Effector function enhanced recombinant antibody composition
View Patent ↗The present invention relates to a recombinant antibody composition which is a human IgG1 antibody, comprises a CH2 domain in which amino acids at positions 276 and 339 indicated by the EU index as in Kabat, et al. are replaced by other amino acids and has more improved complement-dependent cytotoxic activity than an antibody comprising a CH2 domain before the amino acids are replaced; a DNA encoding the antibody molecule or a heavy chain constant region of the antibody molecule contained in the recombinant antibody composition; a transformant obtainable by introducing the DNA into a host cell; a process for producing the recombinant antibody composition using the transformant; and a medicament comprising the recombinant antibody composition as an active ingredient.
1. A recombinant antibody composition comprising a human IgG1 antibody, wherein said antibody comprises a CH2 domain in which the amino acids at positions 276 and 339, as indicated by the EU index as in Kabat, et al., are substituted with lysine and threonine, respectively, and wherein said antibody exhibits improved complement-dependent cytotoxic activity over the IgG1 antibody prior to said substitutions.
2. The recombinant antibody composition according to claim 1 , wherein the CH3 domain in the Fc region of said antibody has the same amino acid sequence as the CH3 domain of human IgG3.
3. The recombinant antibody composition according to claim 1 , wherein said antibody comprises complex-type N-glycoside-linked sugar chains in the Fc region, and wherein the ratio of sugar chains in which fucose is not bound to N-acetylglucosamine in the reducing terminal of the sugar chains among the total complex-type N-glycoside-linked sugar chains which bind to the Fc region contained in the composition is 20% or more.
4. The recombinant antibody composition according to claim 1 , wherein said antibody comprises complex-type N-glycoside-linked sugar chains in the Fc region, wherein the complex-type N-glycoside-linked sugar chains bound to the Fc region of the antibody are sugar chains in which fucose is not bound to N-acetylglucosamine in the reducing terminal in the sugar chains.
5. A pharmaceutical composition comprising the recombinant antibody composition described in claim 1 as an active ingredient.
6. A process for producing the recombinant antibody composition of claim 1 , comprising culturing a transformant in a medium to form and accumulate the antibody composition in the culture; and recovering and purifying the antibody composition from the culture, said transformant containing a DNA encoding the human IgG1 antibody contained in the recombinant antibody composition.