Human monoclonal antibodies to programmed death ligand 1 (PD-L1)
First Claim
1. An isolated human monoclonal antibody, or an antigen-binding portion thereof, wherein the antibody or antigen-binding portion thereof cross-competes for binding to PD-L1 with a reference antibody or reference antigen-binding portion thereof comprising:
- (a) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
1 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
11;
(b) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
2 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
12;
(c) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
3 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
13;
(d) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
4 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
14;
(e) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
5 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
15;
(f) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
6 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
16;
(g) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
7 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
17;
(h) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
8 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
18;
(i) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
9 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
19;
or(j) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
10 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
20.
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Accused Products
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.
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Citations
26 Claims
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1. An isolated human monoclonal antibody, or an antigen-binding portion thereof, wherein the antibody or antigen-binding portion thereof cross-competes for binding to PD-L1 with a reference antibody or reference antigen-binding portion thereof comprising:
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(a) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
1 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
11;(b) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
2 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
12;(c) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
3 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
13;(d) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
4 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
14;(e) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
5 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
15;(f) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
6 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
16;(g) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
7 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
17;(h) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
8 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
18;(i) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
9 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
19;
or(j) a human heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
10 and a human light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO;
20. - View Dependent Claims (2, 3, 4, 5, 6, 21, 22, 23, 24, 25)
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7. An isolated human monoclonal antibody, or an antigen-binding portion thereof, comprising:
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(a) a heavy chain variable region that comprises amino acids having a sequence derived from a human VH 1-18 germline sequence; and (b) a light chain variable region that comprises amino acids having a sequence derived from a human VK L6 germline sequence; wherein the antibody specifically binds to PD-L1.
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8. An isolated human monoclonal antibody, or an antigen-binding portion thereof, comprising:
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(a) a heavy chain variable region that comprises amino acids having a sequence derived from a human VH 1-69 germline sequence; and (b) a light chain variable region that comprises amino acids having a sequence derived from a human VK L6 germline sequence;
wherein the antibody specifically binds to PD-L1.
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9. An isolated human monoclonal antibody, or an antigen-binding portion thereof, comprising:
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(a) a heavy chain variable region that comprises amino acids having a sequence derived from a human VH 1-3 germline sequence; and (b) a light chain variable region that comprises amino acids having a sequence derived from a human VK L15 germline sequence;
wherein the antibody specifically binds to PD-L1.
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10. An isolated monoclonal antibody, or antigen binding portion thereof, comprising a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains;
- and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains, wherein the heavy chain variable region and light chain variable region CDR3 domains are selected from the group consisting of;
(a) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
41; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
71 and conservative modifications thereof;(b) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
42; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
72 and conservative modifications thereof;(c) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
43; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
73 and conservative modifications thereof;(d) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
44; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
74 and conservative modifications thereof;(e) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
45; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
75 and conservative modifications thereof;(f) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
46; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
76 and conservative modifications thereof;(g) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
47; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
77 and conservative modifications thereof;(h) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
48; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
78 and conservative modifications thereof;(i) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
49; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
79 and conservative modifications thereof; and(j) a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
50; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
80 and conservative modifications thereof;wherein the antibody specifically binds to human PD-L1. - View Dependent Claims (11, 12)
- and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains, wherein the heavy chain variable region and light chain variable region CDR3 domains are selected from the group consisting of;
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13. An isolated monoclonal antibody, or antigen binding portion thereof, comprising a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains;
- and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains, wherein the heavy chain variable region and light chain variable region CDR1, CDR2, and CDR3 domains are selected from the group consisting of;
(a) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
21;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
31;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
41;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
51;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
61; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
71;(b) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
22;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
32;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
42;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
52;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
62; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
72;(c) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
23;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
33;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
43;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
53;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
63; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
73;(d) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
24;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
34;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
44;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
54;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
64; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
74;(e) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
25;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
35;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
45;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
55;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
65; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
75;(f) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
26;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
36;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
46;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
56;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
66; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
76;(g) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
27;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
37;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
47;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
57;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
67; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
77;(h) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
28;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
38;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
48;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
58;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
68; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
78;(i) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
29;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
39;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
49;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
59;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
69; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
79; and(j) a heavy chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
30;
a heavy chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
40;
a heavy chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
50;
a light chain variable region CDR1 comprising amino acids having the sequence set forth in SEQ ID NO;
60;
a light chain variable region CDR2 comprising amino acids having the sequence set forth in SEQ ID NO;
70; and
a light chain variable region CDR3 comprising amino acids having the sequence set forth in SEQ ID NO;
80;wherein the antibody specifically binds to PD-L1. - View Dependent Claims (14, 15, 16)
- and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains, wherein the heavy chain variable region and light chain variable region CDR1, CDR2, and CDR3 domains are selected from the group consisting of;
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17. An isolated monoclonal antibody, or antigen binding portion thereof, comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region and light chain variable region are selected from the group consisting of:
-
(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; and(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;wherein the antibody specifically binds to PD-L1. - View Dependent Claims (18, 19, 20)
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26. An isolated human monoclonal antibody, or an antigen-binding portion thereof, comprising:
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(a) a heavy chain variable region that comprises amino acids having a sequence derived from a human VH 1-69 germline sequence; and
a light chain variable region that comprises amino acids having a sequence derived from a human VK A27 germline sequence;(b) a heavy chain variable region that comprises amino acids having a sequence derived from a human VH 3-9 germline sequence; and
a light chain variable region that comprises amino acids having a sequence derived from a human VK L15 germline sequence;
or(c) a heavy chain variable region that comprises amino acids having a sequence that is derived from a human VH 3-9 germline sequence; and
a light chain variable region that comprises amino acids having a sequence derived from a human VK L18 germline sequence;wherein the antibody specifically binds to PD-L1.
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Specification