Monoclonal antibody to PD-L1
The present invention relates to the field of biotechnology and provides antibodies that specifically binds to PD-L1. The invention also relates to DNA encoding said antibodies, to corresponding expression vectors and to methods of producing, and to methods of treatment using said antibodies.
1. A monoclonal antibody or antigen binding fragment thereof that specifically binds to PD-L1, wherein
a heavy chain variable domain comprises CDR1, CDR2, CDR3, wherein CDR1 comprises the amino acid sequence of SEQ ID NO: 1, CDR2 comprises the amino acid sequence of SEQ ID NO: 2 and CDR3 comprises the amino acid sequence of SEQ ID NO: 3; and
a light chain variable domain comprises CDR1, CDR2, CDR3 wherein CDR1 comprises the amino acid sequence of SEQ ID NO: 5, CDR2 comprises the amino acid sequence of SEQ ID NO: 6 and CDR3 comprises the amino acid sequence of SEQ ID NO: 7.
2. The monoclonal antibody or the antigen binding fragment thereof according to claim 1 , wherein the heavy chain variable domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 4.
3. The monoclonal antibody or the antigen binding fragment thereof according to claim 1 , wherein the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 4.
4. The monoclonal antibody or the antigen binding fragment thereof according to claim 1 , wherein the light chain variable domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 8.
5. The monoclonal antibody or the antigen binding fragment thereof according to claim 1 , wherein the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 8.
6. The monoclonal antibody or the antigen binding fragment thereof according to claim 1 , wherein
the heavy chain variable domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 4; and
the light chain variable domain comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 8.
7. The monoclonal antibody or the antigen binding fragment thereof according to claim 1 , wherein
the heavy chain variable domain comprises the amino acid sequence of SEQ ID NO: 4; and
the light chain variable domain comprises the amino acid sequence of SEQ ID NO: 8.
8. The monoclonal antibody according to claim 1 , comprising:
the heavy chain comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 9; and
the light chain comprising an amino acid sequence that is at least 90% identical to SEQ ID NO: 10.
9. The monoclonal antibody according to claim 1 , wherein:
the heavy chain comprises the amino acid sequence of SEQ ID NO: 9; and
the light chain comprises the amino acid sequence of SEQ ID NO: 10.
10. The monoclonal antibody according to claim 1 , wherein the antibody that specifically binds to PD-L1 is a full-length IgG antibody.
11. The monoclonal antibody according to claim 10 , wherein the full-length IgG antibody is an isotype of human antibody IgG1, IgG2, IgG3, IgG4.
12. A pharmaceutical composition for relieving a disease or disorder mediated by PD-L1, comprising the antibody or the antigen binding fragment according to claim 1 and one or more pharmaceutically acceptable excipients.
13. The pharmaceutical composition according to claim 12 for relieving a disease or disorder mediated by PD-L1, wherein the disease or disorder mediated by PD-L1 is one of: SCCHN (squamous cell carcinoma of the head and neck), cervical cancer, cancer of unknown primary origin, glioblastoma, esophageal cancer, bladder cancer, TNBC (triple-negative breast cancer), CRC (colorectal cancer), hepatocellular carcinoma, melanoma, NSCLC (non-small-cell lung cancer), kidney cancer, ovarian cancer, Hodgkin's lymphoma, MSI-H CRC (high microsatellite instability colorectal cancer).
14. A method of relieving a PD-L1 mediated disease or disorder in a subject, comprising administrating to the subject a therapeutically effective amount of the pharmaceutical composition of claim 12 .
15. The method according to claim 14 , wherein the disease or disorder is one of: SCCHN (squamous cell carcinoma of the head and neck), cervical cancer, cancer of unknown primary origin, glioblastoma, esophageal cancer, bladder cancer, TNBC (triple-negative breast cancer), CRC (colorectal cancer), hepatocellular carcinoma, melanoma, NSCLC (non-small-cell lung cancer), kidney cancer, ovarian cancer, Hodgkin's lymphoma, MSI-H CRC (high microsatellite instability colorectal cancer).
16. A pharmaceutical combination for relieving a disease or disorder mediated by PD-L1, comprising the antibody or the antigen binding fragment according to claim 1 and at least one therapeutic antitumor compound.
17. The pharmaceutical combination according to claim 16 for relieving a disease or disorder mediated by PD-L1, wherein the disease or disorder mediated by PD-L1 is one of: SCCHN (squamous cell carcinoma of the head and neck), cervical cancer, cancer of unknown primary origin, glioblastoma, esophageal cancer, bladder cancer, TNBC (triple-negative breast cancer), CRC (colorectal cancer), hepatocellular carcinoma, melanoma, NSCLC (non-small-cell lung cancer), kidney cancer, ovarian cancer, Hodgkin's lymphoma, MSI-H CRC (high microsatellite instability colorectal cancer).
18. A method for inhibiting of biological activity of PD-L1 in a subject in need thereof, comprising administrating to the subject a therapeutically effective amount of the antibody or the antigen binding fragment as defined in claim 1 .
19. A method of relieving a PD-L1 mediated disease or disorder in a subject, comprising administrating to the subject a therapeutically effective amount of the antibody or the antigen binding fragment of claim 1 .
20. The method according to claim 19 , wherein the disease or disorder is one of: SCCHN (squamous cell carcinoma of the head and neck), cervical cancer, cancer of unknown primary origin, glioblastoma, esophageal cancer, bladder cancer, TNBC (triple-negative breast cancer), CRC (colorectal cancer), hepatocellular carcinoma, melanoma, NSCLC (non-small-cell lung cancer), kidney cancer, ovarian cancer, Hodgkin's lymphoma, MSI-H CRC (high microsatellite instability colorectal cancer).
21. A monoclonal antibody or antigen binding fragment thereof that specifically binds to PD-L1 comprising:
a) a heavy chain variable domain comprising the amino acid sequences corresponding to SEQ ID NO: 1, 2 and 3; a light chain variable domain comprising the amino acid sequences corresponding to SEQ ID NO: 5, 6 and 7; or
b) a variant of a) comprising a combination of amino acid substitutions selected from the following group:
i) the first amino acid of SEQ ID NO: 1 is A, the second amino acid of SEQ ID NO: 1 is N, the seventh amino acid of SEQ ID NO: 3 is T, the fourth amino acid of SEQ ID NO: 7 is V, the sixth amino acid of SEQ ID NO: 7 is T and the eighth amino acid of SEQ ID NO: 7 is S;
ii) the first amino acid of SEQ ID NO: 1 is N, the fourth amino acid of SEQ ID NO: 3 is P, the seventh amino acid of SEQ ID NO: 3 is T, the fourth amino acid of SEQ ID NO: 7 is T, the sixth amino acid of SEQ ID NO: 7 is T and the eighth amino acid of SEQ ID NO: 7 is S;
iii) the first amino acid of SEQ ID NO: 1 is N, the second amino acid of SEQ ID NO: 1 is N, the seventh amino acid of SEQ ID NO: 3 is T, the fourth amino acid of SEQ ID NO: 7 is T, the sixth amino acid of SEQ ID NO: 7 is T and the eighth amino acid of SEQ ID NO: 7 is S;
iv) the first amino acid of SEQ ID NO: 1 is A, the second amino acid of SEQ ID NO: 1 is N, the fourth amino acid of SEQ ID NO: 3 is P, the seventh amino acid of SEQ ID NO: 3 is T, the fourth amino acid of SEQ ID NO: 7 is V, the sixth amino acid of SEQ ID NO: 7 is T and the eighth amino acid of SEQ ID NO: 7 is S;
v) the first amino acid of SEQ ID NO: 1 is K, the second amino acid of SEQ ID NO: 1 is S, the fifth amino acid of SEQ ID NO: 1 is I, the fourth amino acid of SEQ ID NO: 3 is M, the seventh amino acid of SEQ ID NO: 3 is A, the fourth amino acid of SEQ ID NO: 7 is Y, the sixth amino acid of SEQ ID NO: 7 is T and the eighth amino acid of SEQ ID NO: 7 is S;
vi) the first amino acid of SEQ ID NO: 1 is S, the second amino acid of SEQ ID NO: 1 is T, the fourth amino acid of SEQ ID NO: 3 is V, the seventh amino acid of SEQ ID NO: 3 is I, the fourth amino acid of SEQ ID NO: 7 is T, the sixth amino acid of SEQ ID NO: 7 is T and the eighth amino acid of SEQ ID NO: 7 is S;
vii) the first amino acid of SEQ ID NO: 1 is A, the fourth amino acid of SEQ ID NO: 3 is P, the fifth amino acid of SEQ ID NO: 3 is S, the seventh amino acid of SEQ ID NO: 3 is I, the fourth amino acid of SEQ ID NO: 7 is E, the sixth amino acid of SEQ ID NO: 7 is T and the eighth amino acid of SEQ ID NO: 7 is S; and
viii) the first amino acid of SEQ ID NO: 1 is N, the second amino acid of SEQ ID NO: 1 is N, the seventh amino acid of SEQ ID NO: 3 is T, the fourth amino acid of SEQ ID NO: 7 is T, the sixth amino acid of SEQ ID NO: 7 is T and the eighth amino acid of SEQ ID NO: 7 is S.