Site-directed dual pegylation of proteins for improved...

C - Chemistry – Metallurgy – 07 – K

Patent

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C07K 17/08 (2006.01) A61K 38/22 (2006.01) A61K 47/48 (2006.01) A61P 3/04 (2006.01) A61P 3/06 (2006.01) A61P 3/10 (2006.01) C07K 14/575 (2006.01)

Patent

CA 2345027

The present invention relates generally to the chemical modification of biologically active agents. More specifically, the invention relates to a novel approach to engineer, through mutagenesis and site-directed chemical conjugation, specific, well-defined dualPEGylated-protein bioconjugates, consisting of two polyethylene glycol (PEG) macromolecules chemically conjugated to the protein at two specifically defined amino acid residues. The described dualPEGylated-protein bioconjugates show substantially improved bioefficacy and biocompatibility.

De manière générale, cette invention concerne la modification chimique d'agents biologiquement actifs. Plus particulièrement, l'invention concerne une nouvelle approche de génie biologique reposant sur des bioconjugués de protéine à double polyéthylèneglycolation, bien définis, spécifiques, obtenus par mutagenèse et par la conjugaison chimique dirigée sur site. Ces bioconjugués se compose de deux macromolécules de polyéthylèneglycol (P.E.G) chimiquement conjuguées à la protéine par des résidus d'acide aminé spécifiquement définis. Les bioconjugués de protéine à double polyéthylèneglycolation présentent essentiellement une bioefficacité et une biocompatibilité accrues.

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