Serum half-life extension using igbd

Abstract

The present invention relates to complexes comprising (i) an immunoglobulin (Ig) binding moiety and (ii) a pharmaceutically active moiety, wherein the Ig binding moiety specifically binds to the constant domain 1 of the heavy chain (C H 1) of an Ig molecule and their use for therapy and prophylaxis.

1 . A complex comprising
 (i) an immunoglobulin (Ig) binding moiety and   (ii) a pharmaceutically active moiety,   wherein the Ig binding moiety specifically binds to the constant domain 1 of the heavy chain (CH1) of an Ig molecule.   
     
     
         2 . The complex of  claim 1 , wherein the Ig binding moiety specifically binds to the surface-exposed region of the C H 1 domain of an Ig molecule. 
     
     
         3 . The complex of  claim 1 , wherein the Ig binding moiety specifically binds to the Fc portion of the Ig molecule. 
     
     
         4 . The complex of  claim 1 , wherein the Ig molecule is an IgG molecule, preferably an IgG1, IgG2, or IgG4 molecule. 
     
     
         5 . The complex of  claim 1 , wherein the Ig binding moiety specifically binds to an epitope formed by amino acid positions 122-127 and/or 207-214 of an Ig molecule according to EU index. 
     
     
         6 . The complex of  claim 1 , wherein the Ig binding moiety comprises an immunoglobulin binding domain (IgBD), preferably a  streptococcus -derived IgBD. 
     
     
         7 . The complex of  claim 1 , wherein the Ig binding moiety comprises a C H 1 binding-IgBD of streptococcal protein G. 
     
     
         8 . The complex of  claim 1 , wherein the Ig binding moiety comprises an amino acid sequence according to SEQ ID NO: 1 or variants thereof. 
     
     
         9 . The complex of  claim 1 , wherein the pharmaceutically active moiety comprises a biological and/or chemical pharmaceutical. 
     
     
         10 . The complex of  claim 9 , wherein the biological is a pharmaceutically active polypeptide, preferably an antigen-binding molecule. 
     
     
         11 . The complex of  claim 10 , wherein the antigen-binding molecule is selected from the group consisting of an antibody fragment, a Fab fragment, a Fab′ fragment, a F(ab′) 2  fragment, a heavy chain antibody, a single-domain antibody (sdAb), a single-chain variable fragment (scFv), a di-scFv, a bispecific T-cell engager (BITEs), a diabody, a single-chain diabody, a DART, a triple body, an alternative scaffold protein, and a fusion protein thereof. 
     
     
         12 . The complex of  claim 10 , wherein said antigen-binding molecule further comprises a radioactive moiety, a cytotoxic drug, a chelating moiety, a photosensitizer, or an imaging reagent. 
     
     
         13 . The complex of  claim 11 , wherein said antigen binding molecule is a fusion protein, which further comprises a proapoptotic protein, an immuno-(co)stimulatory protein, immuno-suppressive protein, a cytokine, a chemokine, a toxin, a growth factor or an enzyme, preferably an RNase, a prodrug-converting enzmye, or a kinase. 
     
     
         14 . The complex of  claim 1 , wherein the Ig binding moiety and the pharmaceutically active moiety are connected via covalent or non-covalent bond(s). 
     
     
         15 . The complex of  claim 1 , wherein the Ig binding moiety and the pharmaceutically active moiety are connected directly or indirectly via one or more linkers. 
     
     
         16 . The complex of  claim 14 , wherein the one or more linkers comprise peptide linkers, preferably flexible peptide linkers. 
     
     
         17 . The complex of  claim 16 , wherein the one or more peptide linker comprise one or more cleavage sites, preferably one or more endopeptidase cleavage sites. 
     
     
         18 . A nucleic acid molecule comprising a sequence encoding the complex of  claim 1 . 
     
     
         19 . A vector comprising the nucleic acid of  claim 18 . 
     
     
         20 . A cell comprising the complex of  claim 1 , the nucleic acid of  claim 18  and/or the vector of  claim 19 . 
     
     
         21 . A pharmaceutical composition comprising the complex of  claim 1 , the nucleic acid of  claim 18  and/or the vector of  claim 19 . 
     
     
         22 . The pharmaceutical composition of  claim 21 , which further comprises a pharmaceutically acceptable carrier and/or excipient and optionally one or more additional active substances. 
     
     
         23 . A method of extending the serum half-life of an agent comprising combining that agent with the complex of  claim 1 . 
     
     
         24 . A method of treating a subject by administration of a medicament comprising the complex of  claim 1  to a subject in need thereof.