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.