Anti-TIGIT antibodies
The present invention relates to anti-TIGIT antibodies, as well as use of these antibodies in the treatment of diseases such as cancer and infectious disease.
1. A method of treating a human subject with cancer in need thereof, comprising administering to the subject an effective amount of a monoclonal antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:89, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93,
optionally in association with a further therapeutic agent or therapeutic procedure.
2. A method of treating a human subject having an infection or infectious disease, comprising administering to the subject an effective amount of a monoclonal antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:89, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93,
optionally in association with a further therapeutic agent or therapeutic procedure.
3. A method of treating a human subject with cancer in need thereof, comprising administering to the subject an effective amount of a monoclonal antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:134, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.
4. The method of claim 3 , wherein the monoclonal antibody and antigen binding fragment thereof comprise:
a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:132;
b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:127 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:130;
c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:133;
d) a heavy chain variable region comprising at least 97% identity to SEQ ID NO: 128 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 132, wherein any sequence variations occur in the framework regions of the monoclonal antibody;
e) a heavy chain variable region comprising at least 97% identity to SEQ ID NO:127 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 130, wherein any sequence variations occur in the framework regions of the monoclonal antibody; or
f) a heavy chain variable region comprising at least 97% identity to SEQ ID NO:128 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 133, wherein any sequence variations occur in the framework regions of the monoclonal antibody.
5. The method of claim 1 , wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region comprising at least 97% identity to the amino acid sequence of SEQ ID NO: 94 and a light chain variable region comprising at least 97% identity to the amino acid sequence of SEQ ID NO:95.
6. The method of claim 3 , wherein the monoclonal antibody and antigen binding fragment thereof comprise two heavy chains and two light chains.
7. The method of claim 3 , wherein the monoclonal antibody comprises a human IgG1 constant domain and a human kappa constant domain.
8. The method of claim 7 , wherein the human IgG1 constant domain comprises SEQ ID NO: 86 and the human kappa constant domain comprises SEQ ID NO: 56.
9. A method of treating a human subject having an infection or infectious disease, comprising administering to the subject an effective amount of a monoclonal antibody or antigen binding fragment thereof that binds to human TIGIT, wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:134, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.
10. The method of claim 9 , wherein the monoclonal antibody and antigen binding fragment thereof comprise:
a) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:132;
b) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:127 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:130;
c) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:133;
d) a heavy chain variable region comprising at least 97% identity to SEQ ID NO:128 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 132, wherein any sequence variations occur in the framework regions of the monoclonal antibody;
e) a heavy chain variable region comprising at least 97% identity to SEQ ID NO: 127 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 130, wherein any sequence variations occur in the framework regions of the monoclonal antibody; or
f) a heavy chain variable region comprising at least 97% identity to SEQ ID NO:128 and a light chain variable region comprising at least 97% identity to SEQ ID NO: 133, wherein any sequence variations occur in the framework regions of the monoclonal antibody.
11. The method of claim 3 , wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:132.
12. The method of claim 9 , wherein the monoclonal antibody and antigen binding fragment thereof comprise a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:128 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:132.
13. The method of claim 12 , wherein the monoclonal antibody and antigen binding fragment thereof comprise a human IgG1 constant domain comprising SEQ ID NO: 86 and a human kappa constant domain comprising SEQ ID NO: 56.
14. A method of treating a human subject with cancer in need thereof, comprising administering to the subject (a) an effective amount of a monoclonal antibody that binds to human TIGIT and (b) an effective amount of pembrolizumab, wherein the monoclonal antibody comprises two heavy chains and two light chains;
wherein each of the heavy chains comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 128; and
wherein each of the light chains comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO:132.
15. The method of claim 14 , wherein the monoclonal antibody comprises a human IgG1 constant domain and a human kappa constant domain.
16. The method of claim 15 , wherein the human IgG1 constant domain comprises SEQ ID NO: 86 and the human kappa constant domain comprises SEQ ID NO: 56.
17. The method of claim 16 , wherein the cancer is lung cancer.
18. The method of claim 17 , wherein the cancer is non-small cell lung cancer.
19. A method of treating a human subject with cancer in need thereof, comprising administering to the subject (a) an effective amount of a monoclonal antibody that binds to human TIGIT and (b) an effective amount of pembrolizumab,
wherein the monoclonal antibody comprises two heavy chains and two light chains; and
wherein the monoclonal antibody comprises a heavy chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:88, a heavy chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:134, a heavy chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:90, a light chain variable region CDR1 comprising the amino acid sequence of SEQ ID NO:91, a light chain variable region CDR2 comprising the amino acid sequence of SEQ ID NO:92, and a light chain variable region CDR3 comprising the amino acid sequence of SEQ ID NO:93.
20. The method of claim 19 , wherein the monoclonal antibody comprises a human IgG1 constant domain and a human kappa constant domain.
21. The method of claim 20 , wherein the human IgG1 constant domain comprises SEQ ID NO: 86 and the human kappa constant domain comprises SEQ ID NO: 56.
22. The method of claim 21 , wherein the cancer is lung cancer.
23. The method of claim 22 , wherein the cancer is non-small cell lung cancer.
24. The method of claim 8 , wherein the cancer is lung cancer.
25. The method of claim 24 , wherein the cancer is non-small cell lung cancer.
26. The method of claim 11 , wherein the monoclonal antibody or antigen binding fragment thereof is a monoclonal antibody, wherein the monoclonal antibody comprises two heavy chains and two light chains.
27. The method of claim 26 , wherein the monoclonal antibody comprises a human IgG1 constant domain and a human kappa constant domain.
28. The method of claim 27 , wherein the human IgG1 constant domain comprises SEQ ID NO: 86 and the human kappa constant domain comprises SEQ ID NO: 56.
29. The method of claim 28 , wherein the cancer is lung cancer.
30. The method of claim 29 , wherein the cancer is non-small cell lung cancer.