Aggregation time machine : a platform for the prediction and optimization of long-term antibody stability using short-term kinetic analysis

Bunc, Marko (author), Hadži, San (author), Graf, Christian (author), Bončina, Matjaž (author), Lah, Jurij (author)

Monoclonal antibodies are the fastest growing class of therapeutics. However, aggregation limits their shelf life and can lead to adverse immune responses. Assessment and optimization of the long-term antibody stability are therefore key challenges in the biologic drug development. Here, we present a platform based on the analysis of temperature-dependent aggregation data that can dramatically shorten the assessment of the long-term aggregation stability and thus accelerate the optimization of antibody formulations. For a set of antibodies used in the therapeutic areas from oncology to rheumatology and osteoporosis, we obtain an accurate prediction of aggregate fractions for up to three years using the data obtained on a much shorter time scale. Significantly, the strategy combining kinetic and thermodynamic analysis not only contributes to a better understanding of the molecular mechanisms of antibody aggregation but has already proven to be very effective in the development and production of biological therapeutics.

• Language: English
• Keywords: mAb, monoclonal antibody, formulation, aggregation
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: Str. 2623-2632
• Numbering: Vol. 65, iss. 3
• PID: 20.500.12556/RUL-136958
• UDC: 577.322
• ISSN on article: 0022-2623
• DOI: 10.1021/acs.jmedchem.1c02010
• COBISS.SI-ID: 97795331
• Publication date in RUL: 26.05.2022

Record is a part of a journal

• Title: Journal of medicinal chemistry
• Shortened title: J. med. chem.
• Publisher: American Chemical Society
• ISSN: 0022-2623
• COBISS.SI-ID: 25763328

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: mAb, monoklonska protitelesa, formulacije, agregacija

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0201
• Name: Fizikalna kemija

• Funder: ARRS - Slovenian Research Agency
• Project number: J1-1706
• Name: Stabilnost nove vrste kvadruplesov DNA (AGCGA) in njihovo prepoznavanje z nanotelesi