Anti-TSPAN8/anti-CD3 bispecific antibody and anti-TSPAN8 antibody

Patent metadata

Field	Value
Publication number	US-12304951-B2
Application number	US-202318396461-A
Country	US
Kind code	B2
Filing date	Dec 26, 2023
Priority date	Nov 16, 2020
Publication date	May 20, 2025
Grant date	May 20, 2025

Abstract

An objective of the present invention is to provide an anti-TSPAN8/anti-CD3 bispecific antibody and an anti-TSPAN8 antibody usable in treatment or prevention in human. A human monoclonal antibody producing mouse was immunized with a peritoneal disseminated cancer cell isolated from a patient, to obtain an antibody 16B11 and an antibody 16B12 that selectively bind to a peritoneal disseminated cancer cell. These antibodies were anti-TSPAN8 antibodies that bind to the region from amino acid positions 126 to 155 of TSPAN8 and exhibited strong binding activity to TSPAN8 expressed in the peritoneal disseminated cancer cell. Further, an anti-TSPAN8(16B11)-anti-CD3 bispecific antibody produced based on the sequence of 16B11 exhibited a cytotoxic activity against the TSPAN8-expressing cancer cell in vitro, exerted an anti-tumor action on TSPAN8-expressing cancer cell-bearing mice in vivo, and extended the lifetime of peritoneal dissemination model mice.

First claim

The invention claimed is:

1. An anti-TSPAN8 antibody or an antigen-binding fragment thereof selected from the following (a) and (b):
(a) an anti-TSPAN8 antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 consisting of an amino acid sequence from amino acid positions 31 to 35 of SEQ ID NO: 4, a CDR2 consisting of an amino acid sequence from amino acid positions 50 to 66 of SEQ ID NO: 4, and a CDR3 consisting of an amino acid sequence from amino acid positions 99 to 110 of SEQ ID NO. 4, and a light chain variable region comprising a CDR1 consisting of an amino acid sequence from amino acid positions 24 to 34 of SEQ ID NO: 8, a CDR2 consisting of an amino acid sequence from amino acid positions 50 to 56 of SEQ ID NO: 8, and a CDR3 consisting of an amino acid sequence from amino acid positions 89 to 96 of SEQ ID NO. 8; and
(b) an anti-TSPAN8 antibody or an antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 consisting of an amino acid sequence from amino acid positions 31 to 35 of SEQ ID NO: 10, a CDR2 consisting of an amino acid sequence from amino acid positions 50 to 66 of SEQ ID NO: 10, and a CDR3 consisting of an amino acid sequence from amino acid positions 99 to 110 of SEQ ID NO. 10, and a light chain variable region comprising a CDR1 consisting of an amino acid sequence from amino acid positions 24 to 34 of SEQ ID NO: 12, a CDR2 consisting of an amino acid sequence from amino acid positions 50 to 56 of SEQ ID NO: 12, and a CDR3 consisting of an amino acid sequence from amino acid positions 89 to 96 of SEQ ID NO. 12.

2. The anti-TSPAN8 antibody or the antigen-binding fragment thereof according to claim 1 , selected from the following (a) and (b):
(a) an anti-TSPAN8 antibody or an antigen-binding fragment thereof comprising a heavy chain variable region consisting of an amino acid sequence from amino acid positions 1 to 121 of SEQ ID NO: 4, and a light chain variable region consisting of an amino acid sequence from amino acid positions 1 to 107 of SEQ ID NO: 8; and
(b) an anti-TSPAN8 antibody or an antigen-binding fragment thereof comprising a heavy chain variable region consisting of an amino acid sequence from amino acid positions 1 to 121 of SEQ ID NO: 10, and a light chain variable region consisting of an amino acid sequence from amino acid positions 1 to 107 of SEQ ID NO: 12.

3. The anti-TSPAN8 antibody according to claim 1 , selected from the following (a) and (b):
(a) an anti-TSPAN8 antibody comprising a heavy chain consisting of an amino acid sequence of SEQ ID NO: 4 and a light chain consisting of an amino acid sequence of SEQ ID NO: 8; and
(b) an anti-TSPAN8 antibody comprising a heavy chain consisting of an amino acid sequence of SEQ ID NO: 10 and a light chain consisting of an amino acid sequence of SEQ ID NO: 12.

4. The anti-TSPAN8 antibody or the antigen-binding fragment thereof according to claim 1 , wherein the antibody is post-translationally modified.

5. The anti-TSPAN8 antibody or the antigen-binding fragment thereof according to claim 4 , wherein the post-translational modification is pyroglutamylation at a N-terminal of a heavy chain variable region, lysine deletion at a heavy chain C-terminal, or a combination thereof.

6. A fusion or complex of the anti-TSPAN8 antibody or the antigen-binding fragment thereof according to claim 1 , or a cell on a surface of which the anti-TSPAN8 or the antigen-binding fragment thereof according to any claim 1 is expressed.

7. A polynucleotide selected from the group consisting of the following (a) to (d):
(a) a polynucleotide comprising a nucleotide sequence encoding a heavy chain variable region of an anti-TSPAN8 antibody consisting of an amino acid sequence from amino acid positions 1 to 121 of SEQ ID NO: 4;
(b) a polynucleotide comprising a nucleotide sequence encoding a light chain variable region of an anti-TSPAN8 antibody consisting of an amino acid sequence from amino acid positions 1 to 107 of SEQ ID NO: 8;
(c) a polynucleotide comprising a nucleotide sequence encoding a heavy chain variable region of an anti-TSPAN8 antibody consisting of an amino acid sequence from amino acid positions 1 to 121 of SEQ ID NO: 10; and
(d) a polynucleotide comprising a nucleotide sequence encoding a light chain variable region of an anti-TSPAN8 antibody consisting of an amino acid sequence from amino acid positions 1 to 107 of SEQ ID NO: 12.

8. An expression vector, comprising the polynucleotide according to claim 7 .

9. A host cell transformed with the expression vector according to claim 7 .

10. A method for producing an anti-TSPAN8 antibody or an antigen-binding fragment thereof, comprising a step of culturing the host cell according to claim 9 .

11. A pharmaceutical composition comprising:
the anti-TSPAN8 antibody or the antigen-binding fragment thereof according to claim 1 , and
a pharmaceutically acceptable excipient.

12. A method for treating cancer, comprising a step of administering, to a subject, a therapeutically effective amount of the anti-TSPAN8 antibody or the antigen-binding fragment thereof according to claim 1 .

13. A pharmaceutical composition comprising:
a fusion or complex of the anti-TSPAN8 antibody or the antigen-binding fragment thereof according to claim 1 , or a cell on a surface of which the anti-TSPAN8 or the antigen-binding fragment thereof according to any claim 1 is expressed, and
a pharmaceutically acceptable excipient.

Assignees

• Astellas Pharma Inc
• Nat Cancer Ct

Inventors

• Tenda Yoshiyuki
• Yuri Masatoshi
• Yamajuku Daisuke
• Tsutsumi Takeshi
• Kusuzaki Yuko
• Sasaki Hiroki
• Chiwaki Fumiko
• Komatsu Masayuki

Classifications

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/622

  Single chain antibody (scFv) · CPC title

• C07K2317/55

  Fab or Fab' · CPC title

• C07K2317/52

  Constant or Fc region; Isotype · CPC title