Polypeptide complex comprising non-peptidyl polymer having three functional ends

摘要

Disclosed is a protein complex, comprising a physiologically active polypeptide, a dimeric protein and a non-peptidyl polymer having three functional ends (3-arm), with the linkage of both the physiologically active polypeptide and the dimeric protein to the 3-arm non-peptidyl polymer via respective covalent bonds. The protein complex guarantees the long acting activity and biostability of a physiologically active polypeptide. Having the ability to maintain the bioactivity of physiologically active polypeptides or peptides highly and to significantly improve the serum half life of the polypeptides or peptides, the protein complex can be applied to the development of sustained release formulations of various physiologically active polypeptide drugs. Also, it utilizes raw materials including the physiologically active polypeptides without significant loss, thereby increasing the production yield. Further, it can be easily purified.

主权项

1. A protein complex, comprising a physiologically active polypeptide, a dimeric protein, and a non-peptidyl polymer linker, said non-peptidyl polymer linker having three functional ends,
wherein the physiologically active polypeptide and the dimeric protein are linked to the functional ends of the non-peptidyl polymer via respective covalent bonds, wherein two of the three functional ends of the non-peptidyl polymer are covalently linked to two N-terminal amino groups of the dimeric protein, respectively, and remaining one of the three functional ends of the non-peptidyl polymer is covalently linked to the physiologically active polypeptide, wherein the dimeric protein is an immunoglobulin Fc domain, and wherein the non-peptidyl polymer has three functional aldehyde groups at respective termini thereof.