Human monoclonal anti-PD-L1 antibodies and methods of use
The present invention comprises human monoclonal antibodies that bind to PD-L1 (also known as programmed death ligand 1 or B7H1). Binding of the invented antibody to PD-L1 inhibits binding to its receptor, PD1 (programmed death 1), and ligand-mediated activities and can be used to treat cancer and chronic viral infections.
1. An isolated humanized monoclonal antibody having:
a heavy chain with three CDRs comprising the amino acid sequences SYAIS (SEQ ID NO:57), GIIPIFGTANYAQKFQG (SEQ ID NO:78), and GRQMFGAGIDF (SEQ ID NO:93) respectively and a light chain with three CDRs comprising the amino acid sequences TRSSGSIDSNYVQ (SEQ ID NO:108), EDNQRPS (SEQ ID NO:115), and QSYDSINNRHVI (SEQ ID NO:134) respectively;
wherein said antibody binds human Programmed Death Ligand-1.
2. The antibody of claim 1 , wherein said antibody is monovalent or bivalent.
3. The antibody of claim 1 , wherein said antibody is a single chain antibody.
4. The antibody according to claim 1 , wherein said antibody is a bi-specific antibody that also binds to a tumor-associated antigen, a cytokine or a cell surface receptor.
5. The antibody according to claim 4 , wherein said tumor-associated antigen is CAIX.
6. The antibody according to claim 4 , wherein said cytokine is IL-10.
7. The antibody according to claim 4 , wherein said cell surface receptor is CCR4, IL21R, BTLA, HVEM or TIM3.
8. A single chain antibody encoded by a nucleotide sequence comprising:
a V H nucleotide sequence comprising SEQ ID NO: 29 and a V L nucleotide sequence comprising SEQ ID NO:31, wherein the antibody binds human Programmed Death Ligand-1.
9. A single chain antibody comprising
a V H amino acid sequence comprising SEQ ID NO: 30 and a V L amino acid sequence comprising SEQ ID NO: 32, wherein the antibody binds human Programmed Death Ligand-1.
10. The antibody according to any one of claims 1 - 9 and 4 - 7 , wherein said antibody is linked to a therapeutic agent.
11. The antibody of claim 10 , wherein said therapeutic agent comprises a toxin, a radiolabel, a siRNA, a small molecule, or a cytokine.