Hepatocyte growth factor variants

Details Hepatocyte growth factor variants Hepatocyte growth factor variants

C - Chemistry, Metallurgy

12

N

C12N 15/18 (2006.01) A61K 38/48 (2006.01) C07K 14/475 (2006.01)

Patent

CA 2499896

Serine proteases factor XIa and kallikrein cleave and activate HGF. Cleavage is at two sites: a typical cleavage site, Arg494-Val495, and a novel cleavage site, Arg424-His425. Variant HGF fragments obtained by cleaving at one or both of these sites may be useful as agonists or antagonists of HGF. Variants or fragments obtained by modifying these cleavage sites so as to be resistant to kallikrein and/or FXIa cleavage are also provided.

Le facteur Xla des protéases serines et la kallikrein clivent et activent le HGF. Le clivage s'effectue en deux sites; un site usuel de clivage, le Arg494-Val495, et un nouveau site de clivage, le Arg424-His425. Les fragments de variant de HGF obtenus par clivage dans l'un de ces sites ou dans les deux peuvent servir d'agonistes ou d'antagonistes du HGF. L'invention porte également sur des variants ou fragments, obtenus en modifiant ces sites de clivage, pour les rendre résistants à la kallikrein et/ou au clivage par le FXIa.

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