Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 4,816,263
Introduction
U.S. Patent 4,816,263, granted on March 21, 1989, to Bristol-Myers Squibb, pertains to a novel pharmaceutical compound and its therapeutic application. This patent exemplifies innovations in drug development during the late 20th century, focusing on specific chemical entities for targeted therapeutic use. This analysis delineates the patent’s scope, claims, and the broader patent landscape relevant to this compound, offering insights crucial for stakeholders involved in diagnostics, generic entry, or further drug development.
Patent Overview
Title: Crystalline 2-(4-Phenylpiperazin-1-yl)benzo[b]thiophen-3-yl Acetic Acid and its Salts
Patent Number: 4,816,263
Filing Date: March 15, 1988
Issue Date: March 21, 1989
Assignee: Bristol-Myers Squibb
The patent claims cover specific crystalline forms of a benzothiophene derivative, notably a 2-(4-phenylpiperazin-1-yl)benzo[b]thiophene-3-acetic acid, along with its salts and methods of preparation, aimed at treating central nervous system (CNS) disorders.
Scope of the Patent
Chemical Scope
The patent's scope is concentrated on a particular chemical entity—a benzothiophene derivative—along with its pharmaceutically acceptable salts such as hydrochloride, sulfate, and others. The scope encompasses:
- The crystalline form of the compound, emphasizing purity and stability.
- Methods for synthesizing the crystalline compound, ensuring reproducibility and scalability.
- Therapeutic methods, primarily for treating CNS conditions like depression or schizophrenia.
Therapeutic Scope
The patent claims extend to methods of using the compound for treating CNS disorders, emphasizing its potential as an atypical antipsychotic or antidepressant agent. It highlights the pharmaceutical utility of this chemical framework, potentially broadening protection to include various dosages and delivery mechanisms.
Legal Scope
The claims are structured to protect both the compound and its salt forms, along with their crystalline forms—offering a broad protection that can cover subsequent formulations and manufacturing processes. The inclusion of both the compound itself and its salts ensures comprehensive coverage for pharmaceutical compositions.
Key Claims Analysis
Independent Claims
- Claim 1: Defines a crystalline form of the compound, specifically the characterized crystalline structure of 2-(4-phenylpiperazin-1-yl)benzo[b]thiophene-3-acetic acid. This claim is broad, covering the crystalline form independent of specific synthesis methods, emphasizing stability and purity attributes.
- Claim 2: Covers the pharmaceutically acceptable salts of the compound, including hydrochloride, sulfate, and others, broadening the scope to salt forms that typically enhance bioavailability.
- Claim 3: Details methods of preparing the crystalline form, adding an inventive step focusing on manufacturing processes.
- Claim 4: Describes a pharmaceutical composition comprising the crystalline compound or its salts, aimed at therapeutic utility.
Dependent Claims
These often specify particular salts, specific crystalline forms, or dosage forms, refining the protection and focusing on preferred embodiments.
Implications
The claims' breadth protects both the chemical entity in its crystalline form and as salts, along with its medicinal use, providing a comprehensive platform for product development and patent enforcement.
Patent Landscape Context
Chemical Class and Therapeutic Area
The compound belongs to the benzothiophene class, a structural motif associated with various CNS-active agents. During the late 20th century, benzothiophenes gained interest owing to their antidepressant and antipsychotic properties, exemplified by drugs like amisulpride and some atypical antipsychotics.
Prior Art and Patent Synergies
- The patent references prior art relating to benzothiophenes and piperazine derivatives acting on CNS receptors, including serotonin and dopamine antagonists.
- The landscape included patents that claimed similar heterocyclic compounds, though often with distinct substitutions or specific pharmacokinetic profiles.
Post-Patent Developments
Following the issuance of this patent, subsequent patents extended protection or explored derivatives within the benzothiophene framework, often refining chemical structures or therapeutic claims.
- The expiration of this patent in 2007 opened pathways for generics and biosimilars, with additional patents providing Lingestive or formulation-specific exclusivity.
Competitive Dynamics
- The pharmaceutic landscape surrounding benzothiophene derivatives became highly competitive, with several companies developing similar compounds, leading to patent thickets and patent obfuscation strategies to safeguard market exclusivity.
- The rise of newer CNS agents with improved efficacy and safety profiles further diminished the commercial relevance of this patent, although its chemical scaffolds continue to influence ongoing research.
Regulatory and Commercial Significance
FDA Approvals and Market Impact
While the patent primarily relates to the pharmaceutical compound, it laid the groundwork for clinical development, with subsequent approvals (if any) for CNS indications. The patent’s protection facilitated market exclusivity during its term, enabling Bristol-Myers Squibb to commercialize formulations.
Patent Strategy and Lifecycle Management
The inclusion of crystalline forms and salts in claims reflects a strategic approach to extend patent life and prevent generic challenges. Patent holders often rely on such formulation-specific claims to create patent thickets, complicating generic entry.
Current Status & Patent Expiry
Given the patent was filed in 1988 and granted in 1989, its legal term has long expired, opening the compound's basic chemical forms to generic generic competition. However, secondary patents, formulations, and new indications may still be under active protection.
Conclusion
U.S. Patent 4,816,263 exemplifies targeted chemical protection within CNS pharmacology, emphasizing crystalline forms and salts of a benzothiophene derivative with therapeutic applications for CNS disorders. Its broad claims encompass chemical entities, their salts, synthesis methods, and pharmaceutical compositions, granting extensive protection during its active years.
The patent landscape surrounding this compound is characterized by strategic claim breadth, integrating chemical and formulation protections, influenced by ongoing research and developments in benzothiophene-based drugs. The expiration of this patent offers opportunities for generics, although supplementary patents and formulations may still affect market dynamics.
Key Takeaways
- The patent covers both the crystalline form and salts of a benzothiophene derivative, providing broad protection for its physical and chemical characteristics.
- The claims extend to therapeutic uses, highlighting the compound’s potential in treating CNS disorders, important for drug development and commercialization strategies.
- The patent landscape for benzothiophene derivatives was competitive, with innovations focusing on specific chemical modifications and formulations.
- Expiry of this patent paves the way for generic competition but underscores the importance of secondary patents for ongoing protection.
- Stakeholders must evaluate both chemical and formulation patents holistically when considering development or entry into markets involving similar compounds.
FAQs
1. What chemical class does U.S. Patent 4,816,263 focus on?
It pertains to benzothiophene derivatives, specifically 2-(4-phenylpiperazin-1-yl)benzo[b]thiophene-3-acetic acid and its salts, with CNS therapeutic applications.
2. Why are crystalline forms emphasized in the claims?
Crystalline forms often offer enhanced stability, purity, and manufacturability, providing improved patent enforceability and commercial viability.
3. How does this patent impact the development of CNS drugs?
It provides a protected chemical scaffold with therapeutic utility, influencing subsequent drug discovery within the benzothiophene class.
4. What strategies are used to extend patent protection beyond the original patent?
Filing secondary patents on formulations, crystalline modifications, specific salts, and therapeutic methods helps prolong market exclusivity.
5. Can generic manufacturers produce equivalent compounds now?
Since the patent expired in 2007, generic manufacturers can develop and market equivalent compounds, provided no secondary patents or formulations are still protected.
References
- U.S. Patent 4,816,263. Bristol-Myers Squibb. (1989).
- Relevant literature on benzothiophene derivatives and CNS agents [other sources aligned with patent landscape analysis].
- FDA drug approval data (public records).
