Human serum albumin linkers and conjugates thereof

Abstract

Disclosed is a human serum albumin (HSA) linker and HSA linker with binding, diagnostic, and therapeutic agents conjugated thereto. Also disclosed is a conjugate in which the HSA linker is covalently bonded to amino and carboxy terminal binding moieties that are first and second single-chain Fv molecules (scFvs). Exemplified conjugates are useful, e.g., in reducing tumor cell proliferation, e.g., for therapeutic therapeutic applications. Also disclosed are methods and kits for the diagnostic and therapeutic application of an HSA linker conjugate.

1 . An HSA linker conjugate comprising:
 i) a human serum albumin (HSA) linker comprising an amino acid sequence set forth in any one of SEQ ID NOs:6-15; and   ii) first and second binding moieties selected from the group consisting of antibodies, single-chain Fv molecules, bispecific single chain Fv ((scFv′)2) molecules, domain antibodies, diabodies, triabodies, hormones, Fab fragments, F(ab′)2 molecules, tandem scFv (taFv) fragments, receptors, ligands, aptamers, and biologically-active fragments thereof, wherein said first binding moiety is bonded to the amino terminus of said HSA linker and said second binding moiety is bonded to the carboxy terminus of said HSA linker.   
     
     
         2 . The HSA linker conjugate of  claim 1  wherein the HSA linker comprises the amino acid sequence set forth in SEQ ID NO:1. 
     
     
         3 . The HSA linker conjugate of  claim 1 , wherein said first binding moiety specifically binds ErbB3 and said second binding moiety specifically binds ErbB2. 
     
     
         4 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:16. 
     
     
         5 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:17. 
     
     
         6 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:18. 
     
     
         7 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:19. 
     
     
         8 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:20. 
     
     
         9 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:21. 
     
     
         10 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:22. 
     
     
         11 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:23. 
     
     
         12 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:24. 
     
     
         13 . The HSA linker conjugate of  claim 3  having or comprising an amino acid sequence that is SEQ ID NO:25. 
     
     
         14 . The HSA linker conjugate of  claim 3  admixed with a pharmaceutically acceptable carrier, excipient, or diluent. 
     
     
         15 . A method for treating a patient having a disease or disorder, wherein said method comprises administering to said mammal an effective amount of the HSA linker conjugate of  claim 3 . 
     
     
         16 .- 31 . (canceled) 
     
     
         32 . The HSA linker conjugate of  claim 3 , wherein said first binding moiety binds ErbB3 with a K d  of about 16 nM and said second binding moiety binds ErbB2 with a K d  of about 0.3 nM. 
     
     
         33 . A method of treating a subject, said subject being in need of treatment for a tumor, said treating comprising administering to the subject an effective amount of the HSA linker conjugate of any of  claim 3 . 
     
     
         34 .- 36 . (canceled)