . The method of  claim 8 , wherein said angiogenic disease is cancer.