Patent ID: 11939394
Assignee: INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS
Field: Biotechnology (Chemistry)
Classification: CPC C  A | IPC C

Claim 0:
1. A bispecific antibody that comprises a variable domain that binds an extracellular part of EGFR and a variable domain that binds an extracellular part of LGR5, wherein
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAMN (SEQ ID NO:188), WINANTGDPTYAQGFTG (SEQ ID NO: 215), and ERFLEWLHFDY (SEQ ID NO: 242); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SSSSYWG (SEQ ID NO: 192), SFYYSGNTYYNPSLKS (SEQ ID NO: 220), and TYSSSWDGVLYYFDY (SEQ ID NO:247);
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAMN (SEQ ID NO: 188), WINANTGDPTYAQGFTG (SEQ ID NO: 215) and ERFLEWLHFDY (SEQ ID NO: 242); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences TYYWS (SEQ ID NO: 193), YVYYTGRTKYNPSLKS (SEQ ID NO: 221) and GGIVVVPAARDYYYYMDV (SEQ ID NO: 248);
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAMN (SEQ ID NO: 188), WINANTGDPTYAQGFTG (SEQ ID NO: 215) and ERFLEWLHFDY (SEQ ID NO: 242), and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SHWIG (SEQ ID NO: 194), VIYPGDSDTRYSPSFQG (SEQ ID NO: 222) and PNSGSPRYFEF (SEQ ID NO:249);
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAMN (SEQ ID NO: 188), WINANTGDPTYAQGFTG (SEQ ID NO: 215), and ERFLEWLHFDY (SEQ ID NO: 242), and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SHWIA (SEQ ID NO: 196), IVYPGDSDTRYSPSFQG (SEQ ID NO: 224), and HEWELLGPFDY (SEQ ID NO: 251);
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAMN (SEQ ID NO: 188), WINANTGDPTYAQGFTG (SEQ ID NO: 215), and ERFLEWLHFDY (SEQ ID NO: 242) and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences NDAIS (SEQ ID NO: 197), SIIPILDTTDHAQKFQG (SEQ ID NO: 225), and EHIAARQDYFDY (SEQ ID NO: 252);
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAMN (SEQ ID NO: 188), WINANTGDPTYAQGFTG (SEQ ID NO: 215), and ERFLEWLHFDY (SEQ ID NO: 242); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SYTMN (SEQ ID NO: 198), WINTDTGDPTYAQGFTG (SEQ ID NO: 226), and GDCDSTSCYRYSYGYEDY (SEQ ID NO: 253);
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAMN (SEQ ID NO:188), WINANTGDPTYAQGFTG (SEQ ID NO: 215), and ERFLEWLHFDY (SEQ ID NO: 242); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SYAIS (SEQ ID NO: 199), GIIPIFDTRNYAQILQG (SEQ ID NO: 227), and GSDEGDWFDP (SEQ ID NO: 254);
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAMN (SEQ ID NO:188), WINANTGDPTYAQGFTG (SEQ ID NO: 215), and ERFLEWLHFDY (SEQ ID NO: 242); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences NYAIS (SEQ ID NO: 200), SIIPILGTTDHAQKFQD (SEQ ID NO: 228), and EYIAARLDYFDS (SEQ ID NO: 255);
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences ELSMH (SEQ ID NO: 189), GFDPEYGKTFFAQNFQG (SEQ ID NO: 216), and EGYYETTTYYYNLFDS (SEQ ID NO: 243); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SHWIG (SEQ ID NO: 194), VIYPGDSDTRYSPSFQG (SEQ ID NO: 222) and PNSGSPRYFEF (SEQ ID NO: 249);
wherein the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences ELSMH (SEQ ID NO: 189), GFDPEYGKTFFAQNFQG (SEQ ID NO: 216), and EGYYETTTYYYNLFDS (SEQ ID NO: 243); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SYTMN (SEQ ID NO: 198), WINTDTGDPTYAQGFTG (SEQ ID NO:226), and GDCDSTSCYRYSYGYEDY (SEQ ID NO: 253),
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences SYGIS (SEQ ID NO: 187), WISAYNGNTNYAQKLQG (SEQ ID NO: 214), and DRHWHWWLDAFDY (SEQ ID NO: 241); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SHWIG (SEQ ID NO: 194), VIYPGDSDTRYSPSFQG (SEQ ID NO: 222) and PNSGSPRYFEF (SEQ ID NO: 249); or
the VH chain of the variable domain that binds EGFR comprises the CDR1, CDR2 and CDR3 amino acid sequences SYGIS (SEQ ID NO: 187), WISAYNGNTNYAQKLQG (SEQ ID NO: 214), and DRHWHWWLDAFDY (SEQ ID NO: 241); and the VH chain of the variable domain that binds LGR5 comprises the CDR1, CDR2 and CDR3 amino acid sequences SYTMN (SEQ ID NO: 198), WINTDTGDPTYAQGFTG (SEQ ID NO: 226), and GDCDSTSCYRYSYGYEDY (SEQ ID NO: 253);
and wherein the first and second variable domains further comprise the light chain variable domain comprising a CDR1 sequence QSISSY (SEQ ID NO: 299), a CDR2 sequence AAS, and a CDR3 sequence QQSYSTPPT (SEQ ID NO: 300).