LONG-ACTING CONJUGATE OF G PROTEIN-COUPLED RECEPTOR POLYPEPTIDE LIGAND AND PREPARATION METHOD OF SAME

摘要

The present invention relates to a G protein-coupled receptor (GPCR) polypeptide ligand; a protein conjugate in which a non-peptidyl polymer and an immunoglobulin Fc region are covalently linked, and a preparation method of the same; and a pharmaceutical composition comprising the same. The protein conjugate of the present invention shows a higher increase in biological half-life and retention time of the GPCR polypeptide ligand than any modified proteins previously reported, and thus has superior biological persistence and activity in vivo, and a negligible risk of producing immune responses, and thus may be beneficially used in the development of a long-acting preparation of the GPCR polypeptide ligand. Additionally, a long-acting preparation of a protein drug according to the present invention may reduce the pain in a patient due to frequent injections, and can maintain the effect of the drug reliably by maintaining the GPCR ligand concentration in blood. Further, the preparation method of the protein conjugate of the present invention has overcome the disadvantages of a production method of fusion protein by genetic modification such as the difficulty of establishing an expression system, glycosylation different from native forms, induction of immune responses, and limited orientation of protein fusion, as well as the problems of a chemical combination method such as low yield due to non-specificity of reactions, and toxicity of chemical materials used as conjugates, and thus can provide protein drugs having increased biological half-life and high activity in a convenient and economic manner.;COPYRIGHT KIPO 2017