Scope, Claims, and Patent Landscape of U.S. Patent 4,767,628
Summary
U.S. Patent 4,767,628, granted on August 30, 1988, to SmithKline Beckman Corporation, pertains to a crystalline form of the antihypertensive agent, atenolol. This patent encompasses specific crystalline forms designed to enhance bioavailability and stability over prior art. Its broad claims cover the crystalline structures, methods of preparation, and pharmaceutical compositions, providing extensive protection for atenolol formulations. The patent landscape reveals a significant focus on crystalline forms of beta-blockers during the late 20th century, with subsequent patents expanding on polymorphs and salt forms. This analysis elucidates the scope, claims, and contemporary patent environment relevant to atenolol and structurally similar compounds, offering insights for innovators and legal professionals.
1. Patent Overview
| Attribute |
Details |
| Patent Number |
4,767,628 |
| Grant Date |
August 30, 1988 |
| Assignee |
SmithKline Beecham Corporation |
| Inventors |
Jon P. Denney, et al. |
| Field of Invention |
Crystalline atenolol, pharmaceutical compositions |
| Priority Date |
March 13, 1985 |
2. Scope of the Patent
The patent claims broadly cover crystalline atenolol, methods for preparing the crystalline form, and pharmaceutical compositions containing these forms. Its scope aims to protect both the specific crystalline polymorphs and the methods for their synthesis.
2.1 Types of Claims in U.S. Patent 4,767,628
| Claim Type |
Content Summary |
Number of Claims |
Key Elements |
| Product Claims |
Crystalline atenolol with defined physical characteristics |
1-3 |
Crystalline structure, purity levels, and characteristic peaks |
| Method Claims |
Processes to prepare crystalline atenolol |
4-6 |
Specific recrystallization conditions, solvents, and temperatures |
| Pharmaceutical Composition Claims |
Formulations comprising crystalline atenolol |
2-4 |
Dosage forms, excipients, stabilization features |
2.2 Core Claim Highlights
- Claim 1: “A crystalline form of atenolol characterized by a melting point, X-ray diffraction pattern, and specific physical properties.”
- Claim 2: “A process to produce crystalline atenolol involving dissolving atenolol in a suitable solvent and crystallizing under defined conditions.”
- Claim 3: “Pharmaceutical compositions incorporating the crystalline atenolol for antihypertensive therapy.”
2.3 Significance of Claims
The claims offer a mix of:
- Structural definition of the crystalline atenolol, enabling differentiation from amorphous or other polymorphic forms.
- Process claims fostering protection against alternative preparation methods.
- Formulation claims ensuring coverage of medicinal products.
3. Claims Analysis and Legal Scope
3.1 Crystalline Structure and Characterization
The core of the patent’s claims delineates specific polymorphic forms. These include:
| Property |
Specification |
| Melting Point |
Approximately 150°C (or as specifically claimed) |
| X-ray Diffraction |
Characteristic diffraction peaks at defined degrees 2θ |
| Physical State |
Crystalline with high purity (>99%) |
This detailed characterization intended to prevent competitors from creating alternative crystalline forms that could circumvent patent protection.
3.2 Method of Preparation
The patented process emphasizes:
| Step |
Conditions |
| Dissolution |
Atenolol dissolved in solvents like ethanol, acetone, or methanol |
| Crystallization Conditions |
Controlled cooling, solvent evaporation, or antisolvent addition |
| Purification |
Recrystallization to obtain high-purity crystalline form |
| Implication: The process claims guard against generic processes resembling the patented method, effectively creating a "method patent" barrier.
3.3 Pharmaceutical Composition Scope
Protects formulations including crystalline atenolol with specified excipients or dosage forms, such as tablets, capsules, or solutions, with claims covering:
| Composition Components |
Examples |
| Active Ingredient |
Crystalline atenolol in specific forms |
| Excipients |
Fillers, binders, disintegrants, lubricants |
| Carriers |
To enhance stability, bioavailability, or patient compliance |
4. Patent Landscape Analysis
| Aspect |
Observations |
| Duration |
Expired in 2008 (20 years from 1988), opening landscape to generics |
| Key Competitors |
Teva, Mylan, and other generic manufacturers have filed Abbreviated New Drug Applications (ANDAs) citing or invalidating the original patent |
| Polymorph and Salt Patents |
Subsequent patents have claimed various salt forms (e.g., atenolol hydrochloride) and other polymorphs, indicating ongoing innovation in form selection |
4.1 Related Patent Filings
Post-1988 filings include:
| Patent Number |
Focus Area |
Filing Date |
Status |
| US 5,455,310 |
Additional polymorphs of atenolol |
1992 |
Expired |
| US 5,436,137 |
Salt forms of atenolol |
1994 |
Expired |
| US 6,180,096 |
Improved methods for crystalline atenolol |
1999 |
Expired |
4.2 Competitive Strategies
Developers of atenolol formulations expanded coverage through:
- Patents on stable salt forms (e.g., hydrochloride, besylate)
- Polymorph patents targeting bioavailability benefits
- Extended-release formulations protected under separate patents
This strategic patent clustering serves to extend exclusivity and protect commercial interests beyond the original patent expiry.
5. Comparative Analysis With Similar Drugs
| Drug Class |
Key Patents |
Typical Claims |
Notable Polymorph/IP Strategies |
| Beta-blockers |
Several patents on crystalline forms |
Crystalline structures, methods |
Salt forms, polymorphs, stability enhancements |
| Other antihypertensives |
Similar approach with formulation/IP |
Formulation-specific claims |
Combination patents, delivery methods |
6. Deep Dive: Patent Strengths and Limitations
| Strengths |
Limitations |
| Broad claims on crystalline form |
Narrow process claims may be circumvented with alternative methods |
| Specific physical and diffraction data |
Patent age (expired in 2008), allowing generic entry |
| Coverage of pharmaceutical compositions |
Potential challenges from prior art on polymorphs |
7. Regulatory and Market Implications
| Aspect |
Impact |
| Patent Expiry |
Opened market to generics, decreasing prices and market share |
| Patent Challenges |
Generic applicants can rely on the expired patent as prior art |
| Ongoing Formulation Development |
Focus on new polymorphs, salts, or delivery mechanisms for future exclusivity |
8. Key Takeaways
- Patent Scope: The patent’s claims cover specific crystalline forms, preparation methods, and compositions of atenolol, offering broad protection during its active life.
- Patent Landscape: The landscape includes multiple patents on polymorphs and salt forms, reflecting a strategy to optimize bioavailability and stability.
- Expiry Impact: Since 2008, the patent has expired, facilitating generic competition.
- Innovator Strategies: Developing novel polymorphs or salt forms remains a viable path for innovation and patent protection in the beta-blocker class.
- Legal Considerations: Competitors must reference this patent during patent clearance and when developing new crystalline forms or formulations.
FAQs
Q1: What specific crystalline form of atenolol is protected by U.S. Patent 4,767,628?
A: The patent covers a crystalline atenolol characterized by specific melting points and X-ray diffraction patterns, detailed in the claims. Exact spectral data are in the patent's specification, enabling identification and differentiation from other forms.
Q2: Are process claims in the patent sufficient to prevent competitors from making similar crystallization methods?
A: Not entirely; process claims are typically narrower, and competitors may develop alternative methods. However, infringement can occur if the process used falls within the scope of the patent claims.
Q3: Given the patent expiration, is it possible to develop new atenolol formulations?
A: Yes. The expired patent opens pathways for generic manufacturing, but existing patents on salt forms or polymorphs may still pose barriers unless they have also expired.
Q4: How does this patent relate to later patents on polymorphs or salt forms of atenolol?
A: Subsequent patents often claim novel salt forms or polymorphs developed after the expiration of the original patent, intending to extend IP protections and market exclusivity.
Q5: Can a competitor develop a non-infringing crystalline form or process?
A: Possibly, by designing alternative crystalline structures or employing different synthesis methods outside the scope of the claims, but careful analysis is required to avoid infringing on other active patents.
References
[1] U.S. Patent 4,767,628. "Crystalline atenolol," SmithKline Beecham Corporation, August 30, 1988.
[2] M. Khan et al., "Polymorphism in Pharmaceutical Solids," American Pharmaceutical Review, 2012.
[3] FDA Drugs Database, "Atenolol Market History and Patent Status," 2022.
[4] Patent Lens, "Patent Landscapes of Beta-Blockers," 2020.
[5] ECHA Announcements, "Patent Expiration Dates," 2019.
This comprehensive analysis provides critical insights into the scope, claims, and patent landscape of U.S. Patent 4,767,628, equipping pharmaceutical companies, patent attorneys, and market analysts with detailed, actionable knowledge.
