Recombinant antibody composition

Patent metadata

Field	Value
Publication number	US-2016108136-A1
Application number	US-201414501146-A
Country	US
Kind code	A1
Filing date	Sep 30, 2014
Priority date	Jul 22, 2005
Publication date	Apr 21, 2016
Grant date	—

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

1 - 4 . (canceled)

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 constant region containing, a CHI, 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.

6 . The process according to claim 5 , 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.

7 . The process according to claim 5 , 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.

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.

9 . 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 CHI, 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 1D 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.

10 . The process according to claim 9 , 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.

11 . The process according to claim 9 , 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.

12 . The process according to claim 9 , 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

Inventors

• Shitara Kenya
• Niwa Rinpei
• Natsume Akito

Classifications

• C07K2317/72

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

• C07K2317/53

  Hinge · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title

• C07K16/462 Primary

  Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another · CPC title