FR2009/113 PCT PATENT APPLICATION TITLE Novel antagonist antibodies and their Fab fragments against GPVI and uses thereof SANOFI-AVENTIS ABSTRACT The present invention discloses novel antibodies that specifically bind to the human platelet membrane protein Glycoprotein VI (GPVI) and their monovalent fragments or derivatives. The antibodies of the invention are antibodies from hybridoma clone 390 and fragment antibodies thereof able to induce a GPVI depletion phenotype. These antibodies and Fab fragments are able to block collagen binding and thus preventing platelet activation by collagen. The invention also relates to hybridoma clones and expression plasmids for the production of disclosed antibodies and Fab fragments. The present invention further refers to the uses of monovalent antibody fragments to manufacture research, diagnostic and immunotherapeutic agents for the treatment of thrombosis and other vascular diseases. The invention also concerns a Fab bearing a molecule at the C-terminal extremity, as well as method for prevention of recognition of Fab by antibodies using such modified Fab. The invention concerns a method for prevention of platelet activation when an anti-GP VI Fab is used.La présente invention concerne de nouveaux anticorps qui se lient de manière spécifique à la protéine membranaire plaquettaire humaine, Glycoprotéine VI, et leurs fragments ou dérivés monovalents. Les anticorps de linvention sont des anticorps issus du clone dhybridome 390 et des anticorps fragments de ceux-ci capables dinduire un phénotype de déplétion en GPVI. Ces anticorps et fragments Fab sont capables de bloquer la liaison du collagène et ainsi dempêcher lactivation des plaquettes par le collagène. Linvention concerne également des clones dhybridome et des plasmides dexpression pour la production des anticorps et des fragments Fab décrits. La présente invention concerne en outre les utilisations de fragments danticorps monovalents pour fabriquer des agents de recherche,
