Understanding the Scope and Claims of United States Patent 4,085,225: Fluvoxamine Maleate
Introduction
United States Patent 4,085,225, filed and granted in the early 1980s, is a pivotal patent in the pharmaceutical industry, particularly for the preparation and use of fluvoxamine maleate. This patent, which has been a cornerstone for the production of this selective serotonin reuptake inhibitor (SSRI), is crucial for understanding the development and manufacturing process of fluvoxamine maleate.
Background of Fluvoxamine Maleate
Fluvoxamine maleate is an antidepressant used in the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and various anxiety disorders, including panic disorder and post-traumatic stress disorder (PTSD)[1][4][5].
Patent Overview
Patent Number and Date
The patent number is 4,085,225, and it was first disclosed in this patent. The patent has been a subject of interest due to its significance in the pharmaceutical industry.
Claims
The patent claims cover the preparation of fluvoxamine maleate through a specific alkylation reaction. Here are the key aspects of the claims:
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Chemical Process: The patent describes the preparation of fluvoxamine maleate by an alkylation reaction involving 5-methoxy-4'-trifluoromethylvalerophenone oxime (compound of formula III) with 2-chloroethylamine hydrochloride. This reaction is typically conducted in a solvent such as dimethylformamide (DMF) in the presence of a base like potassium hydroxide powder[1][4][5].
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Reaction Conditions: The reaction is carried out at a temperature of around 25°C for a period of two days. This specific condition is crucial for the completion of the alkylation reaction.
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Product Formation: The resulting product, fluvoxamine base, is then treated with maleic acid in water to form fluvoxamine maleate. The precipitated fluvoxamine maleate is filtered, washed with a solvent like toluene, and dried. Additional steps may include recrystallization to achieve the desired purity[1][4][5].
Scope of the Patent
The scope of the patent is broad in terms of the method of preparation but specific in the chemical reactions and conditions involved.
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Method of Preparation: The patent covers a detailed method for preparing fluvoxamine maleate, including the specific reactants, solvents, and reaction conditions. This ensures that the process is reproducible and consistent in terms of the quality of the final product.
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Use of Fluvoxamine Maleate: While the patent primarily focuses on the preparation method, it implicitly covers the use of fluvoxamine maleate in various therapeutic applications due to its status as an SSRI.
Patent Landscape
Patent Term and Extensions
The original patent term for U.S. Patent 4,085,225 would have been 17 years from the date of grant. However, under certain conditions, patent terms can be extended due to regulatory reviews. For instance, Section 156 of Title 35, United States Code, allows for patent term extensions if the product or method has been subject to FDA or Department of Agriculture reviews[2].
Related Patents and Improvements
Over the years, there have been several improvements and variations on the original patent.
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Improved Processes: Later patents, such as EP2981518B1 and US9783492B2, describe improved processes for the preparation of fluvoxamine maleate. These include modifications to the reaction conditions, use of different solvents like toluene and PEG-400, and additional purification steps to enhance yield and purity[4][5].
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Addressing Limitations: The original patent's process has been criticized for potential issues such as incomplete reactions and lower yields at certain temperatures. Subsequent patents address these limitations by optimizing reaction conditions and adding purification steps[4].
Impact on Pharmaceutical Industry
The patent has had a significant impact on the pharmaceutical industry, particularly in the development and manufacturing of SSRIs.
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Standardization of Process: The patent provided a standardized method for preparing fluvoxamine maleate, ensuring consistency in the quality of the drug produced.
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Therapeutic Applications: The availability of a reliable method for producing fluvoxamine maleate has expanded its therapeutic use, benefiting patients with various mental health conditions.
Critique and Evolution
Critique of Patent Scope
The scope of the patent has been subject to scrutiny in broader debates about patent quality. Some argue that patents with overly broad claims can stifle innovation by increasing licensing and litigation costs. However, the specific and detailed nature of this patent's claims helps to mitigate such concerns[3].
Evolution of Patent Claims
The examination process for patents tends to narrow the scope of claims, ensuring that they are more specific and less likely to be overly broad. This has been observed in the evolution of patents related to fluvoxamine maleate, where subsequent patents refine and optimize the original process[3].
Key Takeaways
- Detailed Method of Preparation: U.S. Patent 4,085,225 provides a detailed and reproducible method for preparing fluvoxamine maleate.
- Specific Reaction Conditions: The patent specifies the use of particular reactants, solvents, and reaction conditions.
- Therapeutic Significance: The patent has been crucial for the widespread use of fluvoxamine maleate in treating various mental health disorders.
- Improvements and Variations: Later patents have improved upon the original process, addressing issues such as yield and purity.
- Impact on Industry: The patent has standardized the production of fluvoxamine maleate, ensuring consistency and quality in the pharmaceutical industry.
FAQs
What is the primary use of fluvoxamine maleate?
Fluvoxamine maleate is primarily used for the treatment of major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and various anxiety disorders.
What is the chemical process described in U.S. Patent 4,085,225?
The patent describes an alkylation reaction involving 5-methoxy-4'-trifluoromethylvalerophenone oxime with 2-chloroethylamine hydrochloride in the presence of a base.
Can the patent term of U.S. Patent 4,085,225 be extended?
Yes, the patent term can be extended under Section 156 of Title 35, United States Code, if the product or method has been subject to FDA or Department of Agriculture reviews.
What are some criticisms of the original patent process?
The original process has been criticized for potential issues such as incomplete reactions and lower yields at certain temperatures.
How have subsequent patents improved the process?
Subsequent patents have improved the process by optimizing reaction conditions, using different solvents, and adding purification steps to enhance yield and purity.
Sources
- New Drug Approvals: Fluvoxamine | New Drug Approvals
- United States Patent and Trademark Office: Extension Under 35 U.S.C. 156(e)(1) - OG Date: 29 July 2003
- SSRN: Patent Claims and Patent Scope
- Google Patents: EP2981518B1 - "an improved process for the preparation of fluvoxamine maleate"
- Google Patents: US9783492B2 - Process for the preparation of fluvoxamine maleate
