4.7 Review

Building better biobetters: From fundamentals to industrial application

Journal

DRUG DISCOVERY TODAY
Volume 27, Issue 1, Pages 65-81

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2021.08.009

Keywords

Biobetter; Protein engineering; PEGylation; Glycoengineering; Biodegradable polymer; Fusion protein

Funding

  1. Coordination of Superior Level Staff Improvement (CAPES/Brazil) [001]
  2. State of Sao Paulo Research Foundation (FAPESP/Brazil) [2016/22065-5]
  3. National Council for Scientific and Technological Development (CNPq/Brazil) [301832/20170]
  4. Portuguese Foundation for Science and Technology/MCTES [UIDB/50011/2020, UIDP/50011/2020]
  5. FAPESP [2018/25994-2]

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This article explores the concept and advantages of biobetters, as well as current methods and trends for improving biological drugs, ranging from glycosylation to bioconjugation. Research is ongoing to investigate novel polymers and innovative genetic engineering techniques for drug improvement.
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 were explored as well as current market trends, legislation and future perspectives.

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