Anti-galectin-9 antibodies and uses thereof
Inventors
Koide, Shohei • Miller, George • Koide, Akiko • Chen, Linxiao • Elenko, Eric • Filipovic, Aleksandra • Bolen, Joseph
Assignees
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Publication Number
US-12624108-B2
Publication Date
2026-05-12
Expiration Date
Abstract
Disclosed herein are anti-Galectin-9 antibodies and methods of using such for inhibiting a signaling pathway mediated by Galectin-9 or eliminating pathologic cells expressing Galectin-9. Such anti-Galectin-9 antibodies may also be used to diagnose and/or to treat diseases associated with Galectin-9, such as autoimmune diseases and solid tumors.
Core Innovation
The invention relates to isolated anti-galectin-9 antibodies that bind human galectin-9. The antibody comprises a heavy chain variable region with heavy chain complementarity determining region 1, CDR2, and CDR3 sequences, together with a light chain variable region that includes specified light chain CDR1, CDR2, and CDR3 amino-acid sequences. The disclosed CDR sequences are defined by the cited SEQ ID NOs.
The disclosed embodiments further encompass specific heavy and light chain sequences and combinations, including full heavy-chain and light-chain amino-acid sequences and sequence identity thresholds such as ≥80% identity to listed CDR sets. The disclosure also includes antibody isotype pairings such as IgG1 or IgG4 together with embodiments that involve specified sequence-defined antibody formats, including an S228P mutation and modified/inert Fc variants.
The disclosed antibodies and compositions are positioned for treating galectin-9-mediated diseases, particularly cancer types. The document further describes targeting galectin-9 signaling and relates the activity to modulation of receptors and pathways associated with galectin-9, including Dectin-1, TIM-3, and CD206, and combination approaches with checkpoint inhibitors.
Claims Coverage
The independent claims cover an isolated human galectin-9-binding antibody defined by specific heavy-chain and light-chain variable-region CDR amino-acid sequences, totaling six CDRs. Dependent claims refine the antibody with complete heavy/light chain sequences and antibody format or isotype selections, including IgG1 or IgG4 and the S228P mutation.
Human galectin-9-binding antibody with defined heavy-chain CDRs
An isolated antibody that binds human galectin-9, wherein the heavy chain comprises a VH with CDR1 comprising FTVSSSSIH, CDR2 comprising YISSSSGYTYYADSVKG, and CDR3 comprising YWSYPSWWPYRGMDY.
Human galectin-9-binding antibody with defined light-chain CDRs
An isolated antibody that binds human galectin-9, wherein the light chain comprises a light chain variable region with CDR1 comprising RASQSVSSAVA, CDR2 comprising SASSLYS, and CDR3 comprising QQSSTDPIT.
Full heavy/light chain amino-acid sequence specification
An isolated antibody in which the heavy chain amino-acid sequence is defined by SEQ ID NO: 316 and the light chain amino-acid sequence is defined by SEQ ID NO: 108.
IgG1 or IgG4 antibody format selection
An isolated antibody as an IgG1 or an IgG4 molecule.
S228P mutation in an IgG molecule
An isolated antibody whose IgG molecule contains an S228P mutation.
Overall, the claim coverage centers on an isolated antibody binding human galectin-9, with the binding-determining variable regions defined by specific heavy-chain and light-chain CDR1/2/3 amino-acid sequences, and with additional coverage for complete sequence, isotype, and format variants.
Stated Advantages
Inhibition or modulation of galectin-9 signaling via Dectin-1, TIM-3, and CD206.
Elimination of galectin-9-expressing pathologic cells via Fc-mediated ADCC, CDC, and ADCP.
Retains galectin-9 binding specificity when generating new CRD-mixed antibodies using the disclosed CDRs.
T-cell activation is described in connection with CD4+ activation and induction of CD44 and cytokines including IFNγ and TNFα.
Enhanced anti-tumor activity is expected.
Documented Applications
Therapeutic use for autoimmune diseases.
Therapeutic use for cancers including solid tumors and hematologic malignancies.
Treating solid tumors, with pancreatic cancer specifically emphasized, including checkpoint-inhibitor-refractory settings.
Use in combination therapy framing with checkpoint inhibitors and other immunomodulatory treatments.
Kits for treating anti-galectin-9-associated diseases.
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