Human factor VII

Recombinant activated human factor VII, increasingly popular in the treatment of major bleeding. 

Switzerland factor Vila antihemophilic N ovoSeven NiaStase Recombinant human Factor VII from human clone lambdaHVI 12463, produced in CHO cells Hemophilia... 

Strancar, A., Barut, M., Podgomik, A., Koselj, P, Schwinn, H., Raspor, P, and Josic, D., Application of compact porous tubes from preparative isolation of clotting factor VII from human plasma, /. Chromatogr. A, 760, 117, 1997. 

Factor IX Replacement Hemophilia B therapy may include recombinant (produced via transfection of mammalian cells with the human factor IX gene) or plasma-derived (concentrate from pooled plasma) factor IX (see Table 64-2). Guidelines for choosing the factor-concentrate formulation for hemophilia B are similar to the guidelines for hemophilia A. However, older-generation factor IX concentrates containing other vitamin K-dependent proteins (e.g., factors II, VII, and IX), called prothrombin complex concentrates (PCCs), have been associated with thrombogenic side effects. Consequently, these products are not first-line treatment for hemophilia B.11... 

PCCs contain the vitamin K-dependent factors II, VII, IX, and X. These agents represent another attempt to bypass the factor at which the antibody is directed (see Fig. 64-2). However, PCCs carry the risk of serious thrombotic complications. Porcine factor VIII is most useful when the inhibitor titer is less than 50 BU (see Fig. 64-2 for dose and frequency). Owing to its similarity to human factor VIII, porcine factor VIII participates in the coagulation cascade. However, most inhibitors have very weak neutralizing activity against it. Porcine factor VIII is a third-line agent (only after factor Vila and a PCC have failed) owing to a 15% incidence of cross-reactivity.15... 

Vitamin confers biologic activity upon prothrombin and factors VII, IX, and X by participating in their postribosomal modification. Vitamin is a fat-soluble substance found primarily in leafy green vegetables. The dietary requirement is low, because the vitamin is additionally synthesized by bacteria that colonize the human intestine. Two natural forms exist vitamins Ki and K2. Vitamin K1 (phytonadione Figure 34-5) is found in food. Vitamin K2 (menaquinone) is found in human tissues and is synthesized by intestinal bacteria. 

Morrill, P. R., Gupta, G., Sproule, K., et al. (2002) Rational combinatorial chemistry-based selection, synthesis and evaluation of an affinity adsorbent for recombinant human clotting factor VII. J. Chromatogr. B 774, 1-15. 

McGee MR Devlin R, Saluta G, Koren H. Tissue factor and factor VII messenger RNAs in human alveolar macrophages effects of breathing ozone. Blood 1990 75 122-127. 

McGee MR Wallin R, Devlin R, Rothberger H. Identification of mRNA coding for factor VII protein in human alveolar macrophages. Coagulant expression may be limited due to postribosomal processing. Thromb Haemost 1989 61 170-174. 

Vindevoghel, L., Kon, A., Lechleider, R.J., Uitto, J., Roberts, A.B., and Mauviel, A. 1998a. Smad-dependent transcriptional activation of human type VII collagen gene (COL7A1) promoter by transforming growth factor-beta. J. Biol. Chem. 273 13053-13057. 

Coagulation factors factor VII antihemophilic factor, factor IX (human, recombinant)... 

In two patients with hemophilia with antibodies to both human and porcine factor VIII, continuous recombinant factor Vila resulted in hematuria (21). In neither case was a cause of the hematuria found. The author suggested that mucosal bleeds, such as hematuria, are characterized by high fibrinoljdic activity locally and may require higher peak concentrations of factor VII to generate sufficient thrombin to achieve and sustain hemostasis. The need for a full thrombin burst could relate to the role of thrombin in the activation of thrombin-activatable fibrinolysis inhibitor. 

Linked fucose has been found on the EGF domains of urokinase, tissue plasminogen activator (tPA), factor VII, and factor XII, attached to the consensus sequence Cys-Xaa-Xaa-Gly-Gly-Ser/Thr-Cys. The fucosyltransferase responsible for the initiation of this type of gly-cosylation has been cloned [165]. On human (but not bovine) factor IX the tetrasaccharide Neu5Ac(o 2-6)Gal(jSl—4)GlcNAc( 81-3)Fuc(al-0)Ser (O Fig. 13d) was found [166,167]. In other FGF domains only Fuc(a l-0)Ser/Thr was detected. 

Proconvertin, Plasma thromboplastin VII Factor VII deficiency, increased risk of thrombosis with elevated F-VII concentration Rare 2 per 1,000,000 0.5 0.01 Liver 4-5 IDAN FA7 HUMAN... 

Besides the production of polio and tetanus immunoglobulins, the fast growing company concentrated on the fractionation of human plasma on a larger scale. To this end, plasmapheresis was introduced as early as 1963 to increase the supply of human plasma. The application of Cohn s method of cold ethanol fractionation gradually enabled the production of a variety of common preparations, but also e.g. coagulation factor concentrates (factor VII, VIII and IX). Today the company processes about 10 % of the world supply of human plasma. 

NovoSeven is an unusual product in that it is (a recombinant form of) human coagulation factor VII (FVII). The product is converted in an autocatalytic fashion into the active two-chain form (FVIIa) during its chromatographic purification. NovoSe-... 

The 11 agents show how the sourcing of such agents, all of which are based around Factors VII, VIII or IX, has gone from isolation of purified materials from pooled human plasma in 1982 (Haemate HS ) which was first approved in Germany in 1982, through later versions (improved purification systems) such as Bioclate in... 

Pedersen, A.H., Lund-Hansen, T., Bisgaard-Frantzen, H., Olsen, F., Petersen, L. C. 1989. Autoactivation of human recombinant coagulation factor VII, Biochemistry 28, 9331-9336. 

PPL Therapeutics Bile human gastric Lipase, Fibrinogen, thrombin, Factor VII, Factor IX, alpha-antitrypsin, calcitonin (salmon), collagen, superoxide dismutase, Glucagon lipopeptide, Human serum albumin, Protein C 59-63... 

Fig. 45.5. A. Structures of vitamin K derivatives. Phylloquinone is found in green leaves, and intestinal bacteria synthesize menaquinone. Humans will convert menadione to a vitamin K active form. B. Vitamin K-dependent formation of y-carboxyglutamate residues. Thrombin, Factor VII, Factor IX, and Factor X are bound to their phospholipid activation sites on cell membranes by Ca ". The vitamin K-dependent carboxylase, which adds the extra carboxyl group, uses a reduced form of vitamin K (KH2) as the electron donor and converts vitamin K to an epxjx-ide. Vitamin K epoxide is reduced, in two steps, back to its active form by the enzymes vitamin K epoxide reductase and vitamin K reductase.

The first biotherapeutics— bovine insulin, streptokinase or staphylokinase— were non-human in origin. Subsequent biopharmaceuticals i.e. growth hormone and factor VII) were human in origin. More recently, recombinant proteins i.e. interferon or insulin) have become available. The number of licensed biopharmaceuticals rose from about 10 in 1996 to over 75 in 2006 it is thought that by the end of 2010, approximately half of all newly licensed pharmaceutical agents will be of this type. 

---