PCSK9 inhibitors: a patent review 2018-2023

ABSTRACT

Introduction

Proprotein convertase subtilisin/kexin 9 (PCSK9) plays a crucial role in breaking down the hepatic low-density lipoprotein receptor (LDLR), thereby influencing the levels of circulating low-density lipoprotein cholesterol (LDL-C). Consequently, inhibiting PCSK9 through suitable ligands has been established as a validated therapeutic strategy for combating hypercholesterolemia and cardiovascular diseases.

Area covered

Patent literature claiming novel compounds inhibiting PCSK9 disclosed from 2018 to June 2023 available in the espacenet database, which contains more than 150 million patent documents from over 100 patent-granting authorities worldwide.

Expert opinion

The undisputable beneficial influence of PCSK9 as a pharmacological target has prompted numerous private and public institutions to patent chemical frameworks as inhibitors of PCSK9. While several compounds have advanced to clinical trials for treating hypercholesterolemia, they have not completed these trials yet. These compounds must contend in a complex market where new, costly, and advanced drugs, such as monoclonal antibodies and siRNA, are prescribed instead of inexpensive and less potent statins.

KEYWORDS:

• PCSK9
• hypercholesterolemia
• CVD
• LDL-C
• patents

Article highlights

• PCSK9 inhibitors may become a new generation of drugs for the treatment of hypercholesterolemia and the prevention of fatal or non-fatal cardiovascular events.

• Several chemical scaffolds as PCSK9 inhibitors have been reported to date.

• This review reports on the PCSK9 inhibitors patented from 2018 to June 2023.

• Nineteen patents have been deposited by several companies and universities.

• One PCSK9 inhibitor (MK-0616) entered phase III clinical trial.

Declaration of interest

University of Milan, G Grazioso, A Silvani, and C Lammi are applicant and inventors, respectively, of patent entitled ‘PCSK9 inhibiting compounds’ and publication number WO2021234654, filing date 21 May 2021. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

All authors contributed to gather the patent-related information and to the preparation of the original draft. EMA Fassi created the figures. EMA Fassi and G Grazioso contributed to the manuscript revisions. All authors read and approved the final version of the manuscript.

Additional information

Funding

This paper was granted by “Linea2”, grant from University of Milan.