Human antibodies to PD-L1

Patent metadata

Field	Value
Publication number	US-9938345-B2
Application number	US-201514603808-A
Country	US
Kind code	B2
Filing date	Jan 23, 2015
Priority date	Jan 23, 2014
Publication date	Apr 10, 2018
Grant date	Apr 10, 2018

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.

First claim

What is claimed is:

1. 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 of SEQ ID NO:82; and three light chain CDRs (LCDR1, LCDR2 and LCDR3) contained within a light chain variable region (LCVR) sequence of SEQ ID NO:90.

2. The isolated antibody or antigen-binding fragment thereof of claim 1 , comprising:
(a) a HCDR1 domain having an amino acid sequence of SEQ ID NO:84;
(b) a HCDR2 domain having an amino acid sequence of SEQ ID NO:86;
(c) a HCDR3 domain having an amino acid sequence of SEQ ID NO:88;
(d) a LCDR1 domain having an amino acid sequence of SEQ ID NO:92;
(e) a LCDR2 domain having an amino acid sequence of SEQ ID NO:94; and
(f) a LCDR3 domain having an amino acid sequence of SEQ ID NO:96.

3. The isolated antibody or antigen-binding fragment thereof of claim 2 , wherein the antibody or antigen-binding fragment thereof comprises an HCVR/LCVR amino acid sequence pair of SEQ ID NO:82/90.

4. The isolated antibody or antigen-binding fragment of claim 3 , wherein the antibody or antigen-binding fragment thereof has one or more of the following properties:
(a) binds monomeric PD-L1 with a binding dissociation equilibrium constant (K D ) of less than about 310 pM as measured in a surface plasmon resonance assay at 37° C.;
(b) binds monomeric human PD-L1 with a K D less than about 180 pM in a surface plasmon resonance assay at 25° C.;
(c) binds dimeric human PD-L1 with a K D of less than about 15 pM as measured in a surface plasmon resonance assay at 37° C.; and
(d) binds dimeric human PD-L1 with a K D less than about 8 pM in a surface plasmon resonance assay at 25° C.

5. The isolated antibody or antigen-binding fragment thereof of claim 1 that blocks PD-L1 binding to one of PD-1 or B7-1, as measured by a biosensor or surface plasmon resonance assay.

6. 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 of SEQ ID NO:82; and three CDRs of a LCVR, wherein the LCVR has an amino acid sequence of SEQ ID NO:90.

7. 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 of SEQ ID NO:82; and three CDRs of a LCVR, wherein the LCVR has an amino acid sequence of SEQ ID NO:90.

8. A pharmaceutical composition comprising an isolated monoclonal antibody or antigen-binding fragment thereof that binds PD-L1 according to claim 1 , and a pharmaceutically acceptable carrier or diluent.

Assignees

• Regeneron Pharma

Inventors

• Papadopoulos Nicholas J
• Murphy Andrew J
• Thurston Gavin
• Ioffe Ella
• Burova Elena

Classifications

• C07K16/22

  against growth factors {; against growth regulators} · CPC title

• C07K16/2827 Primary

  against B7 molecules, e.g. CD80, CD86 · CPC title

• C07K2317/565

  Complementarity determining region [CDR] · CPC title

• C07K2317/75

  Agonist effect on antigen · CPC title

• A61P31/14

  for RNA viruses · CPC title