KIM, JUNG KUKKR,김정국,LEE, JONG SOOKR,이종수,PARK, YOUNG JINKR,박영진,JUNG, SUNG YOUBKR,정성엽,KWON, SE CHANGKR,권세창
申请号：
KR1020160023450
公开号：
KR1020170100936A
申请日:
2016.02.26
申请国别(地区):
KR
年份:
2017
代理人:
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 2017본 발명은 G 단백질 연결 수용체(G protein-coupled receptor, GPCR) 폴리펩타이드 리간드, 비펩타이드성 중합체 및 면역글로불린 Fc 영역이 공유결합으로 연결된 단백질 결합체, 이의 제조방법 및 이를 포함하는 약제학적 조성물에 관한 것이다. 본 발명의 단백질 결합체는 GPCR 폴리펩타이드 리간드의 혈중 반감기 및 체류시간 증가가 기존에 보고된 어떠한 변형 단백질보다도 높기 때문에 월등한 혈중 지속성과 생체 내 활성을 가질 뿐만 아니라, 면역반응 유발의 위험도 거의 없어, GPCR 폴리펩타이드 리간드의 지속형 제재 개발에 유용하게 이용될 수 있다. 또한, 본 발명에 따른 단백질 약물의 지속형 제제는 잦은 주사로 인한
