Human Antibodies to PD-L1
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Abstract
The present invention provides antibodies that bind to the T-cell co-inhibitor ligand programmed death-ligand1 (PD-L1) protein, and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that bind to PD-L1. In certain embodiments, the present invention provides multi-specific antigen-binding molecules comprising a first binding specificity that binds to PD-L1 and a second binding specificity that binds to a tumor cell antigen, an infected cell-specific antigen, or a T-cell co-inhibitor. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing PD-L1 activity, thus providing a means of treating a disease or disorder such as cancer or viral infection.
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Citations
64 Claims
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1-42. -42. (canceled)
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43. An isolated human monoclonal antibody or antigen-binding fragment thereof that binds specifically to human programmed death-ligand 1 (PD-L1) protein, wherein the antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2 and HCDR3) contained within a heavy chain variable region (HCVR) sequence selected from the group consisting of SEQ ID NOs:
- 2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 186, 202, 218, 234, 250, 266, 282, 290, 298, 306, 314, 322, 330, and 338; and
three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) sequence selected from the group consisting of SEQ ID NOs;
10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 194, 210, 226, 242, 258, and 274. - View Dependent Claims (44, 45, 46, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64)
- 2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 186, 202, 218, 234, 250, 266, 282, 290, 298, 306, 314, 322, 330, and 338; and
- 47. An isolated antibody or antigen-binding fragment thereof that blocks PD-L1 binding to one of PD-1 or B7-1, as measured by a biosensor or surface plasmon resonance assay.
- 50. An isolated antibody or antigen-binding fragment thereof that binds PD-L1, wherein the antibody or antigen-binding fragment thereof enhances PD-L1 binding to one of PD-1 or B7-1, as measured by a biosensor or surface plasmon resonance assay.
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53. An isolated human monoclonal antibody or antigen-binding fragment thereof that competes for binding to human PD-L1 protein with a reference antibody comprising three CDRs of a HCVR, wherein the HCVR has an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 186, 202, 218, 234, 250, 266, 282, 290, 298, 306, 314, 322, 330, and 338; and
three CDRs of a LCVR, wherein the LCVR has an amino acid sequence selected from the group consisting of SEQ ID NOs;
10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 194, 210, 226, 242, 258, and 274.
- 2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 186, 202, 218, 234, 250, 266, 282, 290, 298, 306, 314, 322, 330, and 338; and
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54. An isolated human monoclonal antibody or antigen-binding fragment thereof that binds to the same epitope on human PD-L1 protein as an antibody or antigen-binding fragment thereof which comprises three CDRs of a HCVR, wherein the HCVR has an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 186, 202, 218, 234, 250, 266, 282, 290, 298, 306, 314, 322, 330, and 338; and
three CDRs of a LCVR, wherein the LCVR has an amino acid sequence selected from the group consisting of SEQ ID NOs;
10, 26, 42, 58, 74, 90, 106, 122, 138, 154, 170, 194, 210, 226, 242, 258, and 274.
- 2, 18, 34, 50, 66, 82, 98, 114, 130, 146, 162, 178, 186, 202, 218, 234, 250, 266, 282, 290, 298, 306, 314, 322, 330, and 338; and
Specification