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1. EP2202245 - METHOD OF MODIFYING ISOELECTRIC POINT OF ANTIBODY VIA AMINO ACID SUBSTITUTION IN CDR

注意: このテキストは、OCR 処理によってテキスト化されたものです。法的な用途には PDF 版をご利用ください。

Claims

1. A method for controlling the plasma pharmacokinetics of an IgG antibody while retaining the antigen-binding activity of the variable region, which method comprises modifying the charge of at least one exposable amino acid residue on the surface of a complementarity determining region (CDR) of the antibody, wherein the exposable amino acid residue on the surface of the CDR region is at least one amino acid residue selected from amino acid residues at positions 31, 61, 62, 64, and 65 in the heavy chain variable region and positions 24, 27, 53, 54, and 55 in the light chain variable region according to Kabat's numbering system.
  2. A method for producing an IgG antibody whose pharmacokinetics in plasma are controlled while retaining the antigen-binding activity of the variable region, which method comprises:

(a) modifying a nucleic acid encoding an IgG antibody so as to modify the charge of at least one exposable amino acid residue on the surface of the CDR region of the antibody, wherein the exposable amino acid residue on the surface of the CDR region is at least one amino acid residue selected from amino acid residues at positions 31, 61, 62, 64, and 65 in the heavy chain variable region and positions 24, 27, 53, 54, and 55 in the light chain variable region according to Kabat's numbering system;

(b) culturing a host cell to express the nucleic acid; and

(c) collecting the antibody from the host cell culture.


  3. The method of claim 1 or 2, wherein the antibody is a chimeric antibody, humanized antibody, or human antibody.
  4. The method of any one of claims 1 to 3, wherein the antibody is a multispecific antibody that binds to at least two types of antigens.
  5. The method of any one of claims 1 to 4 for controlling the plasma pharmacokinetics of an IgG antibody or for producing an IgG antibody whose pharmacokinetics in plasma are controlled, wherein the control of pharmacokinetics refers to increase or decrease of any one of the parameters of clearance (CL) in plasma, area under the concentration curve (AUC), mean retention time in plasma, and half-life in plasma (t1/2).
  6. A method for producing a multispecific IgG antibody whose pharmacokinetics in plasma are controlled while retaining the antigen-binding activity of the variable region, said antibody comprising a first polypeptide and a second polypeptide each of which comprises an antibody variable region, which method comprises:

(a) modifying a nucleic acid encoding the first and/or second polypeptide so as to modify the charge of at least one exposable amino acid residue on the surface of the CDR region of the first polypeptide and/or second polypeptide, wherein either one or both of a nucleic acid encoding the amino acid residues of the first polypeptide and a nucleic acid encoding the amino acid residues of the second polypeptide are modified, so as to increase the difference between the isoelectric points of the first polypeptide and/or second polypeptide when compared to said polypeptides before modification, and wherein the exposable amino acid residue on the surface of the CDR region is at least one amino acid residue selected from amino acid residues at positions 31, 61, 62, 64, and 65 in the heavy chain variable region and positions 24, 27, 53, 54, and 55 in the light chain variable region according to Kabat's numbering system;

(b) culturing a host cell to express the nucleic acids; and

(c) collecting a multispecific antibody from the host cell culture.


  7. The method of claim 6, wherein the step of collecting the multispecific IgG antibody comprising the first polypeptide and second polypeptide from the host cell culture is achieved by a standard chromatography.
  8. The method of claim 6 or 7, wherein the nucleic acid is modified so that the peaks for homomultimer of the first polypeptide, homomultimer of the second polypeptide, and heteromultimer of the first polypeptide and second polypeptide are more clearly separated in a standard chromatographic analysis when compared to those of said polypeptides before modification.