Anti-GITR antibodies and methods of use thereof
Inventors
Seibert, Volker • Léger, Olivier • van Dijk, Marc • Merghoub, Taha • Schaer, David • Ritter, Gerd • TSUJI, Takemasa
Assignees
Ludwig Institute for Cancer Research Ltd • Memorial Sloan Kettering Cancer Center • Agenus Inc
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Publication Number
US-11897962-B2
Publication Date
2024-02-13
Expiration Date
Abstract
The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.
Core Innovation
The invention relates to isolated antibodies that specifically bind human GITR. The antibodies are defined by VH comprising VH CDR1, VH CDR2, and VH CDR3 amino acid sequences and VL comprising VL CDR1, VL CDR2, and VL CDR3 amino acid sequences, with the specific VH and VL CDR sequence sets mapped to SEQ ID NO pairs and named VH and VL variants.
The antibody binding specificity to human GITR is maintained across multiple VH/VL combinations using explicit SEQ ID NO listings. The disclosure also identifies antibodies by VH and VL amino acid sequences corresponding to specified SEQ ID NO pairs, and describes small CDR boundary or length variants while maintaining GITR binding.
In addition to the binding-defined variable-region framework, dependent embodiments further constrain the antibodies using human-derived framework regions and optional amino acid substitutions at Kabat-numbered positions. Other dependent embodiments further specify human immunoglobulin constant-region types, including IgG and IgA classes, non-fucosylated IgG1 and point mutations including N297A/N297Q, S228P, and C127S, and a pharmaceutical composition comprising the defined antibody and a pharmaceutically acceptable carrier or excipient.
Claims Coverage
The provided independent claims are directed to isolated antibodies that specifically bind human GITR. Across the independent claims, the inventive features are centered on precise CDR and variable-region sequence definitions using SEQ ID NOs, with dependent refinements for framework, constant-region, mutation, and formulation aspects.
Isolated human GITR-binding antibody with VH and VL CDR sequences defined by SEQ ID NO pairs
An isolated antibody that specifically binds to human GITR, comprising a VH comprising the VH CDR1, VH CDR2, and VH CDR3 amino acid sequences and a VL comprising the VL CDR1, VL CDR2, and VL CDR3 amino acid sequences of specified SEQ ID NO pairs.
Isolated human GITR-binding antibody with defined VH and VL CDR sequences by SEQ ID NOs
An isolated antibody that specifically binds to human GITR comprising a VH CDR1, a VH CDR2, a VH CDR3, a VL CDR1, a VL CDR2, and a VL CDR3 comprising specified amino acid sequences of SEQ ID NOs.
Isolated human GITR-binding antibody with VH and VL amino acid sequences defined by SEQ ID NO pairs
An isolated antibody that specifically binds to human GITR, wherein the antibody comprises a VH and a VL comprising the amino acid sequences of specified SEQ ID NO pairs.
The claim coverage is focused on isolated antibodies that specifically bind human GITR, with binding defined by specified VH and VL CDR sequence sets or specified VH and VL amino acid sequences using enumerated SEQ ID NOs. The claim family summaries also indicate further dependent refinements including human-derived framework regions with optional Kabat-position substitutions, specified human immunoglobulin constant-region types, non-fucosylated IgG1 and point mutations, and a pharmaceutical composition with a pharmaceutically acceptable carrier or excipient.
Stated Advantages
Provides quantitative binding/competition behavior of anti-GITR antibodies or fragments against hGITRL, including retained binding and inhibition thresholds across increasing antibody concentrations.
Includes binding kinetics parameter targets for GITR binding, including k_off, k_on, and K_D.
Provides a defined assay format and control conditions for evaluating hGITRL binding in a Luminex suspension array assay.
Documented Applications
Quantitative binding and competition assessment of anti-GITR antibodies or fragments against hGITRL using a Luminex suspension array assay with GITR-coupled beads and PE-labeled hGITRL.
Binding kinetics characterization and reporting targets for GITR binding (k_off, k_on, K_D).
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