BPS 2024
Biopharmaceutical Manufacturing of Boehringer Ingelheims Next Generation Peptides
Alicia Engelbrecht
Post Doc Process Science, Project Lead, Boehringer Ingelheim RCV GmbH & Co KG.
ABSTRACT
Boehringer Ingelheim boasts a robust developmental pipeline and an expanding portfolio of peptides. Due to the speed, flexibility, and suitability for molecular design optimization, solid-phase peptide synthesis (SPPS) remains the preferred method for peptide synthesis during the internal research and initial development phase. This includes the incorporation of non-canonical amino acids and the addition of fatty acids for half-life extension. However, scaling up SPPS presents challenges such as process complexity, yield limitations, and the use of environmentally detrimental chemical solvents. Therefore, the potential of biotechnological production processes for cost-effective, sustainable, large-scale commercial peptide synthesis with reduced environmental impact is increasingly recognized.
To address these issues, we are exploring biotechnological production processes for large-scale commercial peptide synthesis. Such technologies include the application of a genetic toolbox for E. coli in recombinant peptide synthesis, particularly the expression tag-assisted Npro and CAPSON peptide expression technology. These tools have shown promise in improving expression solubility and facilitating high-level production of recombinant peptides in E. coli. The presentation will further explore the potential of the CAPSON technology in providing platform-based affinity purification. It will also emphasize the need for high-throughput systems to increase efficiency and reduce development timelines.
Yet, the complexity of chemically designed peptides necessitates a hybrid manufacturing strategy for modified peptides. This may involve the recombinant expression of larger peptide fragments and their fusion to a separate smaller building block via chemical or enzymatic ligation. Additional modification tools, such as half-life-extension or non-canonical amino acids ligation, and C-terminal amination, are integral to the success of such hybrid production approaches. This presentation delves into the potential of innovative technologies in overcoming the current challenges associated with recombinant peptide production.
BIO
Alicia Engelbrecht is a dedicated and accomplished scientist with a strong background in biotechnological microbiology and biopharmaceutical process development. demonstrating her deep understanding and expertise in these areas. She holds a Master’s degree in Microbiology and further pursued her passion for science by earning a PhD in Pharmaceutical Biology from the University of Tuebingen, Germany. Her research during her doctoral studies focused on natural product research and the biosynthesis of proteasome inhibitor molecules.
Since the beginning of 2022, Alicia has been serving as a PostDoc at Boehringer Ingelheim RCV in Vienna, specifically in the Development Operations Process Science Upstream department. In this role, she has been leading an internal development project within the matrix organization, focused on recombinant peptide production and modification processes for Boehringer Ingelheim’s pipeline peptides. This innovative work serves as an alternative approach to solid phase peptide synthesis, showcasing Boehringer Ingelheims commitment to advancing the field through novel approaches.