ENGINEERED ANTIBODIES WITH REDUCED IMMUNOGENICITY AND METHODS OF MAKING

摘要

Hybrid antibodies and antibody binding fragments thereof having decreased immunogenicity and methods of making them are provided. The methods involve replacing one or more amino acid residues within at least one donor framework region of a hybrid antibody or antigen binding fragment thereof that has undergone somatic hypermutation with the amino acid residue from the corresponding position of a germline framework sequence. Also provided are hybrid antibodies or antigen binding fragments thereof containing at least two donor framework regions that are derived from the same germline gene family or germline gene family member and wherein at least one amino acid residue within a framework region has been replaced with an amino acid residue from the corresponding position within a germline framework region. The hybrid antibodies or antigen binding fragments thereof may contain human framework regions and nonhuman CDRs.