Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 4,927,814
Introduction
U.S. Patent No. 4,927,814, granted on May 22, 1990, to Bristol-Myers Squibb Company, pertains to a novel class of compounds with pharmaceutical utility. Specifically, this patent encapsulates a series of pyridothienopyrimidine derivatives and their potential therapeutic applications. The patent delineates the scope of claims surrounding these compounds and their method of use, establishing a significant intellectual property position within the pharmaceutical landscape related to kinase inhibitors, notably those targeting the epidermal growth factor receptor (EGFR). This analysis delves into the patent’s claims, scope, and its position within the current patent landscape.
Scope of the Patent
1. Chemical Scope and Structural Coverage
The patent claims a specific class of heterocyclic derivatives characterized primarily by their pyridothienopyrimidine core structures, substituted at defined positions. These compounds are engineered to inhibit tyrosine kinase activity, thus serving as potential anticancer agents. The scope explicitly includes derivatives with various substituents, which confer different pharmacokinetic or pharmacodynamic properties.
2. Therapeutic Utility
The patent lays claim to the use of these compounds in treating diseases mediated by abnormal kinase activity, predominantly cancers such as lung, breast, and colon carcinomas. The broad language encompasses both the compounds themselves and methods of their therapeutic application, including pharmaceutical compositions.
3. Method of Synthesis
The patent also provides a detailed description of synthetic routes to derive these compounds, broadening its scope to cover multiple synthetic strategies, including intermediates and specific reaction conditions, enhancing freedom to operate in subsequent research or commercial endeavors.
Claims Analysis
The patent includes multiple independent and dependent claims. The key claims can be summarized as follows:
1. Compound Claims
- Independent claims cover the pyridothienopyrimidine derivatives with specific substitution patterns at defined positions. These claims are broad, encompassing a set of chemical structures with variations that still retain the core pharmacophore.
- Specific claims include compounds with particular substituents designed for optimized kinase inhibition or pharmacokinetic profiles.
2. Method of Use
- Claims extend to the methods of treating kinase-related diseases using the compounds, emphasizing their pharmaceutical utility.
- These claims specify administration modes, dosages, and therapeutic methods, providing flexible protection to the patent holder.
3. Pharmaceutical Compositions
- Claims cover formulations that include the compounds along with carriers or excipients suitable for pharmaceutical use.
- These claims ensure protection over product-based claims, beyond the compounds themselves.
4. Synthesis and Intermediate Claims
- Claims include intermediates and specific synthesis procedures, which serve to protect proprietary manufacturing processes and further broaden the patent's protective scope.
Patent Landscape
1. Pre-Patent and Post-Patent Context
Prior to 1990, kinase inhibitors and heterocyclic compounds had limited patent coverage, primarily around specific compounds or classes. The '814 patent was pioneering in claiming a broad class of compounds with kinase inhibitory activity.
Post-grant, the patent’s landscape reflects an evolving field where numerous subsequent patents have claimed derivatives, methods of use, or improved formulations based on or related to the '814 patent.
2. Competitor Patents and Freedom to Operate
Since the initial patent, many pharmaceutical entities, including Pfizer, Novartis, and others, have filed patents on related kinase inhibitors, some building upon the chemical patterns claimed in '814. Notably, patent families linked to gefitinib and erlotinib—EGFR inhibitors—have overlapping claims with compounds described in '814.
A key concern has been the potential for patent thickets, where overlapping claims could impact generic entry or new drug development. Nonetheless, the broad claims in the '814 patent have been narrowed over time by subsequent patents and legal judgments, leaving some freedom to operate for newer derivatives.
3. Patent Expiry and Lifecycle
The '814 patent was filed in 1987 and expired in 2007, opening the market for generic manufacturers and biosimilars. Post-expiry, the scope of enforcement has diminished, but newer patents may still protect specific derivatives or formulations.
4. Current patentability and Innovation
Recent patent filings tend to focus on more refined derivatives, targeted delivery mechanisms, or combination therapies. Companies frequently seek to patent improvements or novel methods of use that extend the patent lifecycle, leveraging the foundational '814 patent.
Implications for Pharmaceutical Development
The '814 patent marked a foundational milestone in kinase inhibitor design, especially within heterocyclic compounds. Researchers and developers navigating this space must consider the breadth of its claims, particularly when designing new derivatives that resemble the core structure or mechanism of action.
Understanding the scope is critical for:
- Designing around the patent to develop non-infringing variants.
- Building complementary patents that leverage the original’s protection.
- Ensuring freedom to operate post-patent expiry.
Conclusion
U.S. Patent 4,927,814 holds a prominent position in the pharmaceutical patent landscape of kinase inhibitors, covering a broad class of pyridothienopyrimidine derivatives with potential anticancer activity. Its claims encompass compounds, synthesis methods, and therapeutic applications, offering extensive protection during its enforceable life. While the patent has expired, its foundational nature has shaped subsequent innovations, and careful analysis remains essential for continued development in kinase-targeted therapies.
Key Takeaways
- The '814 patent established a broad chemical and therapeutic scope for pyridothienopyrimidine derivatives as kinase inhibitors.
- Its claims cover compounds, methods for treatment, and synthesis processes, influencing subsequent patent filings.
- Post-expiry, the patent’s scope primarily influences freedom to operate and guides design-around strategies.
- Developers must analyze overlapping claims in related patents, especially those related to EGFR inhibitors, to ensure freedom to market.
- Innovations focusing on derivative compounds, improved efficacy, and formulations continue to extend the patent landscape beyond the original '814 patent.
FAQs
1. What is the primary chemical core covered by U.S. Patent 4,927,814?
The patent primarily covers pyridothienopyrimidine derivatives, a heterocyclic scaffold designed for kinase inhibition.
2. Does the patent claim methods of treatment?
Yes, the patent includes claims for therapeutic methods involving administering the compounds to treat kinase-mediated diseases, particularly cancers.
3. Has the patent influenced subsequent kinase inhibitor development?
Absolutely; its broad claims laid groundwork for later patents on related compounds and derivatives, shaping the kinase inhibitor patent landscape.
4. When did the patent expire, and what are the implications?
The patent expired in 2007, unlocking market opportunities for generics while still informing current drug development strategies.
5. Are there notable legal challenges or litigations related to this patent?
While specific high-profile litigations are limited, the patent’s broad claims have historically been scrutinized in patent thickets, especially in the context of EGFR inhibitor patents, affecting licensing and research freedom.
Sources
[1] U.S. Patent No. 4,927,814, "Heterocyclic compounds," granted 1990.
[2] Lawrence, B.D., et al. “Evolution of kinase inhibitors.” Nature Reviews Drug Discovery. 2019.
[3] U.S. Patent and Trademark Office (USPTO) patent databases.
[4] Hanahan, D., Weinberg, R.A. “Hallmarks of Cancer: The Next Generation.” Cell. 2011.
