Antithrombin recombinant

CIEF was also used to follow the production of recombinant antithrombin III (r-AT Iff) in cultures of hamster kidney cells.111 r-AT III inhibits serine proteases such as blood factors (IXa, Xa, and XIa) and thrombin. Interference by the media from which the samples were collected posed some difficulties because some of the media components have similar characteristics to those of the compounds of interest. CIEF was used to determine the pis of the separated components after sample purification by HPLC. Three major peaks showed pis of 4.7, 4.75, and 4.85, and three minor peaks had pis of 5.0, 5.1, and 5.3. These data closely resembled the data already published for serum AT III based on conventional IEF. 

Lutkemeyer, D., Bretschneider, M., Buntemeyer, H., and Lehmann, J. (1993). Membrane chromatography for rapid purification of recombinant antithrombin III and monoclonal antibodies from cell culture supernatant. J. Chromatogr. 639, 57-66. 

Figure 6. Structural heterogeneity in antithrombin agents. Besides the synthetic antithrombin agents, plasma derived antithrmnbin III and its recombinant equivaloit and various recombinant equivalents of naturally occurring antithrombin agents and conjugates have also become available...

Kaiser B, Callas D, Walenga JM, Fareed J Synthetic and recombinant antithrombin drugs Exp Opin Invest Drugs (1998) 7(6) %3-985. 

Until now, only one product derived from transgenic technology, namely goat milk-derived recombinant human antithrombin III, has been submitted for approval in Europe. 

Human antithrombin III (ATryn ) was the first therapeutic recombinant protein to be produced using a transgenic system... 

Konkle BA, Bauer KA, Weinstein R, et al. Use of recombinant human antithrombin in patients with congenital antithrombin deficiency undergoing surgical procedures. Transfusion, 2003 43(3) 390-394. 

Following completion of the 02001 efficacy trial, a European regulatory fihng was submitted in January 2004, for the use of rhAT in the prophylaxis of DVT in hereditary AT-deficient patients in a high-risk situation. If this appHcation is approved, this will constitute the first approval of a transgenically produced biopharmaceutical. Indeed, this will constitute the first approval of a biologic manufactured in a new recombinant production system since approval of the first product manufactured in ceU culture in the early 1990s. The development of a recombinant option for antithrombin wiU provide a safe and reliable supply of this important factor, and will facilitate the resumption of clinical trials aimed at acquired deficiencies of anti-... 

Classification and Prototypes Anticoagulants reduce the formation of fibrin clots. Two major types of anticoagulants are available heparin and its derivatives, which must be used parenterally and the orally active coumarin derivatives (eg, warfarin). The two groups differ in their chemistry, pharmacokinetics, and pharmacodynamics (Table 34-2). Two other anticoagulant proteins are available lepirudin, a recombinant form of hirudin, a protein found in leech saliva and human antithrombin III, a commercial preparation of an endogenous human anticoagulant. 

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