Anti-TIGIT antibodies and their use as therapeutics and diagnostics
Inventors
Zhang, Tong • Xue, Liu • Liu, Qi • Wei, Min • Li, Kang
Assignees
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Publication Number
US-12234286-B2
Publication Date
2025-02-25
Expiration Date
Abstract
Provided are antibodies that specifically bind to TIGIT (T cell immunoreceptor with Ig and ITIM domains, WUCAM or Vstm3) and inhibit Tigit-mediated cellular signaling and activities in immune cells. The anti-TIGIT antibodies can be used to treat or diagnose cancer, infectious diseases or other pathological disorders that may be modulated by Tigit-mediated functions.
Core Innovation
The invention concerns anti-TIGIT monoclonal antibodies and antigen-binding fragments that bind human TIGIT. The disclosed binding specificity targets human Tigit, with defined heavy chain variable region CDR1, CDR2, and CDR3 and defined light chain variable region CDR1, CDR2, and CDR3, provided as amino acid sequence identities associated with SEQ ID NOs for the heavy and light chain CDRs.
The antibody is described as inhibiting TIGIT-mediated immune signaling and countering TIGIT-mediated immune suppression. The invention provides a rationale for therapeutic and diagnostic use in cancer and chronic viral infection by restoring T/NK/DC function, with functional effects on human T cells and NK cells including induction of IFN-gamma and effects on NK-cell cytotoxicity.
The disclosed antibody design includes humanization from a murine mAb mu1217 to humanized variants, including hu1217-1-1 and hu1217-2-2. The partial content also describes pH-dependent binding enhancement at pH 6.0 versus pH 7.4, blockade of TIGIT ligand interactions involving PVR and PVR-L2, and Fc-mediated functional outcomes including FcγR-mediated trogocytosis and ADCC with limited or no CDC activity.
Claims Coverage
The partial content identifies one independent claim directed to treating a cancer or a tumor by administering a TIGIT-binding antibody or antigen-binding fragment with defined VH and VL CDRs. The coverage includes dependent claims that refine the treated indication, antibody format, and variable-domain sequence constraints.
Treating a cancer or tumor with a human Tigit-binding antibody with specified VH and VL CDRs
A method for treating a cancer or a tumor by administrating to a subject an antibody capable of binding to human Tigit, or an antigen-binding fragment thereof, comprising a heavy chain variable region with CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 3, 13, and 5, respectively, and a light chain variable region with CDR1, CDR2, and CDR3 amino acid sequences of SEQ ID NOs: 6, 7, and 8, respectively.
Across the disclosed claim set, the central inventive concept is a treatment method using a TIGIT-binding antibody or antigen-binding fragment defined by specific VH and VL CDR sequence identities, with dependent refinements narrowing the therapeutic scope and antibody variable-domain sequence characteristics.
Stated Advantages
Restoring T/NK/DC function by inhibiting TIGIT-mediated immune signaling.
Inducing functional immune responses in human T cells, including IFN-gamma induction.
Blocking TIGIT ligand interactions involving PVR and PVR-L2.
Producing functional Fc-mediated effects, including FcγR-mediated trogocytosis and ADCC with limited or no CDC activity.
Exhibiting pH-dependent binding enhancement at pH 6.0 versus pH 7.4.
Documented Applications
Treating a cancer or a tumor by administering an antibody capable of binding human Tigit or an antigen-binding fragment thereof.
Treating non-small cell lung cancer.
Therapeutic and diagnostic use in cancer and chronic viral infection, including chronic viral infection contexts stated in the partial disclosure.
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