United States Patent 6,504,030: A Detailed Analysis of Scope and Claims
Introduction
United States Patent 6,504,030, titled "Polymorphic form of clopidogrel hydrogen sulphate," is a significant patent in the pharmaceutical industry, particularly in the context of cardiovascular medications. This patent, held by Sanofi-Aventis and Bristol-Myers Squibb, pertains to a novel polymorphic form of clopidogrel hydrogen sulfate, a key ingredient in the drug Plavix.
Background of Clopidogrel
Clopidogrel is a platelet aggregation inhibitor used to prevent heart attacks and strokes. It was first described in European Patent EP 281459 and has since become a widely prescribed medication under the brand name Plavix[4].
Patent Overview
The patent 6,504,030 focuses on a specific polymorphic form of clopidogrel hydrogen sulfate, known as Form 2. This form is distinct from the previously known Form 1 in terms of its stability, physical properties, and spectral characteristics.
Claims of the Patent
The patent claims are centered around the following key aspects:
Polymorphic Form 2
- The patent describes the preparation and isolation of clopidogrel hydrogen sulfate in a novel crystalline form, Form 2. This form is characterized by its X-ray powder diffraction profile, melting point, and differential enthalpic analysis (DSC) data[4].
Physical and Spectral Characteristics
- Form 2 is distinguished by its melting point of 176°C, determined by DSC, and specific absorptions in the infrared and near-infrared spectra. The X-ray powder diffraction profile of Form 2 is detailed in the patent, including interlattice distances and relative intensities[4].
Synthetic Process
- The patent outlines the synthetic process for preparing clopidogrel hydrogen sulfate, which leads to the formation of Form 2. This process is crucial for ensuring the consistent production of this polymorphic form[4].
Pharmaceutical Compositions
- The patent also covers pharmaceutical compositions containing Form 2 of clopidogrel hydrogen sulfate. These compositions are important for the formulation of drugs like Plavix, which rely on the specific properties of this polymorphic form[4].
Patent Scope
The scope of this patent is defined by the specific claims related to the polymorphic form of clopidogrel hydrogen sulfate. Here are some key aspects:
Novelty and Non-Obviousness
- The patent asserts that Form 2 is a novel crystalline form that was not previously known. This novelty is a critical factor in the patent's validity, as it must meet the criteria for non-obviousness and novelty under U.S. patent law[4].
Utility
- The utility of the patent lies in the improved stability and physical properties of Form 2, which can enhance the efficacy and shelf life of clopidogrel-based medications[4].
Regulatory and Legal Context
The approval and protection of this patent are governed by the U.S. regulatory system:
FDA Approval Process
- Before a drug like Plavix can be sold in the U.S., it must undergo the FDA's new drug application (NDA) process. The NDA must reference relevant patents, which are then listed in the "Orange Book"[2].
Patent Litigation
- The patent has been involved in significant litigation, particularly with generic manufacturers seeking to produce versions of Plavix. For example, Apotex's attempt to market a generic version of Plavix led to a lawsuit by Sanofi, resulting in a 30-month delay in FDA approval for the generic version[2].
Impact on the Pharmaceutical Industry
This patent has substantial implications for the pharmaceutical industry:
Innovation and Competition
- The patent protects the intellectual property related to the specific polymorphic form of clopidogrel, which can influence innovation and competition in the development of cardiovascular medications. Generic manufacturers must either wait for the patent to expire or develop non-infringing alternatives[2].
Economic Considerations
- The exclusivity provided by the patent allows Sanofi and Bristol-Myers Squibb to maintain market dominance for Plavix, which has significant economic implications. The patent's expiration can lead to increased competition from generic versions, potentially reducing prices and altering market dynamics[2].
Patent Landscape
The patent landscape surrounding clopidogrel is complex and involves multiple patents:
Related Patents
- Other patents, such as U.S. Patent 4,847,265, also cover aspects of clopidogrel and its formulations. These patents collectively form a robust intellectual property portfolio that protects the drug's various forms and uses[2].
Generic Challenges
- Generic manufacturers often challenge the validity of these patents through Paragraph IV certifications, alleging that the patents are invalid or not infringed by their generic products. These challenges can lead to lengthy litigation and delays in market entry for generic versions[2].
Key Takeaways
- Novel Polymorphic Form: The patent introduces a novel polymorphic form of clopidogrel hydrogen sulfate, Form 2, with distinct physical and spectral characteristics.
- Regulatory Protection: The patent is part of the FDA's regulatory framework, listed in the "Orange Book," and has been involved in significant patent litigation.
- Industry Impact: The patent influences innovation, competition, and market dynamics in the pharmaceutical industry, particularly in the cardiovascular medication sector.
- Economic Implications: The patent's exclusivity affects market prices and competition, with its expiration potentially leading to increased generic competition.
Frequently Asked Questions
Q1: What is the main subject of United States Patent 6,504,030?
A1: The main subject is a novel polymorphic form of clopidogrel hydrogen sulfate, known as Form 2.
Q2: How is Form 2 of clopidogrel hydrogen sulfate characterized?
A2: Form 2 is characterized by its X-ray powder diffraction profile, melting point of 176°C, and specific absorptions in the infrared and near-infrared spectra.
Q3: What is the significance of this patent in the pharmaceutical industry?
A3: The patent protects the intellectual property related to a specific form of clopidogrel, influencing innovation, competition, and market dynamics for cardiovascular medications.
Q4: How does the FDA approval process relate to this patent?
A4: The patent is listed in the FDA's "Orange Book" as part of the new drug application (NDA) process, which governs the approval of drugs like Plavix.
Q5: What are the economic implications of this patent?
A5: The patent's exclusivity allows Sanofi and Bristol-Myers Squibb to maintain market dominance, affecting prices and competition. Its expiration can lead to increased generic competition and reduced prices.
Cited Sources
- US6504030B1 - Polymorphic form of clopidogrel hydrogen sulphate - Google Patents
- Kroger Co. v. Sanofi-Aventis, 701 F. Supp. 2d 938 - Casetext
- Patent Claims and Patent Scope - SSRN
- US6504030B1 - Polymorphic form of clopidogrel hydrogen sulphate - Google Patents
