Recombinant antibody composition

Patent metadata

Field	Value
Publication number	US-9475886-B2
Application number	US-201414501146-A
Country	US
Kind code	B2
Filing date	Sep 30, 2014
Priority date	Jul 22, 2005
Publication date	Oct 25, 2016
Grant date	Oct 25, 2016

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Kyowa Hakko Kirin Co Ltd
• Kyowa Hakko Kirin Co Ltd

Inventors

• Shitara Kenya
• Niwa Rinpei
• Natsume Akito

Classifications

• C07K2317/53

  Hinge · CPC title

• C07K16/2887 Primary

  against CD20 · CPC title

• C07K2317/72

  Increased effector function due to an Fc-modification · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• A61K2039/505

  comprising antibodies · CPC title