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ERBB2 is a tyrosine kinase receptor which can act as homodimers or heterodimers with other members of the ERBB family. Nearly 30% of breast cancers overexpress ERBB2, which can be effectively targeted by anti-ERBB2 monoclonal antibodies. Trastuzumab directed against an epitope on subdomain IV of the extracellular domain (ECD) of ERBB2 is a clinically used therapeutics but the response rate is poor and acquired resistance is frequent. Pertuzumab that binds to subdomain II and inhibits receptor dimerization is another promising therapeutics under clinical trials. Anti-ERBB2 antibodies directed to novel epitopes are potentially useful tools for replacement and combinatorial therapies. We produced five new anti-ERBB2 antibodies, all directed against epitope (s) present only on the native ECD. They performed selective growth inhibitory effects depending on the level of ERBB2 expression and cellular …