BINDING MOLECULES SPECIFIC FOR HER3 AND USES THEREOF

摘要

Provided herein are antibodies and antigen binding fragments thereof that bind the extracellular domain of the HER3 receptor and inhibit various HER3 receptor related functions via ligand-dependent and/or ligand-independent mechanisms. Also provided are compositions with increased half-life, as well as compositions and methods for diagnosing and treating diseases associated with HER3 mediated signal transduction.

主权项

1. A method of resensitizing a tumor or tumor cell in a subject to a HER targeted therapy, comprising 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
(i) the antibody or antigen binding fragment thereof binds to the same HER3 epitope as an antibody or antigen-binding fragment thereof comprising the heavy chain variable region (VH) and light chain variable region (VL) of CL16 or 2C2; or (ii) the antibody or antigen binding fragment thereof competitively inhibits HER3 binding by an antibody or antigen-binding fragment thereof comprising the VH and VL of CL16 or 2C2; or (iii) the antibody or antigen binding fragment thereof comprises
(A) an antibody VL, wherein the VL comprises the amino acid sequence:[FW1]X1GSX2SNIGLNYVS[FW2]RNNQRPS[FW3]AAWDDX3X4X5GEX6[FW4] wherein [FW1], [FW2], [FW3] and [FW4] represent VL framework regions, andwherein
(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[FW6]X7IGSSGGVTNYADSVKG[FW7]VGLGDAFDI[FW8] wherein [FW5], [FW6], [FW7] and [FW8] represent VH framework regions, andwherein X7 represents amino acid residues Tyrosine (Y), Isoleucine (I) or Valine (V).