Novel Antiangiogenic Peptide Agents and Their Therapeutic and Diagnostic Use

Abstract

The current invention concerns novel antiangiogenic peptides which correspond to about 10 to about 150 consecutive amino acids of N-terminal sequences of human growth hormone, human placental lactogen, human growth hormone variant hGH-V, and prolactin, and their use in inhibiting angiogenesis and in the diagnosis of diseases of human pregnancy involving abnormalities of placental vascularization.

1 - 26 . (canceled)  
     
     
         27 . An isolated peptide having the amino acid sequence of SEQ ID NO: 18 or having an amino acid sequence that has 90% sequence identity with the amino acid sequence of SEQ ID NO:18.  
     
     
         28 . The isolated peptide of  claim 27 , wherein the peptide has the sequence of SEQ ID NO:18.  
     
     
         29 . The isolated peptide of  claim 27 , wherein the peptide inhibits capillary endothelial cell proliferation and organization; inhibits angiogenesis in chick chorioallantoic membrane; and binds to at least one specific receptor which does not bind an intact full length growth hormone.  
     
     
         30 . The isolated peptide of  claim 28 , wherein the peptide inhibits capillary endothelial cell proliferation and organization; inhibits angiogenesis in chick chorioallantoic membrane; and binds to at least one specific receptor which does not bind an intact full length growth hormone.  
     
     
         31 . A method of treating an angiogenic disease in a subject, the method comprising administering to a subject in need of such treatment an angiogenesis inhibitory effective amount of the isolated peptide of  claim 27 .  
     
     
         32 . The method of  claim 31 , wherein the isolated peptide has the sequence of SEQ ID NO:18.  
     
     
         33 . The method of  claim 31 , wherein the patient has preeclampsia, intrauterine growth retardation, or placental dysfunction.  
     
     
         34 . The method of  claim 32 , wherein the patient has preeclampsia, intrauterine growth retardation, or placental dysfunction.  
     
     
         35 . A method of inhibiting tumor formation or growth in a patient, the method comprising administering to the patient an angiogenesis inhibitory effective amount of the isolated peptide of  claim 27 .  
     
     
         36 . The method of  claim 35 , wherein the isolated peptide has the sequence of SEQ ID NO:18.  
     
     
         37 . A pharmaceutical formulation, comprising: 
 a therapeutically effective amount of an isolated peptide that has the amino acid sequence of SEQ ID NO:18 or that has 90% sequence identity with the amino acid sequence of SEQ ID NO:18; and    a pharmaceutically acceptable carrier.    
     
     
         38 . The pharmaceutical formulation of  claim 37 , wherein the isolated peptide has the sequence of SEQ ID NO: 18.  
     
     
         39 . A method of treating a tumor, comprising: 
 diagnosing a patient as having a tumor; and    administering to the patient an angiogenesis inhibitory effective amount of the formulation of  claim 37 .    
     
     
         40 . The method of  claim 39 , wherein the isolated peptide has the sequence of SEQ ID NO:18.