Exendins and exendin analogs for diabetic therapy: a patent review (2012-2015)

ABSTRACT

Introduction: Since exendin-4 (exenatide) was approved for diabetes therapy in 2005, several exendin analogs have been developed for the treatment of type 2 diabetes mellitus. As exenatide is a relatively short-acting injectable agent, major approaches have focused on developing long-acting exendin analogs to improve patient compliance and convenience.

Areas covered: In this review, the authors report on patents related to exendins and exendin analogs from 2012 to 2015. The patents have been divided into three categories based on the technologies used to develop the new chemical entities: 1) chemical bioconjugate analogs; 2) recombinant fusion protein analogs; and 3) multifunctional peptide analogs.

Expert opinion: Recently, research on exendins and their analogs has grown significantly, leading to the development of long-acting analogs and multifunctional peptides. While long-acting injectable agents are still the major products in the pharmaceutical industry, a significant growth is expected in the development of orally available exendins.

KEYWORDS:

• Diabetes
• exendins
• exendin analogs
• glucagon-like peptide-1 receptor agonists
• incretin mimetics

Article highlights

• Since synthetic exendin-4 was approved in 2005, five glucagon-like peptide-1 receptor agonists were commercialized for diabetes therapy and several exendin analogs are in preclinical and clinical development.

• In order to improve patient compliance and convenience, long-acting exendin analogs using lipidation, PEGylation, and recombinant protein fusion technologies have been widely developed. We reviewed patents for such analogs in this article.

• Recent patents also indicate intense efforts to design multifunctional exendin analogs that have dual or triple agonistic effects.

• In order to overcome the problems of current injectable agents, intense research efforts by academia and the pharmaceutical industry are expected to result in orally administered exendins or controlled-release drug delivery systems.

This box summarizes key points contained in the article.

Declaration of interest

This work was supported by Basic Science Research Programs through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2014R1A1A2008937 to EJ Park and NRF-2013R1A1A2064165 to SM Lim) and the Ministry of Science, ICT and Future Planning (NRF-2016R1A2B4006914 to KC Lee and NRF-2013R1A2A2A01068858 to DH Na). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.