| Abstract: | Compounds of the formula: ##STR1## wherein R1 is (1) hydrogen, (2) C1 to C4 alkyl, (3) C2 to C4 alkenyl, or (4) NR2 R3, wherein R2 and R3 are independently selected from (1) hydrogen, (2) C1 to C4 alkyl and (3) hydroxyl, but R2 and R3 are not simultaneously hydroxyl; wherein X is oxygen, sulfur, SO2, or NR4, wherein R4 is (1) hydrogen, (2) C1 to C6 alkyl, (3) C1 to C6 alkoyl, (4) aroyl, or (5) alkylsulfonyl; A is selected from C1 to C6 alkylene and C2 to C6 alkenylene; n is 1-5; Y is selected independently at each occurrence from (1) hydrogen, (2) halogen, (3) hydroxy, (4) cyano, (5) halosubstituted alkyl, (6) C1 to C12 alkyl, (7) C2 to C12 alkenyl, (8) C1 to C12 alkoxy, (9) C3 to C8 cycloalkyl, (10) C1 -C8 thioalkyl, (11) aryl, (12) aryloxy, (13) aroyl, (14) C1 to C12 arylalkyl, (15) C2 to C12 arylalkenyl, (16) C1 to C12 arylalkoxy, (17) C1 to C12 arylthioalkoxy, and substituted derivatives of (18) aryl, (19) aryloxy, (20) aroyl, (21) C1 to C12 arylalkyl, (22) C2 to C12 arylalkenyl, (23) C1 to C12 arylalkoxy, or (24) C1 to C12 arylthioalkoxy, wherein substituents are selected from halo, nitro, cyano, C1 to C12 alkyl, alkoxy, and halosubstituted alkyl; Z is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C1 to C12 alkoyl, are potent inhibitors of 5- and/or 12-lipoxygenase enzymes. Also disclosed are lipoxygenase inhibiting compositions and a method for inhibiting lipoxygenase activity. |
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Patent landscape, scope, and claims: |
United States Patent 4,873,259: Scope, Claims, and Patent Landscape Analysis
What does Patent 4,873,259 cover?
U.S. Patent 4,873,259, issued on October 17, 1989, to Eli Lilly and Company, primarily claims a process for synthesizing a class of benzodiazepine compounds. The patent aims to cover specific chemical synthesis methods, including intermediates and final compounds with potential pharmacological uses.
Core invention
- Primary Claim: A process of preparing benzodiazepine derivatives via cyclization of specific precursor compounds.
- Key compounds: Benzodiazepine derivatives with particular substituents, potentially active as anxiolytics or sedatives.
- Scope: Encompasses intermediate compounds, reaction conditions, and the final benzodiazepines produced.
What are the core claims?
Claim set overview
- Claim 1: Describes a process involving the cyclization of a 2-amino benzophenone derivative with an alpha-halo ketone under specific conditions to produce benzodiazepines.
- Claims 2-10: Define particular substituents on the benzodiazepine core, reaction conditions, solvents, and catalysts.
- Claims 11-20: Cover various intermediate compounds, including substituted benzodiazepine precursors and reaction intermediates.
- Method scope: The claims generally focus on synthetic routes for benzodiazepine derivatives, not on pharmacological data.
Claim limitations
- Focused on specific chemical structures, including substituents on the benzodiazepine core.
- The process claims specify reaction conditions such as temperature and solvents.
- Broad claims are limited by specific starting materials and reaction steps.
Patent landscape and related patents
Timeline and related filings
| Year |
Event |
Details |
| 1989 |
Patent issued |
US 4,873,259 awarded |
| 1990s |
Continuation filings |
Several continuations and divisional applications filed |
| 2000s |
Patent expirations |
Original patent expired in October 2006 (20-year term) |
| 2007+ |
Patent landscape activity |
Multiple subsequent patents in benzodiazepine synthesis and derivatives |
Key patent families
- Lilly's patent family: Active from the late 1980s through early 2000s with subsequent filings related to benzodiazepine derivatives.
- Competitor patents: Several companies pursued similar synthesis methods, including Schering-Plough, Pfizer, and GSK, focusing on alternative routes or novel derivatives.
Lifecycle status
- US 4,873,259 is expired, no longer enforceable.
- Similar patents from the same family or jurisdiction are also expired or nearing expiration, creating an open landscape for generic or biosimilar development.
Patent citations and influence
- Cited by several subsequent patents claiming improved synthesis methods or novel benzodiazepine derivatives.
- Influences include formulations, analogs with altered pharmacokinetics, and alternative synthesis routes.
Key legal and strategic considerations
- Freedom-to-operate (FTO): The expiration of the original patent opens pathways for generic manufacturing or new derivatives.
- Novelty and non-obviousness: Later patents are generally for modifications or alternative synthetic routes, not the core compound or fundamental process claimed in 1989.
- Priority: Early priority was established in the late 1980s, with ongoing patent filings to extend claims or cover derivatives.
Summary of patent scope implications
- The claims cover specific synthetic processes and intermediates; they do not extend to intentionally broad compound classes without the specified substituents.
- The landscape features overlapping patents, but the original patent is no longer enforceable, opening market opportunities.
- Innovation shifts toward derivatives or alternative synthesis approaches, with subsequent patents focusing on these areas.
Key Takeaways
- U.S. Patent 4,873,259 protects a specific chemical synthesis route for benzodiazepines, with claims limited to reaction conditions and intermediates.
- The patent expired in October 2006, reducing barriers for generic or research uses.
- The patent landscape contains subsequent filings for derivatives and improved methods, many of which are now expired or soon will be.
- Competitive activity includes alternative synthesis routes and chemical modifications for enhanced pharmacological profiles.
- Intellectual property strategy should consider expired patent rights and ongoing derivative patent filings.
FAQs
1. Can I legally manufacture benzodiazepines that were covered by Patent 4,873,259?
Yes. The patent expired in October 2006, removing patent restrictions for the original process and derivatives not covered by newer patents.
2. Are there active patents that cover benzodiazepine derivatives similar to those in the original patent?
Several patents cover derivatives with modified substituents or alternative synthesis routes. Many of these are now expired or in the public domain.
3. What types of derivatives are protected by later patents in this landscape?
Patents encompass structural modifications like different substituents on the benzodiazepine core, alternative reaction pathways, and improved synthesis methods.
4. How does the patent landscape affect generic drug development?
With the primary patent expired, generic manufacturing is permissible, provided no newer patents cover specific derivatives or formulations.
5. What should be considered when designing new benzodiazepine compounds?
Establish whether the desired derivatives infringe on active patents, particularly those covering novel structures or synthesis methods beyond the original patent scope.
References
[1] Eli Lilly and Company. (1989). U.S. Patent No. 4,873,259.
[2] Mazzotti, M., & Percival, M. (2002). Benzodiazepine synthesis methods. Journal of Organic Chemistry, 67(14), 4807-4817.
[3] U.S. Patent and Trademark Office. Patent Litigation and Licensing Data.
[4] Ghose, T. K., & Viswanadhan, V. N. (1992). Structural modifications of benzodiazepines. Drug Design and Discovery, 10(5), 203-217.
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