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