Understanding the Scope and Claims of United States Patent 4,277,479
Introduction
United States Patent 4,277,479, granted for the production of cilostazol, is a significant patent in the pharmaceutical industry. This patent, filed and granted in the early 1980s, outlines a method for synthesizing cilostazol, a medication used to treat intermittent claudication, a symptom of peripheral artery disease. Here, we delve into the scope, claims, and the broader patent landscape surrounding this invention.
Background of Cilostazol
Cilostazol is a phosphodiesterase 3 inhibitor that improves blood flow and reduces symptoms of intermittent claudication. The synthesis of this compound is complex and involves several steps, each critical for the final product's efficacy and safety.
Scope of the Patent
The scope of U.S. Patent 4,277,479 is defined by its claims, which describe the specific process for producing cilostazol. Here are the key aspects:
Process Overview
The patent describes a multi-step synthesis process involving the alkylation of a precursor compound. This process can be conducted either neat (without a solvent) or in a solvent, with various solvents listed as suitable, including methanol, ethanol, and others[1].
Key Steps and Reagents
- Alkylation Step: This critical step involves the use of a base such as 1,8-diazabicyclo[5,4.0]undec-7-ene (DBU) and a solvent like ethanol.
- Precursor Stability: The patent notes that one of the precursor compounds (compound III) is unstable to certain bases, necessitating careful handling and the use of an excess of this compound to achieve satisfactory yields[1].
Work-Up Procedures
The original process disclosed in the patent involves complicated work-up procedures, including column chromatography, which can be time-consuming and inefficient on a large scale[1].
Claims Analysis
The claims of U.S. Patent 4,277,479 are detailed and specific, ensuring that the process described is protected against infringement.
Independent Claims
The independent claims outline the core steps of the synthesis process, including the alkylation reaction and the use of specific bases and solvents. These claims are crucial as they define the boundaries of the invention and what constitutes infringement.
Dependent Claims
Dependent claims further specify the conditions under which the process can be carried out, such as the use of particular solvents or reaction conditions. These claims provide additional protection by covering variations of the core process.
Patent Landscape and Subsequent Developments
The patent landscape surrounding U.S. Patent 4,277,479 has evolved significantly since its grant.
Later Patents and Improvements
Later patents, such as U.S. Patents 6,515,128 and 6,630,590, addressed some of the inefficiencies and complexities of the original process. These patents introduced phase transfer catalysts and reaction promoters to improve yields and simplify the process. However, these improvements also introduced new complexities, such as the use of heterogeneous mixtures and additional chemicals, which can increase costs and generate more chemical waste[1].
Challenges and Criticisms
The original process and subsequent improvements have faced challenges related to scalability and efficiency. The use of phase transfer catalysts and reaction promoters, while beneficial, adds complexity and cost to the production process. Additionally, the need for continuous dispersers in some later processes is not conventional in commercial plants, posing practical challenges[1].
Impact on Patent Quality and Litigation
The broader patent landscape, including the creation of the Patent Trial and Appeal Board (PTAB) under the Leahy-Smith America Invents Act (AIA), has significant implications for patent quality and litigation.
PTAB and Inter Partes Review
The PTAB and inter partes review (IPR) procedures provide a more efficient and cost-effective way to challenge patent validity compared to federal court litigation. This has been particularly relevant for patents like U.S. Patent 4,277,479, where the validity and scope of claims can be scrutinized in a more streamlined process[5].
Patent Scope and Quality
Research on patent scope, such as the metrics of independent claim length and count, suggests that narrower claims are associated with a higher probability of grant and shorter examination processes. This is relevant for understanding the evolution of patent claims in the pharmaceutical industry, where the scope and clarity of claims are critical for innovation and litigation[3].
Economic and Innovation Implications
The economic and innovation implications of U.S. Patent 4,277,479 are substantial.
Cost and Efficiency
The production process of cilostazol, as described in the patent and subsequent improvements, has significant economic implications. The complexity and cost of the process can affect the availability and affordability of the medication, impacting public health and pharmaceutical innovation[1].
Innovation Incentives
The patent system, including the challenges and improvements surrounding U.S. Patent 4,277,479, influences innovation incentives. Clear and valid patents are essential for encouraging investment in research and development, while overly broad or invalid patents can hinder innovation by increasing litigation costs and uncertainty[5].
Key Takeaways
- Process Complexity: The synthesis of cilostazol involves complex steps, including alkylation reactions and specific solvent and base requirements.
- Patent Scope: The claims of U.S. Patent 4,277,479 define the scope of the invention, with later patents addressing some of the original process's inefficiencies.
- Economic Implications: The production process affects the cost and availability of cilostazol, with broader implications for pharmaceutical innovation.
- Patent Quality: The evolution of patent claims and the role of PTAB in challenging patent validity are crucial for maintaining patent quality and encouraging innovation.
FAQs
Q: What is the main process described in U.S. Patent 4,277,479?
A: The main process is the synthesis of cilostazol through a multi-step reaction, including an alkylation step using a base like DBU and a solvent like ethanol.
Q: Why is the stability of precursor compounds important in this patent?
A: The stability of precursor compounds, particularly compound III, is crucial because it is unstable to certain bases, requiring careful handling and the use of an excess to achieve satisfactory yields.
Q: How have later patents improved the original process?
A: Later patents introduced phase transfer catalysts and reaction promoters to improve yields and simplify the process, although these improvements also introduced new complexities and costs.
Q: What is the role of PTAB in patent litigation?
A: PTAB provides a more efficient and cost-effective way to challenge patent validity through inter partes review (IPR) and post-grant review (PGR), which can be faster and less expensive than federal court litigation.
Q: How does the scope of patent claims impact innovation?
A: The scope of patent claims, particularly narrower claims, is associated with higher grant probabilities and shorter examination processes, which can encourage innovation by providing clearer and more valid patents.
Sources
- US20070105898A1 - Process for the production of cilostazol
- Patent Claims Research Dataset - USPTO
- Patent Claims and Patent Scope - Search eLibrary :: SSRN
- What Is the Probability of Receiving a US Patent?
- The Patent Trial and Appeal Board and Inter Partes Review
