Drug compositions, fushions and conjugates

Abstract

Drug compositions, fusions and conjugates are provided. The drug fusions and conjugates contain a therapeutic or diagnostic agent that is fused or conjugated to an antigen-binding fragment of an antibody that binds serum albumin. The drug compositions, fusions and conjugates have a longer in vivo half-life in comparison with the unconjugated or unfused therapeutic or diagnostic agent.

What is claimed is: 
     
         1 . A drug fusion having the formula:
   a-(X) n1 -b-(Y) n2 -c-(Z) n3 -d Or a-(Z) n3 -b-(Y) n2 -c-(X) n1 -d,   wherein
 X is a polypeptide drug that has binding specificity for a first target; 
 Y is an immunoglobulin heavy chain variable domain (V H ) that has binding specificity for serum albumin, or an immunoglobulin light chain variable domain (V L ) that has binding specificity for serum albumin; 
 Z is a polypeptide drug that has binding specificity for a second target; 
 a, b, c and d are independently a polypeptide comprising one to about 100 amino acid residues or absent; 
 n1 is one to about 10; 
 n2 is one to about 10; and 
 n3 is zero to about 10, 
   with the proviso that when n1 and n2 are both one and n3 is zero, X does not comprise an antibody chain or a fragment of an antibody chain.   
     
     
         2 . The drug fusion of  claim 1 , wherein n1 and n3 are both one, and n2 is two to about 10. 
     
     
         3 . The drug fusion of  claim 1 , wherein Y comprises an amino acid sequence selected from the group consisting of SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:24, SEQ ID NO:25 and SEQ ID NO:26. 
     
     
         4 . The drug fusion of  claim 1 , wherein Y comprises an amino acid sequence selected from the group consisting of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22 and SEQ ID NO:23. 
     
     
         5 . The drug fusion of  claim 1 , wherein X is IL-1ra or a functional variant of IL-1ra. 
     
     
         6 . The drug fusion of  claim 1 , wherein X is an analgesic agent, an anti-cancer agent, a hormone or an antimicrobial polypeptide or peptide. 
     
     
         7 . The drug fusion of  claim 1 , wherein X is an immunosuppressive agent, an antiviral agent, an antibiotic, an anti-inflammatory agent, a cytotoxin or cytotoxic agent. 
     
     
         8 . The drug fusion of  claim 1 , wherein X is a protease inhibitor. 
     
     
         9 . The drug fusion of  claim 1 , wherein said V H  and V L  have binding specificity for human serum albumin. 
     
     
         10 . A recombinant nucleic acid encoding the drug fusion of  claim 1 . 
     
     
         11 . A nucleic acid construct comprising the recombinant nucleic acid of  claim 10 . 
     
     
         12 . A host cell comprising the recombinant nucleic acid of  claim 10 . 
     
     
         13 . A method for producing a drug fusion comprising maintaining the host cell of  claim 12  under conditions suitable for expression of said recombinant nucleic acid, whereby a drug fusion is produced. 
     
     
         14 . A method for treating an individual having an inflammatory disease, comprising administering to said individual a therapeutically effective amount of a drug fusion of any one of  claim 1 . 
     
     
         15 . The method of  claim 14 , wherein said inflammatory disease is arthritis.