Selective targeting of tumor vasculature using antibody...

Details Selective targeting of tumor vasculature using antibody... Selective targeting of tumor vasculature using antibody...

C - Chemistry, Metallurgy

12

N

C12N 15/13 (2006.01) A61K 39/395 (2006.01) A61K 51/10 (2006.01) A61P 9/00 (2006.01) A61P 35/00 (2006.01) C07K 16/18 (2006.01) C07K 16/46 (2006.01) C12P 21/02 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2478414

The present invention relates to selectively targeting tumoral vasculature in vivo using a human recombinant scFv, L19, to the angiogenesis marker ED-B domain of fibronectin. In preferred embodiments, a complete human IgG1 is employed having the variable regions of L19. In other embodiments is employed a mini-immunoglobulin generated by fusing the scFv L19 to the constant CH4 domain of a secretory IgE isoform that naturally contains a cysteine in its COOH terminal and which forms a covalently linked dimer. Different in vivo behaviour of the antibody formats is exploitable for different diagnostic and/or therapeutic purposes, depending on clinical needs and disease. The antibody molecules may be labelled as described.

La présente invention concerne le ciblage sélectif d'un système vasculaire tumoral in vivo au moyen d'un scFv recombinant, L19, sur le domaine ED-B du marqueur d'angiogenèse de la fibronectine. Dans des modes de réalisation préférés, on utilise une IgG1 humaine complète comprenant les régions variables de L19. Dans d'autres modes de réalisation, on utilise une mini-immunoglobuline produite par fusion du scFv L19 avec le domaine CH4 constant d'une isoforme d'IgE sécrétrice contenant naturellement une cystéine dans sa terminaison COOH et formant un dimère lié par covalence. On peut utiliser un comportement in vivo différent des formats d'anticorps à diverses fins diagnostiques et/ou thérapeutiques, selon les besoins cliniques et la maladie. Ces molécules d'anticorps peuvent être marquées comme indiqué dans la description.

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