Building better biobetters: From fundamentals to industrial application

Karin M Torres-Obreque; Giovanna P Meneguetti; Jorge J Muso-Cachumba; Valker A Feitosa; João H P M Santos; Sónia P M Ventura; Carlota O Rangel-Yagui

doi:10.1016/j.drudis.2021.08.009

Building better biobetters: From fundamentals to industrial application

Drug Discov Today. 2022 Jan;27(1):65-81. doi: 10.1016/j.drudis.2021.08.009. Epub 2021 Aug 28.

Authors

Karin M Torres-Obreque¹, Giovanna P Meneguetti², Jorge J Muso-Cachumba¹, Valker A Feitosa², João H P M Santos³, Sónia P M Ventura⁴, Carlota O Rangel-Yagui⁵

Affiliations

¹ Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
² Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; Bionanomanufacturing Center, Institute for Technological Research (IPT), São Paulo, Brazil.
³ Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil; CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
⁴ CICECO-Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, Aveiro, Portugal.
⁵ Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: corangel@usp.br.

PMID: 34461236
DOI: 10.1016/j.drudis.2021.08.009

Abstract

Biological drugs or biopharmaceuticals off patent open a large market for biosimilars and biobetters, follow-on biologics. Biobetters, in particular, are new drugs designed from existing ones with improved properties such as higher selectivity, stability, half-life and/or lower toxicity/immunogenicity. Glycosylation is one of the most used strategies to improve biological drugs, nonetheless bioconjugation is an additional alternative and refers to the covalent attachment of polymers to biological drugs. Extensive research on novel polymers is underway, nonetheless PEGylation is still the best alternative with the longest clinical track record. Innovative trends based on genetic engineering techniques such as fusion proteins and PASylation are also promising. In this review, all these alternatives wereexplored as well as current market trends, legislation and future perspectives.

Keywords: Biobetter; Biodegradable polymer; Fusion protein; Glycoengineering; PEGylation; Protein engineering.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Biological Products* / pharmacology
Biological Products* / standards
Biosimilar Pharmaceuticals* / pharmacology
Biosimilar Pharmaceuticals* / standards
Drug Therapy / trends
Humans
Metabolic Engineering / methods
Protein Engineering / methods
Quality Improvement

Substances

Biological Products
Biosimilar Pharmaceuticals