Case study of patents related to captopril, Squibb’s first blockbuster

ABSTRACT

Introduction: Arterial hypertension affects over one billion people around the world, making the prevention and treatment of this disease vital. Despite the efforts made to develop new antihypertensive drugs, few new therapies have become available. Angiotensin-converting enzyme (ACE) inhibitors have heralded major steps forward in the treatment of arterial hypertension and cardiovascular diseases since the first compound of this class, captopril, was approved for clinical use in 1981.

Areas covered: In this review, the authors investigated the patent documents that cite the priority patent for captopril, Squibb’s first blockbuster, or any other patent from its patent family. The documents were classified into the following: new compounds, new compositions, treatment, process (preparation of a compound), use of a compound, and process for the preparation of an intermediate. Therefore, the readers can identify potential innovations in the field.

Expert opinion: The pharmaceutical sector has attempted to provide significant technological developments on anti-hypertensive drugs based on the patenting of captopril, including the development of new compositions further comprising an ACE inhibitor and other antihypertensive agent, along with dual action compounds, novel molecules with dual activity. The target is to find a new agent with better blood pressure-lowering efficacy, improved safety and good tolerability profile.

KEYWORDS:

• Hypertension
• captopril
• patents

Article highlights

• This review analyzes the claims in the documents that cite the priority patent for captopril, the first ACE inhibitor, approved in the early 1980s.

• The claims in the documents were classified into: new compounds (products), new compositions, methods of use (treatment), process (preparation of a compound), use of a compound, and process for the preparation of an intermediate.

• ER Squibb and Bristol-Myers Squibb are the main patent assignees, holding 47% of the patents, dating from 1976 to 2005.

• The United States are the top center for the R&D of captopril-related technologies.

• The greater part of the applications claims new compounds analogous to captopril with the same mechanism of action and differing primarily in their potency or pharmacokinetic profile. Pharmaceutical compositions comprising an ACE inhibitor plus an additional antihypertensive agent, as well as dual action compounds containing structural features of an ACE inhibitor and another class of antihypertensive were also found.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) for the access to the Derwent Innovation Index database, available at the CAPES Journal Portal (www.periodicos.capes.gov.br/).

Declaration of interest

The authors have no 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.

Notes

1. Given that the rights granted to patent holders are territorial – i.e. they are only valid in the territory where the patent was filed and granted – the patent holder may file patent applications for the same technology in however many territories they wish the technology in question to be protected by patent. Interestingly, a patent may be granted for a given technology in one country and not in another, since national industrial property laws differ.

2. Numbers of the patents from the first family of patents for captopril, deriving from the priority patent, US19760657792: AR214649, AR222445, AR222783, AR226290, AT365569, ATA98977, AU2134777, AU509899, BG37074, BG37075, BG37375, CA1101864, CH622503, CH624931, CH624932, DD129442, DE2703828, DE2759862, DK157487, DK59677, ES455803, ES467050, ES467051, ES467052, ES467053, FI66596, FI770437, FR2340932, GB1576161, GR69811, HK20281, HU181965, IE44707, IL51297, IT1062293, JP52116457, JPS604815, KE3136, MY8200075, NL168509, NL7701457, NO146985, NO770464, NZ183130, PH12970, PL118161, PL195965, RO69941, SE423812, SE426697, SE7701561, SE8104660, SU747422, US4046889, US4105776, YU33177, YU40664.

3. System that organizes technical and production-related information and enables information from patents to be retrieved. It is organized by the World Intellectual Property Organization and is used by over 70 countries.

4. Subclass C07C is related to acyclic or carbocyclic compounds, while C07D is related to heterocyclic compounds.

5. The Patent Cooperation Treaty (PCT) is a multilateral treaty overseen by the WIPO, which enables parties to file for patent protection for an invention simultaneously in multiple countries by filing a single international patent application. Its main objective is to simplify and reduce the cost of protecting inventions when such protection is sought in several countries. A PCT application can be filed by any entity that is a citizen or resident of any country that is a contracting state of the treaty.

Additional information

Funding

This paper was not funded.