READILY ISOLATED BISPECIFIC BINDING MOLECULES WITH NATIVE FORMAT HAVING MUTATED CONSTANT REGIONS

摘要

The invention provides heterodimer bispecific antigen-binding molecules that include a first polypeptide that does not include an IgG CH1 domain and a second polypeptide having an immunoglobulin constant region where there is at least one mutation in the IgG CH3 domain that abolishes the ability of the second polypeptide to bind CH3-specific affinity media such that the first and second polypeptides have different affinities with respect to CH1 and CH3 specific affinity reagents that allows rapid isolation by differential binding of the first and second polypeptides to these affinity reagents. The invention also provides bispecific antibodies that have IgG CH1 and CH3 regions with different affinities with respect to affinity reagents that allows rapid isolation by differential binding of the IgG regions to these affinity reagents. The invention also concerns bispecific antibodies which are heterodimers of heavy chains, i.e., two immunoglobulin heavy chains that differ by at least two amino acids that allow for the isolation of the bispecific antibody based on a differential affinity of one mutated immunoglobulin heavy chain and a second mutated immunoglobulin heavy chain toward two different affinity reagents.