BINDING MOLECULE SPECIFIC FOR LRIG-1 PROTEIN AND USE THEREOF

• US 20200131261A1
• Filed: 04/18/2018
• Published: 04/30/2020
• Est. Priority Date: 04/18/2017
• Status: Active Grant

• Current Assignee: Good T Cells, Inc.
• Original Assignee: Good T Cells, Inc.
• Inventors: Kim, Jung Ho, Kim, Beom Seok
• Granted Patent: US 11,279,756 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention relates to a binding molecule capable of specifically binding to Lrig-1 protein, which is located on the surface of a regulatory T cell. The binding molecule provided in the present invention can activate the function of regulatory T cells to effectively prevent, ameliorate, or treat diseases caused by excessive activation or expression of various immune cells and inflammatory cells, for example, immune-related diseases such as autoimmune disease, graft-versus-host disease, organ transplant rejection, asthma, atopy, acute or chronic inflammatory disease, etc. In addition, the binding molecule, preferably the antibody, specific for the Lrig-1 protein according to the present invention has advantages of more effectively targeting the Lrig-1 protein as compared with antibodies against Lrig-1 which are previously commercially available, and also possessing very good binding capacity thereto.

Claims

1. A binding molecule which specifically binds to leucine-rich and immunoglobulin-like domains 1 (Lrig-1) protein,

wherein the binding molecule comprises:

a heavy chain variable region that contains a heavy chain CDR1 consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs;

5, 13, 21, and 29;

a heavy chain CDR2 consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs;

6, 14, 22, and 30;

a heavy chain CDR3 consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs;

7, 15, 23, and 31; and

a light chain variable region that contains a light chain CDR1 consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs;

8, 16, 24, and 32;

a light chain CDR2 consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs;

9, 17, 25, and 33;

a light chain CDR3 consisting of an amino acid sequence selected from the group consisting of SEQ ID NO;

10, 18, 26, and 34.

5. The binding molecule according to claim 1, comprising:

a heavy chain variable region, selected from the group consisting of the following (a) to (d);

(a) a heavy chain variable region that contains a heavy chain CDR1 represented by SEQ ID NO;

5, a heavy chain CDR2 represented by SEQ ID NO;

6, and a heavy chain CDR3 represented by SEQ ID NO;

7;

(b) a heavy chain variable region that contains a heavy chain CDR1 represented by SEQ ID NO;

13, a heavy chain CDR2 represented by SEQ ID NO;

14, and a heavy chain CDR3 represented by SEQ ID NO;

15;

(c) a heavy chain variable region that contains a heavy chain CDR1 represented by SEQ ID NO;

21, a heavy chain CDR2 represented by SEQ ID NO;

22, and a heavy chain CDR3 represented by SEQ ID NO;

23; and

(d) a heavy chain variable region that contains a heavy chain CDR1 represented by SEQ ID NO;

29, a heavy chain CDR2 represented by SEQ ID NO;

30, and a heavy chain CDR3 represented by SEQ ID NO;

31; and

a light chain variable region, selected from the group consisting of the following (e) to (h);

(e) a light chain variable region that contains a light chain CDR1 represented by SEQ ID NO;

8, a light chain CDR2 represented by SEQ ID NO;

9, and a light chain CDR3 represented by SEQ ID NO;

10;

(f) a light chain variable region that contains a light chain CDR1 represented by SEQ ID NO;

16, a light chain CDR2 represented by SEQ ID NO;

17, and a light chain CDR3 represented by SEQ ID NO;

18;

(g) a light chain variable region that contains a light chain CDR1 represented by SEQ ID NO;

24, a light chain CDR2 represented by SEQ ID NO;

25, and a light chain CDR3 represented by SEQ ID NO;

26; and

(h) a light chain variable region that contains a light chain CDR1 represented by SEQ ID NO;

32, a light chain CDR2 represented by SEQ ID NO;

33, and a light chain CDR3 represented by SEQ ID NO;

34.

6. The binding molecule according to claim 1,

wherein the binding molecule is selected from the group consisting of the following (1) to (4):

(1) a binding molecule comprising a heavy chain variable region that contains a heavy chain CDR1 represented by SEQ ID NO;

5, a heavy chain CDR2 represented by SEQ ID NO;

6, and a heavy chain CDR3 represented by SEQ ID NO;

7; and

a light chain variable region that contains a light chain CDR1 represented by SEQ ID NO;

8, a light chain CDR2 represented by SEQ ID NO;

9, and a light chain CDR3 represented by SEQ ID NO;

10;

(2) a binding molecule comprising a heavy chain variable region that contains a heavy chain CDR1 represented by SEQ ID NO;

13, a heavy chain CDR2 represented by SEQ ID NO;

14, and a heavy chain CDR3 represented by SEQ ID NO;

15; and

a light chain variable region that contains a light chain CDR1 represented by SEQ ID NO;

16, a light chain CDR2 represented by SEQ ID NO;

17, and a light chain CDR3 represented by SEQ ID NO;

18;

(3) a binding molecule comprising a heavy chain variable region that contains a heavy chain CDR1 represented by SEQ ID NO;

21, a heavy chain CDR2 represented by SEQ ID NO;

22, and a heavy chain CDR3 represented by SEQ ID NO;

23; and

a light chain variable region that contains a light chain CDR1 represented by SEQ ID NO;

24, a light chain CDR2 represented by SEQ ID NO;

25, and a light chain CDR3 represented by SEQ ID NO;

26;

(4) a binding molecule comprising a heavy chain variable region that contains a heavy chain CDR1 represented by SEQ ID NO;

29, a heavy chain CDR2 represented by SEQ ID NO;

30, and a heavy chain CDR3 represented by SEQ ID NO;

31; and

a light chain variable region that contains a light chain CDR1 represented by SEQ ID NO;

32, a light chain CDR2 represented by SEQ ID NO;

33, and a light chain CDR3 represented by SEQ ID NO;

34.

7. The binding molecule according to claim 1, comprising:

a heavy chain variable region consisting of any one amino acid sequence selected from the group consisting of SEQ ID NOs;

11, 19, 27, and 35; and

a light chain variable region consisting of any one amino acid sequence selected from the group consisting of SEQ ID NO;

12, 20, 28, and 36.

8. The binding molecule according to claim 1,

wherein the binding molecule is selected from the group consisting of the following binding molecules:

a binding molecule comprising a heavy chain variable region represented by SEQ ID NO;

11, and a light chain variable region represented by SEQ ID NO;

12;

a binding molecule comprising a heavy chain variable region represented by SEQ ID NO;

19, and a light chain variable region represented by SEQ ID NO;

20;

a binding molecule comprising a heavy chain variable region represented by SEQ ID NO;

27, and a light chain variable region represented by SEQ ID NO;

28; and

a binding molecule comprising a heavy chain variable region represented by SEQ ID NO;

35, and a light chain variable region represented by SEQ ID NO;

36.

9. The binding molecule according to claim 1, further comprising:

an Fc region or a constant region.

10. The binding molecule according to claim 9,

wherein the Fc region is an Fc region of an IgG1, IgG2, IgG3, or IgG4 antibody, or a hybrid Fc region.

11. The binding molecule according to claim 1, further comprising:

a heavy chain constant region consisting of an amino acid sequence selected from the group consisting of SEQ ID NOs;

37, 39, 41, 42, 43, and 44.

12. The binding molecule according to claim 1, further comprising:

a light chain constant region consisting of an amino acid sequence represented by SEQ ID NO;

38 or 40.

13. The binding molecule according to claim 1, further comprising:

a heavy chain constant region consisting of an amino acid sequence represented by SEQ ID NO;

37; and

a light chain constant region consisting of an amino acid sequence represented by SEQ ID NO;

38.

14. The binding molecule according to claim 1, further comprising:

a heavy chain constant region consisting of an amino acid sequence represented by SEQ ID NO;

39, 41, 42, or 43; and

a light chain constant region consisting of an amino acid sequence represented by SEQ ID NO;

40.

15. The binding molecule according to claim 1, further comprising:

a heavy chain constant region consisting of an amino acid sequence represented by SEQ ID NO;

44.

16. The binding molecule according to claim 1,

wherein the binding molecule is selected from the group consisting of the following binding molecules:

a binding molecule comprising a heavy chain represented by SEQ ID NO;

45, and a light chain represented by SEQ ID NO;

46;

a binding molecule comprising a heavy chain represented by SEQ ID NO;

47, and a light chain represented by SEQ ID NO;

48;

a binding molecule comprising a heavy chain represented by SEQ ID NO;

49, and a light chain represented by SEQ ID NO;

50; and

a binding molecule comprising a heavy chain represented by SEQ ID NO;

51, and a light chain represented by SEQ ID NO;

52.

17. The binding molecule according to claim 1,

wherein the binding molecule is an antibody or a fragment thereof.

18. The binding molecule according to claim 17,

wherein the antibody is a chimeric antibody, a humanized antibody, a bivalent, bispecific molecule, a minibody, a domain antibody, a bispecific antibody, an antibody mimetic, a diabody, a triabody, or a tetrabody, or a fragment thereof.

23. A pharmaceutical composition for preventing or treating immune-related diseases, comprising as an active ingredient:

the binding molecule according to claim 1.

24. The pharmaceutical composition according to claim 23,

wherein the immune-related disease is autoimmune disease, graft versus host disease, organ transplant rejection, asthma, atopy, or acute or chronic inflammatory disease.

25. A method for preventing or treating immune-related diseases, comprising:

a step of administering the binding molecule according to claim 1 to a subject in need of treatment, so as to prevent or treat the immune-related disease.

2-4. -4. (canceled)

19-22. -22. (canceled)