Engineered biopharmaceuticals

Table 1.3 Selected engineered biopharmaceutical types/products that have now gained marketing approval. These and additional such products will be discussed in detail in subseguent chapters...

The advent of genetic engineering and monoclonal antibody technology underpinned the establishment of literally hundreds of start-up biopharmaceutical (biotechnology) companies in... 

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. 

The biopharmaceutical sector is largely based upon the application of techniques of molecular biology and genetic engineering for the manipulation and production of therapeutic macromolecules. The majority of approved biopharmaceuticals (described from Chapter 8 onwards) are proteins produced in engineered cell lines by recombinant means. Examples include the production of insulin in recombinant E. coli and recombinant S. cerevisiae, as well as the production of EPO in an engineered (Chinese hamster ovary) animal cell line. 

Table 3.3 Some approved biopharmaceuticals that have been altered by post-translational engineering Engineered product Effect of engineering...

The expression of recombinant proteins in cells in which they do not naturally occur is termed heterologous protein production (Chapter 3). The first biopharmaceutical produced by genetic engineering to gain marketing approval (in 1982) was recombinant human insulin (tradename Humulin ), produced in E. coli. An example of a more recently approved biopharmaceutical that is produced in E. coli is that of Kepivance, a recombinant keratinocyte growth factor used to treat oral mucositis (Chapter 10). Many additional examples are provided in subsequent chapters. 

Table 5.2 Some biopharmaceuticals currently on the market which are produced by genetic engineering in either E. coli or animal cells...

In order to overcome environmental concerns in particular, some companies are investigating the use of engineered plant cell lines as opposed to intact transgenic plants in the context of biopharmaceutical production. One company (DowAgroSciences) gained approval in 2006 for a veterinary subunit vaccine against Newcastle disease in poultry produced by such means. 

Stephanie Mouhat is an engineer and has a Ph.D. in biology. She is affiliated to the ERT 62 laboratory and holds a position as a researcher in a biopharmaceutical company. She works in the field of therapeutic peptides derived from venomous animal toxins, and has contributed to more than 10 scientific articles, above 20 communications, and 2 patents in the field. She won the prize for the best Ph.D. thesis at the Universite de la Mediterranee in 2006. 

Ludovic Mouhat is an engineer in bioinformatics. He is affiliated to the ERT 62 laboratory and holds a position as a researcher in a biopharmaceutical company. He is involved in the design and chemical production of candidate therapeutic peptide drugs. 

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... 

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