A conjugate of a collagen ii-binding fragment and an...

A - Human Necessities – 61 – K

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A61K 38/39 (2006.01) A61K 38/17 (2006.01) C07K 14/78 (2006.01) C07K 14/81 (2006.01) C07K 19/00 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2392175

The invention provides a conjugate of a collagen II-binding chondroadherin fragment and an arthritis-affecting pharmaceutical substance, such as a cytokine, a cytokine antagonist and/or a protease inhibitor. It has turned out that chondroadherin specifically interacts with collagen II thereby forming a complex. Release of cartilage extracellular matrix components, such as chondroadherin and collagen II is a symptom of arthitis. By providing a conjugate according to the present invention it is therefore possible to direct arthitis-affecting pharmaceutical substances directly to the pathogenic tissue. The inventive conjugate can be manufactured by chemical crosslinking. In case the arthitis-affecting pharmaceutical substance is a protein or a peptide, the conjugate can be a fusion protein and be produced by genetic engineering techniques.

La présente invention concerne un conjugué constitué d'un fragment de chondroadhérine se liant au collagène II et d'un principe actif anti-arthritique tel que la cytokine, un agoniste de la cytokine et/ou un inhibiteur de protéase. Il est apparu que la chondroadhérine est capable d'une interaction spécifique avec le collagène aboutissant à la formation d'un complexe. L'un des symptômes de l'arthrite est la libération de composants de la matrice extracellulaire des cartilages, et notamment de la chondroadhérine et du collagène II. En utilisant un conjugué selon la présente invention, on a la possibilité d'amener directement sur le tissu atteint les principes actifs anti-arthritiques. Le conjugué de l'invention peut s'obtenir par chimio-réticulation. Dans le cas où le principe actif anti-arthritique est une protéine ou un peptide, le conjugué peut se présenter sous forme d'une protéine fusionnelle obtenue par génie génétique.

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