Binding molecules specific for HER3 and uses thereof

A method of resensitizing a HER3-expressing tumor characterized by unregulated cell growth or HER3-expressing tumor cell characterized by unregulated cell growth in a subject to a HER targeted therapy, comprising a) administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof which specifically binds to an epitope within the extracellular domain of HER3, wherein the tumor or tumor cell had previously acquired resistance to the HER targeted therapy following treatment with the HER targeted therapy, wherein the HER targeted therapy is an EGFR targeted therapy, and wherein the antibody or antigen binding fragment thereof is a monoclonal antibody or antigen binding fragment thereof that comprises

• (A) an antibody VL, wherein the VL comprises the amino acid sequence:
• [FW1]X1GSX2SNIGLNYVS(SEQ ID NO:
• 49)[FW2]RNNQRPS(SEQ ID NO:
• 50)[FW3]AAWDDX3X4X5GEX6(SEQ ID NO:
• 51)[FW4]
• wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, and wherein
• (a) X1 represents amino acid residues Arginine (R) or Serine (S),
• (b) X2 represents amino acid residues Serine (S) or Leucine (L),
• (c) X3 represents amino acid residues Serine (S) or Glycine (G),
• (d) X4 represents amino acid residues Leucine (L) or Proline (P),
• (e) X5 represents amino acid residues Arginine (R), Isoleucine (I), Proline (P) or Serine (S), and
• (f) X6 represents amino acid residues Valine (V) or Alanine (A), and
• (B) an antibody VH, wherein the VH comprises the amino acid sequence:
• [FW5]YYYMQ(SEQ ID NO:
• 52)[FW6]X7IGSSGGVTNYADSVKG(SEQ ID NO:
• 53)[FW7]VGLGDAFDI(SEQ ID NO:
• 54)[FW8] wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, and wherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V);
• and b) simultaneously administering to the subject a therapeutically effective amount of the HER targeted therapy.