Antagonist anti-cd40 monoclonal antibodies and methods for...

A - Human Necessities – 61 – P

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A61P 35/02 (2006.01) A61K 39/395 (2006.01) C07K 16/28 (2006.01)

Patent

CA 2564296

Compositions and methods for inhibiting CD40-directed activities that are mediated via the binding of C4BP to CD40 are provided. The compositions of the invention include anti-CD40 antibodies, or antigen-binding fragments thereof, that have the following characteristics: 1) are free of significant CD40 agonist activity when bound to CD40 antigen; and 2) are capable of specifically binding to CD40 antigen expressed on the surface of cells, wherein this binding to CD40 antigen blocks C4BP-mediated CD40 signaling, thereby inhibiting one or more CD40-directed activities. These antagonist anti- CD40 antibodies can effectively be used to treat CD40-associated diseases that are mediated by C4BP stimulation of CD40 signaling, including cancers, such as B cell-related cancers and solid tumors, and diseases or disorders that have an autoimmune and/or inflammatory component, including organ and tissue transplant rejection.

L'invention concerne des compositions et des méthodes d'inhibition d'activités dirigées vers CD40 à médiation de liaison de C4BP à CD40. Lesdites compositions renferment des anticorps anti-CD40 ou des fragments associés de liaison à l'antigène qui présentent les caractéristiques suivantes: (1) ils sont exempts d'une activité agoniste CD40 importante lorsqu'ils sont liés à l'antigène CD40 et (2) ils sont capables de se lier spécifiquement à l'antigène CD40 exprimé à la surface des cellules, la liaison à l'antigène CD40 bloquant la signalisation CD40 à médiation C4BP, ce qui permet d'inhiber au moins une activité dirigée vers CD40. Ces anticorps anti-CD40 antagonistes peuvent être utilisés efficacement pour traiter des maladies associées à CD40 qui sont médiées par une stimulation C4BP de la signalisation CD40, notamment, des cancers tels que des cancers liés au lymphocyte B et des tumeurs solides et des maladies ou des troubles qui ont un composé auto-immun et/ou inflammatoire, y compris, un rejet de greffe de tissu ou d'organe.

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