A number of antibody drugs are currently in clinical development and 22 antibodies (including five diagnostic antibodies) have received FDA market approval in the last decade. A number of different technologies are now being used successfully to isolate potent therapeutic antibodies with minimal immunogenicity and improved safety. These include chimerisation (mouse/human antibodies), humanisation (complementarity-determining region [CDR] grafting), transgenic mice, phage display, ribosome display, and other emerging technologies. The phage and ribosome display technologies used at Cambridge Antibody Technology (CAT) are based on the physical linkage of gene to gene product which enables the recovery and enrichment of genetic material encoding the selected antibody…
Tag: <span>scale-up</span>
The developing biotechnology community may offer solutions and hope for recent world events that have focused attention on the vulnerability of the world’s population. Concerns about new pandemics have been raised by the emergence of new influenza strains and the re-emergence of older and even more highly virulent strains. In addition, there are fears that bioterrorism could involve agents such as anthrax or smallpox, and these threats become even more of a concern when you consider the increased mobility of such organisms via today’s commercial aviation. The ability of the biomedical community to respond rapidly to these shifting threats is more important than ever…
The baculovirus expression vector system, which is based on infecting insect cells with recombinant Autographa californica nuclear polyhedrosis virus (AcNPV), is one of the most commonly used eukaryotic expression systems aimed at producing functionally active mammalian proteins. It offers advantages such as high-level protein expression and post-translational processing capabilities that are extremely important to the biological activity of certain proteins. This system utilizes a strong promoter of the very late gene, polyhedrin, to drive heterologous protein overexpression. Nevertheless, in order to generate milligram amounts of recombinant proteins, cell culture often needs to be scaled up to as much as 25 liters….
Today concentrated efforts are underway to improve the bioactivity of therapeutic proteins with the aim of reducing: (i) the number and concentration of the applied doses of the therapeutic protein, (ii) undesired side effects, and (iii) the cost of a therapy. A very promising strategy is to optimise the glycosylation of these biotherapeutics. A novel expression platform, GlycoExpress™, has been developed to produce proteins with fully human glycosylation, optimised sialylation, and improved bioactivity…
It has been reported that the biotechnology-derived medicines area of the pharmaceutical industry led to 133 marketed entities with sales of $22 billion by the year 2001. By 2002, the therapeutic protein market had reached $32 billion, with biologics representing more than 50 percent of all drugs approved by FDA — up from a modest 16 percent in 1995. The biopharmaceutical market is predicted to grow to $50 billion by 2008. Currently, approximately 40 percent of biopharmaceutical products are in Phase I and Phase II clinical trials. It is anticipated that from 2003 to 2008 there will be a more than 45-fold increase in demand for access to product development facilities capable of supplying clinical material…
Proteins and their promise for revolutionizing drug discovery have come virtually full circle in just a few decades. The advent of genetic engineering and the emergence of early recombinant proteins such as insulin and interferon dramatically boosted the perceived value of proteins in pharmaceutical research and of protein drugs in particular. Although the lights dimmed somewhat on the promise of therapeutic proteins in subsequent years, more recent times have seen a resurgence of interest in proteins, particularly monoclonal antibodies. Perhaps most telling has been the dawn of the post-genomic era, which has cast a bright spotlight on proteins, long respected as the work-horses of the cell, for their usefulness in exploring cell function, unraveling biochemical pathways, understanding disease, and for their massive value as novel drug targets…
Neurodegenerative diseases such as Parkinson’s disease and multiple sclerosis, along with injuries such as stroke affect millions of individuals worldwide and costs healthcare systems billions of dollars each year in North America alone. The diseases result from the death of specific cell types within the central nervous system. Current treatment efforts have focused primarily on alleviating symptoms using pharmaceuticals. However, recent advances in our understanding of these conditions, coupled with advances in biology, genomics, transplantation, and biochemical engineering are making cell therapy (the transplantation of viable cells to replace dead cells) more attractive as a potential avenue of treatment…
The biopharmaceutical manufacturing sector is rapidly gearing up production capacity to satisfy the steadily escalating global demand for complex biologics to combat a number of treatable illnesses. Frequently, the biotherapeutics in demand are too complicated to be chemically synthesized and thus are beyond the reach of traditional pharmaceutical approaches. To effectively address this issue, these products must be developed and produced using viable and robust biological systems…
At the onset of modern-day biotechnology, products typically fell into two distinct categories, the traditional high volume, low value products (e.g. beer and industrial enzymes) that had come to characterize the biotechnology industry, and low volume, high cost products. Recombinant proteins, the result of technological advances in molecular biology, have come to typify these latter products. Recombinant protein therapeutics have been hugely successful, potentially outstripping production capacity and continue to drive much of the biotechnology. Meanwhile, many recombinant proteins, those characterized as research tools and reagents, are governed by a price-volume relationship typical of industrial enzymes. In a competitive environment, they are fast becoming commodities — price sensitive, packaged as kits, coupled to instrumentation, and relying on heavy marketing and brand recognition. Ominously, the advantage protein therapeutics have enjoyed with patent protection and regulatory constraints on production is being threatened as patents expire and competition from generics increases…