Orexin research: patent news from 2016

ABSTRACT

Introduction: The orexin system consists of two G-protein-coupled receptors, orexin 1 and orexin 2 and two endogenous ligands, orexin A and orexin B . It is evolutionarily highly conserved. It is involved in the promotion of wakefulness as well as in anxiety and addictive disorders. In addition, its activation via the Ox1 receptor triggers apoptosis in several cancer cell lines. Dual orexin receptor antagonists are successfully used to treat primary insomnia. The major open questions are now related to the clinical validation of Ox1 selective antagonists. A strong rationale exists for orexin agonism in the treatment of narcolepsy with cataplexy.

Areas covered: The patent applications from Thomson Reuters Integrity Database added in 2016 are summarized and discussed together with the most important findings published in the scientific literature.

Expert opinion: The large number of patents shows the continuing interest in the orexin receptors as targets. The structural scope covered is narrow. Questions about novelty and inventiveness are evident. The additional information published on X-ray structures on both orexin receptors opens new ways of optimizing antagonists. It might also influence the efforts in the identification of orexin receptor agonists. Being potential treatments for narcolepsy with cataplexy.

KEYWORDS:

• Addiction
• anxiety
• G-protein-coupled receptors
• insomnia
• narcolepsy
• neuropeptides
• orexin peptides
• orexin receptors
• sleep

Article highlights

• The orexin system is evolutionarily conserved and consists of two GPCR’s and two endogenous ligands and is involved in the regulation of wakefulness and arousal states

• A huge amount of industrial as well as academic research has been performed on diverse aspects of the orexin system. These efforts so far culminated in the FDA approval of Belsomra® for the treatment of insomnia.

• The patenting and publishing activities in 2016 showed the continued interest in the orexin system and showed first promising efforts in the identification of orexin receptor agonists and confirmed the importance of the Ox1 receptor in the regulation of apoptotic processes in several cancer cell lines.

• The focus in the patenting activities in the antagonist field in 2016 was on either Ox1- or Ox2-receptor subtype selective antagonists.

This box summarizes key points contained in the article.

Declaration of interest

No potential conflict of interest was reported by the authors.