The use of peptides and small proteins as potential therapeutic drugs is concomitant with the challenge of short half-life <i>in vivo</i>. To overcome this challenge, proteins and peptides can be conjugated or fused with other molecules, such as albumin, to increase serum half-life. In addition to the benefits of half-life extension, albumin-fusion constructs potentially offer the opportunity to use established process platforms. Since albumin typically constitutes a large portion of the fusion protein mass, it often dominates physiochemical characteristics. For a platform approach to be successful, the purification strategy must therefore leverage properties of the carrier protein. In this work, we describe a platform approach to purify albumin-fusion proteins using scalable techniques suitable for clinical or commercial manufacturing. The initial steps in the purification process were optimized to reduce process related impurities, such as host-cell proteins, DNA, and viruses. The final chromatography step was designed to control product related impurities including a non-potent oxidized variant. The process was scaled up to 500L bioreactor scale, where it demonstrated robust performance resulting in consistent yields and product quality. Lastly, the fusion protein process was tested using native albumin to illustrate its potential application as an albumin-fusion protein purification platform.

Platform approach to purification of albumin-fusion proteins

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.