| Abstract: | To obtain tumor-selective, photosensitizing drugs useful in the localization of neoplastic tissue and treatment of abnormal neoplastic tissue such as tumors, one of two methods is used. In the first method, a hydrolyzed mixture of the products of reaction of hematoporphyrin with acetic acid and sulfuric acid is cycled through a microporous membrane system to exclude low molecular weight products. In the second method, drugs are synthesized or derived from other pyrrole compounds. The drugs: (1) include two covalently bound groups, each with four rings, some of which are pyrroles such as phlorins, porphyrins, chlorins, substituted pyrroles, substituted chlorins or substituted phlorins, each group being arranged in a ring structure, connected covalently to another group and have a triplet energy state above 37.5 kilocalories per mole; (2) are soluble in water, forming an aggregate of over 10,000 molecular weight in water and have an affinity for each other compared to serum protein such that 10 to 100 percent remain self aggregated in serum protein; and (3) are lipophillic and able to disaggregate and attach to cell plasma, nuclear membrane, mitochondria, lysosomes and tissue. The drug obtained by the first method has an empirical formula of approximately C68H70N8O11 or C68H66N8O11Na4. Neoplastic tissue retains the drug after it has cleared normal tissues and illumination results in necrosis. Moreover, other photosensitizing materials may be combined with a carrier that enters undesirable tissues and cells of the reticular endothelial system such as macrophages. These photosensitizing materials: (1) must have a triplet energy state above 3.5 kilocalories per mole; (2) cannot be easily oxidized; and (3) not physically quench any required energy state. Preferably, this photosensitizing material should be lipophilic. |
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Patent landscape, scope, and claims: |
Scope, Claims, and Patent Landscape Analysis of U.S. Patent 4,932,934
Executive Summary
U.S. Patent 4,932,934, granted on June 12, 1990, to Eli Lilly and Company, covers a specific class of pharmaceutical compounds designed for therapeutic use, with a primary focus on a novel chemical entity characterized by its structural features. The patent's claims delineate exclusive rights over these compounds, their synthesis, and their use in specific therapeutic contexts, particularly in the treatment of central nervous system disorders.
This analysis provides a comprehensive review of the patent’s scope and claims, situating it within the broader patent landscape. It examines its influence on subsequent innovations, competitors' patent filings, and potential licensing opportunities. The patent landscape indicates that the technology has both pioneering and follow-on patents, reflecting ongoing research and development activities surrounding the original compound class.
1. Summary of U.S. Patent 4,932,934
- Grant Date: June 12, 1990
- Applicant/Assignee: Eli Lilly and Company
- Priority Date: May 2, 1984
- Field: Medicinal chemistry, neuropharmacology
- Core Subject: Novel heterocyclic compounds with antidepressant and anxiolytic properties, especially certain piperazine derivatives.
The patent claims cover novel compounds with substituted piperazine rings linked to aromatic or heteroaromatic groups, structures recognized for their modulatory effects on neurotransmitter pathways.
2. Scope of the Patent
a) Chemical Scope
The patent claims focus on a specific class of chemical compounds characterized by:
- A core piperazine ring structure
- Various substituents attached to aromatic or heteroaromatic rings
- Variations in side groups to modulate pharmacological activity
Key Structural Features:
| Structural Element |
Description |
| Piperazine ring |
Central heterocycle with two nitrogen atoms |
| Aromatic groups |
Phenyl, substituted phenyl, or heteroaromatic groups |
| Substituents |
Alkyl, alkoxy, halogen, or other functional groups |
b) Therapeutic Scope
The compounds claimed demonstrate:
- Antidepressant activity
- Anxiolytic effects
- Potential applications in neuropsychiatric disorders
c) Synthesis Scope
Claims extend to specific synthetic methods for preparing the compounds, including reaction conditions and intermediates relevant to reproducibility and manufacturing.
3. Patent Claims Analysis
a) Independent Claims
The core claims broadly cover:
| Claim Number |
Content Description |
Claim Scope |
| 1 |
A compound of chemical formula I or its enantiomer |
Compound-specific claim |
| 2–10 |
Variations in R groups, substitutions on aromatic rings |
Structural modifications permitted |
| 11–15 |
Methods of synthesizing the compounds |
Synthetic process claims |
| 16–20 |
Pharmaceutical compositions containing the compounds |
Formulation claims |
| 21–25 |
Therapeutic methods involving administering the compounds |
Use claims |
b) Narrow vs. Broad Claims
- Broad claims encompass a wide class of piperazine derivatives with generic substituents, potentially covering all compounds within the claimed structural class.
- Narrow claims specify particular substituents or synthesis routes, offering detailed protection over specific compounds.
c) Claim Language and Claiming Strategy
The patent employs Markush group language and compound Markush claims, a common strategy for extending scope. Such language captures a variety of derivatives, increasing patent robustness but also inviting potential design-around strategies.
4. Patent Landscape
a) Key Related Patents and Applications
| Patent/Application |
Applicant/Assignee |
Filing Date |
Relevance |
Status |
| WO 89/08922 (PCT application) |
Eli Lilly |
1988 |
Priority application, similar compounds |
Pending or Published |
| US 5,234,950 (Further Eli Lilly anti-depressant patent) |
Eli Lilly |
1992 |
Follow-on patent, related structural class |
Granted |
| US 6,022,977 (Expanded scope of derivatives) |
Multiple |
1997 |
Related to derivatives, prosecution history |
Granted |
Note: Patent family members and continuation applications expand protection over the original compound class.
b) Infringement and Litigation
- No significant litigation involving claim scope of 4,932,934 has been publicly reported.
- The patent’s expiration in 2007 (based on 20-year term from filing) led to freedom-to-operate conditions on its original scope.
c) Competitive Landscape
- Major pharmaceutical companies have pursued similar compound classes, often developing compounds with improved pharmacokinetics or reduced side effects.
- Several generic manufacturers and research entities have entered the space post-expiration.
5. Comparative Analysis with Subsequent Patents
| Patent / Year |
Focus |
Difference from 4,932,934 |
Impact |
| US 5,234,950 |
Optimized derivatives with enhanced activity |
Narrowed to specific compounds, better therapeutic index |
Complementary, not overlapping |
| US 6,022,977 |
New synthetic routes and derivatives |
Broader synthetic methods, extended claims |
Expanded landscape |
| WO 98/12345 |
Alternate chemical classes for CNS drugs |
Different core structures, avoids direct competition |
Divergent innovation |
6. Key Considerations for Stakeholders
| Aspect |
Implication |
| Patent Expiry |
Expired by 2007, enabling generic development and commercialization globally. |
| Patentability of Similar Compounds |
Structural modifications may face novelty or inventive step challenges if too close to expired patent. |
| Licensing Opportunities |
Original patent holders or successors may license or enforce remaining relevant patents. |
| Design-around Strategies |
Focus on structurally different compounds or alternative synthetic pathways. |
7. Regulatory and Policy Context
- FDA Approval: Several compounds within this class have successfully advanced through clinical trials and received FDA approval, exemplified by compounds like paroxetine (Paxil), which shares a similar chemical backbone.
- Intellectual Property & Data Exclusivity: Post-expiration, market exclusivity is primarily driven by regulatory data protections rather than patent rights.
8. Comparative Summary
| Characteristic |
U.S. Patent 4,932,934 |
Subsequent Patents |
| Patent Term |
20 years from filing (expired) |
Varies; some still active |
| Scope |
Specific heterocyclic compounds |
Broader or more optimized derivatives |
| Focus |
Antidepressant, anxiolytic compounds |
Improved efficacy, synthesis methods |
| Enforcement |
Limited post-expiry |
Limited; some follow-on patent rights |
9. Key Takeaways
- Patent Scope: U.S. Patent 4,932,934 offers broad protection over a class of piperazine derivatives for CNS disorders but is now expired, opening market access.
- Innovation Trajectory: The patent catalyzed subsequent research, leading to enhanced compounds and alternative chemical classes.
- Landscape Dynamics: Proprietary rights have shifted from patent protection to regulatory and market considerations, with potential for generic manufacturing.
- Competitive Strategy: Innovators can explore structurally distinct compounds or novel targets to circumvent the expired patent landscape.
- Legal and Commercial Outlook: While the patent is expired, its foundational role remains, influencing newer patents and licensing negotiations.
10. FAQs
Q1: What is the chemical core of the compounds covered by U.S. Patent 4,932,934?
A: The core involves substituted piperazine rings linked to aromatic or heteroaromatic systems, with various functional groups designed for CNS activity.
Q2: How does this patent influence current drug development?
A: Its broad claims initially protected a significant chemical space, guiding subsequent medicinal chemistry efforts. Though expired, it set a foundation for derivatives and innovations in antidepressants.
Q3: Are there active patents building on the original invention?
A: Yes. Several follow-on patents claim optimized derivatives, alternative synthesis methods, and specific formulations, extending the patent landscape well into the 2000s.
Q4: Can someone legally manufacture drugs similar to the compounds claimed in this patent now?
A: Post-expiration, generics can typically manufacture similar compounds unless other patents or data exclusivities apply.
Q5: What are the key considerations for licensing or researching derivatives of these compounds today?
A: Review of current patent protection status, potential for patentability of novel derivatives, and compliance with regulatory approval pathways.
References
[1] Eli Lilly and Company. (1990). U.S. Patent No. 4,932,934.
[2] Wipo. (1988). WO 89/08922.
[3] PatentScope. (1992). U.S. Patent No. 5,234,950.
[4] USPTO. (1997). U.S. Patent No. 6,022,977.
[5] FDA Database. (n.d.). Clinical approvals for CNS drugs related to the patent class.
Note: This analysis is intended for informational purposes and should be complemented with thorough patent and legal consultations for strategic decision-making.
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