Bispecific antigen-binding constructs targeting HER2

A method of treating a subject having a HER2 (human epidermal growth factor receptor 2) expressing (HER2+) tumor comprising administering an effective amount of an antigen binding construct to the subject, wherein the antigen binding construct comprises a first antigen-binding polypeptide construct, a second antigen-binding polypeptide construct, a dimeric Fc comprising a first Fc polypeptide and a second Fc polypeptide, a first linker polypeptide, and a second linker polypeptide, wherein:

• the first antigen-binding polypeptide construct comprises a first antigen binding moiety which specifically binds a HER2 ECD2 (extracellular domain 2) antigen on a HER2-expressing cell and the first antigen binding moiety comprises three VH CDR sequences having the amino acid sequences of SEQ ID NO:335 (CDR-H2), SEQ ID NO:336 (CDR-H3), and SEQ ID NO:348 (CDR-H1) and three VL CDR sequences having the amino acid sequences of SEQ ID NO:338 (CDR-L2), SEQ ID NO:347 (CDR-L3), and SEQ ID NO:340 (CDR-L1);
• and
• the second antigen-binding polypeptide construct comprises a second antigen binding moiety which specifically binds a HER2 ECD4 (extracellular domain 4) antigen on a HER2-expressing cell and the second antigen binding moiety comprises three VH CDR sequences having the amino acid sequences of SEQ ID NO:
• 341 (CDR-H2), SEQ ID NO:342 (CDR-H3) and SEQ ID NO:343 (CDR-H1) and three VL CDR sequences comprising the amino acid sequences of the three VL CDR sequences of SEQ ID NO:
• 344 (CDR-L2), SEQ ID NO:345 (CDR-L3) and SEQ ID NO:346 (CDR-L1);
• and
• the first linker polypeptide is operably linked to the first antigen-binding polypeptide construct and the first Fc polypeptide, and the second linker polypeptide is operably linked to the second antigen-binding polypeptide construct and the second Fc polypeptide and the first and second linker polypeptide each comprise an immunoglobulin hinge region polypeptide selected from an IgG1, IgG2 or IgG4 hinge region.