Antibodies to TIGIT
AssigneesJN Biosciences LLC, Abmuno Therapeutics LLC
InventorsJ. Yun Tso, Naoya Tsurushita, Omar Duramad
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Abstract
The invention provides monoclonal antibodies that specifically bind to TIGIT. The monoclonal antibodies have the capacity for substantial activation of T cells and natural killer cells by inhibiting binding of TIGIT to CD155. The monoclonal antibodies can be used for treatment of cancer and infectious disease, among other applications.
Claims9
A monoclonal antibody that binds to a TIGIT polypeptide, comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 11, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:
- 12, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:
- 13, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 15, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:
- 16, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:
- 17.
A monoclonal antibody that binds to a TIGIT polypeptide, comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 11, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO:
- 12, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO:
- 13, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO:
- 15, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO:
- 16, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO:
- 17, wherein the antibody has one or more of the following properties:
- (a) inhibits binding of TIGIT to CD155 optionally with an IC50 of 15-100 ng/ml,
- (b) increases intrinsic T-cell activation in the presence of antigen presenting cells expressing CD155 as measured by IL-2 production, optionally by 1.5-3 fold, as compared to intrinsic T-cell activation in the presence of antigen presenting cells expressing CD155 and in the absence of the antibody,
- (c) increases antigen-specific T-cell activation as measured by IL-2 production, optionally by 1.5-3 fold, as compared to antigen-specific T-cell activation in the absence of the antibody,
- (d) increases natural killer cell activation as measured by production of any of IL-2, IL-6, TNFα or IFNγ, optionally by 1.5-3 fold, as compared to natural killer cell activation in the absence of the antibody,
- (e) increases T-cell production of at least one pro-inflammatory cytokine, optionally by 1.5-3 fold, as compared to T-cell production of the at least one pro-inflammatory cytokine in the absence of the antibody, and
- (f) reduces T-cell production of a least one anti-inflammatory cytokine, optionally by 1.5-3 fold, as compared to T-cell production of the a least one anti-inflammatory cytokine in the absence of the antibody.
Dependencies are inferred from the claim text.