EP1400536A1 — Method for making humanized antibodies

USPTO Abstract

A method for making a humanized antibody comprising amino acid sequence of a non-human, import antibody and a human antibody, comprising the steps of: a. obtaining the amino acid sequences of at least a portion of an import variable domain and of a consensus human variable domain; b. identifying Complementarity Determining Region (CDR) amino acid sequences in the import and the human variable domain sequences; c. substituting an import CDR amino acid sequence for the corresponding human CDR amino acid sequence; d. aligning the amino acid sequences of a Framework Region (FR) of the import antibody and the corresponding FR of the consensus antibody; e. identifying import antibody FR residues in the aligned FR sequences that are non-homologous to the corresponding consensus antibody residues; f. determining if the non-homologous import amino acid residue is reasonably 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 V L - V H interface; and g. for any non-homologous import antibody amino acid residue which is reasonably expected to have at least one of these effects, substituting that residue for the corresponding amino acid residue in the consensus antibody FR sequence.