Polypeptides that bind trail-r1 and trail-r2

C - Chemistry – Metallurgy – 07 – K

Patent

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Details

C07K 19/00 (2006.01) A61K 38/17 (2006.01) A61P 35/00 (2006.01) C07K 7/00 (2006.01) C07K 7/06 (2006.01) C12N 15/62 (2006.01) C40B 30/04 (2006.01) C07K 14/715 (2006.01)

Patent

CA 2739663

Agonists for TRAIL death receptors including polypeptides having a multimerizing, e.g. trimerizing, domain and a polypeptide sequence that binds to at least one of TRAIL death receptors TRAIL- R1 and TRAIL-R2. Agonists are described that do not bind to TRAIL decoy receptors. The multimerizing domain may be derived from human tetranectin. The agonists can induce apoptosis in pathogenic cells expressing a TRAIL death receptor. Pharmaceutical compositions are described for treating diseases associated with cells expressing DR4 and DR5, such as tumor cells. Methods for selecting polypeptides and preparing multimeric complexes.

Linvention concerne des agonistes des récepteurs de mort TRAIL comprenant des polypeptides qui présentent un domaine de multimérisation, par exemple un domaine de trimérisation, et une séquence polypeptidique qui se lie au moins aux récepteurs de mort TRAIL (TRAIL1 et TRAIL2). Des agonistes décrits ne se lient pas aux récepteurs de facteur de décroissance TRAIL. Le domaine de multimérisation peut être dérivé de la tétranectine humaine. Les agonistes peuvent induire une apoptose dans des cellules pathogènes exprimant un récepteur de mort TRAIL. Les compositions pharmaceutiques décrites permettent de traiter les maladies associées à des cellules exprimant DR4 et DR5, telles que des cellules tumorales. Linvention concerne également des méthodes pour sélectionner des polypeptides et préparer des complexes multimères.

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