Antagonists of hmgb1 and/or rage and methods of use thereof

Details Antagonists of hmgb1 and/or rage and methods of use thereof Antagonists of hmgb1 and/or rage and methods of use thereof

A - Human Necessities

61

K

A61K 39/395 (2006.01)

Patent

CA 2631212

Compositions and methods are disclosed for inhibiting the release of a proinflammatory cytokine from a vertebrate cell, and for inhibiting an inflammatory cytokine cascade in a patient. The compositions comprise, for example, high affinity antibodies that specifically bind HMG1 and antigenic fragments thereof. The high affinity antibodies of the present invention and pharmaceutical compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of inflammatory diseases and disorders such as sepsis, rheumatoid arthritis, peritonitis, Crohn s disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, lupus, psoriasis, psoriatic arthritis, arthritis, anaphylactic shock, organ ischemia, reperfusion injury, and allograft rejection. In addition, the high affinity antibodies of the present inventions are useful as diagnostic antibodies.

La présente invention a trait à des compositions et des procédés pour l'inhibition de la libération d'une cytokine pro-inflammatoire à partir d'une cellule de vertébré, et pour l'inhibition d'une cascade de cytokines inflammatoires chez un patient. Les compositions comprennent, par exemple, des anticorps d'affinité élevée de liaison spécifique à HMG1 et à des fragments antigéniques de celle-ci. Les anticorps d'affinité élevée de la présente invention et des compositions pharmaceutiques en comportant sont utiles à diverses fins, par exemple, en tant qu'agents thérapeutiques contre une large gamme de maladies et troubles inflammatoires tels que la sepsie, la polyarthrite rhumatoïde, la péritonite, la maladie de Crohn, la lésion consécutive à la perfusion, la septicémie, le choc endotoxique, la mucoviscidose, l'endocardite, le lupus, le psoriasis, l'arthrite psoriatique, l'arthrite, le choc anaphylactique, l'ischémie d'organes, et le rejet de greffe allogénique. En outre, les anticorps d'affinité élevée de la présente invention sont utiles en tant qu'anticorps de diagnostic.

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