Biomedical Engineering Reference
In-Depth Information
cytokines) and gene therapy and antisense-based products also represent signifi cant groupings.
Although most protein-based products likely to gain marketing approval over the next 2-3 years
will be produced in engineered E. coli , S. cerevisiae or animal cell lines, some products now in
clinical trials are being produced in the milk of transgenic animals (Chapter 5). Additionally,
plant-based transgenic expression systems may potentially come to the fore, particularly for the
production of oral vaccines (Chapter 5).
Interestingly, the fi rst generic biopharmaceuticals are already entering the market. Patent
protection for many fi rst-generation biopharmaceuticals (including recombinant human GH
(rhGH), insulin, EPO, interferon-
) and granulocyte-CSF (G-CSF)) has now/is now
coming to an end. Most of these drugs command an overall annual market value in excess of US $1
billion, rendering them attractive potential products for many biotechnology/pharmaceutical
companies. Companies already/soon producing generic biopharmaceuticals include Biopartners
(Switzerland), Genemedix (UK), Sicor and Ivax (USA), Congene and Microbix (Canada) and
BioGenerix (Germany). Genemedix, for example, secured approval for sale of a recombinant CSF
in China in 2001 and is also commencing the manufacture of recombinant EPO. Sicor currently
markets hGH and IFN-α in eastern Europe and various developing nations. A generic hGH also
gained approval in both Europe and the USA in 2006.
To date (mid 2006), no gene-therapy-based product has thus far been approved for general
medical use in the EU or USA, although one such product ('Gendicine'; Chapter 14) has been ap-
proved in China. Although gene therapy trials were initiated as far back as 1989, the results have
been disappointing. Many technical diffi culties remain in relation to, for example, gene delivery
and regulation of expression. Product effectiveness was not apparent in the majority of trials un-
dertaken and safety concerns have been raised in several trials.
Only one antisense-based product has been approved to date (in 1998) and, although several
such antisense agents continue to be clinically evaluated, it is unlikely that a large number of such
products will be approved over the next 3-4 years. Aptamers represent an additional emerging
class of nucleic-acid-based therapeutic. These are short DNA- or RNA-based sequences that adopt
a specifi c three-dimensional structure, enabling them to bind (and thereby inhibit) specifi c target
molecules. One such product (Macugen) has been approved to date. RNA interference (RNAi) rep-
resents a yet additional mechanism of achieving downregulation of gene expression (Chapter 14).
It shares many characteristics with antisense technology and, like antisense, provides a potential
means of treating medical conditions triggered or exacerbated by the inappropriate overexpression
of specifi c gene products. Despite the disappointing results thus far generated by nucleic-acid-based
products, future technical advances will almost certainly ensure the approval of gene therapy and
antisense-based products in the intermediate to longer term future.
Technological developments in areas such as genomics, proteomics and high-throughput
screening are also beginning to impact signifi cantly upon the early stages of drug development
(Chapter 4). By linking changes in gene/protein expression to various disease states, for example,
these technologies will identify new drug targets for such diseases. Many/most such targets will
themselves be proteins, and drugs will be designed/developed specifi cally to interact with. They
may be protein based or (more often) low molecular mass ligands.
Additional future innovations likely to impact upon pharmaceutical biotechnology include the
development of alternative product production systems, alternative methods of delivery and the
development of engineered cell-based therapies, particularly stem cell therapy. As mentioned pre-
viously, protein-based biotechnology products produced to date are produced in either microbial
α
(IFN-
α
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