Serpinf2-Binding Molecules and Method of Use Thereof

Abstract

Compositions and methods of using SerpinF2-binding molecules for preventing and/or reducing organ damage, functional disability or mortality in a patient at risk due to the activity of SerpinF2 and/or plasminogen activators on tissue injury. Also provided are compositions and methods of using SerpinF2-binding molecules for inhibiting hemorrhage, edema, and apoptosis. Methods for the preparation of medicaments for such methods of treatment and prevention are provided.

1 - 28 . (canceled) 
     
     
         29 . A method of treating or preventing hemorrhage or edema in a patient in need thereof, comprising administering to the patient an effective amount of an anti-SerpinF2 antibody or fragment thereof that reduces SerpinF2 activity or concentration, wherein the hemorrhage or edema is cardiac, hepatic, pancreatic, respiratory or renal. 
     
     
         30 . The method of  claim 29 , wherein anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 28-91 nanomoles/kg. 
     
     
         31 . The method of  claim 29 , wherein the anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 17-50 nanomoles/kg. 
     
     
         32 . The method of  claim 29 , wherein the anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 0.5-1.0 moles inhibitor per mole of SerpinF2. 
     
     
         33 . A method of inhibiting disability or death from endogenous or pharmacologic tissue plasminogen activator (TPA) mediated hemorrhage or edema in a patient in need thereof, the method comprising administering to the patient an effective amount of an anti-SerpinF2 antibody or fragment thereof that reduces SerpinF2 activity or concentration, wherein the hemorrhage or edema is cardiac, hepatic, pancreatic, respiratory or renal. 
     
     
         34 . The method of  claim 33 , further comprising determining that the patient is at risk for TPA induced damage. 
     
     
         35 . The method of  claim 34 , wherein the damage comprises cardiac, hepatic, pancreatic, respiratory or renal damage. 
     
     
         36 . The method of  claim 35 , wherein the determining step further comprises determining that the patient has cardiac, hepatic, pancreatic, respiratory or renal symptoms indicative of cardiac, hepatic, pancreatic, respiratory or renal damage. 
     
     
         37 . The method of  claim 33 , wherein the method treats or prevents TPA toxicity. 
     
     
         38 . The method of  claim 37 , wherein the TPA toxicity is due to trauma. 
     
     
         39 . The method of  claim 33 , wherein a plasminogen activator or serine protease enzyme has been previously administered to the patient within 48 hours. 
     
     
         40 . The method of  claim 39 , wherein TPA has been previously administered to the patient within 48 hours. 
     
     
         41 . The method of  claim 33 , wherein anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 28-91 nanomoles/kg. 
     
     
         42 . The method of  claim 33 , wherein the anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 17-50 nanomoles/kg. 
     
     
         43 . The method of  claim 33 , wherein the anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 0.5-1.0 moles inhibitor per mole of SerpinF2. 
     
     
         44 . A method of inhibiting edema or tissue plasminogen activator (TPA) toxicity in a lung of a patient in need thereof comprising administering to said patient an effective amount of an anti-SerpinF2 antibody or fragment thereof that reduces SerpinF2 concentration or activity in said patient to inhibit the organ edema or tissue plasminogen activator (TPA) toxicity. 
     
     
         45 . The method of  claim 44 , wherein TPA has been previously administered to the patient within 48 hours. 
     
     
         46 . The method of  claim 44 , wherein the SerpinF2 binding inhibitor in an antibody and is administered in a dose range from 28-91 nanomoles/kg. 
     
     
         47 . The method of  claim 44 , wherein the anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 17-50 nanomoles/kg. 
     
     
         48 . The method of  claim 44 , wherein the anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 0.5-1.0 moles inhibitor per mole of SerpinF2. 
     
     
         49 . A method of treating or preventing morbidity or disability, or preventing death, from cellular damage, hemorrhage, or organ swelling after tissue injury, due to SerpinF2 activity, in a patient in need thereof, the method comprising administering to the patient an effective amount of an anti-SerpinF2 antibody or fragment thereof that reduces SerpinF2 activity or concentration, wherein the cellular damage, hemorrhage, or organ swelling is cardiac, hepatic, pancreatic, respiratory or renal. 
     
     
         50 . The method of  claim 49 , wherein the SerpinF2 activity is present in conditions associated with increased levels of at least one plasminogen activator. 
     
     
         51 . The method of  claim 50 , wherein the plasminogen activator or a serine protease enzyme has been previously administered to the patient within 48 hours. 
     
     
         52 . The method of  claim 51 , wherein the at least one plasminogen activator comprises tissue plasminogen activator (TPA). 
     
     
         53 . The method of  claim 49 , further comprising determining that the patient has cardiac, hepatic, pancreatic, respiratory or renal symptoms indicative of cardiac, hepatic, pancreatic, respiratory or renal cellular damage, hemorrhage, or organ swelling. 
     
     
         54 . The method of  claim 49 , wherein anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 28-91 nanomoles/kg. 
     
     
         55 . The method of  claim 49 , wherein the anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 17-50 nanomoles/kg. 
     
     
         56 . The method of  claim 49 , wherein the anti-SerpinF2 antibody or fragment thereof is administered in a dose range from 0.5-1.0 moles inhibitor per mole of SerpinF2.