Bispecific single chain antibodies with specificity for high molecular weight target antigens

A bispecific single chain antibody comprising a single chain variable fragment (scFv) comprising a human and primate prostate-specific membrane antigen (PSMA) binding domain and a scFv comprising a human and primate CD3 epsilon (CD3ε) binding domain which binds to CD3ε on a T cell,

• wherein the PSMA binding domain comprises:
• (a) a light chain variable (VL) region comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 269, CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 270, and CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 271, and a heavy chain (VH) region comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 274, CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 275, and CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 276;
• (b) a VL region comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 283, CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 284, CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 285, and a VH region comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 288, CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 289, and CDR-H3 comprising the amino acid sequence of SEQ ID NO:290;
• (c) a VL region comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 297, CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 298, CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 299, and a VH region comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 302, CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 303 and CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 304;
• (d) a VL region comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 311, CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 312, CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 313, and a VH region comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 316, CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 317, and CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 318;
• (e) a VL region comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 325, CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 326, CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 327, and a VH region comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 330, CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 331, and CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 332;
• (f) a VL region comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 255, CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 256, CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 257, and a VH region comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 260, CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 261, and CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 262;
• or
• (g) a VL region comprising CDR-L1 comprising the amino acid sequence of SEQ ID NO:
• 481, CDR-L2 comprising the amino acid sequence of SEQ ID NO:
• 482, CDR-L3 comprising the amino acid sequence of SEQ ID NO:
• 483, and a VH region comprising CDR-H1 comprising the amino acid sequence of SEQ ID NO:
• 476, CDR-H2 comprising the amino acid sequence of SEQ ID NO:
• 477, and CDR-H3 comprising the amino acid sequence of SEQ ID NO:
• 478.