ABSTRACT
Introduction: Diabetes is a metabolic disease characterized by elevated levels of plasma glucose. When untreated, diabetes increases the risk of developing co-morbidities such as cardiovascular disease. Several drugs, often used as part of combination therapies, have been approved to treat the disease, but these drugs will eventually fail to effectively control blood glucose levels, at which point insulin replacement therapy is required. A medical need exists for new antidiabetic drugs that exhibit good efficacy with improved safety/toleration profiles and can be added on top of existing therapies, or that can provide additional benefits beyond glucose lowering such as pancreatic beta (β)-cell protection.
Areas covered: This review analyzes drug targets and applicants of patents that published between 2011–2016 claiming novel small or large molecules for the treatment of diabetes, and compares the results to the 2008–2010 time period.
Expert opinion: A majority of patent activity around the discovery of new antidiabetic drugs in 2011–2016 was directed against 15 targets, most of which were also the focus of drug discovery efforts in the 2008–2010 time period. The top targets by total patent counts were DPP4, GLP1R, INSR, GPR119, and SGLT2 (SLC5A2). With the exception of GPR119, these are the pharmacological targets of some of the best-selling antidiabetic drugs currently on the market. The top targets of patent families with the largest size counts, a metric useful in assessing patent value and applicant interest, were AMPK, CALCR, DPP4, and GLP1R. The patent analysis identified several emerging targets with greater patent activity in 2011–2016 compared to 2008–2010, including FFAR1, FFAR4, and FGFR1. Most of the patent activity in 2011–2016 was directed at established and precedented diabetes targets, the modulation of which may lead to improvements in glucose control and a delay in the progression of the disease. Few targets were identified that promote pancreatic β-cell regeneration and β-cell health, areas where future opportunities may exist for developing transformative drug therapies that may potentially lead to cures for diabetes.
Article highlights
A decrease in total patent counts of pharmacological targets of small and large molecules claimed for the treatment of diabetes was observed in the six year 2011-2016 time period compared to the previous three year 2008-2010 period, possibly reflecting reduced interest in this therapeutic area, even though a medical need for new pharmacological agents exists.
Several large pharmaceutical companies including Merck, Eli Lilly, Boehringer Ingelheim, and Novo Nordisk were actively engaged in 2011-2016 in the discovery of new drugs to treat diabetes, despite the significant regulatory and financial challenges in bringing new antidiabetic drugs to the market.
A majority of the patent activity in the diabetes therapeutic area was focused around 15 targets, each with patent counts of 20 or greater.
A significant amount of patent activity was directed at antidiabetic targets for which marketed drugs already exist (i.e. precedented targets), including DPP4, GLP1R, INSR, and SGLT2.
Some notable targets of patent families with size counts greater than 5, used as a threshold for assessing the value of an invention and interest by the applicant, were APOC3, CALCR, FFAR1, FGFR1, and GLP1R/GCGR.
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Acknowledgments
The authors thank Robert L. Dow and Samit Bhattacharya for reviewing the manuscript and providing critical comments.
Declaration of interest
M Boehm, M Crawford, JE Moscovitz, and PA Carpino are employees of Pfizer, Inc. 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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclosed.