Patent ID: 7575893

Claim:
A method for producing a recombinant antibody or antigen binding fragment thereof with improved yield from a host cell, comprising: (i) providing a nucleic acid encoding a non-human antibody or antigen binding fragment thereof made by a method comprising: (a) aligning a hypervariable region (HVR1) and/or a hypervariable region 2 (HVR2) of a heavy chain variable domain of a non-human antibody or antigen binding fragment thereof to corresponding HVR1 and/or HVR2 sequences of human subgroup variable domain consensus sequences; (b) selecting a human subgroup heavy chain variable domain consensus sequence that has a HVR1 and/or HVR2 amino acid sequence with the most sequence identity with the non-human HVR1 sequence and/or the non-human HVR2 sequence; (c) identifying at least one amino acid position in at least one framework region (FR) of the selected human subgroup variable domain consensus sequence that has a different amino acid residue than that of a corresponding position in a FR of the variable domain of the non-human antibody or antigen binding fragment thereof; and (d) substituting at least one amino acid in the FR of the non-human variable domain of the antibody or the antigen binding fragment thereof identified in step (i)(c) with the corresponding amino acid from the selected subgroup consensus sequence in step (b) to form a substituted FR in the non-human variable domain of the antibody or antigen binding fragment thereof; and (ii) expressing the non-human antibody or antigen binding fragment thereof of having at least one substitution in the FR in the host cell, wherein the non-human antibody or antigen binding fragment thereof having the at least one substitution in the FR has improved yield in a cell or a cell culture as compared to the corresponding unsubstituted antibody or antigen binding fragment thereof.