Proteins Against Aggregation

Although protein based therapeutics is the fastest growing sector of the pharmaceutical industry, production costs remain incredibly high and rapid commercialization of new protein drug candidates are not being fully realized due to the presence of many barriers, namely the physical and chemical instabilities of proteins. Of these degradation pathways, protein aggregation is arguably the most common and troubling manifestation of protein instability, occurring in almost all phases of development. Protein aggregates are usually nonnative in structure, may exhibit reduced biological activity, and can remain soluble and/or precipitate from solution. In addition to reducing efficacy, if administered to a patient, aggregates can cause adverse reactions, such as immune response, sensitization, or even anaphylactic shock. Therefore, if even a small amount of aggregates form during formulation or storage, a product can be rendered unacceptable. Moreover, for the practical application of traditional and novel drug delivery techniques, protein based therapeutics must be formulated at relatively high concentrations and must remain stable for extended periods of time. The structural differences among various proteins are s