Recombinant antibody composition
View Patent ↗The present invention relates to a recombinant antibody composition having higher complement-dependent cytotoxic activity than a human IgG1 antibody and a human IgG3 antibody, wherein a polypeptide comprising a CH2 domain in the Fc region of a human IgG1 antibody is replaced by a polypeptide comprising an amino acid sequence which corresponds to the same position of a human IgG3 antibody indicated by the EU index as in Kabat, et al.; 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 recombinant vector 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 process for producing recombinant antibodies, comprising culturing a transformant in a medium to form and accumulate the recombinant antibodies in the culture; and recovering and purifying the recombinant antibodies from the culture,
wherein said recombinant antibodies have greater complement-dependent cytotoxic activity than human IgG1 and human IgG3 antibodies of the same binding specificity under the same conditions,
wherein said recombinant antibodies contain a heavy chain constant region containing, a CH1, a hinge, a CH2 and a CH3 domain, said region comprising the amino acid sequence of SEQ ID NO:76 in which at least the first 110 amino acids commencing at residue 114 of SEQ ID NO:76 are replaced with the corresponding residues from SEQ ID NO:78, and in which residues 1-113 of SEQ ID NO:76 in said region are not replaced with the corresponding residues from SEQ ID NO:78,
and wherein said transformant contains DNA encoding said recombinant antibodies.
2. The process according to claim 1 , wherein said recombinant antibodies have complex type N-glycoside-linked sugar chains in the Fe region, and wherein the ratio of sugar chains in which fucose is not bound to N-acetylgIncosamine 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.
3. The process according to claim 1 , wherein said recombinant antibodies have 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.
4. The process according to claim 1 , wherein said recombinant antibodies have an activity of binding protein A substantially equal to the binding of protein A to IgG1.
5. A process for producing recombinant antibodies, comprising culturing a transformant in a medium to form and accumulate the recombinant antibodies in the culture; and recovering and purifying the recombinant antibodies from, the culture,
wherein said recombinant antibodies have greater complement-dependent cytotoxic activity than human IgG1 and human IgG3 antibodies of the same binding specificity under the same conditions,
wherein said recombinant antibodies contain a heavy chain cons I:ant region containing CH1, a binge, a CH2 and a CH3 domain, said region comprising the amino acid sequence of SEQ ID NO:76 in which residues selected from the following (1)-(8) are replaced, with the corresponding residues from SEQ ID NO:78:
(1) residues 114-223 of SEQ ID NO:76
(2) residues 114-239 of SEQ ID NO:76;
(3) residues 114-241 of SEQ ID NO:76;
(4) residues 114-267 of SEQ ID No:76;
(5) residues 114-275 of SEQ ID NO:76;
(6) residues 114-280 of SEQ ID NO:76;
(7) residues 114-305 of SEQ ID NO:76; and
(8) residues 114-317 and residues 319-330 of SEQ ID NO:76,
and wherein said transformant contains DNA encoding said recombinant antibodies.
6. The process according to claim 5 , wherein said recombinant antibodies have complex type N-glycoside-linked sugar chains in the Fc region, 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.
7. The process according to claim 5 , wherein said recombinant antibodies have complex type N-glycoside-linked sugar chains in the Fe 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.
8. The process according to claim 5 , wherein said recombinant antibodies have an activity of binding protein A substantially equal to the binding of protein A to IgG1.