Proteins with diagnostic and therapeutic uses

Abstract

A method of treating one or more medical complications associated with aberrant complement regulatory activity in a subject includes the steps of: providing a pharmaceutical composition comprising a 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; and administering to a subject an effective amount of the pharmaceutical composition.

The invention in which an exclusive property or privilege is claimed is defined as follows: 
     
         1 . A method of treating one or more medical complications associated with aberrant complement regulatory activity in a subject, comprising the steps of:
 providing a pharmaceutical composition comprising a 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; and   administering to a subject an effective amount of the pharmaceutical composition.   
     
     
         2 . The method of  claim 1 , wherein the recombinant 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 method of  claim 1 , wherein the recombinant protein comprises a functional fragment or a functional variant of a bacterial virulence factor. 
     
     
         4 . The method of  claim 2 , wherein the recombinant protein comprises a functional fragment or a functional variant of a bacterial virulence factor. 
     
     
         5 . The method of  claim 1 , wherein the recombinant protein comprises a functional fragment or a functional variant of a pneumococcal surface protein. 
     
     
         6 . The method of  claim 5 , wherein the recombinant protein comprises a functional fragment or a functional variant of pneumococcal surface protein C (PspC) from  Streptococcus pneumoniae.    
     
     
         7 . The method of  claim 5 , wherein the recombinant protein comprises a functional fragment or a functional variant of PspC of strain D39 (NCTC no 7466) of  S. pneumoniae  or PspC of strain TIGR4 (NCTC no 7465) of  S. pneumoniae.    
     
     
         8 . The method of  claim 5 , wherein the recombinant protein comprises a functional fragment of PspC, or a functional variant thereof, which is from 70 to 150 amino acids in length. 
     
     
         9 . The method of  claim 2 , wherein the recombinant protein comprises a functional fragment or a functional variant of a pneumococcal surface protein. 
     
     
         10 . The method of  claim 9 , wherein the recombinant protein comprises a functional fragment or a functional variant of pneumococcal surface protein C (PspC) from  Streptococcus pneumoniae.    
     
     
         11 . The method of  claim 9 , wherein the recombinant protein comprises a functional fragment or a functional variant of PspC of strain D39 (NCTC no 7466) of  S. pneumoniae  or PspC of strain TIGR4 (NCTC no 7465) of  S. pneumoniae.    
     
     
         12 . The method of  claim 9 , wherein the recombinant protein comprises a functional fragment of PspC, or a functional variant thereof, which is from 70 to 150 amino acids in length. 
     
     
         13 . The method of  claim 1 , wherein the recombinant protein comprises the sequence:
 ATENEGSTQAATSSNMAKTEHRKAAKQVVDEYIEKMLREIQLDRRKHTQNVALNIKL SAI KTKYLRELNVLEEKSKDELPSEIKAKLDAAFEKFKKDTLKPGEK (SEQ ID NO 1), or a functional variant or fragment thereof; or   KQVVDEYIEKMLREIQLDRRKHTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIK AKLDAAFEKFKKDTLKPGEK (SEQ ID NO 2), or a functional variant or functional fragment thereof; or   ATENEGATQVPTSSNRANESQAEQGEQPKKLDSERDKARKEVEEYVKKIVGESYA KSTKKRHTITVALVNELNNIKNEYLNKIVESTSESQLQILMMESRSKVDEAVSKFEKDSSSSS SSDSSTKPEASDTAKPNKPTEPGEK (SEQ ID NO 9), or a functional variant or functional fragment thereof.   
     
     
         14 . The method of  claim 2 , wherein the recombinant protein comprises the sequence:
 ATENEGSTQAATSSNMAKTEHRKAAKQVVDEYIEKMLREIQLDRRKHTQNVALNIKL SAI KTKYLRELNVLEEKSKDELPSEIKAKLDAAFEKFKKDTLKPGEK (SEQ ID NO 1), or a functional variant or functional fragment thereof; or   KQWDEYIEKMLREIQLDRRKHTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIK AKLDAAFEKFKKDTLKPGEK (SEQ ID NO 2), or a functional variant or functional fragment thereof; or   ATENEGATQVPTSSNRANESQAEQGEQPKKLDSERDKARKEVEEYVKKIVGESYA KSTKKRHTITVALVNELNNIKNEYLNKIVESTSESQLQILMMESRSKVDEAVSKFEKDSSSSS SSDSSTKPEASDTAKPNKPTEPGEK (SEQ ID NO 9), or a functional variant or functional fragment thereof.   
     
     
         15 . The method of  claim 5 , wherein the recombinant protein comprises the sequence:
 ATENEGSTQAATSSNMAKTEHRKAAKQVVDEYIEKMLREIQLDRRKHTQNVALNIKL SAIKTKYLRELNVLEEKSKDELPSEIKAKLDAAFEKFKKDTLKPGEK (SEQ ID NO 1), or a functional variant or functional fragment thereof; or   KQVVDEYIEKMLREIQLDRRKHTQNVALNIKLSAIKTKYLRELNVLEEKSKDELPSEIK AKLDAAFEKFKKDTLKPGEK (SEQ ID NO 2), or a functional variant or functional fragment thereof; or   ATENEGATQVPTSSNRANESQAEQGEQPKKLDSERDKARKEVEEYVKKIVGESYA KSTKKRHTITVALVNELNNIKNEYLNKIVESTSESQLQILMMESRSKVDEAVSKFEKDSSSSS SSDSSTKPEASDTAKPNKPTEPGEK (SEQ ID NO 9), or a functional variant or functional fragment thereof.   
     
     
         16 . The method of  claim 6 , wherein the recombinant protein comprises at least amino acids 68-136 of PspC, or a functional variant thereof. 
     
     
         17 . The method of  claim 1 , wherein the recombinant protein binds to CFH within complement control proteins (CCPs) 8-10 of CFH. 
     
     
         18 . The method of  claim 5 , wherein the recombinant protein binds to CFH within complement control proteins (CCPs) 8-10 of CFH. 
     
     
         19 . The method of  claim 9 , wherein the recombinant protein binds to CFH within complement control proteins (CCPs) 8-10 of CFH.