ANTIBODIES SELECTIVELY ACTING ON CELLS WITH HIGH TARGET DENSITY RECEPTOR EPIDERMAL GROWTH FACTOR (EGFR)

摘要

1. An anti-EGFR antibody that binds selectively and primarily to affected cells with an EGFR density higher than normal; anti-EGFR antibody includes a heavy chain and a light chain, each of which has a constant region and a variable region, each variable region consists of frame sections and complementarity determining regions (CDR hypervariable regions), the amino acid sequence of which is described below: For heavy chain: CDR1 NYGVH (SEQ ID No. 1) CDR2 VIWSGGNTDYNTPFTS (SEQ ID No. 2) CDR3 ALTYYDYEFAY (SEQ ID No. 3) For light chain: CDR1 RASQSIGTNIH (SEQ ID No. 4) CDR2 ASESIS (SEQ ID No. 5) CDR3 QQNNNWTT (SEQ ID No. 6) where at least one of E, D, W, Y, Y, D, and E is substituted with an amino acid that gives this antibody p Reductions EGFR binding affinity (Kd) value of from 1,0 nM and menee.2. The antibody of claim 1, wherein the Kd value is 10 nM or less. The antibody of claim 1, wherein the Kd value is from 10 nM to 500 nM. An antibody according to claim 1, wherein at least one of said substitutions is in the heavy chain. The antibody according to claim 4, in which Y is substituted on A.6. The antibody according to claim 4, in which Y is substituted on A.7. The antibody according to claim 4, in which D is substituted on N.8. The antibody of claim 4, wherein at least one of the substitutions is in the heavy chain and at least one of the substitutions is in the light chain. The antibody of claim 8, wherein the Yea Yoba are substituted. The antibody according to claim 9, in which it is Substituted on Ki and Substituted on A.11. The antibody of claim 10, wherein the heavy chain includes at least two of the substitutions mentioned. The antibody of claim 11, wherein D and Doba are substituted. The antibody of claim 9, wherein D58 is substituted with N58 and D is substituted with N103.14. The antibody according to claim 12, in which it is further Substituted. 15. The antibody of claim 14, wherein it is Substituted on Q.16. The antibody according to claim 1, in which, at least