Ophthalmic disorders are a group of diseases with a rapidly increasing frequency associated with an increase in the aged population. Patients with potentially blinding diseases have become one of the largest segments of the healthcare field, with more than 50 million patients in the United States alone. Their sight is threatened by diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, or retinitis pigmentosa (RP). Until recently, there were essentially no effective treatment options to halt the progression of chronic, potentially blinding diseases. Biotechnological advances have resulted in the development of a variety of promising new protein factors that, if delivered to diseased cells of the retina, hold promise for treatment by interrupting or reversing the disease process…
Tag: <span>therapeutic proteins</span>
The Intraocular Delivery of Neuroprotective Factors to the Retina Using Encapsulated Cell Technology
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…
The use of plants as protein expression hosts for human therapeutic proteins is emerging as a safe and cost-effective alternative to microbial and mammalian cell culture. Pharmaceutical protein production is typically carried out in microbes and mammalian cell culture because of their high production potential and/or ability to produce complex eukaryotic proteins. However, immense costs are typically required for production facilities to support their growth. To offset these costs, companies usually build and expand a production facility over several years. In fact, it has been predicted that the demand for high-value pharmaceuticals produced by cell culture will quickly surpass the ability of pharmaceutical companies to produce them…
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…
lation components that stabilize the molecule in order to provide the desired product storage stability. Generally, an aqueous formulation is preferred; however, the instability of proteins, both physical (e.g. aggregation) and chemical (e.g. deamidation and oxidation), often necessitates the development of lyophilized formulations. In these formulations, selection of the appropriate stabilizing cryoprotectants, lyoprotectants, and bulking agents is critical. Accelerated stability studies are typically used to evaluate the effect of a single factor at a time in order to identify the optimum pH, buffer, and stabilizing excipients. This approach is limited in that many independent time-consuming experiments must be run, the results are obtained only at the evaluated set points, and additional experiments are required to assess potential interactions between the evaluated factors…
Recombinant monoclonal antibodies (rMAbs) are the predominant biotherapeutic protein under development today. FDA requires the structure characterization if rMAbs and other recombinant proteins to grant marketing approval. Characterizing such complex, inherently heterogeneous molecules is a significant analytical challenge that requires a broad array of physico-chemical tests. This article reports the use of reversed phase high-performance liquid chromatography (RP-HPLC) with on-line electrospray ionization mass spectrometry (ESI-MS) to rapidly determine the glycoform composition and the heavy chain C-terminal lysine heterogeneity of an intact rMAb. In addition, a novel multidimensional chromatographic platform was developed to investigate the two-dimensional, size exclusion chromatography (HPSEC) separation of the rMAb followed by RP-HPLC (HPSEC-RP-HPLC) with on-line ESI-MS analysis. Such analyses can characterize, identify, and confirm the structure of an intact rMAb…
Monoclonal antibodies constitute a significant percentage of the protein-based therapeutic molecules currently in clinical trials. The broad applicability and proven commercial success for this class of molecules suggest a larger future market potential. The current biopharmaceutical manufacturing capacity is widely anticipated to be a rate-limiting factor in the growth of the biotech sector. Because antibody therapeutics represent such a large part of this market, and because the therapeutic dosages of antibodies tend to be greater than most biopharmaceuticals, there is an immediate need for novel antibody manufacturing approaches that deliver significantly greater productivity…
Over 25 years have elapsed since Kohler and Milstein electrified the immunology community with their article describing the reliable preparation of monoclonal antibodies (MAbs) by fusing immune splencytes with immortalized myeloma cells. This discovery not only garnered the pair of scientists a Nobel Prize, but also led to the development of a technology which has yielded a number of important therapeutic, prophylactic, and diagnostic products for in vivo human use, and hundreds of in vitro diagnostic products. Some of these products proved to be significant in meeting previously unmet medical needs, and a few have been commercial successes. But the path, from Kohler and Milstein’s discovery to commercial products, was discontinuous and a bit bumpy, and the technology continues to evolve…
More than 130 drug and vaccine approvals for 95 entities over the last 20 years have generated roughly $30 billion in revenue for the biotech industry. The vast majority of this revenue comes from 30 proteins that have manufacturing bottlenecks resulting from the complexities of consistent protein production. The lag times involved in constructing mammalian cell fermentation facilities keeps supply of immensely successful high-volume drugs like Enbrel, Rituxan, and Remicade well below estimated demand. In other cases, the complexities of peptide synthesis threaten the potential of soon-to-be-launched or recently approved drugs like Fuzeon. The Pharmaceutical Research and Manufacturers of America (PhRMA) has documented more than 371 new biotech drugs in development, supporting the view that demand for many biopharmaceuticals will continue to outstrip supply. That number does not include the multitude of biotech drugs still in research stages…