Anti-pd-l1 antibodies and uses thereof

Abstract

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.

What is claimed is: 
     
         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.