Since the first approval for human use of a recombinant protein therapeutic, this sector of the pharmaceutical market has grown rapidly. The first approved protein therapeutics were small, non-glycosylated proteins such as insulin and human growth hormone; they were produced in bacterial systems. With the advent of mammalian cell-based production systems, it became possible to produce more complex, glycosylated proteins for use as recombinant therapeutics…
Tag: <span>recombinant proteins</span>
In order to unravel new protein activities and functions, we have expressed and purified a large number of human proteins. We have chosen to study secreted proteins and the extra-cellular domains of putative single transmembrane domain-containing proteins. In order to retain the natural protein characteristics as far as possible, we have used a mammalian expression system. Human embryonic kidney (HEK293) cells were chosen as they have been shown to possess a high protein-secretory potential. The secreted proteins were expressed with a carboxy-terminal tag and purified by affinity chromatography. Each protein was produced at a routine scale from 500 ml cell cultures, and the secreted protein was purified from the culture supernatant…
With the continued growth of the biopharmaceutical market, the cell culture industry has seen a major shift away from the use of serum and other animal-derived supplements in the manufacture of biopharmaceuticals. Indeed, supporting guidance from the EMEA and FDA for the manufacture of biopharmaceuticals and medical devices encourages the use of “animal-free” components. The key driver for this can be attributed to the increased concern with contamination from adventitious agents such as transmissible encephalopathies…
The analytical characterization of recombinant protein therapeutic drug products has broadened to include the use of more sophisticated technologies. The expansion of technical abilities has translated into increasing the depth and breadth of our knowledge and understanding of the drug product intended for commercialization. With the availability of more precise methods, the regulatory expectations for understanding the characteristics of a protein therapeutic drug product are increasing. A thorough understanding of a therapeutic protein’s biochemical and biophysical characteristics is necessary to support investigational new drug (IND) applications and other drug regulatory filings…
Proteins are widely used in research, medicine and industry, but its extraction from their natural sources can be difficult, tedious and expensive. Therefore, a simple and inexpensive system that allows large-scale production of safe recombinant proteins will always be highly desirable. Traditional production systems that use microbial, insect and mammalian cell cultures have drawbacks, in terms of cost, scalability and product safety. Several studies have shown that molecular farming in plants has many practical, economic, and safety advantages as compared to these conventional methods. Thus, the use of plants for recombinant protein synthesis is gaining wide acceptance…
The biologics market, although difficult to estimate, is currently thought to be in excess of $20 billion. In recent years, the growth in the novel therapeutics market has continued to exceed all but the most optimistic of expectations. The number of products in early stage trials may already be over 1,000, with an estimated 40 or so additional products in the process of finally being released to the market. The biologics market is led by relatively few “blockbuster” drugs, but the breadth of novel products continues to expand. This has resulted in exciting times for clinicians but has resulted in concern related to the bottleneck of production capacities for these drugs, as well as the pressure from healthcare agencies to reduce the cost of goods…
Biopharmaceuticals are predicted to become the main driving force of the pharmaceutical market in the near future. Other than blockbuster products such as erythropoietin, an increasing number of approved recombinant therapeutic proteins are based on antibody technology (e.g., fusion proteins or monoclonal antibodies [MAbs]). In contrast to relatively simple products produced in Escherichia coli bacteria (e.g., insulin), proteins which require complex posttranslational modifications such as glycosylation have to be produced in eukaryotic cells. In this context, production systems have been dominated by mammalian cell culture. Nevertheless, alternative eukaryotic expression technologies based on yeast, insect cells, transgenic animals, or transgenic plants are under development. Plants are a particularly promising alternative to mammalian cell culture because of their excellent safety aspects and estimated cost-efficient upstream/cultivation processes. In addition, plants are well known for their ability to express biologically functional monoclonal antibodies. In comparison to the seed plants most widely used for transgenic protein expression — tobacco, corn, and rice — mosses provide unique, beneficial features…
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…
For more than a decade, transgenic plants have been investigated as alternatives to microbial, mammalian cell, and transgenic animal systems for recombinant protein production. The main advantages of using plants as “bioreactors” are that the cost of upstream production (i.e. biomass creation) is low; plants do not carry viruses and other pathogens dangerous to humans such as human immunodeficiency virus (HIV), prions, hepatitis viruses and so on; and as eukaryotes, plants are capable of producing bioactive proteins. Numerous recombinant proteins have been expressed in various plant hosts, and some recombinant proteins are in various stages of clinical trials…
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…