Patent ID: 8084026

Claim:
A composition comprising bispecific dimeric binding molecules each bispecific binding molecule in the composition having at least four antigen binding sites and at least two polypeptide chains, wherein said at least two polypeptide chains each comprise a complete Ig heavy chain, and a chimeric hinge, wherein said chimeric hinge connects the CH1 and the CH2 domain of the Ig heavy chain, and wherein greater than about 50% of the bispecific dimeric binding molecules comprise polypeptide chains that are linked via at least one interchain disulfide linkage, and wherein amino acids at positions 226-242 (Kabat numbering) comprise: (i) the human IgG1 upper hinge region sequence EPKSCDKTHT (SEQ ID NO:2) or the human IgG4 upper hinge region sequence ESKYGPP (SEQ ID NO:20) at Kabat hinge positions 226-238; (ii) a cysteine residue (C) at Kabat hinge position 239; (iii) a proline residue (P) at Kabat hinge position 240; (iv) a proline (P) or serine (S) residue at Kabat hinge position 241; (v) the human IgG3 middle hinge sequence CPEPKSCDTPPPCPR (SEQ ID NO:24) at Kabat hinge positions 241EE-241SS; and (vi) a cysteine residue (C) at Kabat hinge position 242, and wherein said bispecific dimeric binding molecules comprise: at least a first binding site specific for LTβR and at least a second binding site specific for TRAIL-R2, wherein said antigen binding sites are selected from the group consisting of an antibody, an antigen binding fragment of an antibody, and an scFv molecule.