Human monoclonal antibodies to programmed death ligand 1 (PD-L1)

Patent metadata

Field	Value
Publication number	US-9580507-B2
Application number	US-201615188860-A
Country	US
Kind code	B2
Filing date	Jun 21, 2016
Priority date	Jul 1, 2005
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

The present disclosure provides isolated monoclonal antibodies, particularly human monoclonal antibodies that specifically bind to PD-L1 with high affinity. Nucleic acid molecules encoding the antibodies of this disclosure, expression vectors, host cells and methods for expressing the antibodies of this disclosure are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The disclosure also provides methods for detecting PD-L1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-L1 antibodies.

First claim

We claim:

1. A monoclonal anti-PD-L1 antibody, or an antigen-binding portion thereof, which cross-competes for binding to human PD-L1 with a reference antibody, wherein the reference antibody comprises:
(a) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:1 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:11;
(b) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:2 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:12;
(c) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:3 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:13;
(d) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:4 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:14;
(e) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:5 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:15;
(f) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:6 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:16;
(g) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:7 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:17;
(h) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:8 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:18;
(i) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:9 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:19; or
(j) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:10 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:20; and
wherein the monoclonal anti-PD-L1 antibody or antigen-binding portion thereof comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises a framework region exhibiting at least 90% sequence identity to a framework region of the heavy chain variable region of the reference antibody and/or the VL comprises a framework region exhibiting at least 90% sequence identity to a framework region of the light chain variable region of the reference antibody.

2. The monoclonal anti-PD-L1 antibody or antigen-binding portion thereof of claim 1 , wherein the framework region of the VH exhibits at least 95% sequence identity to the framework region of the heavy chain variable region of the reference antibody and/or the framework region of the VL exhibits at least 95% sequence identity to the framework region of the light chain variable region of the reference antibody.

3. The monoclonal anti-PD-L1 antibody or antigen-binding portion thereof of claim 1 , wherein the VL exhibits at least 90% sequence identity to:
(a) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:11;
(b) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:12;
(c) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:13;
(d) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:14;
(e) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:15;
(f) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:16;
(g) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:17;
(h) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:18;
(i) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:19; or
(j) the light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO:20.

4. The monoclonal anti-PD-L1 antibody or antigen-binding portion thereof of claim 1 , wherein the VL comprises a FR1 selected from:
(a) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:11 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:11 with one amino acid substitution;
(b) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:12 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:12 with one amino acid substitution;
(c) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:13 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:13 with one amino acid substitution;
(d) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:14 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:14 with one amino acid substitution;
(e) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:15 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:15 with one amino acid substitution;
(f) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:16 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:16 with one amino acid substitution;
(g) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:17 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:17 with one amino acid substitution;
(h) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:18 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:18 with one amino acid substitution;
(i) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:19 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:19 with one amino acid substitution; and
(j) the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:20 or the FR1 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:20 with one amino acid substitution.

5. The monoclonal anti-PD-L1 antibody or antigen-binding portion thereof of claim 1 , wherein the VL comprises a FR2 selected from:
(a) the FR2 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:11 or the FR2 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:11 with one amino acid substitution;
(b) the FR2 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:12 or the FR2 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:12 with one amino acid substitution;
(c) the FR2 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:13 or the FR2 of the light chain variable region having the amino acid sequence set forth in SEQ ID NO:13 with one amino acid substitution;
(d) the FR2 of the light chain vari

Assignees

• Squibb & Sons Llc

Inventors

• Korman Alan J
• Selby Mark J
• Wang Changyu
• Srinivasan Mohan
• Passmore David B
• Huang Haichun
• Chen Haibin

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P37/04

  Immunostimulants · CPC title

• A61P39/02

  Antidotes · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title