HUMAN MONOCLONAL ANTIBODIES TO BE PROGRAMMED DEATH LIGAND 1 (PD-L1)
First Claim
1. An isolated human monoclonal antibody, or an antigen-binding portion thereof, wherein the antibody specifically binds to human PD-L1 and wherein the antibody exhibits at least one of the following properties:
- (a) binds to human PD-L1 with a KD of 1×
10−
7M or less;
(b) increases T-cell proliferation in a mixed lymphocyte reaction (MLR) assay;
(c) increases interferon-γ
production in an MLR assay;
or(d) increases interleukin-2 (IL-2) secretion in an MLR assay.
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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.
179 Citations
61 Claims
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1. An isolated human monoclonal antibody, or an antigen-binding portion thereof, wherein the antibody specifically binds to human PD-L1 and wherein the antibody exhibits at least one of the following properties:
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(a) binds to human PD-L1 with a KD of 1×
10−
7M or less;(b) increases T-cell proliferation in a mixed lymphocyte reaction (MLR) assay; (c) increases interferon-γ
production in an MLR assay;
or(d) increases interleukin-2 (IL-2) secretion in an MLR assay. - View Dependent Claims (4, 5, 21, 22, 31, 32, 34, 38, 40, 41, 42, 43, 45, 46, 50, 51, 53, 54, 55, 56, 57, 58)
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2-3. -3. (canceled)
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6. An isolated human monoclonal antibody, or an antigen-binding portion thereof, wherein the antibody cross-competes for binding to PD-L1 with a reference antibody which comprises:
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(a) the human heavy chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;
1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and(b) the human light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;
11, 12, 13, 14, 15, 16, 17, 18, 19, and 20. - View Dependent Claims (7, 8, 9)
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10-14. -14. (canceled)
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15. An isolated monoclonal antibody, or an antigen-binding portion thereof, comprising:
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(a) a heavy chain variable region of a human VH 1-18 gene; and (b) a light chain variable region of a human Vk L6 gene; wherein the antibody specifically binds to PD-L1.
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16. An isolated monoclonal antibody, or an antigen-binding portion thereof, comprising:
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(a) a heavy chain variable region of a human VH 1-69 gene; and (b) a light chain variable region of a human Vk L6 gene;
wherein the antibody specifically binds to PD-L1.
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17. An isolated monoclonal antibody, or an antigen-binding portion thereof, comprising:
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(a) a heavy chain variable region of a human VH 1-3 gene; and (b) a light chain variable region of a human Vk L15 gene;
wherein the antibody specifically binds to PD-L1.
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18. An isolated monoclonal antibody, or antigen binding portion thereof, comprising a heavy chain variable region that comprises CDR1, CDR2, and CDR3 sequences;
- and a light chain variable region that comprises CDR1, CDR2, and CDR3 sequences, wherein;
(a) the heavy chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;
41, 42, 43, 44, 45, 46, 47, 48, 49, and 50, and conservative modifications thereof;(b) the light chain variable region CDR3 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NOs;
71, 72, 73, 74, 75, 76, 77, 78, 79, and 80, and conservative modifications thereof; and(c) the antibody specifically binds to human PD-L1. - View Dependent Claims (19, 20)
- and a light chain variable region that comprises CDR1, CDR2, and CDR3 sequences, wherein;
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23. An isolated monoclonal antibody, or antigen binding portion thereof, comprising:
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(a) a heavy chain variable region CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30;(b) a heavy chain variable region CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
31, 32, 33, 34, 35, 36, 37, 38, 39, and 40;(c) a heavy chain variable region CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
41, 42, 43, 44, 45, 46, 47, 48, 49, and 50;(d) a light chain variable region CDR1 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
51, 52, 53, 54, 55, 56, 57, 58, 59, and 60;(e) a light chain variable region CDR2 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
61, 62, 63, 64, 65, 66, 67, 68, 69, and 70; and(f) a light chain variable region CDR3 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
71, 72, 73, 74, 75, 76, 77, 78, 79, and 80;
wherein the antibody specifically binds PD-L1. - View Dependent Claims (24, 25, 26)
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27. An isolated monoclonal antibody, or antigen binding portion thereof comprising:
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(a) a heavy chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
1, 2, 3, 4, 5, 6, 7, 8, 9, and 10; and(b) a light chain variable region comprising an amino acid sequence selected from the group consisting of SEQ ID NOs;
11, 12, 13, 14, 15, 16, 17, 18, 19, and 20;
wherein the antibody specifically binds PD-L1. - View Dependent Claims (28, 29, 30)
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33. (canceled)
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35-37. -37. (canceled)
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39. (canceled)
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44. (canceled)
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47-49. -49. (canceled)
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52. (canceled)
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59. A method for preparing an anti-PD-L1 antibody comprising:
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(a) providing;
(i) a heavy chain variable region antibody sequence comprising a CDR1 sequence that is selected from the group consisting of SEQ ID NOs;
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, a CDR2 sequence that is selected from the group consisting of SEQ ID NOs;
31, 32, 33, 34, 35, 36, 37, 38, 39, and 40; and
a CDR3 sequence that is selected from the group consisting of SEQ ID NOs;
41, 42, 43, 44, 45, 46, 47, 48, 49, and 50;
or (ii) a light chain variable region antibody sequence comprising a CDR1 sequence that is selected from the group consisting of SEQ ID NOs;
51, 52, 53, 54, 55, 56, 57, 58, 59, and 60, a CDR2 sequence that is selected from the group consisting of SEQ ID NOs;
61, 62, 63, 64, 65, 66, 67, 68, 69, and 70, and a CDR3 sequence that is selected from the group consisting of SEQ ID NOs;
71, 72, 73, 74, 75, 76, 77, 78, 79, and 80;(b) altering at least one amino acid residue within at least one variable region antibody sequence, said sequence being selected from the heavy chain variable region antibody sequence and the light chain variable region antibody sequence, to create at least one altered antibody sequence; and (c) expressing the altered antibody sequence as a protein.
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60. (canceled)
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61-67. -67. (canceled)
Specification