Patent highlights April-May 2018

摘要

A snapshot of noteworthy recent developments in the patent literature of relevance to pharmaceutical and medical research and development. Inflammatory bowel diseases seem to be triggered by an intestinal epithelial dysfunction, probably in response to danger signals that might only suggest the presence of pathogens but nevertheless amplify and sustain the release of proinflammatory cytokines. There is considerable evidence that activation of purinergic receptors by nucleotides such as ATP and UTP, constitutes at least part of these signals and not only in the intestinal tract. This signaling is terminated by nucleoside triphosphate diphosphohydrolases (e.g., NTPDase-1, CD39). NTPDases are expressed by immunosuppressive supTh17 T-helper cells. The inventors have demonstrated that NTPDase-8 is expressed on epithelial cells at the apical surface of the mouse and human colon. Although its gross effect on nucleotide hydrolysis in the entire intestine is minimal, its precise localization makes it a most important regulator of intestinal inflammation. Degradation of nucleotides by apyrase, selective blockade of P2Y6 receptors by MRS 2578 or knockout of the P2Y2 receptor protects mice against dextran sodium sulfate-induced colitis and decreases epithelial permeability and chemokine secretion. Selective P2Y2 and P2Y6 ligands have been described but antagonists are rare.