United States Patent 4,472,380: A Comprehensive Analysis
Introduction
United States Patent 4,472,380, titled "Amino acid derivatives as antihypertensives," is a significant patent in the field of pharmaceuticals, particularly focusing on angiotensin-converting enzyme (ACE) inhibitors. This patent, assigned to Merck & Co., Inc., plays a crucial role in the development and use of lisinopril, a widely used medication for hypertension.
Background and Context
ACE inhibitors are a class of drugs used to treat high blood pressure and heart failure. They work by inhibiting the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor. The patent in question builds upon earlier research and patents, such as U.S. Pat. No. 4,052,511, which disclosed N-carboxyalkanoyl-amino acids as ACE inhibitors[1].
Scope of the Patent
The patent 4,472,380 covers the preparation and use of carboxyalkyl dipeptide derivatives, specifically focusing on lisinopril. Here are the key aspects of its scope:
Chemical Structure and Synthesis
The patent describes the synthesis of lisinopril, which is chemically known as 1-(N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl)-L-proline. It outlines the processes for preparing these dipeptide derivatives, which are more potent than their predecessors due to the replacement of a methylene group with an amino function[1].
Pharmaceutical Compositions
The patent includes claims for pharmaceutical compositions that contain lisinopril. These compositions can be formulated in various ways, including tablets, capsules, and other oral forms. The patent specifies the use of excipients and the methods of tabletting, such as wet granulation or dry direct-compression[4].
Claims
The claims of the patent are critical as they define the legal boundaries of what is protected. Here are some key claims:
Compound Claims
The patent claims the dipeptide derivatives themselves, including lisinopril and its therapeutically acceptable salts. These compounds are characterized by their specific chemical structure and their ability to inhibit ACE[1].
Method of Use Claims
The patent claims the use of these compounds for treating hypertension and other conditions related to ACE activity. This includes the administration of lisinopril in various dosages, which can be as low as 2.5 mg per patient per day[1].
Pharmaceutical Composition Claims
The patent also claims pharmaceutical compositions that include lisinopril along with excipients. These compositions are designed to enhance the stability, bioavailability, and patient compliance of the drug[4].
Patent Landscape
Understanding the patent landscape around U.S. Patent 4,472,380 involves looking at related patents, continuations, and references.
Related Patents
The patent is part of a series of patents related to ACE inhibitors. For example, U.S. Pat. No. 4,374,829, also by Merck & Co., Inc., describes lisinopril and its pharmaceutical compositions in more detail. Other patents, such as U.S. Pat. No. 4,510,083, further expand on the formulations and uses of lisinopril[2].
Continuations and Divisionals
The patent has several continuations and divisionals, such as U.S. Pat. No. 4,510,083, which further refine the claims and compositions. These continuations often address specific aspects of the original patent, such as new formulations or manufacturing processes[2].
References Cited
The patent cites several earlier patents and publications, including U.S. Pat. No. 4,052,511, which laid the groundwork for ACE inhibitors. It also references scientific articles and other patents that contribute to the understanding and development of lisinopril[1][4].
Impact and Clinical Significance
Lisinopril, as described in this patent, has had a significant impact on the treatment of hypertension and heart failure.
Clinical Experience
Lisinopril has extensive clinical experience and is marketed under trademarks such as ZESTRIL® by AstraZeneca and PRINIVIL® by Merck & Co. It is known for its efficacy and safety profile, making it a preferred choice for many patients[4].
Dosage and Administration
The patent's claims regarding low dosages (as low as 2.5 mg per patient per day) have been clinically validated, making lisinopril a convenient and effective treatment option[1].
Patent Analytics and Claim Coverage
To fully understand the protection and opportunities provided by this patent, patent analytics tools can be employed.
Claim Coverage Matrix
Using tools like Claim Coverage Matrix, companies can categorize patents by claims and scope concepts to identify gaps or opportunities in their intellectual property portfolio. This helps in ensuring that the technology intended to be protected is adequately covered by the patent claims[3].
Claim Charts
Interactive claim charts generated by software like ClaimScape® can help technical experts review patent coverage and determine the applicability of specific scope concepts to target products or methods. This facilitates quick and accurate analysis of patent coverage and highlights future design opportunities[3].
Expiry and Legal Status
The patent 4,472,380 has expired, as it was granted in the early 1980s and had a typical patent term of 20 years from the filing date.
Key Takeaways
- Chemical Structure and Synthesis: The patent describes the synthesis of lisinopril and its dipeptide derivatives.
- Pharmaceutical Compositions: It includes claims for various pharmaceutical compositions of lisinopril.
- Claims: The patent claims the compounds, methods of use, and pharmaceutical compositions.
- Patent Landscape: It is part of a broader landscape of ACE inhibitor patents.
- Impact and Clinical Significance: Lisinopril has significant clinical use and is widely prescribed.
- Patent Analytics: Tools like Claim Coverage Matrix and claim charts are essential for analyzing patent protection.
Frequently Asked Questions (FAQs)
Q: What is the chemical structure of lisinopril as described in U.S. Patent 4,472,380?
A: Lisinopril is chemically known as 1-(N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl)-L-proline[1].
Q: What is the significance of replacing a methylene group with an amino function in the dipeptide derivatives?
A: This replacement results in compounds of surprisingly high potency, allowing for lower dosages (as low as 2.5 mg per patient per day)[1].
Q: How is lisinopril typically formulated according to the patent?
A: Lisinopril can be formulated in various ways, including tablets produced by wet granulation or dry direct-compression, and may include excipients like DCPD and mannitol[4].
Q: What is the current legal status of U.S. Patent 4,472,380?
A: The patent has expired, as it was granted in the early 1980s and had a typical patent term of 20 years from the filing date.
Q: How can companies ensure that their intellectual property is adequately protected by patents like 4,472,380?
A: Companies can use patent analytics tools like Claim Coverage Matrix and claim charts to categorize patents by claims and scope concepts, identifying gaps or opportunities in their intellectual property portfolio[3].
Citations
- US4472380A - Amino acid derivatives as antihypertensives.
- US10940177B2 - Lisinopril Formulations.
- Patent Analytics | Intellectual Property Law.
- EP1432407B2 - Lisinopril Compositions Having Large-Particle DCPD.
