Methods and compositions for treating and preventing diseases associated with alphavbeta5 integrin

Abstract

The present invention provides compositions and methods for treating and preventing disease associated with αvβ5 integrin by blocking binding to αvβ5 integrin.

1 . A method of treating or preventing pulmonary edema in a mammalian subject, the method comprising administering a therapeutic amount of an antagonist of (αvβ5 integrin to the subject.  
     
     
         2 . The method of  claim 1 , wherein the antagonist is an agent under 1 kDa.  
     
     
         3 . The method of  claim 1 , wherein the antagonist is an antibody.  
     
     
         4 . The method of  claim 3 , wherein the antibody is a humanized antibody.  
     
     
         5 . The method of  claim 3 , wherein the antibody is selected from the group consisting of: a scFv, a Fab, and a (Fab′) 2 .  
     
     
         6 . The method of  claim 3 , wherein the antibody competes with ALULA (ATCC Deposit No. PTA-5817) for specific binding to αvβ5 integrin.  
     
     
         7 . The method of  claim 6 , wherein the antibody is ALULA.  
     
     
         8 . The method of  claim 6 , wherein the antibody is a humanized ALULA.  
     
     
         9 . The method of  claim 1 , wherein the administration is selected from the group consisting of: intravenous administration, intra-nasal administration, and intra-bronchial administration.  
     
     
         10 . The method of  claim 1 , wherein the mammal is a human.  
     
     
         11 . The method of  claim 10 , wherein the human has pulmonary edema.  
     
     
         12 . The method of  claim 10 , wherein the human is at risk of developing pulmonary edema.  
     
     
         13 . The method of  claim 1 , further comprising administering a second therapeutic agent for treating or preventing acute lung injury to the subject.  
     
     
         14 . The method of  claim 13 , wherein the second therapeutic agent is selected from the group consisting of: a TGFβ pathway inhibitor, activated Protein C, a steroid, GM-CSF, a platelet inhibitor, a diuretic agent; a bronchodilating agent, an antibody that binds to αvβ5 integrin, an antibody that binds to β5, a second antagonist of αvβ5 integrin, an antagonist of αvβ6 integrin, a β-2 agonist, and a surfactant.  
     
     
         15 . An antibody that specifically competes with ALULA (ATCC Deposit No. PTA-5817) for binding to αvβ5.  
     
     
         16 . The antibody of  claim 15 , wherein the antibody is ALULA.  
     
     
         17 . The antibody of  claim 15 , wherein the antibody is a humanized ALULA.  
     
     
         18 . The antibody of  claim 15 , wherein the antibody is selected from the group consisting of: a scFv, a Fab, and a (Fab′) 2 .  
     
     
         19 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an antibody that competes with ALULA (ATCC Deposit No. PTA-5817) for specific binding to αvβ5.  
     
     
         20 . The pharmaceutical composition of  claim 19 , wherein the antibody is ALULA.  
     
     
         21 . The pharmaceutical composition of  claim 19 , wherein the antibody is a humanized ALULA.  
     
     
         22 . The pharmaceutical composition of  claim 19 , further comprising a second therapeutic agent for treating or preventing acute lung injury.  
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein the second therapeutic agent is selected from the group consisting of: a TGFβ pathway inhibitor, activated Protein C, a steroid, GM-CSF, a platelet inhibitor, a diuretic agent; a bronchodilating agent, an antibody that binds to αvβ5 integrin, an antibody that binds to β5, a second antagonist of αvβ5 integrin, an antagonist of αvβ6 integrin, a β-2 agonist, and a surfactant.  
     
     
         24 . A method of identifying an agent for treating pulmonary edema, the method comprising, 
 contacting a plurality of agents with αvβ5;    selecting an agent that competes with a ligand of αvβ5 integrin for binding to αvβ5 integrin; and    determining whether the selected agent has an effect on pulmonary edema, thereby identifying an agent for treating pulmonary edema.    
     
     
         25 . The method of  claim 24 , wherein the plurality of agents is a plurality of antibodies.  
     
     
         26 . The method of  claim 24 , wherein the plurality of agents are each under 1 KDa.  
     
     
         27 . The method of  claim 24 , wherein the ligand is an antibody.  
     
     
         28 . The method of  claim 27 , wherein the antibody is ALULA.  
     
     
         29 . The method of  claim 24 , wherein the ligand is selected from the group consisting of: vitronectin, fibronectin, osteopontin, tenascin c and adenovirus penton base.  
     
     
         30 . A kit for treating or preventing pulmonary edema, the kit comprising: 
 an antagonist of αvβ5 integrin; and    a second therapeutic agent for treating or preventing acute lung injury.    
     
     
         31 . The kit of  claim 30 , wherein the antagonist of αvβ5 integrin is a monoclonal antibody.  
     
     
         32 . The kit of  claim 31 , wherein the monoclonal antibody is ALULA.  
     
     
         33 . The kit of  claim 31 , wherein the monoclonal antibody is humanized ALULA.  
     
     
         34 . The kit of  claim 30 , wherein the second therapeutic agent is selected from the group consisting of: a TGFβ pathway inhibitor, activated Protein C, a steroid, GM-CSF, a platelet inhibitor, a diuretic agent; a bronchodilating agent, an antibody that binds to αvβ5 integrin, an antibody that binds to β5, a second antagonist of αvβ5 integrin, an antagonist of αvβ6 integrin, a β-2 agonist, and a surfactant.