Angiostatin protein

Abstract

Fragments of an endothelial cell proliferation inhibitor and method of use therefor are provided. The endothelial proliferation inhibitor is a protein derived from plasminogen, or more specifically is an angiostatin fragment. The angiostatin fragments generally correspond to kringle structures occurring within the endothelial cell proliferation inhibitor. The endothelial cell inhibiting activity of these fragments provides a means for inhibiting angiogenesis of tumors and for treating angiogenic-mediated disease.

We claim:  
     
         1 . A method of inhibiting endothelial cell proliferation comprising administering to an endothelial cell a proliferation inhibiting amount of a plasminogen fragment having an amino acid sequence substantially similar to the kringle 1-5 region of a plasminogen molecule.  
     
     
         2 . The method of    claim 1   , wherein the plasminogen fragment is derived from murine plasminogen, human plasminogen, Rhesus plasminogen, porcine plasminogen or bovine plasminogen.  
     
     
         3 . The method of    claim 1   , wherein the plasminogen fragment corresponds to approximately amino acids 98 to 560 of a plasminogen molecule.  
     
     
         4 . A method of treating a mammal with an angiogenic-mediated disease comprising administering to the mammal a treatment effective amount of a plasminogen fragment having an amino acid sequence substantially similar to the kringle 1-5 region of a plasminogen molecule.  
     
     
         5 . The method of    claim 4   , wherein the plasminogen fragment is derived from murine plasminogen, human plasminogen, Rhesus plasminogen, porcine plasminogen or bovine plasminogen.  
     
     
         6 . The method of    claim 4   , wherein the plasminogen fragment corresponds to approximately amino acids 98 to 560 of a plasminogen molecule.  
     
     
         7 . A therapeutic composition for inhibiting endothelial cell proliferation comprising a pharmaceutically acceptable excipient and a plasminogen fragment having an amino acid sequence substantially similar to the kringle 1-5 region of a plasminogen molecule.  
     
     
         8 . The composition of    claim 7   , wherein the plasminogen fragment is derived from murine plasminogen, human plasminogen, Rhesus plasminogen, porcine plasminogen or bovine plasminogen.  
     
     
         9 . The composition of    claim 7   , wherein the plasminogen fragment corresponds to approximately amino acids 98 to 560 of a plasminogen molecule.  
     
     
         10 . A composition comprising an isolated nucleotide sequence that codes for a plasminogen fragment having an amino acid sequence substantially similar to the kringle 1-5 region of a plasminogen molecule.  
     
     
         11 . The composition of    claim 10   , wherein the plasminogen fragment is derived from murine plasminogen, human plasminogen, Rhesus plasminogen, porcine plasminogen or bovine plasminogen.  
     
     
         12 . The composition of    claim 10   , wherein the plasminogen fragment corresponds to approximately amino acids 98 to 560 of a plasminogen molecule.  
     
     
         13 . The composition of    claim 12   , further comprising a vector associated with the DNA sequence encoding the plasminogen fragment, wherein the vector is capable of expressing the plasminogen fragment when present in a cell.  
     
     
         14 . The composition of    claim 13   , further comprising a cell containing said vector.  
     
     
         15 . A method of expressing an plasminogen fragment having an endothelial cell proliferation inhibiting activity and having an amino acid sequence substantially similar to the kringle 1-5 region of a plasminogen molecule, comprising transfecting in a mammalian cell a vector, wherein the vector contains a DNA sequence encoding said plasminogen fragment, and wherein the vector is capable of expressing angiostatin fragment when present in the cell.