Increased Production of Recombinant Vitamin K-Dependent Clotting Factors

Recombinant vitamin K-dependent clotting factors are valuable pharmaceuticals in the treatment of various bleeding complications, hemophilia and sepsis. These factors must be synthesized in eukaryotic cells due to the required vitamin K- dependent post-translational modifications. Attempts to increase the yield of functional recombinant proteins in eukaryotic cells have had limited success. The novel technology developed at Wake Forest School of Medicine will help increase the yield of recombinant vitamin K-dependent clotting factors.

Invention Summary

Researchers at Wake Forest School of Medicine have developed a modified eukaryotic cell line that increases the production of fully γ-carboxylated and functional recombinant vitamin K-dependent proteins. This novel method produces a staggering 68% yield of recombinant human Factor VII and 80% yield of recombinant human Factor IX in stabilized cell lines. The modified eukaryotic cell line can also be used to increase the yield of functional protein C that also belongs to the vitamin K-dependent protein family.

Benefits

  • This is the only technology that has shown to produce functional recombinant clotting factors.
  • It increases the yield of the recombinant vitamin K-dependent proteins drastically.

Application Fields

  • Recombinant Factor VII is used to treat blood-clotting disorders.
  • Recombinant Factor IX is used to treat Hemophilia B or Christmas disease.
  • Recombinant Protein C is used to treat inappropriate blood clotting resulting from sepsis.

Status

  • Well-established in vitro cell models demonstrate the increased yield of functional recombinant vitamin K- dependent proteins.

Inventor

Reidar Wallin, PhD

Patents

United States: 8,647,868
Europe: 1963506 (Austria, Belgium, France,Germany, Greece, Italy, Ireland, Netherlands, Spain, Sweden, Switzerland, United Kingdom)
Australia: 2006320168
Canada: 2,632,794

Publications

J Biol Chem. (2005) Sep 9;280(36):31603-7
Blood. (2006) December 1;108(12): 3757–3760.
Thrombosis Research. (2008) 122, 405–410

Licensing Contact

Stephen J. Susalka, PhD, CLP
ssusalka@wakehealth.edu

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