Modified antibody constant regions

Patent metadata

Field	Value
Publication number	US-10150808-B2
Application number	US-201013497269-A
Country	US
Kind code	B2
Filing date	Sep 24, 2010
Priority date	Sep 24, 2009
Publication date	Dec 11, 2018
Grant date	Dec 11, 2018

Abstract

The present inventors successfully provided constant regions capable of enhancing the agonist activity of antibodies through amino acid sequence alterations. Specifically, agonist activity was found to be enhanced in antibodies having a constant region in which amino acids of the antibody heavy chain constant region are substituted or deleted, or antibodies having a constant region in which the hinge region amino acids are substituted. Use of such antibodies as pharmaceutical formulations can provide pharmaceutical formulations with improved performance.

First claim

The invention claimed is:

1. An antibody comprising a heavy chain and a light chain that together comprise a Fab fragment that binds to a target antigen, wherein the antibody agonizes the target antigen, and wherein the heavy chain comprises a constant region that comprises the amino acid sequence of SEQ ID NO: 32 with only the following mutations, wherein all positions are identified by EU numbering:
(a) deletion of the amino acid residues at positions 222, 223, 224, and 225; and
(b) optionally, one of the following (1) to (3):
(1) substitution of the amino acid residues at positions 219 and 220 with Cys and Ser, respectively;
(2) substitution of the amino acid residues at positions 219, 220, and 221 with Cys, Ser, and Val, respectively; or
(3) substitution of the amino acid residues at positions 192, 193, 199, 214, 217, 219, 220, and 221 with Asn, Phe, Thr, Thr, Arg, Cys, Ser, and Val, respectively.

2. The antibody of claim 1 , wherein the heavy chain comprises a constant region that comprises the amino acid sequence of SEQ ID NO: 32 with only the following mutations, wherein all positions are identified by EU numbering:
(a) deletion of the amino acid residues at positions 222, 223, 224, and 225.

3. The antibody of claim 1 , wherein the mutations include substitution of the amino acid residues at EU numbering positions 219 and 220 with Cys and Ser, respectively.

4. The antibody of claim 1 , wherein the mutations include substitution of the amino acid residues at EU numbering positions 219, 220, and 221 with Cys, Ser, and Val, respectively.

5. The antibody of claim 1 , wherein the mutations include substitution of the amino acid residues at EU numbering positions 192, 193, 199, 214, 217, 219, 220, and 221 with Asn, Phe, Thr, Thr, Arg, Cys, Ser, and Val, respectively.

Assignees

• Kuramochi Taichi
• Tanba Shigero
• Igawa Tomoyuki
• Maeda Atsuhiko
• Sakata Kiyoaki
• Endoh Mika
• Chugai Pharmaceutical Co Ltd

Inventors

• Kuramochi Taichi
• Tanba Shigero
• Igawa Tomoyuki
• Maeda Atsuhiko
• Sakata Kiyoaki
• Endoh Mika

Classifications

• C07K16/18 Primary

  against material from animals or humans · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title

• C07K2317/53

  Hinge · CPC title

• C07K2317/24

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

• C07K16/2833

  against MHC-molecules, e.g. HLA-molecules · CPC title