Modified Factor VIII

Abstract

Methods of treating patients with Factor VIII deficiency by administration of modified porcine factor VIII are disclosed. The particular modified porcine factor VIII is one in which most of the B domain has been removed through genetic engineering. This modified factor VIII is particularly useful for treatment of hemophiliacs, especially those undergoing bleeding episodes.

I/we claim: 
     
         1 . A method for treating a patient having factor VIII deficiency comprising administering a composition comprising a therapeutically effective amount of a modified porcine factor Vlll protein that comprises the sequence of amino acids from position 1 through position 1448 of SEQ ID NO:49. 
     
     
         2 . The method according to  claim 1 , wherein the patient having factor VIII deficiency has inhibitory antibodies to human factor VIII. 
     
     
         3 . The method according to  claim 1 , wherein the patient having factor VIII deficiency suffers from uncontrolled bleeding. 
     
     
         4 . The method according to  claim 3 , wherein the uncontrolled bleeding is selected from intra-articular, intracranial, and gastrointestinal hemorrhage. 
     
     
         5 . A method for treating a patient having factor VIII deficiency comprising administering a therapeutically effective amount of a modified porcine factor Vlll protein, wherein the modified porcine factor VIII protein is an expression product of the DNA sequence set forth in SEQ ID NO:48, expressed in a mammalian host cell. 
     
     
         6 . The method according to  claim 5 , wherein the modified porcine factor Vlll is prepared from the supernatant of cultured mammalian host cells containing and expressing the DNA sequence set forth in SEQ ID NO:48. 
     
     
         7 . The method according to  claim 1 , wherein the modified porcine factor VIII protein consists of the sequence of amino acids 1 to 1448 of SEQ ID NO:49. 
     
     
         8 . The method according to  claim 1 , wherein the composition further comprises a physiologically acceptable carrier. 
     
     
         9 . The method according to  claim 8 , wherein the composition further comprises a stabilizer and a delivery vehicle. 
     
     
         10 . The method according to  claim 1 , wherein the composition is infused intravenously. 
     
     
         11 . The method according to  claim 1 , wherein the patient is an acquired hemophilia patient or a congenital hemophilia patient. 
     
     
         12 . A method of treating a patient having factor VIII deficiency comprising the step of administering a composition comprising an effective amount of a modified porcine factor VIII protein, a human-animal hybrid factor VIII protein or a hybrid equivalent factor VIII protein. 
     
     
         13 . The method according to  claim 12 , wherein the hybrid equivalent factor VIII protein is the expression product of SEQ ID NO:38. 
     
     
         14 . The method according to  claim 12 , wherein the hybrid human-animal factor VIII protein is a human-porcine hybrid factor VIII protein. 
     
     
         15 . A method of treating a patient having factor VIII deficiency comprising the step of administering a retrovirus modified to contain and express a hybrid factor VIII protein or a hybrid equivalent factor VIII protein, wherein said retrovirus does not produce virus in said patient. 
     
     
         16 . The method according to  claim 15 , wherein the patient is an acquired hemophilia patient or a congenital hemophilia patient. 
     
     
         17 . The method according to  claim 13 , wherein said hybrid factor VIII protein or a hybrid equivalent factor VIII protein is the expression product of SEQ ID NO:37 or SEQ ID NO:48. 
     
     
         18 . The method according to  claim 13 , wherein the patient having factor VIII deficiency has inhibitory antibodies to human factor VIII. 
     
     
         19 . The method according to  claim 12 , wherein the patient having factor VIII deficiency suffers from uncontrolled bleeding. 
     
     
         20 . The method according to  claim 12 , wherein the uncontrolled bleeding is selected from intra-articular, intracranial, and gastrointestinal hemorrhage.