Pleiotrophin growth factor receptor for the treatment of proliferative, vascular and neurological disorders

Abstract

This invention relates to the discovery that pleiotrophin binds to and activates a pleiotrophin-receptor which is responsible for the events associated with pleiotrophin activity including tumorigenesis, cell proliferation, and cell invasion. By interfering with that association, the cascade of events associated with pleiotrophin activity can be prevented or reversed. Further, by evaluating the effect of different compounds and conditions on the interaction, new drugs and treatments can be identified for use in preventing certain cancers and growth and developmental disorders.

1 - 30 . (canceled) 
     
     
         31 . An isolated monoclonal antibody or antibody fragment which specifically binds the pleiotrophin-receptor protein binding site of a pleiotrophin protein. 
     
     
         32 . The isolated monoclonal antibody or antibody fragment of  claim 31  wherein the pleiotrophin protein is human pleiotrophin (PTN). 
     
     
         33 . (canceled) 
     
     
         34 . The isolated monoclonal antibody or antibody fragment of  claim 31  which is selected from the group consisting of IgG, IgM, Fab fragments, Fv fragments, recombinant antibodies human antibodies, and humanized antibodies. 
     
     
         35 . The isolated monoclonal antibody or antibody fragment of  claim 31  which is monoclonal. 
     
     
         36 . A hybridoma which produces the monoclonal antibody of  claim 35 . 
     
     
         37 - 68 . (canceled) 
     
     
         69 . The isolated monoclonal antibody or antibody fragment of  claim 31  wherein the antibody or antibody fragment inhibits pleiotrophin binding to pleiotrophin receptor. 
     
     
         70 . The isolated monoclonal antibody or antibody fragment of  claim 31  wherein the antibody or antibody fragment inhibits angiogenesis. 
     
     
         71 . The isolated monoclonal antibody or antibody fragment of  claim 31  wherein the antibody or antibody fragment blocks activation of ALK. 
     
     
         72 . A pharmaceutical composition comprising the isolated monoclonal antibody or antibody fragment of  claim 69 . 
     
     
         73 . A method for treating a patient having a proliferative disease comprising administering to the patient a therapeutically effective amount of an isolated monoclonal antibody or antibody fragment which binds pleiotrophin-receptor protein binding site of pleiotrophin protein and inhibits a pleiotrophin-mediated activity. 
     
     
         74 . The method of  claim 73 , wherein the disease is a cancer. 
     
     
         75 . The method of  claim 73 , wherein the isolated monoclonal antibody or antibody fragment inhibits pleiotrophin-mediated angiogenesis. 
     
     
         76 . The method of  claim 73 , wherein the isolated monoclonal antibody or antibody fragment inhibits a pleiotrophin-mediated neoplastic or mitogenic activity.