United States Patent 5,236,952: A Detailed Analysis of Scope, Claims, and Patent Landscape
Introduction
United States Patent 5,236,952, assigned to Hoffmann La Roche Inc., is a significant patent in the field of pharmaceuticals, particularly for the treatment of Parkinson's disease and other neurological disorders. This patent revolves around catechol derivatives, specifically Tolcapone, which is a potent inhibitor of the enzyme catechol-O-methyltransferase (COMT).
Background and Context
The patent was filed on March 6, 1987, and granted on August 17, 1993. It is part of a broader category of patents related to COMT inhibitors, which are crucial in the management of Parkinson's disease by enhancing the efficacy of levodopa therapy[4].
Scope of the Invention
The patent describes a class of catechol derivatives with specific structural formulas, particularly those with nitro or cyano groups attached to the benzene ring. These compounds are designed to inhibit the COMT enzyme, thereby prolonging the action of catecholamines such as dopamine, which is beneficial in treating Parkinson's disease and other neurological conditions.
Chemical Structure and Derivatives
The patent details compounds of the formula:
[ \text{Ra} \, \text{Ia} \, \text{HO} \, \text{Rc} \, \text{HO} \, \text{Rb} ]
where:
- ( \text{Ra} ) is nitro or cyano,
- ( \text{Rb} ) is hydrogen or halogen,
- ( \text{Rc} ) is halogen, nitro, cyano, or specific functional groups[4].
Claims
The patent includes 22 claims that cover various aspects of the invention:
Compound Claims
Claims 1-10 describe the specific catechol derivatives, including Tolcapone, and their structural variations. These claims are broad and encompass a wide range of compounds that fit the defined formula[4].
Method of Preparation Claims
Claims 11-15 outline the methods for preparing these compounds. This includes the synthesis of Tolcapone through specific chemical reactions, such as the reaction of 3,4-dihydroxy-5-nitrobenzoic acid with a chlorinating agent followed by Friedel-Crafts acylation with toluene[1][4].
Pharmaceutical Composition Claims
Claims 16-20 cover the pharmaceutical compositions containing these compounds and their use in treating various diseases. These claims emphasize the therapeutic applications of the catechol derivatives, particularly in the treatment of Parkinson's disease and depression[4].
Use Claims
Claims 21-22 specify the use of these compounds in inhibiting the COMT enzyme and their application in medicaments for treating neurological disorders[4].
Patent Landscape
The patent landscape surrounding US 5,236,952 is complex and involves several related patents and technologies.
Related Patents
Other patents, such as those disclosed by Borgulya et al., describe similar COMT inhibitors with unsubstituted phenyl rings, indicating a broader field of research in this area[1].
Patent Term Extensions
The patent term for US 5,236,952 could have been extended under 35 U.S.C. 156(e)(1) if it had undergone regulatory reviews by the FDA, which is common for pharmaceutical patents. However, specific details on any extensions for this patent are not provided in the available sources[2].
Competitive Landscape
The competitive landscape includes other pharmaceutical companies and research institutions working on COMT inhibitors. The novelty and simplicity of the process described in US 5,236,952, particularly for Tolcapone, positioned Hoffmann La Roche Inc. as a leader in this therapeutic area[1].
Impact and Significance
The patent has significant implications for the treatment of Parkinson's disease and other neurological disorders. Tolcapone, as described in the patent, has been widely used to enhance the efficacy of levodopa therapy, improving the quality of life for patients.
Clinical Use
Tolcapone has been clinically used to inhibit the COMT enzyme, thereby increasing the bioavailability of levodopa and reducing the required dosage. This leads to better symptom management and reduced side effects associated with higher doses of levodopa[4].
Economic Impact
The economic impact of this patent is substantial, given the market demand for effective treatments for Parkinson's disease. The patent has contributed to the commercial success of Tolcapone and has influenced the development of subsequent COMT inhibitors.
Challenges and Limitations
Despite its significance, the patent faces challenges related to the complexity of the synthesis process and the potential for side effects associated with Tolcapone. The patent also highlights the need for continuous innovation in the field to address these challenges.
Future Directions
The future of COMT inhibitors is likely to involve further research into more efficient synthesis methods and the development of new compounds with improved safety profiles. The patent landscape will continue to evolve as new technologies and discoveries are made.
Key Takeaways
- Scope and Claims: The patent covers a broad range of catechol derivatives, including Tolcapone, and their methods of preparation and use.
- Patent Landscape: The patent is part of a larger landscape involving related patents and technologies focused on COMT inhibitors.
- Impact and Significance: The patent has significantly improved the treatment of Parkinson's disease and other neurological disorders.
- Challenges and Limitations: The patent faces challenges related to synthesis complexity and side effects, necessitating ongoing research.
Frequently Asked Questions
Q: What is the main compound described in US 5,236,952?
A: The main compound described is Tolcapone, a COMT inhibitor used in the treatment of Parkinson's disease.
Q: How is Tolcapone synthesized according to the patent?
A: Tolcapone is synthesized by reacting 3,4-dihydroxy-5-nitrobenzoic acid with a chlorinating agent followed by Friedel-Crafts acylation with toluene[1].
Q: What is the therapeutic application of the compounds described in the patent?
A: The compounds are used to inhibit the COMT enzyme, which is beneficial in treating Parkinson's disease and other neurological disorders[4].
Q: Can the patent term for US 5,236,952 be extended?
A: Yes, the patent term could be extended under 35 U.S.C. 156(e)(1) if it underwent regulatory reviews by the FDA[2].
Q: What is the economic impact of this patent?
A: The patent has contributed significantly to the commercial success of Tolcapone and has influenced the development of subsequent COMT inhibitors.
Cited Sources
- WO2014147464A2 - Novel process for the preparation of tolcapone.
- USPTO OG Notices - Extension Under 35 U.S.C. 156(e)(1).
- Patent Analytics - Intellectual Property Law.
- US5236952 - United States Patent (19).
