Blood factor recombinant

Recent reviews Hst more than 400 biotechnology-based pharmaceutical formulations either registered in clinical trials or undergoing review by the regulatory agencies for the treatment of nearly 150 diseases including cancer, infectious diseases, autoimmune diseases, and AIDS/HIV (1,2). Biotechnology-based pharmaceuticals already on the markets include recombinant blood factors, recombinant hormones, cytokines, vaccines, monoclonal antibody-based products, and therapeutic enzymes. 

Here, an overview of biopharmaceutical products thus far approved (within the EU and US at least) is presented. The products have been grouped into nine categories recombinant blood factors, recombinant thrombolytics, recombinant insulins, additional recombinant hormones, recombinant hematopoietic growth factors, recombinant IFNs and ILs, recombinant vaccines, monoclonal and engineered antibodies, and additional biopharmaceuticals (e.g., cell therapy, gene therapy, siRNA). 

The use of recombinant hematopoietic growth factors (i.e., the commercially available forms of the native products) has been evaluated in many disorders affecting all types of blood cells. Recombinant human hematopoietic growth factors are identified as rHu. Not all uses discussed have received regulatory approval in all countries. 

Despite the undoubted advantages of recombinant production, it remains the case that many protein-based products extracted directly from native source material remain on the market. In certain circumstances, direct extraction of native source material can prove equally/more attractive than recombinant production. This may be for an economic reason if, for example, the protein is produced in very large quantities by the native source and is easy to extract/purify, e.g. human serum albumin (HSA Chapter 12). Also, some blood factor preparations purified from donor blood actually contain several different blood factors and, hence, can be used to treat several haemophilia patient types. Recombinant blood factor preparations, on the other hand, contain but a single blood factor and, hence, can be used to treat only one haemophilia type (Chapter 12). 

Many of the initial biopharmaceuticals approved were simple replacement proteins (e.g. blood factors and human insulin). The ability to alter the amino acid sequence of a protein logically coupled to an increased understanding of the relationship between protein structure and function (Chapters 2 and 3) has facilitated the more recent introduction of several engineered therapeutic proteins (Table 1.3). Thus far, the vast majority of approved recombinant proteins have been produced in the bacterium E. coli, the yeast S. cerevisiae or in animal cell lines (most notably Chinese hamster ovary (CHO) cells or baby hamster kidney (BHK) cells. These production systems are discussed in Chapter 5. 

Blood factors, anticoagulants and thrombolytics Activase, Advate, Benefix, Bioclate, Helixate/ Kogenate, Metalyse/TNKase, Novoseven, Recombinate, Refacto, Xigiris... 

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. 

Blood coagulation factors antihemophilic factor (recombinant) eptacog alfa (activated) factor IX contentrate (human) factor IX (recombinant) moroctocog alfa... 

Blood factor VIII (FVIII) is a glycoprotein with 2351 amino acids and 330 kDa. Its deficiency causes hemophilia A. The first products based on recombinant factor VIII to reach the market were Recombinate and Kogenate, expressed in CHO and BHK cells, respectively. Over the last decade, other rFVIII products were approved, with modifications to the molecule (e.g. deletion of the B-domain), in the formulation or in the production processes. 

A total of seven recombinant blood factors have gained marketing approval, mainly throughout the 1990s (Table 1). All aim to treat either hemophilia A or B and all are... 

I Current Status of Biopharmaceuticals Approved Products and Trends in Approvals Table 1 Recombinant blood factors approved to date... 

Recombinant blood factor products have proven to be as effective as the plasma-derived product, without suffering the disadvantage of the potential risk of transmis-... 

Theisen M. Production of recombinant blood factors in transgenic plants. Adv. Exp. Med. Biol., 1999 464 211-220. 

Recombinant Antihemophilic Factor VIII 424 Recombinant blood factor 9 Recombinant factor VIII (rFVII) 420,459 Recombinant HB 1422 Recombinant hematopoietic growth factor 15 Recombinant hepatitis B surface antigen (rHBsAg) 3... 

Armitage JO (1998) Emerging applications of recombinant human granulocyte colony-stimulating factor. Blood 92 4491-4508... 

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