Anti-human CCR7 antibody, hybridoma, nucleic acid, vector, cell, pharmaceutical composition, and antibody-immobilized carrier

Patent metadata

Field	Value
Publication number	US-9505844-B2
Application number	US-201414489898-A
Country	US
Kind code	B2
Filing date	Sep 18, 2014
Priority date	Sep 28, 2010
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

Abstract

An anti-human-CC-motif-receptor-7 (anti-human-CCR7) antibody which is useful as a therapeutic agent for tissue fibrosis or cancer, and a pharmaceutical composition containing the anti-human CCR7 antibody, and the like is described. An anti-human CCR7 antibody specifically binding to an extracellular domain of human CCR7, having a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 7, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 37, SEQ ID NO: 47, SEQ ID NO: 57, SEQ ID NO: 67, or SEQ ID NO: 77 is provided. Also provided is an anti-human CCR7 antibody having heavy chain CDRs 1-3 and light chain CDRs 1-3 containing amino acid sequences represented by SEQ ID NOs: 5-10, 15-20, 25-30, 35-40, 45-50, 55-60, 65-70, or 75-80. The anti-human CCR7 antibody of the present invention may be used as an active ingredient of a therapeutic agent for tissue fibrosis or cancer.

First claim

The invention claimed is:

1. A nucleic acid encoding a heavy chain variable region or a light chain variable region of an anti-human-CC-motif-receptor-7 (anti-human-CCR7) antibody capable of specifically binding to an extracellular domain of human CCR7,
the antibody being produced by a hybridoma FERM BP-11369, FERM BP-11404, FERM BP-11371, FERM BP-11372, FERM BP-11373, FERM BP-11374, FERM BP-11375, or FERM BP-11376, and
wherein the antibody is capable of interfering with a CCR7-dependent intracellular signal transduction mechanism caused by CCR7 ligand stimulation, without relying on complement-dependent cell lysis action or antibody-dependent cell-mediated cytotoxicity.

2. The nucleic acid according to claim 1 , wherein the anti-human-CCR7 antibody is a humanized antibody or a chimeric antibody.

3. The nucleic acid according to claim 2 , wherein the anti-human-CCR7 antibody is an antibody fragment, a single-chain antibody or a diabody.

4. A vector comprising the nucleic acid according to claim 1 .

5. A cell into which the vector according to claim 4 has been introduced.

6. A nucleic acid encoding a heavy chain variable region or a light chain variable region of an anti-human-CC-motif-receptor-7 (anti-human-CCR7) antibody capable of specifically binding to an extracellular domain of human CCR7,
wherein the antibody comprises heavy chain complementarity determining regions 1 to 3 (heavy chain CDRs 1-3) and light chain complementarity determining regions 1 to 3 (light chain CDRs 1-3) of any one of the following (B1) to (B8):
(B1) comprising a heavy chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 5, a heavy chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 6, a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 7, a light chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 8, a light chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 9, and a light chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 10,
(B2) comprising a heavy chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 15, a heavy chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 16, a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 17, a light chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 18, a light chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 19, and a light chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 20,
(B3) comprising a heavy chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 25, a heavy chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 26, a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 27, a light chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 28, a light chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 29, and a light chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 30,
(B4) comprising a heavy chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 35, a heavy chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 36, a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 37, a light chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 38, a light chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 39, and a light chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 40,
(B5) comprising a heavy chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 45, a heavy chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 46, a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 47, a light chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 48, a light chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 49, and a light chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 50,
(B6) comprising a heavy chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 55, a heavy chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 56, a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 57, a light chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 58, a light chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 59, and a light chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 60,
(B7) comprising a heavy chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 65, a heavy chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 66, a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 67, a light chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 68, a light chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 69, and a light chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 70, and
(B8) comprising a heavy chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 75, a heavy chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 76, a heavy chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 77, a light chain CDR1 containing an amino acid sequence represented by SEQ ID NO: 78, a light chain CDR2 containing an amino acid sequence represented by SEQ ID NO: 79, and a light chain CDR3 containing an amino acid sequence represented by SEQ ID NO: 80,
wherein the antibody is capable of interfering with a CCR7-dependent intracellular signal transduction mechanism caused by CCR7 ligand stimulation, without relying on complement-dependent cell lysis action or antibody-dependent cell-mediated cytotoxicity.

7. The nucleic acid according to claim 6 , wherein the anti-human-CCR7 antibody is a humanized antibody or a chimeric antibody.

8. The nucleic acid according to claim 7 , wherein the anti-human-CCR7 antibody is an antibody fragment, a single-chain antibody or a diabody.

9. The nucleic acid according to claim 6 , wherein the antibody comprises a heavy chain variable region and a light chain variable region of any one of the following (C1) to (C8):
(C1) comprising a heavy chain variable region containing an amino acid sequence represented by SEQ ID NO: 2, and a light chain variable region containing an amino acid sequence represented by SEQ ID NO: 4,
(C2) comprising a heavy chain variable region containing an amino acid sequence represented by SEQ ID NO: 12, and a light chain variable region containing an amino acid sequence represented by SEQ ID NO: 14,
(C3) comprising a heavy chain variable region containing an amino acid sequence represented by SEQ ID NO: 22, and a light chain variable region containing an amino acid sequence represented by SEQ ID NO: 24,
(C4) comprising a heavy chain variable region containing an amino acid sequence represented by SEQ ID NO: 32, and a light chain variable region containing an amino acid sequence represented by SEQ ID NO: 34,
(C5) comprising a heavy chain variable region containing an amino acid sequence represented by SEQ ID NO: 42, and a light chain variable region containing an amino acid sequence represented by SEQ ID NO: 44,
(C6) comprising a heavy chain variable region containing an amino acid sequence represented by SEQ ID NO: 52, and a light chain variable region containing an amino acid sequence represented by SEQ ID NO: 54,
(C7) comprising a heavy chain variable region containing an amino acid sequence represented by SEQ ID NO: 62, and a light chain variab

Assignees

• Sekisui Chemical Co Ltd
• Nb Health Laboratory Co Ltd

Inventors

• Nishiguchi Naoki
• Hirayama Akiyoshi
• Furutani Masahiro
• Shimizu Tatsuo
• Takayama Kiyoshi
• Shimizu Tomoko
• Suzuki Kazuya

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P31/20

  for DNA viruses · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title