Patent ID: 9096651
Filing Date: 2015-08-04
Classification: A61K,A61P,C07K,G01N

Abstract:
1. A method for altering the plasma pharmacokinetics of an antigen-binding molecule comprising a heavy chain variable region, a light chain variable region, and an FcRn-binding domain, while retaining 80% or more of the antigen-binding molecule's pre-modification antigen-binding activity under physiological conditions, the method comprising: preparing a modified antigen-binding molecule by substituting at least one amino acid residue in the antigen-binding molecule to make the charge of the antigen-binding molecule more negative than prior to the amino acid substitution, wherein the at least one amino acid residue is selected from the group consisting of amino acid residues at positions 31, 61, 62, 64, and 65 (Kabat numbering) in the heavy chain variable region and positions 24, 27, 53, 54, and 55 (Kabat numbering) in the light chain variable region of the antigen-binding molecule; and determining that a plasma pharmacokinetics parameter of the modified antigen-binding molecule is altered in the modified antigen-binding molecule compared to in the antigen-binding molecule prior to modification, wherein the parameter alteration is: increased mean retention time in plasma, increased half-life in plasma (t1/2), increased area under the concentration curve (AUC), or decreased clearance (CL) from plasma, each as compared to in the antigen-binding molecule prior to modification.