Patent Specification: Computational Identification of Novel Therapeutic Candidates for MASH and Liver Fibrosis via Single-Cell RNA Sequencing and Drug Repurposing (GSE136103)

Patent specification for a computational drug repurposing pipeline applied to a landmark single-cell RNA sequencing atlas of human liver non-parenchymal cells (GEO accession GSE136103; Ramachandran et al., Nature 2019; n=10 donors; 60,506 QC-passed cells; 10x Genomics Chromium). scVI batch correction across 20 FACS fractions, Leiden clustering (19 clusters), and Wilcoxon DE in 10 fibrogenic clusters (31,677 cells; cirrhosis vs healthy) identified 8,211 significant genes. ChEMBL screening (pChEMBL ≥ 7.5; 1,000 DE genes) and PubChem novelty filtration yielded 110 NOVEL_ALL candidates. The dominant theme is cathepsin B/H inhibition: CHEMBL190121 (APP/CTSB/CTSH, score=40.1) leads 15 novel cathepsin inhibitors with zero prior patent citations, mechanistically grounded in TREM2+ scar macrophage-driven MASH fibrogenesis via NLRP3 inflammasome activation. Additional candidates target TSPO and FN1. Inventors: Glen Charles Ritschel (Ritschel Research, Tega Cay SC) and Claude (Anthropic, San Francisco CA). Filed as USPTO provisional (micro-entity). License: CC BY 4.0.