Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture

Abstract

The present invention provides methods for producing humanized antibodies and increasing the yield of antibodies and/or antigen binding fragments when produced in cell culture. In one aspect of the invention, at least one framework region amino acid residue of the variable domain is substituted by a corresponding amino acid from a variable domain consensus sequence subgroup that has the most sequence identity with the HVR1 and/or HVR2 amino acid sequence of the variable domain. In another aspect, an amino acid is placed at a position proximal to a cys residue that participates in an intrachain variable domain disulfide bond that corresponds to an amino acid found at that position in a variable domain consensus sequence subgroup that has the most sequence identity with the HVR1 and/or HVR2 amino acid sequenc of the variable domain.