Method of humanizing antibodies by matching canonical structure types CDRs

A method of making a humanized antibody or a binding fragment thereof comprising,

• identifying canonical CDR structure types for at least two CDRs within a variable region of a light chain of a subject non-human antibody;
• identifying a candidate human antibody light chain variable region sequence that comprises at least two CDR sequences with the same canonical structure type as the at least two CDR sequences from variable region of the light chain of the subject non-human antibody;
• constructing a humanized antibody light chain comprising a variable region that includes three CDRs from the variable region of the light chain of the subject non-human antibody and variable region frameworks from the candidate human antibody light chain variable region sequence, and provided that up to 10 residues in the variable region frameworks from the candidate human antibody light chain variable region sequence can be substituted;
• identifying canonical CDR structure types for two CDRs within a variable region of a heavy chain of the subject non-human antibody;
• identifying a candidate human antibody heavy chain variable region sequence that comprises two human CDR sequences with the same canonical structure type as the two CDR sequences from variable region of the heavy chain of the subject non-human antibody;
• and
• constructing a humanized antibody heavy chain comprising a variable region that includes three CDRs from the variable region of the heavy chain of the subject non-human antibody and variable region frameworks from the candidate human antibody heavy chain variable region sequence and provided that up to 10 residues in the variable region frameworks from the candidate human antibody heavy chain variable region sequence can be substituted,
• wherein the humanized light chain and the humanized heavy chain form a humanized antibody, or a fragment thereof selected from a Fab fragment, a (Fab)′2 molecule, and a single chain Fv molecule, that binds to the same antigen as the non-human antibody;
• provided that residues 61-65 in CDR2 as defined by Kabat of the humanized heavy chain may be corresponding residues from the candidate human antibody heavy chain
• and wherein the candidate human antibody light and heavy chain variable region sequences are selected without regard to comparing the variable region framework sequences of the candidate sequences with the framework sequences of the variable region of the light and heavy chains of the subject non-human antibody;
• and
• wherein residues in the humanized light chain variable region and humanized heavy chain variable region are numbered according to Kabat.