Half-life extension using serum albumin-binding DARPin® domains

Protein Engineering, Design & Selection : PEDS
Daniel SteinerH Kaspar Binz

Abstract

A long systemic half-life is key for therapeutic proteins. To that end we have generated serum albumin-binding designed ankyrin repeat domains. These domains bind serum albumin of different species with nanomolar affinities, and have significantly improved pharmacokinetic properties both in mouse and cynomolgus monkey compared to non-serum albumin-binding DARPin® domains. In addition, they exhibit high thermal stability and long storage stability, which is an essential feature for their use in drug development. Covalently linking a serum albumin-binding DARPin® domain to domains with other target specificities results in improvements of multiple orders of magnitude in exposure and terminal half-life, both in mouse and cynomolgus monkey. Pharmacokinetic assessment of such constructs revealed terminal half-life values ranging from 27 h to 80 h in mouse, and from 2.6 days to 20 days in cynomolgus monkey. Extrapolation by allometric scaling on these findings suggests terminal half-life values of 5-50 days in human, indicating that pharmacokinetic properties in the range of monoclonal antibodies can be achieved with DARPin® drug candidates. Such serum albumin-binding DARPin® domains are thus valuable tools for the generation of mult...Continue Reading

References

Nov 1, 1990·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R M Ings
Jan 1, 1985·Advances in Protein Chemistry·T Peters
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·J HanesA Plückthun
Jul 18, 2002·The Journal of Biological Chemistry·Mark S DennisLisa A Damico
Jan 23, 2003·Protein Engineering·Richard A George, Jaap Heringa
Feb 5, 2003·The Journal of Experimental Medicine·Chaity ChaudhuryClark L Anderson
Mar 4, 2003·Nature Reviews. Drug Discovery·J Milton Harris, Robert B Chess
Apr 21, 2004·Nature Biotechnology·H Kaspar BinzAndreas Plückthun
Oct 8, 2005·Nature Biotechnology·H Kaspar BinzAndreas Plückthun
Apr 20, 2006·Protein Engineering, Design & Selection : PEDS·Allen NguyenMark S Dennis
Mar 1, 2007·Nature Methods·Christian ZahndAndreas Plückthun
Jan 1, 2008·Journal of Molecular Biology·Svava K WetzelAndreas Plückthun
Apr 5, 2008·Protein Engineering, Design & Selection : PEDS·Lucy J HoltIan M Tomlinson
May 24, 2008·Protein Engineering, Design & Selection : PEDS·Andreas JonssonPer-Ake Nygren
Jul 16, 2008·Drug Discovery Today·Michael T StumppPatrick Amstutz
Oct 20, 2009·Journal of Clinical Pharmacology·Jie LingHugh M Davis
Nov 17, 2009·Nature Biotechnology·Volker SchellenbergerWillem P C Stemmer
Jan 23, 2010·Protein Engineering, Design & Selection : PEDS·Adam WalkerChris Herring
Sep 8, 2010·Protein Engineering, Design & Selection : PEDS·Jonas HoppRoland E Kontermann
Oct 3, 2012·Advanced Drug Delivery Reviews·Xiaoying ChenWei-Chiang Shen
Mar 27, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Anna OrlovaVladimir Tolmachev
Mar 27, 2013·Nature Reviews. Nephrology·Marcus J Moeller, Verena Tenten
Apr 1, 2014·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Robert LiebnerAhmed Besheer
Dec 19, 2014·Expert Opinion on Drug Delivery·Darrell Sleep
Jan 7, 2015·Annual Review of Pharmacology and Toxicology·Andreas Plückthun
Jul 17, 2015·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·William R Strohl
Mar 12, 2016·Expert Opinion on Biological Therapy·Roland E Kontermann
Jun 24, 2016·Scientific Reports·Diego M RuizMario T Murakami
Oct 18, 2016·MAbs·Arvind SivasubramanianYasmina Abdiche

❮ Previous
Next ❯

Citations

Feb 8, 2019·Current Pharmaceutical Design·Huanbo TanPeijian Zou
Aug 10, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Alexander V GrishinVladimir G Lunin
Apr 24, 2019·The Journal of Pharmacology and Experimental Therapeutics·A R Satvik IyengarAbhay H Pande
Apr 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Henk van FaassenGreg Hussack
Jun 26, 2020·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Michael T StumppH Kaspar Binz
Oct 4, 2018·Scientific Reports·Jeannette NilsenJan Terje Andersen
Jul 8, 2020·Cancers·Dirk van den BrandWouter P R Verdurmen
Jan 10, 2020·Annual Review of Pharmacology and Toxicology·Michaela Gebauer, Arne Skerra
Oct 25, 2020·Pharmaceutics·Nkiruka IbeanuSahar Awwad
Feb 14, 2021·International Journal of Molecular Sciences·Yuki KawataKiyotaka Fujita
May 1, 2021·Pharmaceutics·Camilo TorresWouter P R Verdurmen
May 16, 2021·The Journal of Allergy and Clinical Immunology·Luke F PenningtonTheodore S Jardetzky
Jun 3, 2021·International Journal of Molecular Sciences·Olga ShilovaSergey Deyev
Aug 28, 2021·International Journal of Pharmaceutics·Huanbo TanPeijian Zou

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.