期刊
THROMBOSIS RESEARCH
卷 124, 期 -, 页码 S6-S8出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0049-3848(09)70157-4
关键词
Half-life extension; Factor IX; Recombinant factor IX; Albumin fusion protein; Albumin fusion technology; Coagulation factor; Cleavable linker; Haemophilia B; Recombinant factor IX fusion protein
资金
- CSL Behring
Haemophilia B is characterized by a deficiency of coagulation factor IX (FIX), a protein that is important in the process of haemostasis and normal blood clotting. Recurrent bleeding into joints and soft tissues is the hallmark of severe haemophilia B. The goal of treatment is to prevent and manage haemorrhage and thereby reduce disabling joint and tissue damage, improve quality of life, and extend life expectancy. Current treatment with FIX replacement concentrates often requires repeated, frequent infusions, owing to the relatively short terminal half-life of FIX in the circulation. We have developed a unique technology for improving the biological characteristics of FIX in vivo. For this approach, recombinant FIX (rFIX) was genetically fused to albumin via a cleavable peptide linker. Constructs of the fusion protein were expressed in mammalian cells and characterized following purification. In vitro activation studies demonstrated that cleavage of the linker occurred in parallel with FIX activation. The molar specific clotting activity of the cleavable fusion protein (rIX-FP) was 10- to 30-fold greater than that of the fusion protein with non-cleavable linkers. In rats, rabbits, and FIX-deficient mice, the pharmacokinetics of rIX-FP were significantly improved compared with rFIX. Using the tail-clip bleeding model in FIX-deficient mice, rIX-FP effectively corrected the bleeding time and blood loss. These findings suggest that rIX-FP may be a promising therapy for the treatment of patients with haemophilia B. (C) 2009 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据