New approaches to high throughput protein isolation purification and concentration

Lead Research Organisation: University of Strathclyde
Department Name: Pure and Applied Chemistry


There is a new generation of medicines under development that are based on natural molecules such as proteins or DNA. These will potentially be safer and more effective than current medicines but they are much more difficult to manufacture. Generally proteins are made in cells by biotechnology methods that are similar to those used in the fermentation of beer and wine. However, separation of the pure protein from the rest of the cell is much more challenging than the harvesting of ethanol. In this project we will investigate a new separation process based on coating proteins on the surface of crystals. This technique is known to work well with pure proteins but here we will investigate if it can be applied to the complex mixtures produced when processing cells. The aim will be to find specific conditions where the target protein can be purified from the other proteins and other cell components. If successful the reseach could potentially help speed up the development and reduce the cost of protein based medicines.

Technical Summary

This project will investigate non-chromatographic methods for purifying proteins based on selective coprecipitation of the target in the form of protein coated microcrystals (PCMC). The resultant precipitated PCMC particles consist of protein immobilised on the surface of a crystalline excipient carrier and are stable for long-term storage. The techniqe is expected to be particularly useful for isolaton of complex protein assemblies not well suited to chromotography. We will investigate how coprecipitation compositions can be tuned to maximise selectivity and stability via changes to parameters such as excipient, solvent, pH and ionic strength. The scale-up potential of the process will be evaluated.
Description We discovered a novel mechanism for the crystallisation of small molecules such as amino-acids. This may lead to improved control over how pharmaceutical drugs are purified and formulated for delivery.
Exploitation Route They will be used by the pharmaceutical and chemical industry to improve crystallisation processes
Sectors Pharmaceuticals and Medical Biotechnology

Description They have been used to guide process development at an SME
First Year Of Impact 2012
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

Description XstalBio R&D 
Organisation Xstalbio Limited
Country United Kingdom 
Sector Private 
PI Contribution This grant provided useful insights into the mechanisms of PCMC formation and XstalBio were able to utilise these to improve their manufacturing processes for producing dry powders of therapeutic proteins.
Collaborator Contribution XstalBio were an end-user of the knowledge generated by this grant
Impact An improved manufacturing process for dry powder formulations of therapeutic proteins
Description The present invention relates to the provision of a novel method for preparing dry amorphous precipitated protein particles. In particular to a method provides amorphous precipitated protein particles suitable for use in dry protein formulations which can be reconstituted to provide clear, foam free concentrated protein solutions. 
IP Reference WO2013093524 
Protection Patent application published
Year Protection Granted 2013
Licensed Yes
Impact This technology is currently being assessed by a top-ten pharma company for use as platform for storing therapeutic proteins as dry powder API
Company Name Xstalbio Ltd 
Description XstalBio specialises in formulation and delivery of therapeutic proteins, biopharmaceuticals and vaccines 
Year Established 2004 
Impact XstalBio has developed and patented disruptive platform technology that will impact on how the next generation of biologic medicines and vaccines are administered resulting in improved patient convenience and better compliance.