Anti-human PD-L1 antibodies and their uses
An anti-PD-L1 antibody, or an antigen-binding fragment thereof, comprising: a heavy chain variable region comprising the three CDRs with the sequences of SEQ ID NOs: 2-4, 6-8, 10-12, 14-16, or 18-20; and/or a light chain variable region comprising the three CDRs with the sequences of SEQ ID NOs: 22-24, 26-28, 30-32, 34-36, or 38-40, wherein the antibody is a chimeric, humanized, composite, or human antibody.
1. An anti-PD-L1 antibody, or an antigen-binding fragment thereof, comprising:
a heavy-chain variable region comprising three heavy-chain complementarity-determining regions, HCDR1, HCDR2, and HCDR3, with the sequences of SEQ ID NOs: 2-4, or 6-8, or 10-12, or 14-16, or 18-20; and
a light-chain variable region comprising three light-chain complementarity-determining regions, LCDR1, LCDR2, and LCDR3, with the sequences of SEQ ID NOs: 22-24, or 26-28, or 30-32, or 34-36, or 38-40.
2. The anti-PD-L1 antibody, or the antigen-binding fragment thereof, according to claim 1 , wherein
the HCDR1 has the sequence of SEQ ID NO: 2, the HCDR2 has the sequence of SEQ ID NO: 3, and the HCDR3 has the sequence of SEQ ID NO: 4, and the LCDR1 has the sequence of SEQ ID NO: 22, the LCDR2 has the sequence of SEQ ID NO: 23, and the LCDR3 has the sequence of SEQ ID NO: 24; or
the HCDR1 has the sequence of SEQ ID NO: 6, the HCDR2 has the sequence of SEQ ID NO: 7, and the HCDR3 has the sequence of SEQ ID NO: 8, and the LCDR1 has the sequence of SEQ ID NO: 26, the LCDR2 has the sequence of SEQ ID NO: 27, and the LCDR3 has the sequence of SEQ ID NO: 28; or
the HCDR1 has the sequence of SEQ ID NO: 10, the HCDR2 has the sequence of SEQ ID NO: 11, and the HCDR3 has the sequence of SEQ ID NO: 12, and the LCDR1 has the sequence of SEQ ID NO: 30, the LCDR2 has the sequence of SEQ ID NO: 31, and the LCDR3 has the sequence of SEQ ID NO: 32; or
the HCDR1 has the sequence of SEQ ID NO: 14, the HCDR2 has the sequence of SEQ ID NO: 15, and the HCDR3 has the sequence of SEQ ID NO: 16, and the LCDR1 has the sequence of SEQ ID NO: 34, the LCDR2 has the sequence of SEQ ID NO: 35, and the LCDR3 has the sequence of SEQ ID NO: 36; or
the HCDR1 has the sequence of SEQ ID NO: 18, the HCDR2 has the sequence of SEQ ID NO: 19, and the HCDR3 has the sequence of SEQ ID NO: 20, and the LCDR1 has the sequence of SEQ ID NO: 38, the LCDR2 has the sequence of SEQ ID NO: 39, and the LCDR3 has the sequence of SEQ ID NO: 40.
3. The anti-PD-L1 antibody, or the antigen-binding fragment thereof, according to claim 1 , wherein
a. the heavy-chain variable region comprises the sequence of SEQ ID NOs: 1, 5, 9, 13, or 17, or a sequence with at least 95% homology to the sequence of SEQ ID NOs: 1, 5, 9, 13, or 17; and/or
b. the light-chain variable region comprises the sequence of SEQ ID NOs: 21, 25, 29, 33, or 37, or a sequence with at least 95% homology to the sequence of SEQ ID NOs: 21, 25, 29, 33, or 37.
4. The anti-PD-L1 antibody, or the antigen-binding fragment thereof, according to claim 3 , wherein
a. the heavy-chain variable region comprises the sequence of SEQ ID NO: 1, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 21, or a sequence with at least 95% homology thereto; or
b. the heavy-chain variable region comprises the sequence of SEQ ID NO: 5, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 25, or a sequence with at least 95% homology thereto; or
c. the heavy-chain variable region comprises the sequence of SEQ ID NO: 9, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 29, or a sequence with at least 95% homology thereto; or
d. the heavy-chain variable region comprises the sequence of SEQ ID NO: 13, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 33, or a sequence with at least 95% homology thereto; or
e. the heavy-chain variable region comprises the sequence of SEQ ID NO: 17, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 37, or a sequence with at least 95% homology thereto.
5. The anti-PD-L1 antibody, or the antigen-binding fragment thereof, according to claim 1 , wherein the antibody or antigen-binding fragment thereof inhibits a PD-L1-mediated signal.
6. The anti-PD-L1 antibody, or the antigen-binding fragment thereof, according to claim 1 , further comprising a drug conjugate covalently linked to the antibody, or the antigen-binding fragment thereof, to form an antibody-drug conjugate (ADC).
7. The anti-PD-L1 antibody, or the antigen-binding fragment thereof, according to claim 1 , wherein the antibody, or the antigen-binding fragment thereof, is linked with a second antibody binding fragment to form a bispecific antibody.
8. A method for treating a cancer mediated by PD-1 or PD-L1, comprising:
administering to a subject in need thereof a pharmaceutical composition comprising the anti-PD-L1 antibody, or the antigen-binding fragment thereof, according to claim 1 .
9. The method of claim 8 , wherein the cancer is lung cancer, breast cancer, prostate cancer, or colorectal cancer.
10. A method for detecting expression of PD-L1, comprising contacting a sample with the anti-PD-L1 antibody, or the antigen-binding fragment thereof, according to claim 1 , and comparing a measurement of PD-L1 and the anti-PD-L1 antibody binding to a background measurement, wherein if the measurement of PD-L1 and the anti-PD-L1 antibody binding is greater than the background measurement, expression of PD-L1 is indicated.
11. The method of claim 8 , wherein
the HCDR1 has the sequence of SEQ ID NO: 2, the HCDR2 has the sequence of SEQ ID NO: 3, and the HCDR3 has the sequence of SEQ ID NO: 4, and the LCDR1 has the sequence of SEQ ID NO: 22, the LCDR2 has the sequence of SEQ ID NO: 23, and the LCDR3 has the sequence of SEQ ID NO: 24; or
the HCDR1 has the sequence of SEQ ID NO: 6, the HCDR2 has the sequence of SEQ ID NO: 7, and the HCDR3 has the sequence of SEQ ID NO: 8, and the LCDR1 has the sequence of SEQ ID NO: 26, the LCDR2 has the sequence of SEQ ID NO: 27, and the LCDR3 has the sequence of SEQ ID NO: 28; or
the HCDR1 has the sequence of SEQ ID NO: 10, the HCDR2 has the sequence of SEQ ID NO: 11, and the HCDR3 has the sequence of SEQ ID NO: 12, and the LCDR1 has the sequence of SEQ ID NO: 30, the LCDR2 has the sequence of SEQ ID NO: 31, and the LCDR3 has the sequence of SEQ ID NO: 32; or
the HCDR1 has the sequence of SEQ ID NO: 14, the HCDR2 has the sequence of SEQ ID NO: 15, and the HCDR3 has the sequence of SEQ ID NO: 16, and the LCDR1 has the sequence of SEQ ID NO: 34, the LCDR2 has the sequence of SEQ ID NO: 35, and the LCDR3 has the sequence of SEQ ID NO: 36; or
the HCDR1 has the sequence of SEQ ID NO: 18, the HCDR2 has the sequence of SEQ ID NO: 19, and the HCDR3 has the sequence of SEQ ID NO: 20, and the LCDR1 has the sequence of SEQ ID NO: 38, the LCDR2 has the sequence of SEQ ID NO: 39, and the LCDR3 has the sequence of SEQ ID NO: 40.
12. The method of claim 8 , wherein
a. the heavy-chain variable region comprises the sequence of SEQ ID NOs: 1, 5, 9, 13, or 17, or a sequence with at least 95% homology to the sequence of SEQ ID NOs: 1, 5, 9, 13, or 17; and/or
b. the light-chain variable region comprises the sequence of SEQ ID NOs: 21, 25, 29, 33, or 37, or a sequence with at least 95% homology to the sequence of SEQ ID NOs: 21, 25, 29, 33, or 37.
13. The method of claim 8 , wherein
a. the heavy-chain variable region comprises the sequence of SEQ ID NO: 1, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 21, or a sequence with at least 95% homology thereto; or
b. the heavy-chain variable region comprises the sequence of SEQ ID NO: 5, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 25, or a sequence with at least 95% homology thereto; or
c. the heavy-chain variable region comprises the sequence of SEQ ID NO: 9, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 29, or a sequence with at least 95% homology thereto; or
d. the heavy-chain variable region comprises the sequence of SEQ ID NO: 13, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 33, or a sequence with at least 95% homology thereto; or
e. the heavy-chain variable region comprises the sequence of SEQ ID NO: 17, or a sequence with at least 95% homology thereto and the light-chain variable region comprises the sequence of SEQ ID NO: 37, or a sequence with at least 95% homology thereto.
14. The method of claim 8 , wherein the antibody, or the antigen-binding fragment thereof, comprises a drug conjugate covalently linked to the antibody, or the antigen-binding fragment thereof, to form an antibody-drug conjugate (ADC).
15. The method of claim 8 , wherein the antibody, or the antigen-binding fragment thereof, is linked with a second antibody binding fragment to form a bispecific antibody.