Project: Yeast based platform for glycoengineered therapeutic proteins
One of the biggest opportunity areas in the protein therapeutics market is biopharmaceuticals (or biologics) which are expected to create a multi-billion dollar market in future. The pharmaceutical contract research and manufacturing market is expected to grow at an unmatched rate on account of high cost factor._x000D_About 70% of identified therapeutic proteins are glycosylated. Their production is carried out COly in mammalian cells such as CHO, as they are the only cells which naturally produce the glycosylation profile compatible with Human._x000D_The cost of this technological approach is important for at least three reasons, facilities, operating costs and finally the quality control necessary for the marketing of the batches produced._x000D_There is also a hidden cost: the risk. Indeed, the production with this type of eukaryotic cells is subject to contamination potentially very dangerous for the patient implying a complete cessation of production with dramatic consequences both in human terms for access to patient care as economically for the company concerned. _x000D_Some alternatives to this expression system have appeared over the past decade, partly because of advances in glycobiology and glycomics._x000D_The analytical methods more efficient and affordable also allowed the emergence of several actors, from producers of expression systems to service companies for glycan analysis._x000D_Plants, mammalian cells and primary eukaryotic organisms such as yeast and fungus are being developed for the market with their own advantages and disadvantages._x000D_The yeast is probably the oldest and the most widely used organism in biotechnology. So when the first company in this area - GlycoFi - has published the first glycosylated proteins in yeast, the largest global company Merck & Co has made its acquisition. The glycosylation is a critical success factor for therapeutic proteins by influencing pharmacokinetics, pharmacodistribution, solubility, stability and receptor binding. Glycosylation patterns of therapeutic proteins depend on the production process chosen (producing cells, manufacturing design etc.) and play a key role in their biological activity._x000D_The bioproduction in yeast is more economical. In addition, the risk of viral contamination does not exist, giving it an obvious interest in security. Since then, the interest of industry for this organism has accelerated and companies such as Novozymes and Lonza (CMO) or Novartis and Merck Serono have invested in this scope. _x000D_Glycode is a biotechnology company which aims at becoming a leader in the field of protein glycosylation. The company has developed proprietary innovative and powerful technologies, GlycodExpress™ and YACExpress™, which consist of a bank of yeast strains genetically optimized for the production of recombinant therapeutic glycoproteins. These strains have been genetically glycoengineered to synthesize fully humanized N-glycans. Different yeast strains with different glycoforms production have been developed at the bench scale. The goal of the project is the validation of these innovative and powerful technologies by studying two different model protein produced in different glycoengineered yeast strains at the industrial scale, and assess the pharmaceutical bioproduction market. _x000D_Glucocerebrosidase is widely used worldwide for disease Gaucher patients and the recent contamination issue of Genzyme has emphasized the need of an alternative production solution. _x000D_As the patent on the drug will expire on next year, there is a large market to address in despite of the competition. _x000D_Interferon Beta for SEP does rank at the third place in term of worldwide revenue for Biological drugs. The last development on the molecules have concerned an extended half-life with pegylation. There is a particular interest to screen different glycosylation isoforms to improve the molecule properties in term of toxicity, efficacy and cost of production. _x000D__x000D_Relying upon the human-like glycosylation in yeast and the biopharmaceutical production in yeast from Glycode and Eurogentec respectively, the scope for the collaboration is to:_x000D_o Evaluate and improve the performance of the Glycode’s strains in processes developed by Eurogentec to manufacture glycosylated proteins at clinical scale;_x000D_o Establish an optimized and ready-to-use manufacturing technology platform (strain characterisation, fermentation, extraction, purification, characterization of the glycosylated protein);_x000D_o Initiate a co-marketing effort for the promotion of the technology and the two model proteins.
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Acronym
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Therap'Yeast
(Reference Number: 6998)
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Duration
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01/02/2012 - 31/01/2015
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Project Topic
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Validation and industrialization of a glycoengineered yeast based platform dedicated to high quality protein production such as antibodies and cytokines, at lower costs._x000D_ Two high potential market “biobetters” harboring basic to complex N-glycans structures will be developed.
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Network
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Eurostars
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Call
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Eurostars Cut-Off 7
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Project partner
