Rational optimization of a monoclonal antibody improves the aggregation propensity and enhances the CMC properties along the entire pharmaceutical process chain.

In silico CMC properties antibody engineering bioinformatic biotherapeutic development pharmaceutical industry

Journal

mAbs
ISSN: 1942-0870
Titre abrégé: MAbs
Pays: United States
ID NLM: 101479829

Informations de publication

Date de publication:
Historique:
entrez: 14 7 2020
pubmed: 14 7 2020
medline: 6 7 2021
Statut: ppublish

Résumé

The discovery of therapeutic monoclonal antibodies (mAbs) primarily focuses on their biological activity favoring the selection of highly potent drug candidates. These candidates, however, may have physical or chemical attributes that lead to unfavorable chemistry, manufacturing, and control (CMC) properties, such as low product titers, conformational and colloidal instabilities, or poor solubility, which can hamper or even prevent development and manufacturing. Hence, there is an urgent need to consider the developability of mAb candidates during lead identification and optimization. This work provides a comprehensive proof of concept study for the significantly improved developability of a mAb variant that was optimized with the help of sophisticated

Identifiants

pubmed: 32658605
doi: 10.1080/19420862.2020.1787121
pmc: PMC7531517
doi:

Substances chimiques

Antibodies, Monoclonal 0
Protein Aggregates 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Video-Audio Media

Langues

eng

Sous-ensembles de citation

IM

Pagination

1787121

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Auteurs

Joschka Bauer (J)

Early Stage Pharmaceutical Development, Pharmaceutical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach/Riss, Germany.

Sven Mathias (S)

Institute of Applied Biotechnology, University of Applied Sciences Biberach , Biberach/Riss, Germany.
Early Stage Bioprocess Development, Bioprocess Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach/Riss, Germany.

Sebastian Kube (S)

Early Stage Pharmaceutical Development, Pharmaceutical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach/Riss, Germany.

Kerstin Otte (K)

Institute of Applied Biotechnology, University of Applied Sciences Biberach , Biberach/Riss, Germany.

Patrick Garidel (P)

Early Stage Pharmaceutical Development, Pharmaceutical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach/Riss, Germany.

Martin Gamer (M)

Early Stage Bioprocess Development, Bioprocess Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach/Riss, Germany.

Michaela Blech (M)

Early Stage Pharmaceutical Development, Pharmaceutical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach/Riss, Germany.

Simon Fischer (S)

Cell Line Development, Bioprocess Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach/Riss, Germany.

Anne R Karow-Zwick (AR)

Early Stage Pharmaceutical Development, Pharmaceutical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co. KG , Biberach/Riss, Germany.

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