Proteins with diagnostic and therapeutic uses

Abstract

A recombinant protein for use in the treatment of one or more medical complications associated with aberrant complement regulatory activity in a subject, the recombinant protein capable of binding to complement factor H (CFH) and inducing increased binding of C3d and C3b by bound CFH compared to unbound CFH.

1 . A recombinant protein for use in the treatment of one or more medical complications associated with aberrant complement regulatory activity in a subject, the recombinant protein capable of binding to complement factor H (CFH) and inducing increased binding of C3d and C3b by bound CFH compared to unbound CFH. 
     
     
         2 . The recombinant protein of  claim 1 , wherein the protein is capable of binding to wild type CFH to form a complex with a K D  of 1×10 −10  M or lower. 
     
     
         3 . The recombinant protein of  claim 1 , wherein the protein is derived from a bacterial virulence factor. 
     
     
         4 . The recombinant protein of  claim 2 , wherein the protein is derived from a bacterial virulence factor. 
     
     
         5 . The recombinant protein of  claim 1 , wherein the protein is derived from a pneumococcal surface protein. 
     
     
         6 . The recombinant protein of  claim 5 , wherein the protein is derived from pneumococcal surface protein C (PspC) from  Streptococcus pneumoniae.    
     
     
         7 . The recombinant protein of  claim 5 , wherein the protein is derived from PspC of strain D39 (NCTC no 7466) of  S. pneumoniae  or PspC of strain TIGR4 (NCTC no 7465) of  S. pneumoniae.    
     
     
         8 . The recombinant protein of  claim 5 , wherein the protein comprises a fragment of PspC, or a variant thereof, which is from 70 to 150 amino acids in length. 
     
     
         9 . The recombinant protein of  claim 2 , wherein the protein is derived from a pneumococcal surface protein. 
     
     
         10 . The recombinant protein of  claim 9 , wherein the protein is derived from pneumococcal surface protein C (PspC) from  Streptococcus pneumoniae.    
     
     
         11 . The recombinant protein of  claim 9 , wherein the protein is derived from PspC of strain D39 (NCTC no 7466) of  S. pneumoniae  or PspC of strain TIGR4 (NCTC no 7465) of  S. pneumoniae.    
     
     
         12 . The recombinant protein of  claim 9 , wherein the protein comprises a fragment of PspC, or a variant thereof, which is from 70 to 150 amino acids in length. 
     
     
         13 . The recombinant protein of  claim 1 , wherein the protein comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO 1) 
                 
                   ATENEGSTQAATSSNMAKTEHRKAAKQVVDEYIEKMLREIQLDRRK 
                 
                     
                 
                   HTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFE 
                 
                     
                 
                   KFKKDTLKPGEK, 
                 
             
                
                
                
                
                
                
               
            
           
         
         or a functional variant or fragment thereof; or 
         KQVVDEYIEKMLREIQLDRRKHTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFEKFKKDTLKPGEK (SEQ ID NO 2), or a functional variant or fragment thereof; or 
         ATENEGATQVPTSSNRANESQAEQGEQPKKLDSERDKARKEVEEYVKKIVGESYAKSTKKRHTITVALVNELNNIKNEYLNKIVESTSESQLQILMMESRSKVDEAVSKFEKDSSSSSSSDSSTKPEASDTAKPNKPTEPGEK (SEQ ID NO 9), or a functional variant or fragment thereof. 
       
     
     
         14 . The recombinant protein of  claim 2 , wherein the protein comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO 1) 
                 
                   ATENEGSTQAATSSNMAKTEHRKAAKQVVDEYIEKMLREIQLDRRK 
                 
                     
                 
                   HTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFE 
                 
                     
                 
                   KFKKDTLKPGEK, 
                 
             
                
                
                
                
                
                
               
            
           
         
         or a functional variant or fragment thereof; or 
         KQWDEYIEKMLREIQLDRRKHTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFEKFKKDTLKPGEK (SEQ ID NO 2), or a functional variant or fragment thereof; or 
         ATENEGATQVPTSSNRANESQAEQGEQPKKLDSERDKARKEVEEYVKKIVGESYAKSTKKRHTITVALVNELNNIKNEYLNKIVESTSESQLQILMMESRSKVDEAVSKFEKDSSSSSSSDSSTKPEASDTAKPNKPTEPGEK (SEQ ID NO 9), or a functional variant or fragment thereof. 
       
     
     
         15 . The recombinant protein of  claim 5 , wherein the protein comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO 1) 
                 
                   ATENEGSTQAATSSNMAKTEHRKAAKQVVDEYIEKMLREIQLDRRK 
                 
                     
                 
                   HTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFE 
                 
                     
                 
                   KFKKDTLKPGEK, 
                 
             
                
                
                
                
                
                
               
            
           
         
         or a functional variant or fragment thereof; or KQVVDEYIEKMLREIQLDRRKHTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFEKFKKDTLKPGEK (SEQ ID NO 2), or a functional variant or fragment thereof; or 
         ATENEGATQVPTSSNRANESQAEQGEQPKKLDSERDKARKEVEEYVKKIVGESYAKSTKKRHTITVALVNELNNIKNEYLNKIVESTSESQLQILMMESRSKVDEAVSKFEKDSSSSSSSDSSTKPEASDTAKPNKPTEPGEK (SEQ ID NO 9), or a functional variant or fragment thereof. 
       
     
     
         16 . The recombinant protein of  claim 6 , wherein the protein comprises at least amino acids 68-136 of PspC, or a functional variant thereof. 
     
     
         17 . The recombinant protein of  claim 1 , wherein the recombinant protein binds to CFH within complement control proteins (CCPs) 8-10 of CFH. 
     
     
         18 . The recombinant protein of  claim 5 , wherein the recombinant protein binds to CFH within complement control proteins (CCPs) 8-10 of CFH. 
     
     
         19 . The recombinant protein of  claim 9 , wherein the recombinant protein binds to CFH within complement control proteins (CCPs) 8-10 of CFH.