US 8,383,796 B2 · Nucleic acids encoding monoclonal antibodies to programmed death ligand 1 (PD-L1)

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.

Claims31

Dependent claims

An isolated nucleic acid encoding a heavy chain variable region of an anti-PD-L1 monoclonal antibody, or antigen-binding portion thereof, comprising CDR1, CDR2, and CDR3 domains, wherein the CDR3 domain comprises

(a) amino acids having the sequence set forth in SEQ ID NO:41 and conservative modifications thereof;
(b) amino acids having the sequence set forth in SEQ ID NO:42 and conservative modifications thereof;
(c) amino acids having the sequence set forth in SEQ ID NO:43 and conservative modifications thereof;
(d) amino acids having the sequence set forth in SEQ ID NO:44 and conservative modifications thereof;
(e) amino acids having the sequence set forth in SEQ ID NO:45 and conservative modifications thereof;
(f) amino acids having the sequence set forth in SEQ ID NO:46 and conservative modifications thereof,
(g) amino acids having the sequence set forth in SEQ ID NO:47 and conservative modifications thereof;
(h) amino acids having the sequence set forth in SEQ ID NO:48 and conservative modifications thereof;
(i) amino acids having the sequence set forth in SEQ ID NO:49 and conservative modifications thereof;
or
(j) amino acids having the sequence set forth in SEQ ID NO:50 and conservative modifications thereof.

8 more elements

An isolated nucleic acid encoding a heavy chain variable region and a light chain variable region of an anti-PD-1,1 monoclonal antibody, or antigen-binding portion thereof, said variable regions comprising:

(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.

19 more elements

An isolated nucleic acid encoding a heavy chain variable region of an anti-PD-L1monoclonal antibody, or antigen-binding portion thereof, comprising CDR1, CDR2, and CDR3domains, wherein the CDR1, CDR2, and CDR3 domains are:

(a) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:41, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:31, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:21;
(b) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:42, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:32, and a CDR1comprising amino acids having the sequence set forth in SEQ ID NO:22;
(c) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:43, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:33, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:23;
(d) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:44, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:34, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:24;
(e) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:45, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:35, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:25;
(f) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:46, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:36, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:26;
(g) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:47, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:37, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:27;
(h) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:48, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:38, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:28;
(i) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:49, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:39, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:29;
or
(j) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:50, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:40, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:30.

8 more elements

An isolated nucleic acid encoding a light chain variable region of an anti-PD-L1 monoclonal antibody, or antigen-binding portion thereof, comprising CDR1, CDR2, and CDR3 domains, wherein the CDR3, CDR2, and CDR1 domains are:

(a) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:71, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:61, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:51;
(b) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:72, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:62, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:52;
(c) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:73, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:63, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:53;
(d) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:74, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:64, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:54;
(e) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:75, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:65, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:55;
(f) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:76, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:66, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:56;
(g) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:77, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:67, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:57;
(h) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:78, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:68, and a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:58;
(i) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:79, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:69, and CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:59;
or
(j) a CDR3 comprising amino acids having the sequence set forth in SEQ ID NO:80, a CDR2 comprising amino acids having the sequence set forth in SEQ ID NO:70, and CDR1 comprising amino acids having the sequence set forth in SEQ ID NO:60.

8 more elements

Dependencies are inferred from the claim text.

Nucleic acids encoding monoclonal antibodies to programmed death ligand 1 (PD-L1)

Life of this patent

Nucleic acids encoding monoclonal antibodies to programmed death ligand 1 (PD-L1)

Life of this patent

Abstract

Claims31