Anti-CD3 antibody and molecules comprising the antibody

Patent metadata

Field	Value
Publication number	US-11618785-B2
Application number	US-201716472346-A
Country	US
Kind code	B2
Filing date	Dec 21, 2017
Priority date	Dec 22, 2016
Publication date	Apr 4, 2023
Grant date	Apr 4, 2023

Abstract

The present invention provides a novel antibody binding to human CD3, and a molecule having antigen binding activity that includes the antibody.The present invention provides a novel antibody binding to human CD3, a molecule having antigen binding activity that includes the antibody, and a pharmaceutical composition having cytotoxic activity that includes the antibody or the molecule as an active ingredient.

First claim

The invention claimed is:

1. An antibody or an antigen-binding fragment of the antibody, comprising:
a heavy chain sequence comprising
CDRH1 comprising SEQ ID NO: 26,
CDRH2 comprising SEQ ID NO: 98, wherein the first Xaa is selected from the group consisting of R and S, and the second Xaa is S, and
CDRH3 comprising SEQ ID NO: 28; and
a light chain sequence comprising
CDRL1 comprising SEQ ID NO: 29,
CDRL2 comprising SEQ ID NO: 99, wherein Xaa is selected from the group consisting of Q, A, G, S, N, and D, and
CDRL3 comprising SEQ ID NO: 31;
wherein the antibody or antigen-binding fragment binds to human CD3 and to cynomolgus monkey CD3.

2. An antibody or antigen-binding fragment of an antibody according to claim 1 , wherein the heavy chain sequence comprises a heavy chain variable region comprising SEQ ID NO: 100.

3. An antibody or antigen-binding fragment thereof according to claim 2 , wherein in SEQ ID NO: 100,
the first Xaa is R.

4. An antibody or antigen-binding fragment thereof according to claim 2 , wherein in SEQ ID NO: 100, the first Xaa is S.

5. An antibody or antigen-binding fragment thereof according to claim 1 , wherein the light chain sequence comprises a light chain variable region comprising any one of SEQ ID NOs: 101, 102, and 103.

6. An antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region comprising SEQ ID NO: 100 and a light chain variable region comprising any one of SEQ ID NOs: 101, 102, and 103.

7. An antibody or antigen-binding fragment thereof according to claim 6 , wherein
in SEQ ID NO: 100 the first Xaa is R.

8. An antibody or antigen-binding fragment thereof according to claim 6 , wherein the antibody or antigen-binding fragment comprises:
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 60 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 60,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 62 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 62,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 64 and a light chain variable region comprising amino acid residues 135-241 of SEQ ID NO: 64,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 66 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 66,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 68 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 68,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 70 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 70,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 72 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 72,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 74 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 74,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 76 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 76,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 78 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 78,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 80 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 80,
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 82 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 82, or
a heavy chain variable region comprising amino acid residues 2-119 of SEQ ID NO: 84 and a light chain variable region comprising amino acid residues 135-243 of SEQ ID NO: 84.

9. An antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region and a light chain variable region, and further comprising: i) a linker between the variable regions, ii) a glycine residue at the amino-terminal of the variable region on the amino-terminal side, and iii) a linker, FLAG tag and/or HIS tag at the carboxyl terminal of the variable region on the carboxyl terminal side.

10. An antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody is IgG.

11. An antibody or antigen-binding fragment thereof according to claim 1 , wherein the antigen-binding fragment is selected from a group consisting of Fab, F(ab)′, Fv, scFv, and sdAb.

12. An antibody or antigen-binding fragment thereof according to claim 1 , wherein the antibody is a humanized antibody or a human antibody including a human immunoglobulin constant region.

13. A polynucleotide comprising a nucleotide sequence encoding an antibody or an antigen-binding fragment thereof according to claim 1 .

14. A vector comprising a polynucleotide according to claim 13 .

15. A cell comprising a polynucleotide according to claim 13 .

16. A method for producing an antibody or an antigen-binding fragment of the antibody which binds to human CD3 and to cynomolgus monkey CD3, the method comprising the steps of: culturing a cell according to claim 15 ; and recovering an antibody or an antigen-binding fragment of the antibody which binds to human CD3 from the cultures.

17. A pharmaceutical composition comprising an antibody or an antigen-binding fragment thereof according to claim 1 as an active ingredient.

18. A molecule having antigen binding activity, comprising an antibody or an antigen-binding fragment of the antibody according to claim 1 .

19. A molecule according to claim 18 , wherein the molecule is multispecific.

20. A molecule according to claim 18 , further comprising 1 or 2 or more additional antibodies or antigen-binding fragments of the antibodies in addition to the antibody or antigen-binding fragment.

21. A molecule according to claim 20 , wherein the antigen-binding fragment of the additional antibody is Fab, F(ab)′, Fv, scFv, or sdAb.

22. A molecule according to claim 20 , wherein the molecule comprises Fc.

23. A molecule according to claim 20 , wherein the additional antibody is a humanized antibody or a human antibody comprising a human immunoglobulin constant region.

24. A molecule according to claim 20 , wherein the antibody or antigen-binding fragment and the 1 or 2 or more additional antibodies or antigen-binding fragments are bound via a linker or without a linker.

25. A molecule according to claim 24 , wherein a carboxyl terminus of the amino acid sequence of the additional antibody or antigen-binding fragment is bound with a linker, and a carboxyl terminus of the amino acid sequence of the linker is further bound with the antibody or antigen-binding fragment.

26. A molecule according to claim 18 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region and a light chain variable region, and further comprising: i) a linker between the variable regions, ii) a glycine residue at the amino-terminal of the variable region on the amino-terminal side, and i

Assignees

• Daiichi Sankyo Co Ltd

Inventors

• Takahashi Tohru
• Yoshimura Chigusa
• Kozuma Shiho
• Nakamura Kensuke
• Suzuki Chikako
• Ichikawa Junya

Classifications

• A61K2039/505

  comprising antibodies · CPC title

• C07K2317/732

  Antibody-dependent cellular cytotoxicity [ADCC] · CPC title

• C07K2317/92

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

• C07K2317/52

  Constant or Fc region; Isotype · CPC title

• C07K2317/33

  Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity · CPC title