Stabilized proteins with engineered disulfide bonds

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/12 (2006.01) A61K 31/7088 (2006.01) A61K 38/17 (2006.01) A61K 38/36 (2006.01) A61K 38/37 (2006.01) A61K 48/00 (2006.01) A61P 7/02 (2006.01) A61P 7/04 (2006.01) C07K 1/107 (2006.01) C07K 14/47 (2006.01) C07K 14/475 (2006.01) C07K 14/745 (2006.01) C07K 14/755 (2006.01) C12N 9/64 (2006.01) C12N 9/74 (2006.01) C12N 15/09 (2006.01) G01N 33/68 (2006.01) G06F 17/50 (2006.01) A61K 38/00 (2006.01) G06F 19/00 (2006.01)

Patent

CA 2450732

The present invention relates to methods of introducing one or more cysteine residues into a polypeptide which permit the stabilization of the polypeptide by formation of at least one bond, preferably a disulfide bond, between different domains of the polypeptide. The invention also relates to polypeptides containing such introduced cysteine residue(s), nucleic acids encoding such polypeptides and pharmaceutical compositions comprising such polypeptides or nucleic acids. The invention also relates to vectors, viral particles and host cells containing such nucleic acids, and methods 0f using them to produce the polypeptides of the invention. Exemplified polypeptides include plasma proteins, including hepatocyte growth factor activator and plasma hyaluronin binding protein, as well as blood coagulation factors, such as Factor VIII, Factor V, Factor XII and prothrombin.

La présente invention concerne des procédés d'insertion d'un ou des résidus de cystéine dans un polypeptide permettant la stabilisation du polypeptide par la formation d'au moins une liaison, de préférence une liaison disulfure, entre les domaines du polypeptide. L'invention concerne également des polypeptides contenant un/de tel(s) résidu(s) de cystéine, de acides nucléiques codant pour de tels polypeptides et des compositions pharmaceutiques comprenant de tels polypeptides ou acides nucléiques. L'invention concerne en outre des vecteurs, des particules virales et des cellules hôtes contenant de tels acides nucléiques, et des procédés pour leur mise en oeuvre en vue de produire des polypeptides de l'invention. Des exemples de tels polypeptides comprennent les protéines plasmatiques, y compris la protéine d'activation de croissance des hépatocytes et la protéine de liaison à l'hyaluronine plasmatique, ainsi que les facteurs de coagulation sanguine, tels que le Facteur VIII, le Facteur V, le Facteur XII et la prothrombine.

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