Disclosed herein are methods for humanizing antibodies based on selecting
variable region framework sequences from human antibody genes by
comparing canonical CDR structure types for CDR sequences of the variable
region of a non-human antibody to canonical CDR structure types for
corresponding CDRs from a library of human antibody sequences, preferably
germline antibody gene segments. Human antibody variable regions having
similar canonical CDR structure types to the non-human CDRs form a subset
of member human antibody sequences from which to select human framework
sequences. The subset members may be further ranked by amino acid
similarity between the human and the non-human CDR sequences. Top ranking
human sequences are selected to provide the framework sequences for
constructing a chimeric antibody that functionally replaces human CDR
sequences with the non-human CDR counterparts using the selected subset
member human frameworks, thereby providing a humanized antibody of high
affinity and low immunogenicity without need for comparing framework
sequences between the non-human and human antibodies. Chimeric antibodies
made according to the method are also disclosed.