Discovery of compounds with viscosity-reducing effects on biopharmaceutical formulations with monoclonal antibodies

Proj, Matic (author), Zidar, Mitja (author), Lebar, Blaž (author), Strašek Benedik, Nika (author), Miličić, Goran (author), Žula, Aleš (author), Gobec, Stanislav (author)

For the development of concentrated monoclonal antibody formulations for subcutaneous administration, the main challenge is the high viscosity of the solutions. To compensate for this, viscosity reducing agents are commonly used as excipients. Here, we applied two computational chemistry approaches to discover new viscosity-reducing agents: fingerprint similarity searching, and physicochemical property filtering. In total, 94 compounds were selected and experimentally evaluated on two model monoclonal antibodies, which led to the discovery of 44 new viscosity-reducing agents. Analysis of the results showed that using a simple filter that selects only compounds with three or more charge groups is a good ‘rule of thumb’ for selecting potential viscosity-reducing agents for two model monoclonal antibody formulations.

• Language: English
• Keywords: viscosity, protein formulations, biopharmaceuticals, viscosity-reducing agents, computational screening
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: Str. 5420-5429
• Numbering: Vol. 20
• PID: 20.500.12556/RUL-153982
• UDC: 532.13+541.8
• ISSN on article: 2001-0370
• DOI: 10.1016/j.csbj.2022.09.035
• COBISS.SI-ID: 123845891
• Publication date in RUL: 17.01.2024

Record is a part of a journal

• Title: Computational and structural biotechnology journal
• Publisher: Elsevier, Research Network of Computational and Structural Biotechnology
• ISSN: 2001-0370
• COBISS.SI-ID: 5068826

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: viskoznost, proteinske formulacije, biofarmacevtski izdelki, sredstva za zmanjševanje viskoznosti, računalniško preverjanje