Albumin binding Nanofitins, a new scaffold to extend half-life of biologics - a case study with exenatide peptide.

Autor: Michot N; Sanofi, Biologics Research, Vitry sur Seine, 94430, France., Guyochin A; Sanofi, Biologics Research, Vitry sur Seine, 94430, France., Cinier M; Affilogic, Nantes 44200, France. Electronic address: mathieu@affilogic.com., Savignard C; Affilogic, Nantes 44200, France., Kitten O; Affilogic, Nantes 44200, France., Pascual MH; Sanofi, Drug Safety & Animal Research, Alfortville 94430, France., Pouzieux S; Sanofi, Integrated Drug Discovery, Vitry sur Seine, 94430, France., Ozoux ML; Sanofi, Drug Safety & Animal Research, Alfortville 94430, France., Verdier P; Sanofi, Drug Safety & Animal Research, Alfortville 94430, France., Vicat P; Sanofi, Drug Safety & Animal Research, Alfortville 94430, France., Dumas J; Sanofi, Biologics Research, Vitry sur Seine, 94430, France.
Jazyk: angličtina
Zdroj: Peptides [Peptides] 2022 Jun; Vol. 152, pp. 170760. Date of Electronic Publication: 2022 Feb 09.
DOI: 10.1016/j.peptides.2022.170760
Abstrakt: A new strategy of peptide half-life extension has been evaluated. We investigated libraries of a small and very stable protein scaffold called Nanofitin, capable of high affinity for protein targets. We have identified Nanofitins targeting Human and mouse Serum Albumin, which could significantly improve the pharmacokinetics of an active associated peptide, mobilizing the patient's own albumin without external source. To demonstrate the impact of this approach on half-life extension, a genetic fusion of an Exenatide peptide with an Albumin Binding Nanofitin (ABNF) was performed. Specific activity of Exenatide-ABNF was measured and unaffected by the fusion. In vivo mice results provided convincing data (t½ of 8 min for Exenatide peptide compared to 20 h for Exenatide-ABNF) with sustained pharmacological activity over 3 days. This study constitutes a proof-of-concept of in vivo half-life extension of a biologic using an ABNF. Besides, the absence of cysteine in the Nanofitin scaffold, which is therefore devoid of structuring disulfide bonds, allows manufacturing in microbial cost effective systems.
(Copyright © 2022. Published by Elsevier Inc.)
Databáze: MEDLINE
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