Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing
Alpha-fetoprotein (AFP) is a commercially valuable biopharmaceutical candidate for autoimmune indications. Transgenically-derived recombinant AFP has recently successfully completed a Phase Two clinical trial study for rheumatoid arthritis indications at Merrimack Pharmaceuticals (Cambridge, MA, USA...
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| Format: | Thesis |
| Language: | English |
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2011
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| Online Access: | https://hdl.handle.net/10356/43987 |
| _version_ | 1811688357570281472 |
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| author | Chen, Yu |
| author2 | Susanna Leong Su Jan |
| author_facet | Susanna Leong Su Jan Chen, Yu |
| author_sort | Chen, Yu |
| collection | NTU |
| description | Alpha-fetoprotein (AFP) is a commercially valuable biopharmaceutical candidate for autoimmune indications. Transgenically-derived recombinant AFP has recently successfully completed a Phase Two clinical trial study for rheumatoid arthritis indications at Merrimack Pharmaceuticals (Cambridge, MA, USA). The launch of this protein on market shelves in the future will subsequently demand cheaper second-generation product when product patent expires, thus necessitating new processes that can reduce product cost. The production of AFP as inclusion bodies (IBs) in Escherichia coli (E. coli) is advantageous for process-scale commercial manufacture due to speed, simplicity and cost reasons but conversion of the inactive protein aggregate into biologically active protein requires an efficient refolding step. The use of dilution refolding in previously reported recombinant human AFP (rhAFP) laboratory processes has resulted in low refolding yields, which negatively impacts the overall process yield and productivity. A superior refolding and bioprocessing route is clearly needed to facilitate efficient and rapid product delivery to market, if a commercial process for rhAFP is to be possible.
In this thesis, chromatography refolding was researched to address the poor refolding performance or rhAFP in previous ‘dilution refolding’-based rhAFP processes. |
| first_indexed | 2024-10-01T05:30:55Z |
| format | Thesis |
| id | ntu-10356/43987 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:30:55Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | ntu-10356/439872023-03-03T16:02:41Z Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing Chen, Yu Susanna Leong Su Jan School of Chemical and Biomedical Engineering DRNTU::Engineering::Chemical engineering::Biotechnological production Alpha-fetoprotein (AFP) is a commercially valuable biopharmaceutical candidate for autoimmune indications. Transgenically-derived recombinant AFP has recently successfully completed a Phase Two clinical trial study for rheumatoid arthritis indications at Merrimack Pharmaceuticals (Cambridge, MA, USA). The launch of this protein on market shelves in the future will subsequently demand cheaper second-generation product when product patent expires, thus necessitating new processes that can reduce product cost. The production of AFP as inclusion bodies (IBs) in Escherichia coli (E. coli) is advantageous for process-scale commercial manufacture due to speed, simplicity and cost reasons but conversion of the inactive protein aggregate into biologically active protein requires an efficient refolding step. The use of dilution refolding in previously reported recombinant human AFP (rhAFP) laboratory processes has resulted in low refolding yields, which negatively impacts the overall process yield and productivity. A superior refolding and bioprocessing route is clearly needed to facilitate efficient and rapid product delivery to market, if a commercial process for rhAFP is to be possible. In this thesis, chromatography refolding was researched to address the poor refolding performance or rhAFP in previous ‘dilution refolding’-based rhAFP processes. DOCTOR OF PHILOSOPHY (SCBE) 2011-05-18T04:18:44Z 2011-05-18T04:18:44Z 2011 2011 Thesis Chen, Y. (2011). Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/43987 10.32657/10356/43987 en 185 p. application/pdf |
| spellingShingle | DRNTU::Engineering::Chemical engineering::Biotechnological production Chen, Yu Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing |
| title | Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing |
| title_full | Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing |
| title_fullStr | Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing |
| title_full_unstemmed | Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing |
| title_short | Chromatography refolding of recombinant alpha-fetoprotein for high refolding productivity and intensified bioprocessing |
| title_sort | chromatography refolding of recombinant alpha fetoprotein for high refolding productivity and intensified bioprocessing |
| topic | DRNTU::Engineering::Chemical engineering::Biotechnological production |
| url | https://hdl.handle.net/10356/43987 |
| work_keys_str_mv | AT chenyu chromatographyrefoldingofrecombinantalphafetoproteinforhighrefoldingproductivityandintensifiedbioprocessing |