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 presente invención se refiere a nuevos anticuerpos que se unen específicamente a la proteína de las membranas plaquetarias humanas Glicoproteína VI (GPVI) y sus fragmentos monovalentes o derivados. Los anticuerpos de la invención son anticuerpos de clon 390 de hibridoma y sus fragmentos de anticuerpo capaces de inducir un fenotipo de reducción de GPVI. Estos anticuerpos y fragmentos Fab pueden bloquear la unión de colágeno y evitar así la activación plaquetaria por colágeno. La invención también se refiere a clones de hibridoma y plásmidos de expresión para la producción de anticuerpos y fragmentos Fab descritos. La presente invención se refiere además a los usos de fragmentos de anticuerpos monovalentes para fabricar agentes de investigación, de diagnóstico e inmunoterap
