Bispecific antibody

Patent metadata

Field	Value
Publication number	US-12344674-B2
Application number	US-202117799648-A
Country	US
Kind code	B2
Filing date	Mar 29, 2021
Priority date	Mar 30, 2020
Publication date	Jul 1, 2025
Grant date	Jul 1, 2025

Abstract

An antibody that can be used as an anti-tumor agent and an anti-tumor agent comprises a molecule containing such an antibody. Such an antibody or a binding fragment thereof comprises: a heavy chain CDRH1 consisting of SEQ ID NO: 54, a heavy chain CDRH2 consisting of SEQ ID NO: 55, a heavy chain CDRH3 consisting of SEQ ID NO: 56, a light chain CDRL1 consisting of SEQ ID NO: 57 or a light chain CDRL1 consisting of an amino acid sequence derived from SEQ ID NO: 57 in which amino acid 7 is W and/or amino acid 8 is K, a light chain CDRL2 consisting of SEQ ID NO: 58, and a light chain CDRL3 consisting of SEQ ID NO: 59 or a light chain CDRL3 consisting of an amino acid sequence derived from SEQ ID NO: 59 in which amino acid 2 is A or S.

First claim

The invention claimed is:

1. A bispecific antibody that comprises a site which binds specifically to human HLA/NY-ESO and a site which binds specifically to human CD3, wherein the site which binds specifically to human HLA/NY-ESO comprises:
a heavy chain CDRH1 consisting of the amino acid sequence as shown in SEQ ID NO: 54,
a heavy chain CDRH2 consisting of the amino acid sequence as shown in SEQ ID NO: 55,
a heavy chain CDRH3 consisting of the amino acid sequence as shown in SEQ ID NO: 56,
a light chain CDRL1 consisting of an amino acid sequence derived from the amino acid sequence as shown in SEQ ID NO: 57 in which amino acid 7 is W,
a light chain CDRL2 consisting of the amino acid sequence represented by DNN, and
a light chain CDRL3 consisting of the amino acid sequence as shown in SEQ ID NO: 59.

2. The bispecific antibody according to claim 1 , wherein the site which binds specifically to human HLA/NY-ESO comprises:
a heavy chain variable region consisting of an amino acid sequence having 95% or higher sequence identity to an amino acid sequence of amino acids 21 to 140 of the amino acid sequence as shown in SEQ ID NO: 53 and a light chain variable region consisting of an amino acid sequence having 95% or higher sequence identity to an amino acid sequence of amino acids 156 to 266 of the amino acid sequence as shown in SEQ ID NO: 53, or
a heavy chain variable region consisting of an amino acid sequence having 95% or higher sequence identity to an amino acid sequence of amino acids 21 to 140 of the amino acid sequence as shown in SEQ ID NO: 156 and a light chain variable region consisting of an amino acid sequence having 95% or higher sequence identity to an amino acid sequence of amino acids 161 to 271 of the amino acid sequence as shown in SEQ ID NO: 156.

3. The bispecific antibody according to claim 1 which comprises:
a heavy chain variable region consisting of an amino acid sequence derived from an amino acid sequence as shown in SEQ ID NO: 53 by substitution, deletion, addition or insertion of one or more amino acids and a light chain variable region consisting of an amino acid sequence derived from an amino acid sequence as shown in SEQ ID NO: 53 by substitution, deletion, addition or insertion of one or more amino acids, or
a heavy chain variable region consisting of an amino acid sequence derived from an amino acid sequence of amino acids 21 to 140 of the amino acid sequence as shown in SEQ ID NO: 156 by substitution, deletion, addition or insertion of one or more amino acids and a light chain variable region consisting of an amino acid sequence derived from an amino acid sequence of amino acids 161 to 271 of the amino acid sequence as shown in SEQ ID NO: 156 by substitution, deletion, addition or insertion of one or more amino acids.

4. The bispecific antibody according to claim 1 , wherein the site which binds specifically to human HLA/NY-ESO is scFv.

5. The bispecific antibody according to claim 1 , wherein the site which binds specifically to human CD3 comprises:
(CCH1) a heavy chain CDRH1 consisting of the amino acid sequence as shown in SEQ ID NO: 141;
(CCH2) a heavy chain CDRH2 consisting of the amino acid sequence as shown in SEQ ID NO: 142 or a heavy chain CDRH2 consisting of an amino acid sequence derived from the amino acid sequence as shown in SEQ ID NO: 142 in which amino acid 3 is N or S;
(CCH3) a heavy chain CDRH3 consisting of the amino acid sequence as shown in SEQ ID NO: 143;
(CCL1) a light chain CDRL1 consisting of the amino acid sequence as shown in SEQ ID NO: 144;
(CCL2) a light chain CDRL2 consisting of the amino acid sequence represented by RDD or a light chain CDRL2 consisting of an amino acid sequence derived from the amino acid sequence represented by RDD in which amino acid 2 is N; and
(CCL3) a light chain CDRL3 consisting of the amino acid sequence as shown in SEQ ID NO: 146.

6. The bispecific antibody according to claim 1 , wherein the site which binds specifically to human CD3 comprises:
(CH1) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 136,
(CH2) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 137,
(CH3) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 147,
(CH4) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 138,
(CH5) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 139,
(CH6) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 140,
(CH7) a heavy chain variable region consisting of an amino acid sequence of amino acids 272 to 389 of the amino acid sequence as shown in SEQ ID NO: 155,
(CH8) a heavy chain variable region consisting of an amino acid sequence of amino acids 277 to 394 of the amino acid sequence as shown in SEQ ID NO: 156; or
(CH9) a heavy chain variable region consisting of an amino acid sequence of amino acids 277 to 394 of the amino acid sequence as shown in SEQ ID NO: 157; and
(CL1) a light chain variable region consisting of an amino acid sequence of amino acids 135 to 243 of the amino acid sequence as shown in SEQ ID NO: 136,
(CL2) a light chain variable region consisting of an amino acid sequence of amino acids 135 to 241 of the amino acid sequence as shown in SEQ ID NO: 137,
(CL3) a light chain variable region consisting of an amino acid sequence of amino acids 135 to 243 of the amino acid sequence as shown in SEQ ID NO: 147,
(CL4) a light chain variable region consisting of an amino acid sequence of amino acids 135 to 241 of the amino acid sequence as shown in SEQ ID NO: 138,
(CL5) a light chain variable region consisting of an amino acid sequence of amino acids 135 to 243 of the amino acid sequence as shown in SEQ ID NO: 139,
(CL6) a light chain variable region consisting of an amino acid sequence of amino acids 135 to 243 of the amino acid sequence as shown in SEQ ID NO: 140,
(CL7) a light chain variable region consisting of an amino acid sequence of amino acids 405 to 511 of the amino acid sequence as shown in SEQ ID NO: 155,
(CL8) a light chain variable region consisting of an amino acid sequence of amino acids 410 to 516 of the amino acid sequence as shown in SEQ ID NO: 156, or
(CL9) a light chain variable region consisting of an amino acid sequence of amino acids 410 to 516 of the amino acid sequence as shown in SEQ ID NO: 157.

7. The bispecific antibody according to claim 1 , wherein the site which binds specifically to human CD3 comprises:
(CH1CL1) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 136 and a light chain variable region consisting of an amino acid sequence of amino acids 135 to 243 of the amino acid sequence as shown in SEQ ID NO: 136;
(CH2CL2) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 137 and a light chain variable region consisting of an amino acid sequence of amino acids 135 to 241 of the amino acid sequence as shown in SEQ ID NO: 137;
(CH3CL3) a heavy chain variable region consisting of an amino acid sequence of amino acids 2 to 119 of the amino acid sequence as shown in SEQ ID NO: 147 and a light chain variable region consisting of an amino acid sequence of amino acids 135 to 243 of the amino acid sequence as

Assignees

• Univ Mie
• Daiichi Sankyo Co Ltd

Inventors

• Shiku Hiroshi
• Akahori Yasushi
• Tanaka Kento
• YATSU Ayaka
• Ichikawa Junya
• Ohtsuka Toshiaki
• Kozuma Shiho
• Hashimoto Ryuji
• Nakayama Makiko
• Shinozaki Naoya
• Nakamura Kensuke
• Watanabe Ichiro
• Furuzono Shinji

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/94

  Stability, e.g. half-life, pH, temperature or enzyme-resistance · CPC title

• C07K2317/92

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

• C07K2317/73

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

• C07K2317/622

  Single chain antibody (scFv) · CPC title