Compositions and methods for crystallizing antibody fragments

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 16/24 (2006.01) A61K 39/395 (2006.01) C07K 16/00 (2006.01)

Patent

CA 2713342

The invention provides methods of crystallizing antibodies and fragments thereof as well as crystals produced thereby. More particularly, the invention provides methods of crystallizing human and non-human Fab fragments of antibodies, either alone or as co-crystals with their target ligand. For example, a crystal comprising a murine Fab fragment of the antibody 125-2H or a human Fab fragment of the antibody ABT-325, which bind to IL- 18, are provided as well as a co-crystal of a murine Fab fragment bound to IL-18. ABT-325 and 125-2H differ significantly in combining site character and architecture, thus explaining their ability to bind IL-18 simultaneously at distinct epitopes.

L'invention porte sur des procédés de cristallisation d'anticorps et de fragments danticorps, ainsi que sur des cristaux obtenus par ces procédés. Plus particulièrement, l'invention porte sur des procédés de cristallisation de fragments Fab d'anticorps humains et non humains, soit individuellement soit en tant que co-cristaux avec leur ligand cible. Par exemple, linvention propose un cristal comprenant un fragment Fab de souris de l'anticorps 125-2H ou un fragment Fab humain de l'anticorps ABT-325 qui se lient à IL-18, ainsi qu'un co-cristal d'un fragment Fab de souris lié à IL-18. ABT-325 et 125-2H diffèrent de façon significative par le caractère et larchitecture du site de combinaison, ce qui explique leur aptitude à se lier à IL-18 simultanément sur des épitopes distincts.

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