Anti-TIM-3 antibodies and methods of use thereof
Inventors
van Dijk, Marc • Breous-Nystrom, Ekaterina Vladimirovna • Wilson, Nicholas Stuart • Waight, Jeremy Dale • Underwood, Dennis John
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11839653-B2
Publication Date
2023-12-12
Expiration Date
Abstract
Antibodies that specifically bind to TIM 3 and antagonize TIM-3 function pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.
Core Innovation
The invention provides anti-TIM-3 antibodies and polynucleotides encoding antibody variable regions, including heavy chain variable regions (VH) and light chain variable regions (VL) comprising complementarity determining regions CDRH1, CDRH2 and CDRH3, and CDRL1, CDRL2 and CDRL3. The disclosed VH and VL regions are defined by amino acid sequences set forth in specific SEQ ID NOs, and the document focuses on defined antibody sequence sets and their use in antibody/antigen detection and characterization.
The invention further describes generation and identification of anti-TIM-3 antibodies using transgenic mice carrying human immunoglobulin loci, together with human antibody production via phage display libraries and mouse-human hybridomas. It also describes anti-idiotype antibodies in the context of TIM-3 targeting, and reports functional binding and selectivity profiles against TIM-3 relative to TIM-1 and TIM-4.
The invention additionally addresses characterization and functional activity through binding assays, ligand blocking of TIM-3-phosphatidylserine interaction, epitope mapping, and structural analysis by HDX-MS with peptide-level protection differences. It further describes internalization and delivery studies, including ADC delivery, and functional enhancement of IFNγ in PBMC and TIL assays with SEA/anti-PD-1 co-stimulation.
Claims Coverage
The provided claims cover isolated polynucleotides encoding antibody variable-region sequences defined by specific CDR amino-acid sequences, and extend to vectors, host cells, and methods of antibody production. Across the independent coverage, there are 2 inventive features centered on the VH and VL sequence sets.
Isolated polynucleotide encoding a VH defined by specific CDRH1/2/3 sequences
An isolated polynucleotide encoding a heavy chain variable region (VH) comprising complementarity determining regions CDRH1, CDRH2 and CDRH3 comprising the amino acid sequences set forth in SEQ ID NOs: 1, 2, and 3; 4, 2, and 3; 5, 2, and 3; 6, 2, and 3; 7, 2, and 3; 8, 2, and 3; 9, 2, and 3; 10, 2, and 3; 11, 2, and 3; or 12, 2, and 3, respectively.
Isolated polynucleotide encoding a VL defined by specific CDRL1/2/3 sequences
An isolated polynucleotide encoding a light chain variable region (VL) comprising complementarity determining regions CDRL1, CDRL2 and CDRL3 comprising the amino acid sequences set forth in SEQ ID NOs: 14, 21, and 22; or 15, 18, and 22, respectively.
The core inventive subject matter is the isolated polynucleotide(s) encoding antibody variable regions defined by specific VH and optional VL CDR amino acid sequence sets. The broader claim family further includes vectors, host cells, and methods to express the defined polynucleotide(s) and produce the antibody.
Stated Advantages
Antagonist activity.
Reduced binding to a TIM-3 ligand (phosphatidylserine).
Increased cytokine production, including IFN-gamma and TNF-alpha.
Internalization upon TIM-3 binding.
Antagonizes TIM-3-mediated immune suppression.
Reduced survival of TIM-3-expressing cells.
Enhanced T-cell activation.
Treats or prevents cancer and infectious diseases.
Documented Applications
Therapeutic use in cancer, alone or combined with other immunotherapies.
Therapeutic use in infectious disease, alone or combined with other immunotherapies.
Use in antibody/antigen detection and characterization.
Therapeutic use to increase T-cell activation and treat or prevent cancer.
Therapeutic use to increase T-cell activation and treat or prevent infectious diseases.
ADC delivery.
Interested in licensing this patent?