Advances in the Purification of Antisense Oligonucleotides
27th October 2021 | 10:00am EST | Robert Gronke, Ph.D., Senior Principal Scientist, Technical Development, Biogen and John Cyganowski, Director of Customer Application, Downstream, Merck |WATCH FOR FREE
Following on the commercial success of Spinraza® (the first successful treatment for patients with spinal muscular atrophy), antisense oligonucleotides (ASO) are now an important part of Biogen’s drug portfolio that enables us to better treat neuromuscular diseases. Development of the ASO process employs orthogonal chromatography to achieve industry high purities while maintaining good yield along with detritylation and UF/DF steps. This purification platform process is all aqueous based on green chemistry principles that easily fit into our existing biologics manufacturing facilities. To date, we now leverage this ASO platform process to purify 13+ ASO molecules that contain different sequences, chemistries, and most recently incorporating conjugation reactions.
Having completed process characterization for our lead ASO candidate, we have achieved a greater understanding of the process, its capabilities to clear process and product related impurities, and understand the mechanisms that control the chromatography. On the manufacturing side, Biogen recently completed at-scale PPQ validation batches of an ASO clinical candidate. Case studies and learnings will be presented on results from characterization studies and PPQ batches.
Presented by Robert Gronke, PhD, Senior Principal Scientist, Technical Development, Biogen
Robert Gronke is a Senior Principal Scientist in the Antisense Oligonucleotide department at Biogen, Inc. For the past 31 years, he’s been involved in the purification process development, CMC team leadership, regulatory liaison, and new technology assessments for recombinant biopharmaceuticals including Biogen’s commercial products AVONEX (Interferon Beta-1a), a serum-free version of AVONEX, PLEGRIDY (PEG IFN Beta-1a), BENEPALI (Enbrel biosimilar), SPINRAZA (SMA antisense oligonucleotide), APROLIX (Factor IX-Fc), and AMEVIVE (glycosylated fusion protein), along with more than 20 clinical products including monoclonal antibodies, fusion proteins, glycoproteins, antisense oligonucleotides, and conjugates. Rob currently manages a group of 5 associate scientists.
Prior to joining Biogen, Inc., Dr. Gronke was a post-doctoral fellow in the Pharmacology Department at Merck Sharp & Dohme Research Laboratories in West Point, Pennsylvania. He received his Ph.D. degree in Biochemistry from the University of Kansas, Lawrence Kansas. Prior to receiving his Ph.D., he was employed as a Research Associate at the University of Illinois, Chicago. Dr. Gronke received a BS degree in Biochemistry from Northern Illinois University, DeKalb, Illinois.
Followed by John Cyganowski, Director of Customer Application, Downstream, Merck
John Cyganowski has 29 years of experience in Biotechnology focusing on Downstream Purification. The Customer Applications Downstream team are a multidisciplinary commercial team of application, industry and Go-To-Market experts that collaborate with customers to develop integrated solutions with Merck’s capabilities and portfolio, to help solve their BioProduction challenges. John has specialized in Tangential Flow Filtration, Aseptic Processing, Clarification and Viral Clearance both in Process Development roles and in Manufacturing Science and Technology. He was an instructor of Tangential Flow Filtration for the ASME course, “Bio-Downstream Process Design & Economics”, (PD481). John co-authored the Recovery and System Design chapters in “Lutz, Herb, Ultrafiltration for Bioprocessing (Woodhead Publishing Series in Biomedicine), Copyright 2015, H. Lutz, ISBN 978-1907568466. John holds a Bachelor of Science in Chemical Engineering degree from Northeastern University in Boston.