TLR9 ligand trap
US11976104B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Feb 22, 2021 |
| Grant date | May 7, 2024 |
| Priority date | — |
| Expiry date | Jan 18, 2043 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07K2319/30
- WIPO fieldMeasurement
- WIPO sectorInstruments
Abstract
Myelodysplastic syndrome (MDS) hematopoietic stem and progenitor cells (HSPC) translocate endosomal Toll-Like receptor (TLR)-9 to the plasma membrane, thereby sensitizing these clonal propagating cells to respective ligands in the microenvironment. TLR9 is the cognate receptor for RNA:DNA hybrids (R-loops) and unmethylated CpG oligonucleotides in oxidized mitochondrial DNA, the latter of which is abundant in the bone marrow microenvironment as a result of massive medullary pyroptotic cytolytic cell death. Both ligands are important danger-associated molecular patterns (DAMPs) triggering innate immune activation and chronic inflammation that contributes to MDS pathogenesis. In an effort to neutralize these DAMPs and disrupt this feed-forward inflammatory cascade, a chimeric protein was designed fusing the external epitopes of TLR9 to the Fc domain of human IgG4 to serve as a decoy receptor or ligand trap recognizing extracellular RNA:DNA hybrids (R-loops) and oxidized mitochondrial DNA.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.