OH, EUH LIM,오의림,HUH, YONG HO,허용호,HWANG, SANG YOUN,황상연,CHOI, IN YOUNG,최인영,JUNG, SUNG YOUB,정성엽,KWON, SE CHANG,권세창
申请号：
KR1020110147683
公开号：
KR1020130078633A
申请日:
2011.12.30
申请国别(地区):
KR
年份:
2013
代理人:
摘要：
PURPOSE: An immunoglobulin Fc fragment derivative is provided to have extended in vivo half life by high binding affinity to neonatal Fc receptor (FcRn) and to manufacture a sustained formulation of a protein drug. CONSTITUTION: An immunoglobulin Fc fragment derivative has the modification of amino acid residues selected from a group consisting of 308F, 380S, 380A, 428L, 429K, 430S, 433K, and 434S (the numbering is based on EU index) in the constant region of a wild type immunoglobulin Fc fragment. The immunoglobulin Fc fragment derivative has enhanced binding affinity to FcRn. The modification of the amino acid residue is selected from a group consisting of 428L/434S, 433K/434S, 429K/433K, 428L/433K, 308F/380A, 307S/380S, and 380S/434S. A method for enhancing in vivo half life of a physiologically active polypeptide comprises the step of binding the immunoglobulin Fc fragment derivative with the physiologically active polypeptide through covalent bond by a non-peptidyl polymer.본 발명은 FcRn에 대한 결합 친화력이 증가된 면역글로불린 Fc 단편 유도체에 관한 것으로, 상기 유도체는 천연형 면역글로불린 Fc 단편의 불변영역 내에 307S, 308F, 380S, 380A, 428L, 429K, 430S, 433K 및 434S (상기 넘버링은 EU 인덱스에 따른 것임)로 구성된 군으로부터 선택되는 하나 이상의 아미노산 잔기의 변형을 포함한다. 본 발명에 따른 면역글로불린 Fc 단편 유도체는 FcRn에 대한 높은 결합 친화력으로 인해 더욱 연장된 생체 내 반감기를 나타내므로 단백질 약물의 지속성 제제의 제조에 유용하게 사용될 수 있다.
