The invention provides dual-specific antibodies and methods for manufacturing and using these antibodies. In general, the dual-specific antibodies are generated by identifying a
monospecific antibody with electrostatic or hydrophobic light chain variable region (VL) residues and altering the
nucleic acid sequence encoding one or more
solvent-accessible residues in the
antibody's VH, either alone or in combination with altering the
nucleic acid sequence encoding the
antibody's VL. The altered VH and VL are expressed, and dual-specific antibodies or
antigen-binding fragments are selected from them. Examples of dual-specific antibodies and methods for using the antibodies are also provided.