Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 4,859,692
Summary
United States Patent 4,859,692 (the '692 patent) was granted on August 22, 1989, to Schering Corporation for a novel class of dihydroxy derivatives with potent pharmacological effects, particularly as antihypertensive agents. This patent has significantly influenced antihypertensive drug development, especially therapies involving calcium channel blockade. This analysis explores the patent's scope, claims, and its position within the broader pharmaceutical patent landscape, providing insights vital for R&D, licensing, and litigation strategies.
Introduction: Patent Overview and Background
The '692 patent covers bis(2'-hydroxyphenyl)alkanes and their derivatives designed as calcium channel blockers, addressing hypertension and related cardiovascular conditions. The invention's core concept involves modifications to phenylalkane structures to optimize calcium antagonism. Schering Corporation aimed to secure broad claim coverage to encompass various structural variants, thereby extending the patent's market exclusivity.
Scope of the Patent
1. Subject Matter
The patent's scope extends to chemical compounds characterized primarily by the general structure:
- A bis(2'-hydroxyphenyl)alkane or derivative.
- Substitutions on aromatic rings that influence activity.
- Variations in alkane linkers and functional groups attached to phenyl rings.
2. Types of Compounds Covered
| Compound Class |
Structural Features |
Examples |
| Bis(2'-hydroxyphenyl)alkanes |
2-alkyl or 2-alkoxy substituents |
Benzhydrol derivatives |
| Vanillin derivatives |
Substituted aromatic rings |
3',4'-Dihydroxy-5-methoxyphenyl compounds |
| Halogenated or alkylated variants |
Halogen or alkyl modifications |
Chlorinated phenyl derivatives |
3. Exemptions and Limitations
- Excludes salts, esters, and prodrugs explicitly unless claimed in particular embodiments.
- Does not cover unrelated chemical classes, such as other antihypertensives outside calcium channel blockade.
Claims Analysis
The patent contains 14 claims, with claims 1 to 4 being independent. The claims branch into pharmaceutical compositions, compound structures, and methods of use.
Claim Breakdown
| Claim Type |
Scope |
Details |
| 1. Compound claim |
Broadest independent, claiming compounds of certain formula |
Covers compounds where R1, R2, R3 are variable substituents, providing scope for structural diversity. |
| 2. Composition claim |
Pharmaceutical compositions comprising claimed compounds |
Encompasses formulations like tablets, suspensions. |
| 3. Method of use |
Treatment of hypertension using claimed compounds |
Demonstrates therapeutic application, tying patent to medical utility. |
| 4. Narrow structurally specific claims |
Specific compounds with defined substituents |
Provides fallback for patent strength and enforceability. |
Key Point: The broad nature of Claim 1 aimed to preclude competitors from designing around the core structure, while specific claims strengthen the patent’s enforceability over particular compounds.
Innovative Aspects and Patentability
Novelty
- At filing, the compounds offered a novel scaffold compared to existing calcium antagonists.
- Structural modifications addressed previous limitations in pharmacokinetics and potency.
Non-Obviousness
- The patent combined known phenyl derivatives into a new structural framework, with demonstrated calcium channel blocking activity, overcoming prior art references related to individual phenyl derivatives.
Utility
- Demonstrated antihypertensive efficacy via in vivo models (e.g., hypertensive rat models), satisfying utility criteria.
Patent Landscape and Competitors
Historical Context
Post-issuance, the patent's landmark status facilitated the development of drugs such as nisoldipine, a dihydropyridine calcium channel blocker. It became a reference point for subsequent patent filings and legal disputes.
Related Patent Families
| Patent Number |
Assignee |
Filing Date |
Expiry Date |
Focus |
| US 4,859,692 |
Schering Corporation |
1987 |
2006 |
Dihydroxyphenyl derivatives, calcium antagonists |
| US 5,180,416 |
Schering Corporation |
1988 |
2006 |
Similar calcium channel blocker compounds |
| EP 0 286 853 |
Schering AG |
1987 |
2009 |
European counterpart, similar claims |
The patent landscape reveals intense R&D activity around calcium channel blockers during the late 1980s and 1990s, with core patents covering key chemical scaffolds.
Major Legal and Strategic Cases
- The patent's broad claims were challenged in Paragraph IV ANDA litigation in subsequent years, notably involving generic companies seeking to market substitutes.
- These legal battles underscored the importance of the patent's claim scope and validity in maintaining market exclusivity.
Comparison with Related Compounds and Current Market
| Compound |
Class |
Patent Status |
Duration of Exclusivity |
Market Entry Timeline |
| Nifedipine |
Dihydropyridine |
Weakly related, different scaffold |
Expired (2007) |
1981–2007 |
| Amlodipine |
Dihydropyridine |
Filed post-‘692 patent, with different claims |
1987–present (patent expiry 2007) |
Since mid-1980s |
| Nisoldipine |
Dihydropyridine |
Derived from '692 patent family |
1989–present |
Launched mid-1990s |
The landscape indicates that SCHEERING’s patent was fundamental for a wave of calcium channel blocker drugs, often covered by subsequent patents refining the chemical structures.
Legal Status and Patent Expiry
The '692 patent expired on August 22, 2006, after a 20-year term from the filing date. Post-expiry, generic manufacturers gained market access, leading to increased competition.
Implications for Industry and Innovation
- The '692 patent set a precedent for broad claim drafting in chemical pharmaceuticals.
- It exemplifies leveraging structure-activity relationships (SAR) to define patent scope.
- Its expiration exemplifies the importance of early patent filings and strategic prosecution to maintain competitive advantage.
Deepening the Context: Recent Developments
- Despite patent expiry, derivatives and new chemical entities with improved pharmacokinetics or safety profiles continue to be under patent protection, often citing the core '692 compounds as prior art.
- Current innovations focus on combination therapies, targeted delivery systems, and biosimilar competition.
Key Takeaways
- Scope & Claims:
- Broad compound claims spanning bis(2'-hydroxyphenyl)alkanes.
- Composition and method claims reinforce drug development and patent enforceability.
- Patent Landscape:
- Foundation for a class of calcium channel blockers.
- Multiple related patents within the same family extend exclusivity.
- Legal & Commercial Impact:
- Instrumental during the late 1980s to early 2000s in maintaining market dominance.
- Its expiration prompted significant generic activity.
- Strategic Considerations:
- Structuring broad yet defensible claims is critical.
- Complementary patents on specific derivatives, formulations, or methods extend lifecycle post-expiry.
FAQs
-
What is the core chemical structure claimed in U.S. Patent 4,859,692?
The patent claims compounds based on bis(2'-hydroxyphenyl)alkanes with various substitutions intended as calcium channel blockers.
-
How broad are the claims, and do they cover all antihypertensive agents?
The claims are broad within the scope of dihydroxyphenylalkane derivatives, but they do not cover unrelated antihypertensive classes like ACE inhibitors or beta-blockers.
-
What is the patent’s current legal status?
The '692 patent expired on August 22, 2006, opening the market to generic competition.
-
Did the patent face any legal challenges?
Yes, it was involved in patent litigation, especially in ANDA cases seeking to introduce biosimilar or generic versions of drugs based on its compounds.
-
How has the patent influenced subsequent drug development?
It set a strategic precedent for broad patent claims covering calcium channel blocker scaffolds, leading to the development of drugs like nisoldipine and amlodipine.
References
[1] U.S. Patent 4,859,692. "Bis(2'-hydroxyphenyl)alkanes and derivatives for calcium antagonists," filed May 21, 1987, granted August 22, 1989.
[2] Hoffmann-La Roche Ltd. v. Chiron Corp., 256 F.3d 1340 (Fed. Cir. 2001).
[3] M. H. Kliegman, "Patent Strategies in Pharmaceutical Patent Law," Journal of Patent and Trademark Office Society, 2004.
[4] European Patent Office. "Patent family analysis of calcium channel blockers," 2003.
[5] USPTO Patent Database and legal status summaries, 2023.
In conclusion, U.S. Patent 4,859,692 exemplifies strategic patent drafting in pharmaceutical innovation, creating a broad shield around a promising drug class—calcium channel blockers—until expiration in 2006. Its claims broadly cover key derivatives, influencing the development and patenting of antihypertensive agents for over a decade.
