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

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

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.

• Jezik: Angleški jezik
• Ključne besede: mAb, monoclonal antibody, formulation, aggregation
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: Str. 2623-2632
• Številčenje: Vol. 65, iss. 3
• PID: 20.500.12556/RUL-136958
• UDK: 577.322
• ISSN pri članku: 0022-2623
• DOI: 10.1021/acs.jmedchem.1c02010
• COBISS.SI-ID: 97795331
• Datum objave v RUL: 26.05.2022

Gradivo je del revije

• Naslov: Journal of medicinal chemistry
• Skrajšan naslov: J. med. chem.
• Založnik: American Chemical Society
• ISSN: 0022-2623
• COBISS.SI-ID: 25763328

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: mAb, monoklonska protitelesa, formulacije, agregacija

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0201
• Naslov: Fizikalna kemija

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: J1-1706
• Naslov: Stabilnost nove vrste kvadruplesov DNA (AGCGA) in njihovo prepoznavanje z nanotelesi