Recombinant Factor IX for Clinical and Research Use

Department of Pediatrics, Gene Therapy Center, Harold R. Roberts Comprehensive Hemophilia Treatment Center, University or North Carolina at Chapel Hill, Chapel Hill, NC 27599-7236, USA.
Seminars in Thrombosis and Hemostasis (Impact Factor: 3.88). 07/2010; 36(5):498-509. DOI: 10.1055/s-0030-1255444
Source: PubMed


The last significant advance in the therapy of hemophilia B was the introduction of recombinant factor IX (FIX), ensuring an advanced level of safety from potential infectious contaminants of plasma-derived clotting factors. Since that time, recombinant DNA techniques have been applied in research to elucidate the role of FIX and its functional domains within coagulation. At the same time, recombinant DNA technology has been applied to engineer an expanding spectrum of novel FIX therapies that are now being translating into clinical trials. The experience with the existing recombinant FIX product is reviewed with a focus on the novel products and the potential to improve the quality of life for individuals with hemophilia B.

6 Reads
  • Source
    • "IX powodują zmiany w jego farmakokinetyce, czego skutkiem jest o około 30% mniejsze odzyskanie rcz. IX w porównaniu z osoczopochodnym [15]. Czas półtrwania obu rodzajów cz. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The treatment of patients with haemophilia A and B is based on substitution of factor VIII and factor IX. The half-life of factor VIII (about 11 hours) and factor IX (about 18 hours) are rather short, so frequency of prophylactic infusions of factor VIII and factor IX concentrates are not less than 3 or 2 times a week. The development of new factor VIII and factor IX concentrates with longer half-lives makes possible the prolongation of time between doses and the improvement of prophylaxis efficacy. The fusion of factor IX to polyethylene glycol, Fc fragment of immunoglobulin G or albumin prolonged half-life of this coagulation protein to almost 100 hours. The half-life of factor VIII concentrate, with recombinant factor VIII combined with polyethylene glycol or Fc fragment of immunoglobulin G is prolonged to about 19 hours. Modification of factor VIII structure to produce single-chain protein with increased binding to von Willebrand factor is a new promising project as well. The introduction of coagulation concentrates with prolonged half-life will improve the quality of life of patients with severe type of haemophilia.
    Acta haematologica Polonica 05/2015; DOI:10.1016/j.achaem.2015.04.006
  • Seminars in Thrombosis and Hemostasis 07/2010; 36(5):471-6. DOI:10.1055/s-0030-1255440 · 3.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications.
    Biochemical Journal 04/2011; 435(1):1-16. DOI:10.1042/BJ20100965 · 4.40 Impact Factor
Show more