Multimeric complexes with improved in vivo stability, pharmacokinetics and efficacy
The present invention concerns multimeric complexes based on antibody fusion proteins comprising an AD moiety attached to the C-terminal end of each antibody light chain. The complexes further comprise effector moities attached to DDD moieties. Two copies of the DDD moiety form a dimer that binds to the AD moiety. The complexes may be trimers, pentamers, hexamers or other multimers. The effector moieties may be selected from a second antibody or antigen-binding fragment thereof, a cytokine, an interferon, a toxin, an antigen, a xenoantigen, a hapten, a protamine, a hormone, an enzyme, a ligand-binding protein, a pro-apoptotic agent and an anti-angiogenic agent. Surprisingly, attachment of the AD moiety to the C-terminal end of the antibody light chain results in improved pharmacokinetics and in vivo stability and efficacy, compared to homologous complexes wherein the AD moiety is attached to the antibody heavy chain.
IBC Pharmaceuticals, Inc.
C C C A C C C C A C C A C C C C C C C A C C A A A C C A A C C A C C C C A C A C C C C
C07K C12N C07K A61P C07K C07K C12N C12N A61P C07K C07K A61K C12N C07K C07K C07K C12Y C07K C07K A61K C07K C07K A61P A61P A61P C12N C07K A61K A61K C07K C07K A61K C07K C07K C12Y C07K A61K C07K A61K C12N C07K C12N C07K
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David M. Edmund A. Chien-Hsing
Goldenberg Rossi Chang