ANTIGEN-BINDING MOLECULES THAT BIND THE EPIDERMAL GROWTH FACTOR RECEPTOR (FGFR) CODING THEIR VECTORS AND THEIR APPLICATION

摘要

1. An antigen binding molecule (AFM) comprising one or more specifically determinable residues (SDRs) in one or more hypervariable regions (CDRs) of a rat monoclonal antibody ICR62, and a sequence derived from a heterologous polypeptide, wherein said AFM specifically binds to EGFR but not causes a clinically significant level of toxicity when administered to a subject in a therapeutically effective amount, in addition, the indicated AFM does not include a sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID N O: 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 23, SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 29, SEQ ID NO: 31, SEQ ID NO: 33, SEQ ID NO: 35, SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 43, SEQ ID NO: 45, SEQ ID NO: 49, SEQ ID NO: 51 and SEQ ID NO: 121.! 2. The AFM according to claim 1, wherein said one or more SDRs are in one or more heavy chain CDRs. ! 3. The AFM according to claim 2, wherein said one or more heavy chain SDRs are selected from the group consisting of phenylalanine at position Kabat 29, asparagine at position 52 Kabat, tyrosine at position 56 Kabat, and valine at position 100 b Kabat Kabat. ! 4. The AFM according to claim 3, wherein said one or more heavy chain SDRs are tyrosine at position 56 according to Kabat and valine at position 100 b according to Kabat. ! 5. The AFM of claim 3, wherein the one or more heavy chain SDRs are phenylalanine at position Kabat 29, asparagine at position 52 Kabat, tyrosine at position 56 Kabat, and valine at position 100 b Kabat. ! 6. The AFM according to claim 1, wherein said one or more SDRs are in one or more light chain CDRs. ! 7. The AFM of claim 6, wherein said one or more light chain SDRs include asparagine at position 50 according to Kabat. ! 8. AFM according to claim 6, in which it is indicated