Antibody that binds to human pd-l1

Abstract

Provided are an antibody that binds to human PD-L1, and a tetravalent bispecific antibody against PD-1 and PD-L1 constructed based on the antibody that binds to human PD-L1. The tetravalent bispecific antibody requires no Fc modification, has no mismatch problems, and the preparation method thereof is simple. The biological activities and physical and chemical properties of the tetravalent bispecific antibody are similar with or even better than those of the monoclonal antibodies.

What is claimed is: 
     
         1 . An antibody that binds to human PD-L1 or an antigen-binding fragment thereof, comprising:
 (a) heavy chain complementarity determining regions H-CDR1, H-CDR2, H-CDR3, the H-CDR1 having an amino acid sequence as shown in SEQ ID NO: 17, the H-CDR2 having an amino acid sequence as shown in SEQ ID NO: 18, and the H-CDR3 having an amino acid sequence as shown in SEQ ID NO:19, and   (b) light chain complementarity determining regions L-CDR1, L-CDR2, L-CDR3, the L-CDR1 having an amino acid sequence as shown in SEQ ID NO: 20, the L-CDR2 having an amino acid sequence as shown in SEQ ID NO: 21, and the L-CDR3 having an amino acid sequence as shown in SEQ ID NO: 22.   
     
     
         2 . The antibody that binds to human PD-L1 or the antigen-binding fragment thereof according to  claim 1 , wherein the antibody is a monoclonal antibody or a polyclonal antibody. 
     
     
         3 . The antibody that binds to human PD-L1 or the antigen-binding fragment thereof according to  claim 1 , wherein the antibody is a murine antibody, a chimeric antibody, or a humanized antibody. 
     
     
         4 . The antibody that binds to human PD-L1 or the antigen-binding fragment thereof according to  claim 1 , wherein the antigen-binding fragment comprises a Fab fragment, a F(ab′)2 fragment, a Fv fragment or a single chain antibody. 
     
     
         5 . The antibody that binds to human PD-L1 or the antigen-binding fragment thereof according to  claim 1 , wherein the antibody that binds to human PD-L1 or the antigen-binding fragment thereof comprises a heavy chain variable region having an amino acid sequence as shown in SEQ ID NO: 9, and a light chain variable region having an amino acid sequence as shown in SEQ ID NO: 10. 
     
     
         6 . The antibody that binds to human PD-L1 or the antigen-binding fragment thereof according to  claim 1 , wherein the antibody that binds to human PD-L1 or the antigen-binding fragment thereof comprises a heavy chain having an amino acid sequence as shown in SEQ ID NO: 13, and a light chain having an amino acid sequence as shown in SEQ ID NO: 15. 
     
     
         7 . An isolated nucleotide, wherein the nucleotide encodes the antibody that binds to human PD-L1 or the antigen-binding fragment thereof of  claim 1 . 
     
     
         8 . The isolated nucleotide according to  claim 7 , wherein the nucleotide sequence encoding the heavy chain of the antibody that binds to human PD-L1 or the antigen-binding fragment thereof is shown in SEQ ID NO: 14, and the nucleotide sequence encoding the light chain is shown in SEQ ID NO: 16. 
     
     
         9 . An expression vector, wherein the expression vector comprises the isolated nucleotide of  claim 7 . 
     
     
         10 . A host cell, wherein the host cell comprises the expression vector of  claim 9 . 
     
     
         11 . A method of preparing an antibody that binds to human PD-L1 or an antigen-binding fragment thereof, wherein the method comprises the following steps:
 a) culturing the host cell of  claim 10  under expression conditions, to express the antibody that binds to human PD-L1 or the antigen-binding fragment thereof;   b) isolating and purifying the antibody that binds to human PD-L1 or the antigen-binding fragment thereof of step a).   
     
     
         12 . A pharmaceutical composition, wherein the pharmaceutical composition comprises the antibody that binds to the human PD-L1 or the antigen-binding fragment thereof of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         13 . A method of treating PD-L1 overexpression diseases, the method comprises administering the antibody that binds to human PD-L1 or the antigen-binding fragment thereof of  claim 1  to a subject in need. 
     
     
         14 . The method according to  claim 13 , wherein the PD-L1 overexpression disease is cancer. 
     
     
         15 . The method according to  claim 14 , wherein the cancer is selected from a group consisting of melanoma, kidney cancer, prostate cancer, pancreatic cancer, breast cancer, colon cancer, lung cancer, esophageal cancer, head and neck squamous cell carcinoma, liver cancer, ovarian cancer, cervical cancer, thyroid cancer, glioblastoma, glioma, leukemia and lymphoma. 
     
     
         16 . A method of treating PD-L1 overexpression diseases, the method comprises administering the antibody that binds to human PD-L1 or the pharmaceutical composition of  claim 12  to a subject in need. 
     
     
         17 . The method according to  claim 16 , wherein the PD-L1 overexpression disease is cancer. 
     
     
         18 . The method according to  claim 17 , wherein the cancer is selected from a group consisting of melanoma, kidney cancer, prostate cancer, pancreatic cancer, breast cancer, colon cancer, lung cancer, esophageal cancer, head and neck squamous cell carcinoma, liver cancer, ovarian cancer, cervical cancer, thyroid cancer, glioblastoma, glioma, leukemia and lymphoma.