Blood factors

Blood factors Blood flukes Blood glucose... 

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. 

Proteolytic processing Various proteins become biologically active only upon their proteolytic cleavage (e.g. some blood factors)... 

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

Monoclonal antibodies for in vivo use Cytokines (e.g. interferons and interleukins) Therapeutic enzymes Thrombolytic agents Hormones Growth factors Additional miscellaneous proteins Blood Blood proteins (e.g. albumin and blood factors) Vaccines Cell- and tissue-based products Gene therapy products Antitoxins, venoms and antivenins Allenergic extracts... 

Many small proteins, in particular those that function extracellularly (e.g. insulin, GH and various cytokines) are quite stable and may be fractionated on a variety of HPLC columns without significant denaturation or decrease in bioactivity. Preparative HPLC is used in industrial-scale purification of insulin and of IL2. In contrast, many larger proteins (e.g. blood factor VIII) are relatively labile, and loss of activity due to protein denaturation may be observed upon high-pressure fractionation. 

Cows and calves fed low-zinc diets of 25 mg Zn/kg ration showed a decrease in plasma zinc from 1.02 mg/L at start to 0.66 mg/L at day 90 cows fed 65 mg Zn/kg diet had a significantly elevated (1.5 mg Zn/L) plasma zinc level and increased blood urea and plasma proteins (Ram-achandra and Prasad 1989). Biomarkers used to identify zinc deficiency in bovines include zinc concentrations in plasma, unsaturated zinc-binding capacity, ratio of copper to zinc in plasma, and zinc concentrations in other blood factors indirect biomarkers include enzyme activities, red cell uptake, and metallothionein content in plasma and liver (Binnerts 1989). 

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. 

Proteins obtained by direct extraction from native source (e.g. blood derived clotting factors) No Yes Some (e.g. blood factors and polyclonal antibodies)... 

Many of the initial biopharmaceuticals approved were simple replacement proteins (e.g. blood factors and human insulin). The ability to logically alter the amino acid sequence of a protein, coupled to an increased understanding of the relationship between protein structure and function has facilitated the more recent introduction of several engineered therapeutic... 

Antithrombotic. Preventing or interfering with the formation of thrombi (an aggregation of blood factors). 

Arterial thrombosis. The formation of an aggregate of blood factors (thrombus), primarily platelets and fibrin, with entrapment of cellular elements in the arteries. Arthritis. Inflammation of a joint. 

---