Anti-PD-L1 antibodies and their use as therapeutics and diagnostics
Provided are antibodies that specifically bind to Programmed Death-1 (PD1, Pdcd-1, or CD279) ligand (PD-L1) and inhibit PD-L1-mediated cellular signaling and activities in immune cells, antibodies binding to a set of amino acid residues required for its ligand binding, and uses of these antibodies to treat or diagnose cancer, infectious diseases or other pathological disorders modulated by PD-L1-mediated functions.
1. An antibody antigen binding domain which binds to human PD-L1, selected from the group consisting of:
(1) an antibody antigen binding domain comprising a heavy chain CDR1 comprising residues 6-10 of SEQ ID NO: 9, a heavy chain CDR2 comprising SEQ ID NO: 25, a heavy chain CDR3 comprising residues 3-11 of SEQ ID NO: 26, a light chain CDR1 comprising SEQ ID NO: 12, a light chain CDR2 comprising SEQ ID NO: 13, and a light chain CDR3 comprising SEQ ID NO: 14;
(2) an antibody antigen binding domain comprising a heavy chain CDR1 comprising residues 6-10 of SEQ ID NO: 9, a heavy chain CDR2 comprising SEQ ID NO: 24, a heavy chain CDR3 comprising residues 3-11 of SEQ ID NO: 26, a light chain CDR1 comprising SEQ ID NO: 12, a light chain CDR2 comprising SEQ ID NO: 13, and a light chain CDR3 comprising SEQ ID NO: 14;
(3) an antibody antigen binding domain comprising a heavy chain CDR1 comprising residues 6-10 of SEQ ID NO: 9, a heavy chain CDR2 comprising SEQ ID NO: 10, a heavy chain CDR3 comprising residues 3-11 of SEQ ID NO: 11, a light chain CDR1 comprising SEQ ID NO: 12, a light chain CDR2 comprising SEQ ID NO: 13, and a light chain CDR3 comprising SEQ ID NO: 14;
(4) an antibody antigen binding domain comprising a heavy chain CDR1 comprising residues 6-10 of SEQ ID NO: 9, a heavy chain CDR2 comprising SEQ ID NO: 24, a heavy chain CDR3 comprising residues 3-11 of SEQ ID NO: 11, a light chain CDR1 comprising SEQ ID NO: 12, a light chain CDR2 comprising SEQ ID NO: 13, and a light chain CDR3 comprising SEQ ID NO: 14; and
(5) an antibody antigen binding domain comprising a heavy chain CDR1 comprising residues 6-10 of SEQ ID NO: 9, a heavy chain CDR2 comprising SEQ ID NO: 25, a heavy chain CDR3 comprising residues 3-11 of SEQ ID NO: 11, a light chain CDR1 comprising SEQ ID NO: 12, a light chain CDR2 comprising SEQ ID NO: 13, and a light chain CDR3 comprising SEQ ID NO: 14.
2. The antibody antigen binding domain according to claim 1 , comprising a heavy chain CDR1 comprising SEQ ID NO: 9, a heavy chain CDR2 comprising SEQ ID NO: 25, a heavy chain CDR3 comprising SEQ ID NO: 26, a light chain CDR1 comprising SEQ ID NO: 12, a light chain CDR2 comprising SEQ ID NO: 13, and a light chain CDR3 comprising SEQ ID NO: 14.
3. The antibody antigen binding domain according to claim 1 , comprising a heavy chain variable region (Vh) and a light chain variable region (Vk) selected from the group consisting of:
(1) a Vh comprising SEQ ID NO: 22 and a Vk comprising SEQ ID NO: 23,
(2) a Vh comprising SEQ ID NO: 21 and a Vk comprising SEQ ID NO: 23,
(3) a Vh comprising SEQ ID NO: 6 and a Vk comprising SEQ ID NO: 8,
(4) a Vh comprising SEQ ID NO: 15 and a Vk comprising SEQ ID NO: 16,
(5) a Vh comprising SEQ ID NO: 17 and a Vk comprising SEQ ID NO: 16,
(6) a Vh comprising SEQ ID NO: 18 and a Vk comprising SEQ ID NO: 23,
(7) a Vh comprising SEQ ID NO: 19 and a Vk comprising SEQ ID NO: 23, and
(8) a Vh comprising SEQ ID NO: 20 and a Vk comprising SEQ ID NO: 23.
4. An antibody antigen binding domain according to claim 1 , comprising a heavy chain variable region (Vh) consisting of SEQ ID NO: 22 and a light chain variable region (Vk) consisting of SEQ ID NO: 23.
5. An antibody antigen binding domain according to claim 1 , wherein the antibody antigen binding domain specifically binds PD-L1 residues: D26 and R113.
6. A monoclonal IgG antibody comprising an antibody antigen binding domain according to claim 1 .
7. A method of using an antibody antigen binding domain according to claim 1 , comprising the step of administering the domain or an antibody comprising the domain to a person determined to have a PD-L1 expressing cancer or a viral infection in which virus-infected cells express PD-L1.
8. An expression vector encoding an antibody antigen binding domain according to claim 1 .
9. A cultured cell expressing an antibody antigen binding domain according to claim 1 .
10. A monoclonal antibody comprising the antibody antigen binding domain of claim 1 , wherein the antibody comprises a heavy chain and a light chain selected from the group consisting of:
(1) a heavy chain comprising SEQ ID NO: 33 and a light chain comprising SEQ ID NO: 32,
(2) a heavy chain comprising SEQ ID NO: 30 and a light chain comprising SEQ ID NO: 32, and
(3) a heavy chain comprising SEQ ID NO: 31 and a light chain comprising SEQ ID NO: 32.
11. A method of treating a PD-L1 expressing cancer in a subject in need thereof, comprising administering to the subject an antibody comprising the antibody antigen binding domain of claim 1 .
12. A method of treating a viral infection in which virus-infected cells express PD-L1 in a subject in need thereof, comprising administering to the subject an antibody comprising the antibody antigen binding domain of claim 1 .