Anti-human PD-L1 antibodies and their uses
Inventors
YU, CHENG-CHOU • YANG, Shih-Rang • Hsieh, Tsung-Han • CHAN, Mei-Chi • YEH, SHU-PING • Hsu, Chuan-Lung • HU, Ling-Yueh • HSIAO, Chih-Lun
Assignees
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Publication Number
US-12202899-B2
Publication Date
2025-01-21
Expiration Date
Abstract
An anti-PD-L1 antibody, or an antigen-binding fragment thereof, comprising: a heavy chain variable region comprising the three CDRs with the sequences of SEQ ID NOs: 2-4, 6-8, 10-12, 14-16, or 18-20; and/or a light chain variable region comprising the three CDRs with the sequences of SEQ ID NOs: 22-24, 26-28, 30-32, 34-36, or 38-40, wherein the antibody is a chimeric, humanized, composite, or human antibody.
Core Innovation
The invention relates to human anti-human PD-L1 antibodies, including chimeric, humanized, composite, human, and full-length forms, as well as antigen-binding fragments. The antibodies comprise a heavy-chain variable region with three heavy-chain complementarity-determining regions, HCDR1, HCDR2, and HCDR3, defined by specific SEQ ID NO sets, and a light-chain variable region with three light-chain complementarity-determining regions, LCDR1, LCDR2, and LCDR3, defined by specific SEQ ID NO sets.
The antibodies bind PD-L1 with tight specificity as characterized by ELISA and BIACORE. They block the PD-1/PD-L1 interaction and induce PD-L1 internalization in a 37°C-dependent manner. The antibody binding enables PD-L1 detection using immunohistochemistry and flow, including on PD-L1-high tumor cells.
The described antibodies further include epitope targeting details, including PD-L1 residues Lys178 and Thr179 and epitope regions 171–180 and 206–210. Comparative pharmacokinetic rationale is discussed, linking distinct epitope regions to longer in vivo half-life and tumor homing compared with atezolizumab, and anti-tumor efficacy is reported in an MC38 colorectal cancer mouse model.
Claims Coverage
The independent claim covers an anti-PD-L1 antibody, or antigen-binding fragment thereof, defined by specific heavy- and light-chain CDR sequence sets. The inventive features are directed to a sequence-defined antibody binding PD-L1 through specified HCDR1/HCDR2/HCDR3 and LCDR1/LCDR2/LCDR3 combinations.
Sequence-defined heavy-chain and light-chain CDR sets
An anti-PD-L1 antibody, or an antigen-binding fragment thereof, comprising a heavy-chain variable region comprising three heavy-chain complementarity-determining regions, HCDR1, HCDR2, and HCDR3, with the sequences of SEQ ID NOs: 2-4, or 6-8, or 10-12, or 14-16, or 18-20; and a light-chain variable region comprising three light-chain complementarity-determining regions, LCDR1, LCDR2, and LCDR3, with the sequences of SEQ ID NOs: 22-24, or 26-28, or 30-32, or 34-36, or 38-40.
Across the covered independent claim scope, the core inventive concept is a PD-L1 binding antibody defined by specified sets of heavy-chain CDR sequences together with specified sets of light-chain CDR sequences.
Stated Advantages
Tight specificity for PD-L1 as characterized by ELISA and BIACORE.
Blocks the PD-1/PD-L1 interaction.
Induces PD-L1 internalization in a 37°C-dependent manner.
Enables PD-L1 detection using immunohistochemistry and flow, including on PD-L1-high tumor cells.
Longer in vivo half-life and tumor homing compared with atezolizumab.
Anti-tumor efficacy is reported in an MC38 colorectal cancer mouse model.
Documented Applications
PD-L1 expression detection using an anti-PD-L1 antibody or antigen-binding fragment with an indication based on a measurement greater than a background measurement.
Treatment of PD-1/PD-L1-mediated cancer by administering a pharmaceutical composition containing an anti-PD-L1 antibody or antigen-binding fragment.
The treatment use is specified for lung cancer, breast cancer, prostate cancer, or colorectal cancer.
Antibody-drug conjugate (ADC) format including a covalently linked drug conjugate.
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