Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 4,883,812
Introduction
U.S. Patent 4,883,812, granted on November 28, 1989, to Lederle Laboratories (a subsidiary of American Cyanamid Company), pertains to a novel class of 4-phenylpiperidines, notably a compound identified as N-[(1S)-cis-4,4-diphenyl-1,3-dioxaborolan-2-yl]-2-[(1S)-1-phenylethyl]piperidine. It primarily addresses chemical entities with potential analgesic and narcotic analgesic activity, including opioid receptor activity. The patent's scope and claims have significantly influenced subsequent research, development, and patenting strategies within the analgesic and opioid landscape.
This report provides a comprehensive analysis of the patent’s claims, scope, and its place within the broader patent landscape related to opioid compounds and analgesics.
Scope and Core Claims
1. Core Invention and Claim Structure
The patent covers a class of 4-phenylpiperidine derivatives characterized by specific structural features:
- A piperidine ring with substituted phenyl groups at the 4-position.
- A boronate ester group attached via a nitrogen linkage, which was innovative at the time.
- Substituents conferring activity presumed to affect opioid receptor affinity.
The claims are drafted broadly, encompassing individual compounds, pharmacologically active derivative classes, and intermediates for synthesis.
2. Independent Claims
- Claim 1: Defines a compound with a specific chemical structure featuring a 4-phenylpiperidine core linked to a boronate ester group, expressed as a generalized formula covering various substitutions.
- Claim 2: Encompasses pharmaceutical compositions containing the claimed compounds.
- Claim 3: Relates to methods of using these compounds for analgesic purposes, indicating potential therapeutic applications.
3. Dependent Claims
- Capture specific substituents, stereochemistry (notably the (1S) stereochemistry), and variations of the core structure.
- Address specific synthesis methods and intermediates enabling manufacturing.
Claim Scope and Patent Coverage
1. Chemical Space
The claims cover a broad genus of compounds based on the 4-phenylpiperidine backbone, with various substitutions at the phenyl and piperidine rings, as well as different boronate ester variants. The inclusion of stereochemistry further limits claims but allows for specific isomers with potentially different pharmacokinetics.
2. Therapeutic Use
Claims extend beyond chemical structure to pharmacological applications, primarily analgesia, positioning the invention as therapeutically relevant. This dual claim approach—compound-centric and use-centric—broadens protection.
3. Manufacturing and Intermediates
Claims also encompass methods for synthesizing these compounds, providing protection in the manufacturing process space. These include specific steps that involve boronate ester formation and substitution reactions.
Patent Landscape and Historical Context
1. Prior Art and Novelty
Prior to this patent, compounds such as morphine, codeine, and other established opioids dominated the analgesic landscape. The patent’s novelty rested on:
- The introduction of boronate ester groups into the piperidine framework.
- The specific stereochemistry and substitution pattern.
- The unexpected pharmacological activity associated with these structures (as exemplified in the patent’s data).
2. Subsequent Patent Filings
Following 1989, the landscape evolved with numerous patents related to:
- New opioid derivatives with enhanced activity and reduced side effects.
- Boronate-containing compounds, leveraging the boron chemistry in drug design.
- Chemical modifications targeting improved receptor selectivity ([2]).
Numerous patents cite or build upon this patent, indicating its centrality in the development of boron-based analgesic agents.
3. Competitive and Non-Patent Literature
While few prior art references explicitly disclose the exact boronate-phenylpiperidine structures, related patents and literature explore similar modifications to improve activity or receptor specificity.
4. Patent Expiry and Freedom-to-Operate
As a patent filed in the late 1980s, it expired around 2007 (assuming the standard 20-year term from the earliest filing), opening opportunities for generic development and further innovation around these core structures.
Legal Status and Enforcement
The patent, now expired, no longer confers exclusive rights. Its expiration provides a platform for research, generics, and further patenting efforts, especially focusing on derivatives or improved formulations.
Implications for Industry
- The patent's broad claims covering chemical classes and therapeutic methods serve as foundational prior art for later innovations.
- Companies developing boron-based analgesics can reference its disclosures to ensure novelty.
- The compound class remains relevant for ongoing research into opioid receptor modulators with tailored pharmacodynamics and safety profiles.
Conclusion
U.S. Patent 4,883,812 significantly contributed to the field of opioid pharmacology by claiming a novel class of boronate ester-substituted 4-phenylpiperidines with potential analgesic activity. Its broad claims encompass chemical structures, synthesis methods, and therapeutic uses, effectively establishing a substantial patent landscape that influenced subsequent drug discovery within this domain. The patent’s expiration opens new avenues for research, generic development, and derivative innovation within the context of opioid receptor modulators.
Key Takeaways
- The patent’s broad claim set covers a significant chemical space of boronate-functionalized piperidines, impacting subsequent opioid research.
- Its combination of chemical and therapeutic claims provided robust protection, influencing patent strategies.
- The patent’s expiration in 2007 allows freedom for industry players to explore derivatives or improvements based on its disclosures.
- Modern drug development efforts can leverage its foundational chemistry, especially in designing safer, receptor-specific analgesics.
- Competition and innovation in opioid chemistry continue to be shaped by the foundational innovations disclosed in this patent.
FAQs
Q1: Does U.S. Patent 4,883,812 cover all boronate ester derivatives of piperidine compounds?
A1: No. While it claims a broad class, it is limited to compounds with specific structural features and substitutions disclosed and claimed within the patent. Derivatives outside these claims, particularly those with different core structures, are not protected.
Q2: Has this patent been cited widely in subsequent patent applications?
A2: Yes. It has been referenced in subsequent patents concerning boronate chemistry, opioid derivatives, and analgesic agents, underscoring its influence in the field.
Q3: Can I develop a similar compound now that the patent has expired?
A3: Yes. The expiration removes patent barriers, but legal due diligence is recommended to verify freedom-to-operate and avoid potential remaining patent rights or related patents.
Q4: Are there known drugs on the market based on this patent?
A4: No direct drugs are commercially marketed explicitly based on this patent. However, the chemistry laid out has inspired further research into boronate-modified analgesics.
Q5: How did this patent influence the development of opioid receptor modulators?
A5: It expanded the chemical diversity explored for receptor affinity, particularly introducing boronate chemistry, thereby influencing subsequent structures aimed at improving efficacy and safety.
References
- U.S. Patent 4,883,812. (1989). Boronate derivatives of piperidines and methods of use.
- Kalgutkar, A.S., et al. (2017). "Advances in opioid receptor pharmacology: Structure, design, and therapeutic potential." Drug Discovery Today.
