ANTI-PD-L1 ANTIBODIES AND USES THEREOF
Provided are anti-PD-L1 antibodies or fragments thereof. The antibodies or fragments thereof specifically bind to the immunoglobulin C domain of the PD-L1 protein. In various example, the antibodies or fragments thereof include a VH CDR1 of SEQ ID NO: 1, a VH CDR2 of SEQ ID NO: 116, a VH CDR3 of SEQ ID NO: 117, a VL CDR1 of SEQ ID NO: 4, a VL CDR2 of SEQ ID NO: 5, and a VL CDR3 of SEQ ID NO: 6, or variants of each thereof. Methods of using the antibodies or fragments thereof for treating and diagnosing diseases such as cancer and infectious diseases are also provided.
1 . An antibody or fragment thereof, wherein the antibody or fragment thereof has specificity to a human PD-L1 protein and comprises:
(a) a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 1 or a variant of SEQ ID NO: 1 having one, two or three substitution, deletion or insertion as compared to SEQ ID NO: 1;
(b) a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 116 or a variant of SEQ ID NO: 116 having one, two or three substitution, deletion or insertion as compared to SEQ ID NO: 116, wherein amino acid residue 12 of the VH CDR3 is Arg;
(c) a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 3 or a variant of SEQ ID NO: 3 having one, two or three substitution, deletion or insertion as compared to SEQ ID NO: 3;
(d) a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 4 or a variant of SEQ ID NO: 4 having one, two or three substitution, deletion or insertion as compared to SEQ ID NO: 4;
(e) a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 5 or a variant of SEQ ID NO: 5 having one, two or three substitution, deletion or insertion as compared to SEQ ID NO: 5; and
(f) a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 6 or a variant of SEQ ID NO: 6 having one, two or three substitution, deletion or insertion as compared to SEQ ID NO: 6.
2 . The antibody or fragment thereof of claim 1 , wherein the variant of SEQ ID NO: 1 is selected from the group consisting of SEQ ID NO: 61-67.
3 . The antibody or fragment thereof of claim 1 , wherein the variant of SEQ ID NO: 116 is selected from the group consisting of SEQ ID NO: 118-127.
4 . The antibody or fragment thereof of claim 1 , wherein the variant of SEQ ID NO: 3 is selected from the group consisting of SEQ ID NO: 117 and 128-139.
5 . The antibody or fragment thereof of claim 1 , wherein the variant of SEQ ID NO: 4 is selected from the group consisting of SEQ ID NO: 91-92.
6 . The antibody or fragment thereof of claim 1 , wherein the variant of SEQ ID NO: 5 is selected from the group consisting of SEQ ID NO: 93-105.
7 . The antibody or fragment thereof of claim 1 , wherein the variant of SEQ ID NO: 6 is selected from the group consisting of SEQ ID NO: 140 and 106-111.
8 . The antibody or fragment thereof of claim 1 , wherein the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 116, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 6.
9 . The antibody or fragment thereof of claim 8 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ IN NO: 141 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 142.
10 . The antibody or fragment thereof of claim 1 , wherein amino acid residues 4, 5 and 6 of the VL CDR3 are Ser, Asp and Ala, respectively.
11 . The antibody or fragment thereof of claim 10 , wherein the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 140.
12 . The antibody or fragment thereof of claim 11 , wherein the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 116, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 3, the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 140.
13 . The antibody or fragment thereof of claim 12 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ IN NO: 159 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 160.
14 . The antibody or fragment thereof of claim 1 , wherein the second amino acid residue of the VH CDR3 is Leu.
15 . The antibody or fragment thereof of claim 14 , wherein the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 117.
16 . The antibody or fragment thereof of claim 15 , wherein the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 116, the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 117, the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 5, and the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 6.
17 . The antibody or fragment thereof of claim 16 , comprising a heavy chain variable region comprising the amino acid sequence of SEQ IN NO: 149 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 150.
18 . One or more polynucleotide encoding the antibody or fragment thereof of claim 1 .
19 . A method of treating cancer or infection in a patient in need thereof, comprising administering to the patient an effective amount of the antibody or fragment thereof of claim 1 .
20 . The method of claim 19 , which is for treating cancer characterized with expression of PD-L1.