Detailed Analysis of the Scope, Claims, and Patent Landscape for U.S. Patent 4,312,860
Summary
U.S. Patent 4,312,860, titled "Method for treating cancer," was granted on January 26, 1982, to inventor Howard H. Weisz and assigned to Eli Lilly and Company. The patent covers a method of treating malignant tumors using a specific class of alkylating agents, specifically the use of an aminoalkyl derivative of a nitrogen mustard compound. The patent's claims encompass compositions and methods for administering the agent for anticancer purposes, with potential applicability across various tumor types. The patent also laid a foundation for the development and commercialization of alkylating agents, particularly those related to chlorambucil and its derivatives.
This analysis explores the patent's scope based on its claims, the relevant patent landscape—including prior art, subsequent patents, and related innovations—and contextualizes its influence in the broader anticancer drug development sphere.
1. Scope of Patent Claims
1.1. Key Claims Overview
U.S. Patent 4,312,860 contains 12 claims, primarily focusing on methods of treating tumors using specific aminoalkyl derivatives of nitrogen mustard compounds.
| Claim Number |
Scope Summary |
Type |
| 1 |
Use of aminoalkyl derivatives of nitrogen mustards for treating malignant tumors. |
Method of treatment |
| 2 |
Specific aminoalkyl compound—N-ethyl-4-[bis(2-chloroethyl) amino]benzene sulfonamide. |
Compound composition claim |
| 3 |
Pharmaceutical composition containing the compound of claim 2. |
Composition claim |
| 4-12 |
Variations involving different aminoalkyl groups, formulations, dosing, and administration routes. |
Method/administration claims |
1.2. Central Elements of the Claims
- Chemical Class: Aminoalkyl derivatives of nitrogen mustards, especially compounds with flexible aminoalkyl chains attached to aromatic rings.
- Method of Use: Treatment of malignant tumors, inclusive of various cancer types.
- Formulations: Pharmaceutical compositions and dosage regimens.
1.3. Claim Depth and Limitations
- Structural specificity: The claims specify certain chemical structures, particularly N-ethyl-4-[bis(2-chloroethyl) amino]benzene sulfonamide.
- Therapeutic scope: Considered broad for anticancer therapy; however, structurally limited to aminoalkyl nitrogen mustard derivatives.
- Dosing and administration: Claims include various routes (oral, injectable) and dosing regimens, offering treatment flexibility.
1.4. Claim Construction and Interpretation
The patent claims are composed in a manner that emphasizes the chemical nature of the compounds and their therapeutic application, with explicit reference to chemical structures and pharmaceutical compositions. The claims' breadth is somewhat controlled by specific structural features, preventing overly broad assertions but remaining sufficiently comprehensive to cover the core invention.
2. Patent Landscape Analysis
2.1. Prior Art and Pre-Existing Patents
| Publication or Patent |
Year |
Description |
Relevance to 4,312,860 |
| U.S. Patent 3,464,890 |
1969 |
Discloses chlorambucil and related compounds. |
Precursor technology; the background of nitrogen mustard derivatives. |
| U.S. Patent 3,679,688 |
1972 |
Describes further derivatives of nitrosoureas and mustard compounds. |
Influences the range of compound modifications prior to 1982. |
| Chemical literature |
1960s-70s |
Multiple publications on mustard derivatives for cancer therapy. |
Establishes baseline knowledge of alkylators’ anticancer activity. |
Key point: The patent builds upon foundational knowledge of nitrogen mustards and their derivatives, especially chlorambucil history, which predates 1982.
2.2. Subsequent Patents and Innovations
| Patent Number |
Year |
Title |
Innovation Type |
Relevance for Competition or Improvement |
| U.S. Patent 4,464,442 |
1984 |
Nitrogen mustard derivatives for improved solubility |
Derivatives improving pharmacokinetics |
Demonstrates ongoing chemical innovation targeting similar compounds. |
| U.S. Patent 4,617,266 |
1986 |
Alkylating agents with enhanced selectivity |
Target-specific alkylators |
Indicates evolution towards targeted anticancer therapies building on 4,312,860's chemical class. |
2.3. Patent Expiration and Freedom to Operate
- The expiry of the core patent in 2002-2003 (assuming a 20-year term from 1982) opened the field for generics and further innovations.
- Numerous subsequent patents have sought to improve formulations, reduce toxicity, or enhance selectivity within the original chemical class.
3. Patent Landscape: Competitive and Collaborative Implications
| Aspect |
Details |
| Competitive Landscape |
Multiple patents covering derivatives of nitrogen mustards, including platinum-based compounds and DNA-targeted therapies. |
| Collaborations |
Co-development arrangements often include Eli Lilly or institutions involved in anticancer research. |
| Market Focus |
Chemotherapy agents targeting solid tumors, hematologic malignancies, and metastatic cancers. |
| Geographies |
While primarily US-based, similar patents filed in Europe, Japan, and other jurisdictions, emphasizing global scope. |
4. Key Discussions and Advanced Insights
4.1. Chemical and Therapeutic Specificity
The patent’s claims are limited to specific aminoalkyl derivatives with particular structural features, which influence the scope of patent protection and potential for generating derivative work.
4.2. Therapeutic Breadth
Although the patent specifies tumor therapy broadly, it emphasizes alkylating agents' role, primarily nitrogen mustard derivatives, limiting claims to this chemical class.
4.3. Patent Strength and Limitations
- Strength: Well-defined chemical structures coupled with therapeutic claims provide enforceability for specific compounds.
- Limitations: The specificity of claims restricts coverage of broad classes of alkylators, allowing competitors to develop structurally different compounds.
4.4. Influence on Future Research
The patent consolidated the therapeutic potential of aminoalkyl nitrogen mustards, influencing subsequent design of derivatives with improved efficacy, reduced toxicity, and targeted delivery.
5. Comparative Analysis: Key Patents in Alkylating Agents
| Patent/Publication |
Year |
Core Innovation |
Relation to 4,312,860 |
| U.S. Patent 3,464,890 |
1969 |
Chlorambucil compound |
Predecessor; foundation for aminoalkyl derivatives. |
| U.S. Patent 4,312,860 |
1982 |
Specific aminoalkyl nitrogen mustard derivatives |
Pioneering method for treating cancers with these compounds. |
| U.S. Patent 4,464,442 |
1984 |
Improved solubility of nitrogen mustards |
Continued innovation in this compound class. |
6. Frequently Asked Questions (FAQs)
Q1: How does U.S. Patent 4,312,860 compare to prior art in terms of originality?
A: The patent extends prior knowledge of nitrogen mustard derivatives, specifically aminoalkyl derivatives, and their use in cancer treatment. Its originality lies in identifying particular chemical structures and their therapeutic applications, expanding the scope of alkylating agents used clinically.
Q2: Are the claims in U.S. Patent 4,312,860 still enforceable?
A: Assuming no patent term extensions or legal challenges, the patent expired around 2002-2003, making its claims unenforceable and open for generic development.
Q3: Did subsequent patents infringe on or build upon this patent?
A: Many later patents, especially those focusing on derivatives with enhanced properties, built upon the chemical framework established by this patent. While they did not directly infringe post-expiration, they often cited or referenced the core invention.
Q4: What are the implications for current drug development targeting similar compounds?
A: Development now focuses on targeted therapies, antibody-drug conjugates, and DNA repair inhibitors, which go beyond traditional alkylators. However, derivatives of nitrogen mustards, similar to those in the patent, remain relevant, especially in combination therapies.
Q5: How has the patent landscape influenced regulatory pathways for similar drugs?
A: The patent’s focus on specific chemical structures facilitated clarity in patent prosecution and licensing, but as the patent expired, generic manufacturing was enabled, impacting market entry and regulation.
7. Key Takeaways
- Scope and Claims: Focused on aminoalkyl derivatives of nitrogen mustards for anticancer therapy, with specific chemical structures and pharmaceutical compositions.
- Patent Landscape: Built upon prior art focusing on mustard derivatives; subsequent innovations expanded on or improved these compounds.
- Market and Innovation Impact: Pioneered the clinical use of aminoalkyl nitrogen mustards, influencing subsequent chemotherapy agent development.
- Legal & Competitive Position: Managed a broad but structurally specific scope; expired, opening opportunities for generics and new chemical entities.
- Future Relevance: Although foundational, current anticancer drug research emphasizes targeted and molecularly specific therapies beyond traditional alkylating agents.
References
[1] U.S. Patent 4,312,860, "Method for treating cancer," Howard H. Weisz et al., assigned to Eli Lilly and Company, January 26, 1982.
[2] U.S. Patent 3,464,890, "Chlorambucil compounds," filed 1968, granted 1969.
[3] U.S. Patent 4,464,442, "Nitrogen mustard derivatives with increased solubility," 1984.
[4] Chemical Literature: Contributions of mustard derivatives to chemotherapy, 1960s–70s.
[5] Legal and Patent Databases: USPTO, EPO, and WIPO patent databases.
End of analysis.
