摘要 |
A multivalent antigen-binding protein comprises a first Fv fragment bound to at least one further Fv fragment by a connecting structure which links the Fv fragments to each other but which maintains them spaced apart such that the proteins are capable of binding to adjacent antigenic determinants. Typically the connecting structure comprises a spacing polypeptide sequence, which may be about 3 to 16 amino acids in length, connected to a linkage unit which may be a synthetic chemical linker, e.g., a maleimide linker, or is a polypeptide sequence leading from the spacing sequence. In a particularly preferred embodiment, the multivalent antigen binding protein comprises a VH domain having attached to its C-terminal end a V-C joining sequence and an antibody hinge sequence. Preferably one or more of the Fv fragments is a single chain Fv (scFv). The proteins are preferably prepared by recombinant DNA techniques and are useful for in vivo therapeutic and especially diagnostic applications. |