Ornithodoros Moubata Complement Inhibitor for Use in the treatment of Complement-Mediated Diseases in Patients with C5 Polymorphism

Abstract

The present invention relates to methods of treating or preventing a complement-mediated disease and/or disorder in a subject with a complement C5 polymorphism, including administering to a subject in need thereof a therapeutically or prophylactically effective amount of an agent that a) inhibits the classical complement pathway, the alternative complement pathway and the lectin complement pathway; and/or b) inhibits eicosanoid activity.The invention also relates to methods of identifying patient populations with C5 polymorphisms that are treatable with specific agents that a) inhibit the classical complement pathway, the alternative complement pathway and the lectin complement pathway; and/or b) inhibit eicosanoid activity.

1 . A method of treating or preventing a complement-mediated disease and/or disorder comprising administering to a subject with a complement C5 polymorphism and in need thereof a therapeutically or prophylactically effective amount of an agent that inhibits the classical complement pathway, the alternative complement pathway and the lectin complement pathway. 
     
     
         2 . An agent that inhibits the classical complement pathway, the alternative complement pathway and the lectin complement pathway for treating or preventing a complement-mediated disease and/or disorder in a subject with a complement C5 polymorphism. 
     
     
         3 . A method of treating or preventing a complement-mediated disease and/or disorder comprising the steps of:
 a) identifying a subject with a C5 polymorphism; and   b) identifying an agent that inhibits the classical complement pathway, the alternative complement pathway and the lectin complement pathway in said subject; and   c) administering to said subject a therapeutically or prophylactically effective amount of said agent identified in step (b).   
     
     
         4 . An agent that inhibits the classical complement pathway, the alternative complement pathway and the lectin complement pathway for use in a method of treating or preventing a complement-mediated disease and/or disorder, wherein said method comprises the steps of:
 a) identifying a subject with a C5 polymorphism; and   b) identifying an agent that inhibits the classical complement pathway, the alternative complement pathway and the lectin complement pathway in said subject; and   c) administering to said subject a therapeutically or prophylactically effective amount of said agent identified in step (b).   
     
     
         5 . An agent that inhibits the classical complement pathway, the alternative complement pathway and the lectin complement pathway in a subject with a C5 polymorphism for treating a complement-mediated disease or disorder, wherein said agent is administered to a subject on the basis the subject having been determined to have a C5 polymorphism. 
     
     
         6 . A method or agent according to any one of  claims 1  to  5  wherein the agent binds to C5 but does not block the C5 convertase binding site. 
     
     
         7 . A method or agent according to any one of  claims 1  to  6  wherein the agent is a protein comprising or consisting of amino acids 19 to 168 of the amino acid sequence in SEQ ID NO: 2 or is a functional equivalent of this protein. 
     
     
         8 . A method or agent according to any one of  claims 1  to  7  wherein the agent is a protein comprising or consisting of amino acids 1 to 168 of the amino acid sequence in SEQ ID NO: 2 or is a functional equivalent of this protein. 
     
     
         9 . A method or agent according to any one of  claims 1  to  8  wherein the agent is a nucleic acid molecule encoding a protein as recited in  claim 7  or  8 . 
     
     
         10 . A method or agent according to any one of  claims 1  to  9  wherein the subject is a mammal, preferably a human. 
     
     
         11 . A method or agent according to any one of  claims 1  to  10  wherein the subject has complement C5 polymorphism that decreases the effectiveness of a monoclonal antibody agent that inhibits the classical complement pathway, the alternative complement pathway and the lectin complement pathway. 
     
     
         12 . A method or agent according to any one of  claims 1  to  11  wherein the subject has complement C5 polymorphism that decreases the effectiveness of eculizumab. 
     
     
         13 . A method or agent according to any one of  claims 1  to  12  wherein the subject has complement C5 polymorphism that does not decrease the effectiveness of an agent as recited in any one of  claims 6  to  8 . 
     
     
         14 . A method or agent according to any one of  claims 1  to  13  wherein the subject is a non-responder to anti-C5 monoclonal antibodies 
     
     
         15 . A method or agent according to any one of  claims 1  to  14  wherein the complement C5 polymorphism is Arg885Cys or Arg885His.