Anti B7-H3 antibody

Patent metadata

Field	Value
Publication number	US-9371395-B2
Application number	US-201213455021-A
Country	US
Kind code	B2
Filing date	Apr 24, 2012
Priority date	Apr 25, 2011
Publication date	Jun 21, 2016
Grant date	Jun 21, 2016

Abstract

An antibody exhibiting antitumor activity that binds to B7-H3, a functional fragment of the antibody, a pharmaceutical composition that includes the antibody or the functional fragment, methods for making the antibody or the functional fragment, methods for treating a tumor using the antibody or the functional fragment, and polynucleotides encoding the antibody or the functional fragment.

First claim

The invention claimed is:

1. An antibody characterized by having the following properties:
(a) specific binding to an IgC1 and/or IgC2 domain of B7-H3,
(b) having a constant region that is a human constant region;
(c) comprising CDRH1 consisting of an amino acid sequence comprising SEQ ID NO: 92, CDRH2 consisting of an amino acid sequence comprising SEQ ID NO: 93, and CDRH3 consisting of an amino acid sequence comprising SEQ ID NO: 94 as complementarity determining regions of the heavy chain and comprising CDRL1 consisting of an amino acid sequence comprising SEQ ID NO: 95, CDRL2 consisting of an amino acid sequence comprising SEQ ID NO: 96, and CDRL3 consisting of an amino acid sequence comprising SEQ ID NO: 97 as complementarity determining regions of the light chain;
(d) having an antibody-dependent cell-mediated phagocytosis (ADCP) activity; and
(e) having an in vivo antitumor activity against tumors expressing B7-H3 comprising SEQ ID NO: 6 or SEQ ID NO:10.

2. The antibody according to claim 1 , which has a competitive inhibitory activity against M30 antibody for the binding to B7-H3.

3. The antibody according to claim 1 , which has an antibody-dependent cellular cytotoxicity (ADCC) activity and/or a complement-dependent cytotoxicity (CDC) activity.

4. The antibody according to any one of claims 1 , 2 and 3 , wherein the tumor is cancer.

5. The antibody according to claim 4 , wherein the cancer is lung cancer, breast cancer, prostate cancer, pancreatic cancer, colorectal cancer, a melanoma, liver cancer, ovarian cancer, bladder cancer, stomach cancer, esophageal cancer, or kidney cancer.

6. The antibody according to claim 1 , which comprises a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 51 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 23 to 130 in SEQ ID NO: 53.

7. The antibody according to claim 1 , which comprises a heavy chain consisting of an amino acid sequence comprising SEQ ID NO: 63 and a light chain consisting of an amino acid sequence comprising SEQ ID NO: 59.

8. The antibody according to claim 1 , which is humanized.

9. The antibody according to claim 8 , which comprises a heavy chain variable region consisting of an amino acid sequence selected from the group consisting of (a) an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 85, (b) an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 87, (c) an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 89, (d) an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 91, (e) an amino acid sequence having a homology of at least 95% or more with any of the framework amino acid residues of the sequences (a) to (d), and (f) an amino acid sequence wherein one or several amino acids are deleted, substituted or added within any of the framework region sequences of (a) to (d); and a light chain variable region consisting of an amino acid sequence selected from the group consisting of (g) an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 71, (h) an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 73, (i) an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 75, (j) an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 77, (k) an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 79, (l) an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 81, (m) an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 83, (n) an amino acid sequence having a homology of at least 95% or more with any of the framework amino acids of the sequences (g) to (m), and (o) an amino acid sequence wherein one or several amino acids are deleted, substituted or added within any of the framework region sequences of (g) to (m).

10. The antibody according to claim 9 , which comprises a heavy chain variable region and a light chain variable region selected from the group consisting of a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 85 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 71; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 85 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 73; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 85 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 75; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 85 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 77; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO:85 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 79; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 85 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 81; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 85 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO:83; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 91 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 71; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 91 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 73; a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO:91 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 75; and a heavy chain variable region consisting of an amino acid sequence comprising amino acid numbers 20 to 141 in SEQ ID NO: 91 and a light chain variable region consisting of an amino acid sequence comprising amino acid numbers 21 to 128 in SEQ ID NO: 77.

11. The antibody according to claim 9 , which comprises a heavy chain and a light chain selected from the group consisting of a heavy chain consisting of an amino acid sequence comprising amino acid numbers 20 to 471 in SEQ ID NO: 85 and a light chain consisting of an amino acid sequence comprising amino acid numbers 21 to 233 in SEQ ID NO: 71; a heavy chain consisting of an amino acid sequence comprising amino acid numbers 20 to 471 in SEQ ID NO: 85 and a light chain consisting of an amino acid sequence comprising amino acid numbers 21 to 233 in SEQ ID NO: 73; a heavy chain consisting of an amino acid sequence comprising amino acid numbers 20 to 471 in SEQ ID NO: 85 and a light chain consisting of an amino acid sequence comprising amino acid numbers 21 to 233 in SEQ ID NO: 75; a heavy chain consisting of a

Assignees

• Takahashi Shu
• Matsuoka Tatsuji
• Murakami Kenji
• Takizawa Takeshi
• Hirotani Kenji
• Urano Atsushi
• Fukuchi Keisuke
• Yazawa Mitsuhiro
• Daiichi Sankyo Co Ltd

Inventors

• Takahashi Shu
• Matsuoka Tatsuji
• Murakami Kenji
• Takizawa Takeshi
• Hirotani Kenji
• Urano Atsushi
• Fukuchi Keisuke
• Yazawa Mitsuhiro

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K16/42 Primary

  against immunoglobulins · CPC title

• C07K2317/73

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

• C07K2317/734

  Complement-dependent cytotoxicity [CDC] · CPC title