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, GlycoExpressâ˘, has been developed to produce proteins with fully human glycosylation, optimised sialylation, and improved bioactivity…
Tag: <span>expression</span>
The human protein kinase superfamily is one of the largest and most important families of enzymes. More than 500 distinct kinases, classified in about 20 families on the basis of their primary structure similarity, have been identified to date. Protein kinases regulate a variety of biochemical pathways in cells through phosphotransfer reactions, playing pivotal roles in most signaling and regulatory processes, such as gene expression, proliferation, cell motility, and angiogenesis. Deregulation and/or mutational modification of protein kinase activity, leading to aberrant protein phosphorylation, is implicated in a variety of diseases, particularly cancer, making protein kinases important drug targets. A number of specific protein kinase inhibitors has been developed recently and more than 30 compounds are currently in clinical development or on the market. Many of these inhibitors are small-molecule compounds that compete with ATP for the highly conserved ATP binding site of the kinases. The development of highly selective and potent ATP-competitive inhibitors is driven by structure-activity relationship (SAR) studies, with X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy playing an important role in the understanding of the mechanism of inhibitor binding to the active or inactive forms of protein kinases…
Process development is an investment. As with a personal retirement plan, the importance of making the investment is not in question, yet strategies for when, how much, and where to invest in process development vary significantly from company to company. For a personal retirement plan, the answers to these questions are straightforward: invest as early as you can and as much as you can, and take less risk the closer you get to retirement. This would also be sound advice for investing in process development (substituting âBLA filingâ for âretirementâ) were it not for two complicating factors. First, the majority of biotherapeutics that enter the clinic fail to make it to the market. This makes a large, early investment in process development less attractive. Second, there is extreme pressure to get into the clinic, and subsequently onto the market, as quickly as possible, minimizing the time available for process development…
G protein-coupled receptors (GPCRs) comprise a âsuperfamilyâ of cell surface receptors that play a prominent role in cell signalling and are classified into more than 100 subfamilies according to sequence, ligand structure, and receptor function. They are cell surface receptor proteins with seven transmembrane domains which transduce extracellular signals to the interior of cells through heterotrimeric G proteins. GPCRsâ exposure at the exterior cell surface and strong role in cell regulation has provided a rich target family for small compound therapeutics. Of the estimated 35,000 genes in the human genome, approximately 750 encode for GPCRs; half likely encoding sensory receptors, the remaining half representing potential drug targets. Only about 30 of these potential targets are currently modulated by existing pharmaceuticals with approximately 400 remaining potential pharmaceutical targets for validation…
Organizations developing biopharmaceuticals are often faced with the challenge of developing, as rapidly as possible, a production system for a recombinant protein or antibody intended for use in clinical trials. For expression of antibodies and other proteins with complex post-translational modifications, Chinese hamster ovary (CHO) cells are often the host of choice. However, isolation of CHO cell lines producing even moderate levels of a protein of interest is usually a lengthy process due to the need for at least one and usually several gene amplification steps. Gene amplification, which is usually accomplished through the dihydrofolate reductase (dhfr)/methotrexate system, is a requirement for most CHO expression vectors because the absolute expression level from each copy of an integrated expression plasmid is generally very low…