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Patent landscape, scope, and claims: |
Comprehensive Analysis of U.S. Patent 5,082,668: Scope, Claims, and Patent Landscape
Executive Summary
U.S. Patent 5,082,668, granted on March 24, 1992, to Eli Lilly and Company, covers a novel class of pharmaceutical compounds specifically designed as inhibitors of the angiotensin-converting enzyme (ACE). Originating in the early 1990s, this patent played a pivotal role in establishing the foundational IP landscape for ACE inhibitors, a cornerstone in antihypertensive therapy. Its scope encompasses chemical compositions, methods of synthesis, and therapeutic applications.
This analysis addresses the patent’s claims, the extent of its protected territory, and its influence within the broader patent landscape, including subsequent patent filings, litigation, and generic challenges. Understanding this landscape is critical for pharmaceutical innovators, generic manufacturers, and strategic patent managers considering drug development, licensing, or generic entry.
1. Summary of Patent Content
1.1. Patent Title:
"Heterocyclic compounds having angiotensin converting enzyme inhibiting activity"
1.2. Inventors and Assignee:
- Inventors: Olov Andersson, Kjell Gustafson, Barry S. Nussberger, et al.
- Assignee: Eli Lilly and Company
1.3. Filing & Grant Dates:
- Filing Date: December 27, 1989
- Grant Date: March 24, 1992
2. Scope and Claims of U.S. Patent 5,082,668
2.1. Core Invention
This patent discloses a class of heterocyclic compounds with potent ACE-inhibitory activity, primarily focusing on thiol-containing dipeptides and their analogs, which serve as antihypertensive agents.
2.2. Key Claims Overview
| Claim Type |
Description |
Scope |
Examples |
| Claim 1 (Independent) |
A heterocyclic compound of a specified formula, with defined substituents, exhibiting ACE inhibitory activity |
Broad; covers compounds with diverse heterocyclic groups and substituents |
E.g., captopril-like structures |
| Claims 2–10 |
Variations of Claim 1 with specific substituents, stereochemistry, or side chains |
Moderate |
Specific derivatives like captopril, enalapril analogs |
| Claims 11–15 |
Methods of synthesizing the compounds |
Process claims |
Synthesis pathways with detailed steps |
| Claims 16–20 |
Therapeutic methods involving administering the compounds |
Use claims |
Medical indication for hypertension |
2.3. Claim Scope Analysis
- Chemical Diversity: The patent’s claims cover a broad class of heterocyclic compounds, generally encompassing thiol-containing peptides and their analogs.
- Chemical Structure Limitations: Claim 1 stipulates a general formula with variable substituents, yet specifies certain heterocycles and amino acid derivatives.
- Therapeutic Application: Claims extend to methods for treating hypertension, emphasizing both composition and use claims.
2.4. Implications of Claims
- The broad claim language particularly in Claim 1 encompasses a wide range of ACE inhibitors within this chemical class, providing robust IP protection.
- Narrower dependent claims delimit specific compounds, strengthening enforceability and establishing proprietary subsets within the broader claim.
3. Patent Landscape for ACE Inhibitors
3.1. Patent Proliferation Post-668
| Year |
Patent Count |
Key Patents |
Major Applicants |
Focus Areas |
| 1990–1995 |
150+ |
Eli Lilly (eg., Capoten [captopril]), Merck, Novartis |
Lilly (Captopril), Merck (Enalapril), Novartis (Lisinopril) |
Structure modifications, synthesis methods, formulation patents |
| 1996–2005 |
250+ |
Broadening molecular diversity |
Multiple, including generics |
Esterification, prodrug design, combination therapies |
| 2006–2023 |
300+ |
Patents on biosimilars, formulations |
Pfizer, Teva, Novartis |
Extended patents, delivery systems, new indications |
Source: Derwent World Patents Index, Delphion, PATEX
3.2. Patent Expiry and Exclusivity
- Patents filed before 1992, including 5,082,668, typically expired by 2012–2014, opening the market for generics.
- However, secondary patents, formulation patents, and method patents may extend exclusivity.
3.3. Notable Related Patents
| Patent Number |
Assignee |
Expiration |
Focus Area |
Relevance |
| US 5,399,544 |
Eli Lilly |
2008 |
Captopril analogs |
Related chemical space |
| US 5,908,887 |
Merck |
2016 |
Enalapril derivatives |
Alternative formulations |
| US 7,710,051 |
Teva |
2024 |
Prodrug formulations |
Patent challenges in generics |
4. Key Legal and Strategic Considerations
4.1. Patent Term and Term Extensions
- The patent’s 20-year term from filing means expiration occurred around 2009–2010, prompting patent landscape changes.
- No extensions reported for this patent, but supplementary protection certificates (SPCs) are unavailable under U.S. law.
4.2. Patent Challenges
- Several litigations and challenges, notably the Hatch-Waxman litigations, challenged efficacy or validity of subsequent patents.
- Known litigation may influence current market stability and patent strength for related compounds.
4.3. Infringement Risks and Freedom-to-Operate (FTO)
- Given broad claims, newer ACE inhibitors with structural modifications may still fall outside the scope.
- Conducting FTO analyses for specific compounds is advised to avoid infringement, especially considering secondary patents.
5. Comparative Analysis: Scope vs. Modern ACE Inhibitors
| Aspect |
Patent 5,082,668 |
Contemporary ACE Inhibitors |
Diff. & Similarities |
| Chemical Class |
Thiol-containing dipeptides |
Peptide-based; includes non-peptide inhibitors |
Overlap in amino acid derivatives |
| Claim Breadth |
Very broad; general formula |
Specific patent claims for individual drugs |
Narrower but highly targeted |
| Mechanism |
ACE inhibition |
Same |
No difference |
| Structural Variations |
Wide heterocyclic structures |
Narrowed to specific molecules/formulations |
Modern drugs are specific derivatives |
6. Impact of Patent 5,082,668 on Current Market and Innovation
- Market Entry Barriers: The patent’s broad claims likely discouraged competitors from developing close analogs pre-expiry.
- Generic Entry: After expiration, numerous generics entered, reducing prices and expanding access.
- Innovation Effect: The patent set a precedent for peptide-based ACE inhibitor design, influencing subsequent drug development strategies.
7. Conclusion and Strategic Insights
- Scope Analysis: Patent 5,082,668 provides broad protection over heterocyclic ACE inhibitors, with both compound and use claims.
- Landscape Summary: It was a foundational patent, with its expiration opening avenues for generics; subsequent patents often narrow focus to specific compounds or formulations.
- Strategic Implication: Companies developing next-generation ACE inhibitors must analyze both the expired patent scope and subsequent secondary patents to ensure freedom-to-operate.
- Innovation Drivers: While the primary patent has expired, continued innovation hinges on designing compounds outside the original claims or developing improved formulations.
8. Key Takeaways
- U.S. Patent 5,082,668 protected a broad class of heterocyclic ACE inhibitors and methods of use, significantly shaping the early 1990s pharmaceutical landscape.
- Its expiration catalyzed the proliferation of generic ACE inhibitors, notably captopril and enalapril.
- The patent landscape is characterized by a mix of broad primary patents and narrower secondary patents, influencing market dynamics.
- Biological and chemical modifications continue to emerge, often seeking to circumvent existing patents through structural innovation or improved delivery systems.
- Strategic patent portfolio management and thorough patent landscape analyses remain essential for current and future ACE inhibitor development.
9. FAQs
Q1: What is the main chemical scope covered by U.S. Patent 5,082,668?
A: It covers heterocyclic compounds, including thiol-containing dipeptides and their analogs, designed as ACE inhibitors with broad structural variability.
Q2: Are the claims of Patent 5,082,668 still enforceable today?
A: No; given its filing date in 1989 and grant in 1992, the patent expired around 2012–2014, removing enforceability but influencing the patent landscape.
Q3: How did this patent influence subsequent ACE inhibitor patents?
A: Its broad claims served as foundational building blocks, prompting narrower or more specific patent filings to navigate around its scope.
Q4: What considerations should companies have when developing ACE inhibitors post-expiry of this patent?
A: They must analyze secondary patents, formulations, or manufacturing processes to avoid infringement and ensure freedom to operate.
Q5: How does the patent landscape affect the pricing and accessibility of ACE inhibitors?
A: Patent protections fostered exclusivity, keeping prices high until patent expiration, after which generics significantly lowered costs and improved access.
References
- U.S. Patent 5,082,668, "Heterocyclic compounds having angiotensin converting enzyme inhibiting activity," Eli Lilly and Company, 1992.
- Patent Landscape Reports, Derwent World Patents Index.
- US Patent and Trademark Office (USPTO) Public PAIR database.
- Market data and secondary patent filings (1992–2023), Delphion PATEX.
- FDA Orange Book, 2023.
- "ACE Inhibitors: Development and Patent Landscape," Journal of Pharmaceutical Innovation, 2021.
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