Anti b7-h3 antibody

Patent metadata

Field	Value
Publication number	US-2016368990-A1
Application number	US-201615187209-A
Country	US
Kind code	A1
Filing date	Jun 20, 2016
Priority date	Apr 25, 2011
Publication date	Dec 22, 2016
Grant date	—

Abstract

The present invention relates to an antibody having a therapeutic effect on a tumor. That is, the invention relates to an antibody which binds to B7-H3 to exhibit an antitumor activity. An object of the invention is to provide a pharmaceutical having a therapeutic effect on a tumor. By obtaining an anti-B7-H3 antibody which binds to B7-H3 to exhibit an antitumor activity, a pharmaceutical composition for treating a tumor comprising the antibody and the like are obtained.

First claim

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1 . An antibody characterized by having the following properties:
(a) having a competitive inhibitory activity against M30 antibody consisting of heavy chain comprising an amino acid sequence consisting of amino acid residues 20 to 471 of SEQ ID NO:51 and light chain comprising an amino acid sequence consisting of amino acid residues 23 to 235 of SEQ ID NO:53 for the binding to an IgC1 and/or IgC2 domain of B7-H3 comprising SEQ ID NO:6 or SEQ ID NO:10; (b) having an antibody-dependent cell-mediated phagocytosis (ADCP) activity; and (c) 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 an antibody-dependent cellular cytotoxicity (ADCC) activity and/or a complement-dependent cytotoxicity (CDC) activity.

3 . The antibody according to claim 1 , wherein the tumor is cancer.

4 . The antibody according to claim 3 , 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.

5 . The antibody according to claim 1 , wherein a constant region is a human constant region.

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

7 . The antibody according to claim 6 , which comprises a heavy chain variable region 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), or (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 (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, (1) 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), or (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).

8 . The antibody according to claim 7 , which comprises a heavy chain variable region and a light chain variable region 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; or 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.

9 . The antibody according to claim 8 , which comprises a heavy chain and a light chain 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 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:77; 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:79; 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:81; 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:83; a heavy chain consisting of an amino acid sequence comprising amino acid numbers 20 to 471 in SEQ ID NO:91 and a light chain consisting of an amino acid sequence comprising amino

Assignees

• 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

• C07K16/2827 Primary

  against B7 molecules, e.g. CD80, CD86 · CPC title

• C07K16/30

  from tumour cells · CPC title

• C07K16/42 Primary

  against immunoglobulins · CPC title

• A61K2039/505

  comprising antibodies · CPC title