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AssigneesNational Research Council of Canada, YM Biosciences Inc.
InventorsIlia Alexandre Tikhomirov, Maria L. Jaramillo, Maureen D. O'Connor-McCourt, Traian Sulea, Renald Gilbert, Bruno Gaillet, Jason Baardsnes, Myriam Banville, Suzanne Grothe
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Herein described are antibodies to epidermal growth factor receptor (EGFR) having an EGFR binding affinity that is sufficient to kill disease cells presenting EGFR at high density, but is insufficient for binding to normal cells. A therapeutic effect is thus achieved while avoiding adverse events that result from unintended binding to normal cells.
An EGFR antibody that binds preferentially to disease cells having an EGFR density greater than a normal EGFR density, the EGFR antibody comprising a heavy chain and a light chain, each chain having a constant region and a variable region, each variable region comprising framework regions and complementarity determining regions (CDRs), wherein the CDRs have an amino acid sequence set forth below:
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an EGFR antibody in an amount useful to control the growth of cells presenting EGFR at a density greater than the normal EGFR density, wherein the EGFR antibody has an affinity (Kd) for EGFR that is within the range from about 1.0 nM to about 1 uM, said antibody having insignificant binding affinity for a cell presenting EGFR at a normal EGFR density.
A pharmaceutical composition according to claim 24, wherein the antibody is defined according to claim 1.
A method for treating a subject presenting with disease cells having an EGFR density greater than normal, comprising treating the subject with a pharmaceutical composition comprising a pharmaceutically acceptable carrier and an amount of an EGFR antibody, bivalent fragment thereof or conjugate thereof effective to control the growth of said disease cells while minimizing adverse effects on cells presenting EGFR at a normal density, wherein the EGFR antibody has an affinity (Kd) for EGFR that is within the range from about 1.0 nM to about 1 uM, said antibody having insignificant binding affinity for a cell presenting EGFR at a normal EGFR density.
Dependencies are inferred from the claim text.