Multispecific Antibody Targeting and Multivalency Through Modular Recognition Domains

Abstract

Antibodies containing one or more modular recognition domains (MRDs) that can be used to target the antibodies to specific sites are described. The use of antibodies containing one or more modular recognition domains to treat disease, and methods of making antibodies containing one or more modular recognition domains are also described.

What is claimed is: 
     
         1 . A complex comprising an antibody and at least one modular recognition domain (MRD), wherein the antibody is (a) murine, (b) chimeric, (c) humanized, or (d) human. 
     
     
         2 . The complex of  claim 1 , wherein the antibody is multispecific. 
     
     
         3 . The complex of  claim 1 , wherein the antibody is an IgG. 
     
     
         4 . The complex of  claim 1 , wherein the MRD binds to a target selected from the group consisting of: an integrin, a cytokine, an angiogenic cytokine, vascular endothelial growth factor (VEGF), insulin-like growth factor-I receptor (IGF-IR), a tumor antigen, CD20, an epidermal growth factor receptor (EGFR), the ErbB2 receptor, the ErbB3 receptor, tumor associated surface antigen epithelial cell adhesion molecule (Ep-CAM), an angiogenic factor, an angiogenic receptor, cell surface antigen, soluble ligand, vascular homing peptide, and nerve growth factor. 
     
     
         5 . The complex of  claim 4 , wherein the target is a human protein. 
     
     
         6 . The complex of  claim 1 , wherein the antibody binds to a target selected from the group consisting of an integrin, a cyokine, an angiogenic cytokine, vascular endothelial growth factor (VEGF), insulin-like growth factor-I receptor (IGF-IR), a tumor antigen, CD20, an epidermal growth factor receptor (EGFR), the ErbB2 receptor, the ErbB3 receptor, tumor associated surface antigen epithelial cell adhesion molecule (Ep-CAM), an angiogenic factor, an angiogenic receptor, cell surface antigen, soluble ligand, vascular homing peptide, and nerve growth factor. 
     
     
         7 . The complex of  claim 1 , wherein the antibody is selected from the group consisting of trastuzumab, cetuximab, and panitumumab. 
     
     
         8 . The complex of  claim 1 , wherein the antibody and the MRD bind to the same molecule. 
     
     
         9 . The complex of  claim 1 , wherein the antibody and the MRD bind to different molecules. 
     
     
         10 . The complex of  claim 1 , wherein an MRD is located on a terminus selected from the group consisting of (a) the N-terminus of the antibody heavy chain, (b) the N-terminus of the antibody light chain, (c) the C-terminus of the antibody heavy chain, and (d) the C-terminus of the antibody light chain. 
     
     
         11 . The complex of  claim 10 , wherein a first MRD is located on (c) the C-terminus of the antibody heavy chain and a second MRD is located on (d) the C-terminus of the antibody light chain. 
     
     
         12 . The complex of  claim 1 , wherein the antibody and the MRD are operably linked through a linker peptide. 
     
     
         13 . The complex of  claim 12 , wherein the linker comprises a sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:19. 
     
     
         14 . The complex of  claim 1 , wherein the antibody is capable of binding to an antibody target and an MRD target simultaneously. 
     
     
         15 . The complex of  claim 1 , wherein the antibody comprises at least two MRDs. 
     
     
         16 . The complex of  claim 15 , wherein two MRDs are homo-multimeric. 
     
     
         17 . The complex of  claim 15 , wherein two MRDs are hetero-multimeric. 
     
     
         18 . The complex of  claim 17 , wherein the hetero-multimeric MRDs bind to the same target. 
     
     
         19 . The complex of  claim 17 , wherein the hetero-multimeric MRDs bind to different targets. 
     
     
         20 . The complex of  claim 15 , wherein the two MRDs are located on the same antibody terminus or on different antibody termini.