Detailed Analysis of the Scope, Claims, and Patent Landscape of U.S. Patent 5,037,845
Introduction
United States Patent 5,037,845, granted to Schering Corporation on August 6, 1991, pertains to an innovative class of pharmaceutical compounds with specific therapeutic indications. This patent has significantly influenced the field of chemotherapeutic agents, particularly in the treatment of hormone-dependent cancers. Its scope, claims, and landscape present insights into patenting strategies within the pharmaceutical industry, especially concerning chemical entities with specific therapeutic uses.
Patent Overview and Scope
Patent Title: Hormonal Agents and Processes for Their Manufacture
Inventors: James R. Richardson et al.
Assignee: Schering Corporation (now part of Bayer AG)
Priority Date: March 24, 1987
Filing Date: March 22, 1988
Issue Date: August 6, 1991
Scope Summary:
The patent discloses various arylalkyl and arylalkoxyalkyl derivatives of 4-alkyl-4-aza-spiro[4.5]decanes designed to act as estrogen receptor antagonists. Primarily, these compounds were developed for potential use in hormone-dependent conditions such as breast cancer, uterine fibroids, and other estrogen-mediated disorders. The patent encompasses both the chemical structures and their synthesis processes, along with their pharmacological utility.
Claims Analysis
The scope of the patent is predominantly embodied in its compound claims, supplemented by methodological and use claims. The claims can be classified into three categories:
1. Compound Claims (Chemical Entities)
These claims define classes of compounds broadly, aiming to cover all derivatives within certain structural parameters:
- Core Structure: The compounds feature a spiro[4.5]decan-4-yl backbone linked to various aryl groups via alkoxy or alkyl linkers.
- Substitutions: The claims specify different substituents at particular positions, notably on the aromatic rings (e.g., halogens, alkyl groups), offering broad coverage over similar analogs.
- Functional Group Variations: Inclusion of different alkyl groups (like methyl, ethyl), phenyl, or heteroaryl substituents attached via ether or alkyl linkers.
Implication: The broad scope intends to preempt competitors by covering an extensive family of estrogen receptor modulators, with tailored substitutions to optimize activity and selectivity.
2. Method Claims
Methodological claims detail synthesis procedures enabling large-scale preparation of claimed compounds, emphasizing multi-step organic syntheses involving steps like halogenation, alkylation, and cyclization.
3. Use and Therapeutic Claims
These claims focus on pharmaceutical applications, including:
- Use of compounds in the treatment of hormone-dependent diseases such as breast cancer, endometriosis, and uterine fibroids.
- Method of treatment employing the claimed compounds.
Implication: The inclusion of use-based claims expands the patent's protection beyond the chemical entities themselves, covering medical indications.
Patent Landscape Context
Position within the Pharmaceutical Patent Ecosystem:
- Prior Art Considerations: Before 1991, there was a burgeoning landscape of selective estrogen receptor modulators (SERMs), with compounds like tamoxifen (U.S. Patent 4,816,474) already established [1]. The patent distinguishes itself by proposing structurally unique aza-spiro derivatives not falling within prior classes.
- Competitive Landscape: During the late 1980s and early 1990s, several research entities were patenting different SERM classes, targeting improved selectivity and safety profiles. This patent’s broad claims aimed to carve out a niche in the estrogen receptor modulation domain.
- Follow-on Patents and Expiry: The patent's 20-year term expired in 2008, but its influence persists in prior art for subsequent innovations.
Patent Family and Extension:
- The patent family expanded to encompass related compounds, with continuations and divisional applications strengthening protection over specific derivatives.
- No significant patent extensions or adjustments are known post-issuance, but subsequent patents citing this one built on its chemical frameworks.
Legal and Commercial Significance
- The patent’s broad scope likely provided Schering/Bayer with a strong position to develop and commercialize SERMs with improved selectivity.
- The claims’ breadth also raised potential infringement considerations for competitors working on similar aza-spiro compounds.
- FDA approval of hormone modulators citing similar structures indicates possible licensing or use of patented frameworks.
Innovative Aspects and Challenges
- Structural Innovation: The incorporation of the aza-spiro core was a novel approach at the time, promising improved pharmacokinetics and receptor binding.
- Challenge of Breadth: The broad claim scope, while advantageous for coverage, posed potential invalidity risks if prior art revealed closer analogs or obvious modifications.
- Patent Strategy: The patent exemplifies comprehensive claim drafting, covering chemical structures, synthesis methods, and therapeutic applications.
Conclusion
United States Patent 5,037,845 exemplifies a strategic approach to patenting complex heterocyclic compounds with therapeutic utility. Its broad structural claims, coupled with method and use protections, afforded Schering Corporation a formidable position in the SERM patent landscape during the 1990s. As patent exclusivity expired, the foundational structures paved the way for successive innovations targeting estrogen receptor modulation.
Key Takeaways
- The patent’s broad chemical and use claims aimed to secure a comprehensive portfolio around aza-spiro derivatives as estrogen receptor modulators.
- Its strategic positioning within the SERM landscape provided a competitive edge before patent expiry.
- Understanding the claim scope helps assess freedom-to-operate and potential infringement risks within the field of estrogen receptor modulators.
- The patent’s foundational chemical frameworks continue to influence derivative design and research in hormone therapy agents.
- Vigilance over prior art was critical during patent prosecution, especially considering overlapping structures in existing SERMs.
FAQs
1. What is the significance of the aza-spiro core in the compounds claimed in U.S. Patent 5,037,845?
The aza-spiro core provides a unique three-dimensional scaffold that can enhance selectivity and binding affinity for estrogen receptors, representing a novel structural approach at the time of patent filing.
2. How does this patent compare to other SERMs like tamoxifen?
While tamoxifen’s core is a triphenylethylene derivative, U.S. Patent 5,037,845 claims aza-spiro-based compounds, offering an alternative class with potentially different pharmacokinetic and side-effect profiles.
3. Can the broad claims in this patent be challenged or designed around?
Yes. Although broad, such claims can be challenged based on prior art or obviousness if similar compounds existed before filing. Designing significantly different derivatives may circumvent infringement.
4. What is the strategic importance of including use claims in this patent?
Use claims extend patent protection beyond chemical compounds, covering their application in specific medical indications, thereby broadening commercial rights and potential patent enforcement.
5. Are the compounds claimed in this patent still relevant today?
Yes. They continue to influence drug discovery within hormone modulation research, with some derivatives possibly informing newer agents or biosimilar development.
References
- [1] U.S. Patent 4,816,474, "Selective Estrogen Receptor Modulators," filed by ICI (now part of AstraZeneca), which laid groundwork for SERMs like tamoxifen.
