Biopharmaceutical benchmarks 2006.
The rate of biopharmaceutical approvals has leveled off, but some milestones bode well for the future.
Benchmarking↗
Biomedical subjects
Gary Walsh
Publications and source records attributed to Gary Walsh.
Post-translational modifications in the context of therapeutic proteins.
The majority of protein-based biopharmaceuticals approved or in clinical trials bear some form of post-translational modification (PTM), which can profoundly affect protein properties relevant to their therapeutic application. Whereas glycosylation represents the most common modification, additional PTMs, including carboxylation, hydroxylation, sulfation and amidation, are characteristic of some products. The relationship between structure and function is understood for many PTMs but remains incomplete for others, particularly in the case of complex PTMs, such as glycosylation. A better understanding of such structural-functional relationships will facilitate the development of second-generation products displaying a PTM profile engineered to optimize therapeutic usefulness.
Glycoproteins↗
Biopharmaceuticals: recent approvals and likely directions.
Some 160 biopharmaceuticals have now gained medical approval and several hundred are in the pipeline. Most are protein-based, although two nucleic acid-based products are now on the US/European market. An increasing proportion of approvals are engineered in some way and advances in alternative production systems and delivery methods will also likely impact upon the approvals profile over the remainder of this decade.
Biopharmaceutics↗
Scaling the biobusiness information mountain.
Explore the source record for details and available documents.
Biotechnology↗
Therapeutic insulins and their large-scale manufacture.
Biotechnological innovations over the past 25 years have underpinned the rapid development of a thriving biopharmaceutical sector. Therapeutic insulin remains one of the most commonly used products of pharmaceutical biotechnology and insulin-based products command annual global sales in excess of $4.5 billion. Innovations in its method of production and in particular the advent of engineered insulin analogues provide a fascinating insight into how scientific and technological advances have impacted upon the pharmaceutical biotechnology sector as a whole. Current insulin-based diabetes research is increasingly focused not on the insulin molecule per se, but upon areas such as the development of non-parenteral insulin delivery systems, as well as organ-/cell-based and gene therapy-based approaches to controlling the disease.
Amino Acid Sequence↗
Identification and characterization of a phytase of potential commercial interest.
Phytases catalyse the hydrolytic degradation of phytic acid and its salts and are added to monogastric animal feed to ameliorate the negative environmental and nutritional consequences of dietary phytate. Screening of 58 microbial strains identified a phytase produced by Rhizopus oligosporus ATCC 22959 that displayed physicochemical characteristics likely to render it of potential industrial interest. The 124 kDa enzyme was purified to homogeneity by anion exchange chromatography, gel filtration and chromatofocusing. The monomeric glycosylated enzyme (30.5% total carbohydrate) displayed maximum activity at 65 degrees C and pH 5.0. It displayed a Km of 10.4 microM, a Vmax of 1.32 nmols(-1) and a Kcat of 51 s(-1). It is acid tolerant, retaining full activity after incubation at pH 2.0 for 6h. HPLC analysis indicated the enzyme's ability to almost completely degrade phytate. Substrate specificity studies showed its ability to dephosphorylate several additional phosphorylated molecules. Activity was unaffected or moderately stimulated by a range of metal ions with only Ca2+ exerting a modest (13%) inhibitory effect. The enzyme is significantly more thermostable at 80 degrees C and retains a significantly greater proportion of maximal activity at physiological temperatures than do two commercial phytases tested for comparative purposes. This may render it of industrial interest.
6-Phytase↗
Second-generation biopharmaceuticals.
The majority of first generation biopharmaceuticals are unengineered murine monoclonal antibodies or simple replacement proteins displaying an identical amino acid sequence to a native human protein. While some such products continue to be approved, an increasing number of modern biopharmaceuticals are engineered, second-generation products. Engineering can entail alteration of amino acid sequence, alteration of the glycocomponent of a glycosylated protein, or the covalent attachment of chemical moieties such as polyethylene glycol. Engineering has been applied in order to alter a protein's immunological or pharmacokinetic profile, or in order to generate novel fusion products. Better understanding of the links between protein structure and function will underpin the development of an increasing number of engineered biopharmaceuticals in the future.
Animals↗
Collaborative design for automated DNA storage that allows for rapid, accurate, large-scale studies.
Genomics Collaborative, Inc., a division of Sera Care Life Sciences, Inc. (Cambridge, MA), is among the first commercial entities in the world to enable genetic research on an industrial scale via its Large Scale Global Repository, a biobank of human specimens collected for research purposes. With the demand for large-scale DNA studies increasing, decisions about the strategic direction of sample storage and collection must be made to create a sound plan to support continued demands for drug discovery. Reported here is the approach used by Genomics Collaborative to automate its DNA processing, storage, and retrieval.
Automation↗
Pharmaceutical biotechnology products approved within the European Union.
The manufacture of therapeutic proteins represented the first true industrial application of recombinant DNA technology. Thus far some 88 recombinant proteins/monoclonal antibody-based products have gained marketing approval within the European Union (EU). This represents 36% of all new drug approvals since the introduction of the new centralized European drug approval system in 1995. More recently, an increasing proportion of approved proteins are engineered, tailored to display altered pharmacokinetic profiles or reduced immunogenicity in man. Currently no nucleic acid-based products are approved in the EU. Technical innovations/milestones likely characterizing the biopharmaceutical industry within the next decade include approval of some products produced in transgenic systems, approval of some products administered by non-parenteral means, approval of at least some nucleic acid-based products and the identification of novel biopharmaceuticals/biopharmaceutical targets through discoveries in functional genomics and proteomics.
Biotechnology↗
Purification and characterization of extracellular phytase from Aspergillus niger ATCC 9142.
Extracellular phytase produced by Aspergillus niger ATCC 9142 was purified to homogeneity by employing an initial ultrafiltration step, followed by chromatography using ion exchange, gel filtration and chromatofocusing steps. The purified enzyme was an 84 kDa, monomeric protein. It possessed a temperature optimum of 65 degrees C, and a pH optimum of 5.0. Km and Vmax values of 100 microM and 7 nmol/s, respectively, were recorded and these values fall well within the range of those previously reported for microbial phytases. Substrate specificity studies indicated that, while the enzyme could hydrolyse a range of non-phytate-based phosphorylated substrates, its preferred substrate was phytate. Phytase activity was moderately stimulated in the presence of Mg2+, Mn2+, Cu2+, Cd2+, Hg2+, Zn2+ and F- ions. Activity was not significantly affected by Fe2- or Fe3- and was moderately inhibited by Ca2+. The enzyme displayed higher thermostability at 80 degrees C than did two commercial phytase products. Initial characterisation of the purified enzyme suggested that it could be a potential candidate for use as an animal feed supplement.
6-Phytase↗
Biopharmaceutical benchmarks--2003.
Explore the source record for details and available documents.
Benchmarking↗
Biopharmaceuticals and biotechnology medicines: an issue of nomenclature.
Over the past two decades terms such as 'biopharmaceuticals' and 'biotechnology medicines' have crept into the pharmaceutical vocabulary. Such terms often have different meanings for different people and it is perhaps time that they were more formally defined.
Antibodies, Monoclonal↗