公开(公告)号：US11692045B2

公开(公告)日：2023-07-04

申请号：US17028070

申请日：2020-09-22

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  Université Toulouse III—Paul Sabatier ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

发明人： Nathalie Vergnolle ,  Corinne Rolland ,  Céline Deraison-Manuel

IPC分类号： C07K16/40 ,  C12N15/113 ,  C12N15/115 ,  C12Q1/37 ,  A61K38/57 ,  C12N9/00 ,  C12N9/48 ,  A61P1/04 ,  A61K39/00

CPC分类号： C07K16/40 ,  A61K38/57 ,  A61P1/04 ,  C12N9/00 ,  C12N9/48 ,  C12N15/115 ,  C12N15/1137 ,  C12Q1/37 ,  A61K2039/505 ,  C07K2317/76 ,  C12N2310/11 ,  C12N2310/12 ,  C12N2310/14 ,  C12N2310/16 ,  G01N2333/96433 ,  G01N2500/02 ,  G01N2500/10 ,  G01N2800/065

摘要： The invention is in the field of therapy of gut inflammatory diseases such as Inflammatory Bowel Diseases (IBD) or Irritable Bowel Syndrome (IBS) including Gluten hypersensitivity. The inventors showed that ELA2A secreted by epithelial cells in the extracellular space is over-expressed in IBD conditions degrading tight junction proteins and controlling cytokines expression. Overexpression of ELA2A conferred a pro-inflammatory phenotype both in cell expression systems and in vivo in animal model of IBD. The inventors also showed that ELA2 over-expressing intestinal epithelial cells increase the release of CXCL8 protein compared to control cells. The increased CXCL-8 protein release observed in cells overexpressing ELA2A is inhibited by ELAFIN addition to the culture, in a dose-dependent manner. In particular, the invention relates to inhibitors of Elastase ELA2A, for use in the treatment of Inflammatory Bowel Diseases, such as Crohn's Disease, Ulcerative Colitis, Celiac disease, and Pouchitis.

公开(公告)号：US10829563B2

公开(公告)日：2020-11-10

申请号：US16309280

申请日：2017-06-16

申请人： INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) ,  Université Toulouse III—Paul Sabatier ,  CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS)

发明人： Nathalie Vergnolle ,  Corinne Rolland ,  Céline Deraison-Manuel

IPC分类号： C12Q1/37 ,  C07K16/40 ,  A61K38/57 ,  C12N9/00 ,  C12N9/48 ,  A61P1/04 ,  C12N15/113 ,  C12N15/115 ,  A61K39/00

摘要： The invention is in the field of therapy of gut inflammatory diseases such as Inflammatory Bowel Diseases (IBD) or Irritable Bowel Syndrome (IBS) including Gluten hypersensitivity. The inventors showed that ELA2A secreted by epithelial cells in the extracellular space is over-expressed in IBD conditions degrading tight junction proteins and controlling cytokines expression. Overexpression of ELA2A conferred a pro-inflammatory phenotype both in cell expression systems and in vivo in animal model of IBD. The inventors also showed that ELA2 over-expressing intestinal epithelial cells increase the release of CXCL8 protein compared to control cells. The increased CXCL-8 protein release observed in cells overexpressing ELA2A is inhibited by ELAFIN addition to the culture, in a dose-dependent manner. In particular, the invention relates to inhibitors of Elastase ELA2A, for use in the treatment of Inflammatory Bowel Diseases, such as Crohn's Disease, Ulcerative Colitis, Celiac disease, and Pouchitis.