| |
[摘要]：The application (WO2005001025) details recombinant fusion proteins attached to the constant region of heavy chains of immunoglobulins. They are found to be particularly useful for the treatment of hemostatic disorders, such as hemophilia B. It aims at engineering chimeric proteins comprising of a single molecule of human factor IX (FIX) and the constant region (Fc domain) of one or two heavy chain(s) of human IgG (rFIXFc). cDNA for rFIXFc was generated by a PCR. rFIXFc protein was isolated and purified from stably transfected mammalian cells. The concentration and clotting activity of rFIXFc were assessed in mice, rats, monkeys, and FIX-deficient mice and dogs, after intravenous administration. The half-life of rFIXFc activity is prolonged by three to fourfold, compared with rFIX, when administered intravenously in all animals. The generation of chimeric proteins, comprised of FIX fused to the Fc domain of IgG, extends the clotting activity of the recombinant molecule. rFIXFc represents a promising candidate for the treatment of patients with hemophilia B. The application claims the methods of making recombinant chimeric proteins comprising of one biologically active molecule fused to the Fc region of the heavy chain(s) of immunoglobulins and their use for therapy. |
|
