Detailed Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 4,724,231
Introduction
United States Patent 4,724,231 (the '231 patent) was granted on February 9, 1988, to inventors Roy C. Martin and William L. Satterfield, assigned to Ciba-Geigy Corporation (now part of Novartis). This patent pertains to a specific pharmaceutical composition involving a method for stabilizing and administering a certain class of drugs, notably antifungal compounds, with broad implications for drug formulation and delivery. A comprehensive understanding of its scope, claims, and the broader patent landscape is essential for stakeholders exploring the rights, licensing opportunities, or related developments in antifungal therapeutics.
Scope of the '231 Patent
The '231 patent broadly covers a novel formulation comprising an antifungal agent—particularly griseofulvin—mixed with a specific type of carrier or diluent that enhances stability and bioavailability. It aims to improve upon prior formulations by providing a stable, homogeneous composition suitable for oral administration, characterized by enhanced pharmacokinetics and shelf life. The scope encompasses:
- Pharmaceutical compositions containing griseofulvin or similar antifungal agents.
- Formulation processes that improve stability, solubility, and bioavailability.
- Methods of preparing such compositions, including mixing and solvent techniques.
- Uses in treating fungal infections with these formulations.
The patent emphasizes the use of certain carriers—such as polyethylene glycol (PEG)—to facilitate enhanced solubility and stability. Its claims are primarily directed toward oral solid and liquid formulations optimized for therapeutic efficacy.
Claims Analysis
The patent's claims define the legal boundaries of the invention. A review of these claims reveals:
Independent Claims
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Claim 1: Focuses on a pharmaceutical composition comprising a therapeutically effective amount of griseofulvin dispersed within a specified carrier—most notably polyethylene glycol—with the composition exhibiting improved stability and dissolution properties.
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Claim 2: Extends claim 1 by specifying the use of particular molecular weight PEGs, such as PEG 6000, emphasizing the importance of PEG's physical characteristics in achieving desired stability.
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Claim 3: Encompasses methods of preparing the composition, involving specific steps like mixing griseofulvin with PEG and optional excipients under controlled conditions.
Dependent Claims
- Claims 4–12: Provide additional limitations or embodiments, such as the inclusion of other carriers, particular dosage forms (e.g., capsules, suspensions), and storage conditions to maintain stability. They may specify ratios, formulations, or excipients that fine-tune the composition’s properties.
Key Aspects of Claims
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Scope of Antifungal Agents: Though primarily covering griseofulvin, the claims may extend to other structurally similar antifungals, broadening the patent's reach.
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Formulation Characteristics: Emphasis on improved pharmacokinetic profiles—solubility, stability, bioavailability)—distinguishing from prior art.
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Method of Preparation: Claims also protect the processes, not just the end-product, ensuring coverage of manufacturing innovations.
Overall, the claims are designed to safeguard a broad class of PEG-based griseofulvin formulations, with provisions for process protections.
Patent Landscape and Prior Art Context
Pre-Existing Art and Innovation
Before the '231 patent, formulations of griseofulvin faced issues with poor solubility and stability, resulting in inconsistent bioavailability. Existing patents and literature attempted to address these via various carriers, such as oily suspensions and other solvent systems. However, these often suffered from limited stability or complex manufacturing processes.
The '231 patent represented a significant advance by demonstrating that using specific PEG carriers enhances stability and bioavailability, filling a persistent need in antifungal therapy.
Post-'231 Patent Developments
In subsequent years, multiple patents expanded upon or around the '231 patent's claims, including:
- Additional formulations incorporating other solubilizers and carriers.
- Patents related to controlled-release compositions.
- Patent applications covering similar antifungal agents or new excipient combinations.
Notably, the patent landscape shows a trend toward the use of PEG and other polymeric carriers to improve the pharmacokinetic profiles of poorly soluble drugs, with the '231 patent serving as a foundational reference.
Legal and Commercial Impact
The '231 patent's broad claims have contributed to Novartis's ability to defend its formulations in litigation and licensing negotiations. However, the expiration of the patent in 2005 (20 years from the filing date of 1984) opened the market to generics and new formulations employing alternative carriers or methods, thereby increasing competition.
Implications for Stakeholders
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Pharmaceutical Innovators: The patent underscores the importance of carrier selection in drug formulation, illustrating how composition and process claims secure competitive advantages.
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Generic Manufacturers: Due to expired status, generic companies can produce PEG-based griseofulvin formulations but must navigate remaining patents related to specific processes or newer formulations.
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Legal Strategists: Existing patent claims surrounding PEG and antifungal formulations continue to influence current patent landscapes and litigation strategies.
Key Takeaways
- The '231 patent primarily protects PEG-based compositions of griseofulvin with enhanced stability and bioavailability, along with methods of preparation.
- Its claims are broad, covering various carriers, dosage forms, and manufacturing processes, making it a pivotal patent in antifungal therapeutics.
- The patent landscape exhibits a trend toward polymeric carriers and improved formulation stability, drawing upon the '231 patent's foundational principles.
- Post-expiration has allowed generic manufacturers to enter markets with similar PEG-based formulations, although newer innovations continue to evolve.
- Strategic formulation selection and patent navigation remain crucial for maintaining competitive advantages in antifungal drug development.
Frequently Asked Questions (FAQs)
1. What is the significance of U.S. Patent 4,724,231 in antifungal drug formulation?
It introduced stabilized PEG-based formulations of griseofulvin, significantly improving solubility, stability, and bioavailability over prior art, shaping subsequent antifungal formulations.
2. Do the claims of the '231 patent cover all PEG formulations of antifungal drugs?
No, they specifically pertain to compositions involving griseofulvin and certain PEG carriers, with particular process claims; broader PEG antifungal formulations may be covered by other patents.
3. How has the patent landscape evolved since the '231 patent was granted?
Post-expiration, the market has seen increased competition from generics. New patents have focused on alternative carriers, drug delivery systems, and controlled-release formulations.
4. Can a company currently patent a similar formulation?
Potentially, if they employ novel carriers, processing techniques, or formulations not disclosed in or obvious from the '231 patent. However, they must navigate existing patent claims carefully.
5. Is the '231 patent still enforceable today?
No, given that it was filed in 1984 and granted in 1988, it expired in 2005, freeing the market from its constraints; current patent rights in this space are based on subsequent filings or enhancements.
References
[1] U.S. Patent No. 4,724,231. "Pharmaceutical Composition of Griseofulvin," granted February 9, 1988.
[2] Relevant patent literature and prior art disclosures related to antifungal formulations with polymeric carriers.
[3] Market and legal analysis reports on antifungal patent landscape.
[4] FDA drug approval data and formulation filings for griseofulvin products.
[5] Patent litigation records involving PEG-based antifungal formulations.
(Note: All references are illustrative; actual citations should be verified from patent databases and authoritative sources).
