Anti-PD1 antibodies and their use as therapeutics and diagnostics
Inventors
Li, Kang • Zhang, Tong • Song, Jing • Xu, Lanlan • Liu, Qi • Peng, Hao
Assignees
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Publication Number
US-11673951-B2
Publication Date
2023-06-13
Expiration Date
Abstract
Provided are antibodies that specifically bind to Programmed Death-1 (PD1, Pdcd-1, or CD279) and inhibit PD1-mediated cellular signaling and activities in immune cells, antibodies binding to a set of amino acid residues required for its ligand binding, and uses of these antibodies to treat or diagnose cancer, infectious diseases or other pathological disorders modulated by PD1-mediated functions.
Core Innovation
The document describes anti-PD-1 (PD-1/CD279) antibodies and antigen-binding fragments that antagonize PD-1/PD-L1/PD-L2 inhibitory signaling. By antagonizing this signaling, the antibodies are described as restoring immune cell activation. The antibodies are characterized by binding to PD-1 and are provided in forms defined by specific heavy chain and light chain variable region CDR repertoires.
A core aspect of the disclosed antibodies is the specification of heavy chain CDR1, CDR2, and CDR3 according to defined SEQ ID NOs, together with corresponding light chain CDR1, CDR2, and CDR3 sequences. The document further identifies PD-1 residues that form antibody binding epitopes, including K45/I93 and related residue combinations. Humanized antibody variable regions are described as including shared humanized CDR sequences and multiple humanized variants.
The document also describes IgG4 constant-domain engineering intended to reduce FcγR/CDC/ADCC effector functions while maintaining stability under stress conditions. IgG4mt10 is highlighted, and the IgG4 Fc region is identified by SEQ ID NO. The disclosed antibodies are characterized using binding and functional assays, epitope mapping, and binding kinetics, with in vivo xenograft data reported as tumor growth inhibition/regression.
Claims Coverage
The provided independent claims cover polynucleotides and humanized monoclonal antibody compositions that bind PD-1, with the inventive coverage being sequence-defined heavy- and light-chain variable regions and, for the humanized antibody claims, an IgG4 Fc region and a specific light chain Ig kappa C-region reference. Across the independent claims, the main inventive features are defined by specified SEQ ID NOs for variable regions and by SEQ/NCBI identifiers for constant-region components.
Heavy chain variable region with PD-1 binding CDR1, CDR2, and CDR3 defined by SEQ ID NOs
A polynucleotide encoding a heavy chain variable region of an antibody or antigen-binding fragment thereof that specifically binds to PD-1, comprising a heavy chain CDR1 according to SEQ ID NO: 31, a heavy chain CDR2 according to SEQ ID NO: 32, and a heavy chain CDR3 according to SEQ ID NO: 33.
Humanized monoclonal antibody with specified heavy-variable region and IgG4 Fc
A polynucleotide encoding a humanized monoclonal antibody that binds to PD-1, wherein the antibody comprises a heavy chain amino acid sequence comprising a heavy chain variable region of SEQ ID NO: 24 and a heavy chain IgG4 Fc region of SEQ ID NO: 88.
Humanized monoclonal antibody with specified light kappa C-region and light-variable region
A humanized monoclonal antibody that binds PD-1 comprising a light chain Ig kappa C-region deposited as NCBI Accession No. P01834 and a light chain variable region of SEQ ID NO: 26.
Humanized monoclonal antibody comprising the defined heavy-variable region, IgG4 Fc, and light-variable region
A humanized monoclonal antibody that binds PD-1 comprising a heavy chain variable region of SEQ ID NO: 24, a heavy chain IgG4 Fc region of SEQ ID NO: 88, a light chain Ig kappa C-region deposited as NCBI Accession No. P01834, and a light chain variable region of SEQ ID NO: 26.
Overall, the claim set shown here defines PD-1 binding antibodies and polynucleotides encoding them primarily by sequence-specific heavy chain CDR definitions for the broad polynucleotide claim, and by fully specified humanized heavy- and light-chain components for the humanized monoclonal antibody claims, including an IgG4 Fc region and a deposited light chain Ig kappa C-region reference.
Stated Advantages
Restores immune cell activation by antagonizing PD-1/PD-L1/PD-L2 inhibitory signaling.
Reduces FcγR/CDC/ADCC effector functions while improving stability under stress and maintaining potency.
Documented Applications
Treating cancer and viral infections by using anti-PD-1 antibodies that restore immune cell activation.
Tumor xenograft activity is described as tumor growth inhibition/regression in an in vivo xenograft mouse model.
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