Humanized antibodies and methods for making them

  • US 6,054,297 A
  • Filed: 05/09/1995
  • Issued: 04/25/2000
  • Est. Priority Date: 06/14/1991
  • Status: Expired due to Term
First Claim
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1. A method for making a humanized antibody comprising non-human, import Complementarity Determining Region (CDR) amino acid residues and human Framework Region (FR) amino acid residues, comprising the steps of:

  • (a) obtaining the amino acid sequences of an import variable domain and of a VH subgroup III consensus human variable domain;

    (b) identifying CDR amino acid sequences in the import and the human variable domain sequences;

    (c) substituting import CDRs for the corresponding human CDRs;

    (d) aligning the amino acid sequences of a FR of the import antibody and the corresponding FR of the consensus variable domain;

    (e) identifying import antibody FR residues in the aligned FR sequences that are non-homologous to the corresponding consensus variable domain residues;

    (f) determining if the non-homologous import amino acid residue is expected to have at least one of the following effects;

    (1) non-covalently binds antigen directly;

    (2) interacts with a CDR;

    or(3) participates in the VL -VH interface;

    (g) for any non-homologous import antibody amino acid residue which is expected to have at least one of these effects, substituting that residue for the corresponding amino acid residue in the consensus variable domain FR sequence; and

    (h) preparing a humanized antibody which binds antigen, wherein the humanized antibody comprises an amino acid sequence determined according to the above steps.

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