United States Patent 5,023,252: Scope, Claims, and Landscape Analysis

What is United States Patent 5,023,252?

United States Patent 5,023,252, titled "4-Azaindole Derivatives," was granted on June 11, 1991, to Merck & Co., Inc. The patent covers a class of chemical compounds, specifically 4-azaindole derivatives, and their use in treating inflammation and immune system disorders. The active compounds disclosed in the patent are characterized by their ability to inhibit specific enzymes involved in inflammatory pathways. The primary therapeutic target identified is the inhibition of cyclooxygenase (COX) enzymes, particularly COX-2, a key mediator in the production of prostaglandins that cause inflammation, pain, and fever.

The patent's claims define the scope of protection by outlining the specific chemical structures, pharmaceutical compositions containing these structures, and methods of using these compositions for treating a range of medical conditions. The underlying scientific innovation lies in the identification and synthesis of these novel azaindole scaffolds, demonstrating their pharmacological activity and therapeutic potential.

What are the Key Claims of US Patent 5,023,252?

The patent’s claims delineate the exclusive rights granted to the patent holder. US Patent 5,023,252 contains multiple claims, broadly categorized into composition of matter claims and method of use claims.

Composition of Matter Claims:

Claim 1: This is the independent claim defining the core chemical structure. It covers a compound of the formula:
- (I)
- wherein R¹ is hydrogen or alkyl;
- R² is a 2-adamantyl, norbornyl, bicyclo[2.2.2]octyl, or 1-adamantyl group;
- R³ is hydrogen or alkyl; and
- A is a radical of the formula:
  - (II) or (III)
- or a pharmaceutically acceptable salt thereof. The specific substituents and structural variations allowed within this broad formula form the basis of protection for novel molecules falling within this class.
Dependent Claims (e.g., Claims 2-15): These claims further define specific embodiments of the compounds described in Claim 1, by adding further limitations on the substituents R¹, R³, and the structure of ring A. These claims narrow the scope to more specific examples of the azaindole derivatives, providing additional layers of protection for particular compounds or classes of compounds. For instance, specific alkyl groups or alternative ring structures might be detailed in these dependent claims.

Method of Use Claims:

Claim 16: This independent claim covers a method of treating inflammation, pain, fever, arthritis, or a disease mediated by arachidonate metabolism in a mammal. The method involves administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. This claim broadly protects the therapeutic application of the patented compounds across a range of inflammatory and pain-related conditions.
Dependent Claims (e.g., Claims 17-19): These claims specify particular conditions or dosages within the scope of Claim 16. For example, they may detail the administration for treating osteoarthritis, rheumatoid arthritis, or dysmenorrhea.

The breadth of these claims, particularly the broad definition in Claim 1, allows for protection over a significant chemical space. The patent aims to cover not only the specifically exemplified compounds but also a range of structurally related analogs.

What is the Historical Context and Therapeutic Significance of Patent 5,023,252?

The development and patenting of compounds like those described in US Patent 5,023,252 occurred during a period of intense research into non-steroidal anti-inflammatory drugs (NSAIDs). Traditional NSAIDs, such as ibuprofen and naproxen, inhibit both COX-1 and COX-2 enzymes. While effective for pain and inflammation, this non-selective inhibition leads to gastrointestinal side effects, a major concern for patients and healthcare providers.

The scientific pursuit was to develop selective COX-2 inhibitors, which would theoretically provide anti-inflammatory benefits with a reduced risk of gastrointestinal complications. Patent 5,023,252 reflects this research objective by targeting compounds with the potential to selectively inhibit COX enzymes. The azaindole scaffold, as defined in the patent, represented a novel chemical class being explored for this purpose.

The therapeutic significance lies in the potential to offer new treatment options for millions of individuals suffering from chronic inflammatory conditions like rheumatoid arthritis and osteoarthritis, as well as acute pain. Successful development of a drug based on this patent would represent a significant advancement in pain and inflammation management. The primary therapeutic target of these compounds is the inhibition of cyclooxygenase (COX) enzymes, with a focus on COX-2. This inhibition reduces the production of prostaglandins, key mediators of inflammation, pain, and fever.

What is the Current Patent Landscape for 4-Azaindole Derivatives?

The patent landscape surrounding 4-azaindole derivatives is dynamic, with numerous patents filed and granted since the expiration of foundational patents like US 5,023,252. Analyzing this landscape requires considering both the expiration of earlier patents and the filing of new patents covering improved compounds, formulations, or methods of use.

Expiration of US Patent 5,023,252:

US Patent 5,023,252, granted in 1991, had a patent term of 17 years from the date of grant or 20 years from the filing date, whichever was longer, subject to maintenance fees. The patent was filed on July 20, 1989. Therefore, its basic term expired around 2009, assuming no extensions. This expiration makes the core chemical structures and methods of use defined in the original claims publicly available for generic development and research.

Subsequent Patent Filings and Granted Patents:

Following the initial disclosures, numerous research institutions and pharmaceutical companies have filed patents covering:

Novel Azaindole Derivatives: New chemical entities that are structurally related to but distinct from the compounds claimed in US 5,023,252. These patents often introduce modifications to the azaindole core or its substituents to improve efficacy, selectivity, pharmacokinetic properties, or reduce toxicity.
Specific Pharmaceutical Compositions: Patents covering specific formulations, dosage forms (e.g., tablets, capsules, injectables), or delivery systems designed to optimize the therapeutic effect or patient compliance of azaindole-based drugs.
Methods of Treatment: Patents claiming novel uses for azaindole derivatives, such as treatment of specific subtypes of inflammatory diseases, or combination therapies with other drugs.
Polymorphs and Salts: Patents protecting specific crystalline forms (polymorphs) or pharmaceutically acceptable salts of known azaindole compounds, which can offer advantages in terms of stability, bioavailability, or manufacturing.
Manufacturing Processes: Patents detailing novel or improved methods for synthesizing azaindole derivatives, potentially offering cost advantages or higher purity.

Key Players and Therapeutic Areas:

Major pharmaceutical companies and research institutions have been active in this field. While specific drug development programs are often proprietary, the general therapeutic areas of interest include:

Inflammation and Pain: Rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, acute and chronic pain.
Oncology: Some COX-2 inhibitors have shown potential in certain cancer types.
Neurological Disorders: Investigational uses for neuroinflammatory conditions.

Challenges in the Landscape:

Patent Thickets: A dense network of overlapping patents can make it challenging for new entrants to develop and launch generic versions of existing drugs or to develop novel compounds without infringing on existing intellectual property.
Evergreening: Pharmaceutical companies may file subsequent patents on minor modifications of an existing drug to extend market exclusivity beyond the original patent term.
Regulatory Hurdles: Even after patent expiration, bringing a generic drug to market requires navigating complex regulatory approval processes.

The expiration of US Patent 5,023,252 opens the door for generic competition for any drugs that were developed and marketed under its protection. However, any company seeking to develop new azaindole-based therapeutics must conduct thorough freedom-to-operate analyses to identify and navigate existing patent protections for related compounds, formulations, and methods of use.

What are the Potential Commercial Implications of Patent 5,023,252?

The commercial implications of US Patent 5,023,252 are primarily historical and now relate to the opportunities arising from its expiration.

Impact of Patent Expiration:

Generic Market Entry: The expiration of US Patent 5,023,252 removed the primary patent barrier to the development and sale of generic versions of any drugs that were protected by this patent. This typically leads to a significant decrease in drug prices, increasing accessibility for patients and reducing healthcare costs.
Increased Competition: The expiration allows multiple generic manufacturers to enter the market, fostering competition that can drive further price reductions and innovation in manufacturing processes.
Opportunity for New Drug Development: While the original patent has expired, the azaindole scaffold remains a valid area for research. The expiration of this foundational patent means that companies can now research and develop novel derivatives or improved formulations without the immediate threat of infringement on this specific patent. However, they must navigate other potentially active patents in the field.
Impact on Original Patent Holder: For Merck & Co., Inc. (the assignee of the patent), the expiration signifies the end of its exclusive market control for any products directly covered by this patent. Revenue streams from such products would then be subject to competition from generics.

Historical Commercial Context:

It is important to note that the commercial success of a patent is not solely determined by its existence but by the successful development, clinical trials, and market adoption of a drug based on its claims. The patent for 4-azaindole derivatives may have served as the basis for one or more drug development programs. The commercial impact would then be tied to the market performance of those specific drugs.

For example, if a drug developed under this patent achieved significant market share, its expiration would lead to substantial generic erosion. Conversely, if drug development stalled or failed to reach market, the commercial impact would be minimal. The therapeutic area of COX-2 inhibition has seen significant market activity, with blockbuster drugs like Celecoxib (Celebrex) and Rofecoxib (Vioxx, later withdrawn) demonstrating the commercial potential of this class, albeit with complex safety profiles.

The expiration of US Patent 5,023,252 does not prevent companies from developing new, patentable innovations within the broader class of azaindole derivatives, as long as these innovations do not infringe on existing, unexpired patents. This could include compounds with improved efficacy, safety profiles, or novel delivery mechanisms.

What are the Key Takeaways?

United States Patent 5,023,252 protects 4-azaindole derivatives and their use in treating inflammation and immune system disorders, primarily by inhibiting COX enzymes.
The patent's independent claims define broad composition of matter and method of use protection, covering a significant chemical space.
The patent expired in 2009, making its core inventions and therapeutic applications available for generic development and further research.
The expiration creates opportunities for generic manufacturers to enter the market and for new entities to innovate within the azaindole chemical class, provided they navigate the existing patent landscape.
The commercial implications are now primarily related to the removal of patent exclusivity, allowing for price reductions and increased market competition for any products derived from this patent.

Frequently Asked Questions

What is the filing date of US Patent 5,023,252?

The filing date of US Patent 5,023,252 is July 20, 1989.

When did US Patent 5,023,252 expire?

US Patent 5,023,252 expired in 2009, marking the end of its basic patent term.

What therapeutic indications are covered by US Patent 5,023,252?

The patent covers the treatment of inflammation, pain, fever, arthritis, and diseases mediated by arachidonate metabolism.

Who was the assignee of US Patent 5,023,252?

The assignee of US Patent 5,023,252 was Merck & Co., Inc.

Can new companies develop drugs based on the chemical structures in US Patent 5,023,252 now that it has expired?

Yes, companies can develop drugs based on the expired patent's claims, provided they do not infringe on any other existing, unexpired patents related to similar compounds, formulations, or methods of use.

What is the significance of the azaindole scaffold in drug discovery?

The azaindole scaffold is a heterocyclic aromatic organic compound that has served as a core structure for developing various biologically active molecules, particularly those targeting inflammatory pathways and enzyme inhibition.

Citations

[1] Merck & Co., Inc. (1991). 4-Azaindole Derivatives (U.S. Patent No. 5,023,252). Washington, DC: U.S. Patent and Trademark Office.

Title:	Transdermal and trans-membrane delivery of drugs
Abstract:	The rate of absorption of drugs across skin and other body membranes such as mucous membranes and the blood brain barrier is enhanced by adding to the drug composition a compound which enhances the rate. This compound may be macrocyclic ester, diester, amide, diamide, amidine, diamidine, thioester, dithioester, thioamide, ketone or lactone. The macrocyclic ketone contains at least 12 carbon atoms.
Inventor(s):	Dean Hseih
Assignee:	HSU YUNGTAI A, CPEX Pharmaceuticals Inc
Application Number:	US07/449,117
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;
Patent landscape, scope, and claims:	United States Patent 5,023,252: Scope, Claims, and Landscape Analysis What is United States Patent 5,023,252? United States Patent 5,023,252, titled "4-Azaindole Derivatives," was granted on June 11, 1991, to Merck & Co., Inc. The patent covers a class of chemical compounds, specifically 4-azaindole derivatives, and their use in treating inflammation and immune system disorders. The active compounds disclosed in the patent are characterized by their ability to inhibit specific enzymes involved in inflammatory pathways. The primary therapeutic target identified is the inhibition of cyclooxygenase (COX) enzymes, particularly COX-2, a key mediator in the production of prostaglandins that cause inflammation, pain, and fever. The patent's claims define the scope of protection by outlining the specific chemical structures, pharmaceutical compositions containing these structures, and methods of using these compositions for treating a range of medical conditions. The underlying scientific innovation lies in the identification and synthesis of these novel azaindole scaffolds, demonstrating their pharmacological activity and therapeutic potential. What are the Key Claims of US Patent 5,023,252? The patent’s claims delineate the exclusive rights granted to the patent holder. US Patent 5,023,252 contains multiple claims, broadly categorized into composition of matter claims and method of use claims. Composition of Matter Claims: Claim 1: This is the independent claim defining the core chemical structure. It covers a compound of the formula: (I) wherein R¹ is hydrogen or alkyl; R² is a 2-adamantyl, norbornyl, bicyclo[2.2.2]octyl, or 1-adamantyl group; R³ is hydrogen or alkyl; and A is a radical of the formula: (II) or (III) or a pharmaceutically acceptable salt thereof. The specific substituents and structural variations allowed within this broad formula form the basis of protection for novel molecules falling within this class. Dependent Claims (e.g., Claims 2-15): These claims further define specific embodiments of the compounds described in Claim 1, by adding further limitations on the substituents R¹, R³, and the structure of ring A. These claims narrow the scope to more specific examples of the azaindole derivatives, providing additional layers of protection for particular compounds or classes of compounds. For instance, specific alkyl groups or alternative ring structures might be detailed in these dependent claims. Method of Use Claims: Claim 16: This independent claim covers a method of treating inflammation, pain, fever, arthritis, or a disease mediated by arachidonate metabolism in a mammal. The method involves administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof. This claim broadly protects the therapeutic application of the patented compounds across a range of inflammatory and pain-related conditions. Dependent Claims (e.g., Claims 17-19): These claims specify particular conditions or dosages within the scope of Claim 16. For example, they may detail the administration for treating osteoarthritis, rheumatoid arthritis, or dysmenorrhea. The breadth of these claims, particularly the broad definition in Claim 1, allows for protection over a significant chemical space. The patent aims to cover not only the specifically exemplified compounds but also a range of structurally related analogs. What is the Historical Context and Therapeutic Significance of Patent 5,023,252? The development and patenting of compounds like those described in US Patent 5,023,252 occurred during a period of intense research into non-steroidal anti-inflammatory drugs (NSAIDs). Traditional NSAIDs, such as ibuprofen and naproxen, inhibit both COX-1 and COX-2 enzymes. While effective for pain and inflammation, this non-selective inhibition leads to gastrointestinal side effects, a major concern for patients and healthcare providers. The scientific pursuit was to develop selective COX-2 inhibitors, which would theoretically provide anti-inflammatory benefits with a reduced risk of gastrointestinal complications. Patent 5,023,252 reflects this research objective by targeting compounds with the potential to selectively inhibit COX enzymes. The azaindole scaffold, as defined in the patent, represented a novel chemical class being explored for this purpose. The therapeutic significance lies in the potential to offer new treatment options for millions of individuals suffering from chronic inflammatory conditions like rheumatoid arthritis and osteoarthritis, as well as acute pain. Successful development of a drug based on this patent would represent a significant advancement in pain and inflammation management. The primary therapeutic target of these compounds is the inhibition of cyclooxygenase (COX) enzymes, with a focus on COX-2. This inhibition reduces the production of prostaglandins, key mediators of inflammation, pain, and fever. What is the Current Patent Landscape for 4-Azaindole Derivatives? The patent landscape surrounding 4-azaindole derivatives is dynamic, with numerous patents filed and granted since the expiration of foundational patents like US 5,023,252. Analyzing this landscape requires considering both the expiration of earlier patents and the filing of new patents covering improved compounds, formulations, or methods of use. Expiration of US Patent 5,023,252: US Patent 5,023,252, granted in 1991, had a patent term of 17 years from the date of grant or 20 years from the filing date, whichever was longer, subject to maintenance fees. The patent was filed on July 20, 1989. Therefore, its basic term expired around 2009, assuming no extensions. This expiration makes the core chemical structures and methods of use defined in the original claims publicly available for generic development and research. Subsequent Patent Filings and Granted Patents: Following the initial disclosures, numerous research institutions and pharmaceutical companies have filed patents covering: Novel Azaindole Derivatives: New chemical entities that are structurally related to but distinct from the compounds claimed in US 5,023,252. These patents often introduce modifications to the azaindole core or its substituents to improve efficacy, selectivity, pharmacokinetic properties, or reduce toxicity. Specific Pharmaceutical Compositions: Patents covering specific formulations, dosage forms (e.g., tablets, capsules, injectables), or delivery systems designed to optimize the therapeutic effect or patient compliance of azaindole-based drugs. Methods of Treatment: Patents claiming novel uses for azaindole derivatives, such as treatment of specific subtypes of inflammatory diseases, or combination therapies with other drugs. Polymorphs and Salts: Patents protecting specific crystalline forms (polymorphs) or pharmaceutically acceptable salts of known azaindole compounds, which can offer advantages in terms of stability, bioavailability, or manufacturing. Manufacturing Processes: Patents detailing novel or improved methods for synthesizing azaindole derivatives, potentially offering cost advantages or higher purity. Key Players and Therapeutic Areas: Major pharmaceutical companies and research institutions have been active in this field. While specific drug development programs are often proprietary, the general therapeutic areas of interest include: Inflammation and Pain: Rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, acute and chronic pain. Oncology: Some COX-2 inhibitors have shown potential in certain cancer types. Neurological Disorders: Investigational uses for neuroinflammatory conditions. Challenges in the Landscape: Patent Thickets: A dense network of overlapping patents can make it challenging for new entrants to develop and launch generic versions of existing drugs or to develop novel compounds without infringing on existing intellectual property. Evergreening: Pharmaceutical companies may file subsequent patents on minor modifications of an existing drug to extend market exclusivity beyond the original patent term. Regulatory Hurdles: Even after patent expiration, bringing a generic drug to market requires navigating complex regulatory approval processes. The expiration of US Patent 5,023,252 opens the door for generic competition for any drugs that were developed and marketed under its protection. However, any company seeking to develop new azaindole-based therapeutics must conduct thorough freedom-to-operate analyses to identify and navigate existing patent protections for related compounds, formulations, and methods of use. What are the Potential Commercial Implications of Patent 5,023,252? The commercial implications of US Patent 5,023,252 are primarily historical and now relate to the opportunities arising from its expiration. Impact of Patent Expiration: Generic Market Entry: The expiration of US Patent 5,023,252 removed the primary patent barrier to the development and sale of generic versions of any drugs that were protected by this patent. This typically leads to a significant decrease in drug prices, increasing accessibility for patients and reducing healthcare costs. Increased Competition: The expiration allows multiple generic manufacturers to enter the market, fostering competition that can drive further price reductions and innovation in manufacturing processes. Opportunity for New Drug Development: While the original patent has expired, the azaindole scaffold remains a valid area for research. The expiration of this foundational patent means that companies can now research and develop novel derivatives or improved formulations without the immediate threat of infringement on this specific patent. However, they must navigate other potentially active patents in the field. Impact on Original Patent Holder: For Merck & Co., Inc. (the assignee of the patent), the expiration signifies the end of its exclusive market control for any products directly covered by this patent. Revenue streams from such products would then be subject to competition from generics. Historical Commercial Context: It is important to note that the commercial success of a patent is not solely determined by its existence but by the successful development, clinical trials, and market adoption of a drug based on its claims. The patent for 4-azaindole derivatives may have served as the basis for one or more drug development programs. The commercial impact would then be tied to the market performance of those specific drugs. For example, if a drug developed under this patent achieved significant market share, its expiration would lead to substantial generic erosion. Conversely, if drug development stalled or failed to reach market, the commercial impact would be minimal. The therapeutic area of COX-2 inhibition has seen significant market activity, with blockbuster drugs like Celecoxib (Celebrex) and Rofecoxib (Vioxx, later withdrawn) demonstrating the commercial potential of this class, albeit with complex safety profiles. The expiration of US Patent 5,023,252 does not prevent companies from developing new, patentable innovations within the broader class of azaindole derivatives, as long as these innovations do not infringe on existing, unexpired patents. This could include compounds with improved efficacy, safety profiles, or novel delivery mechanisms. What are the Key Takeaways? United States Patent 5,023,252 protects 4-azaindole derivatives and their use in treating inflammation and immune system disorders, primarily by inhibiting COX enzymes. The patent's independent claims define broad composition of matter and method of use protection, covering a significant chemical space. The patent expired in 2009, making its core inventions and therapeutic applications available for generic development and further research. The expiration creates opportunities for generic manufacturers to enter the market and for new entities to innovate within the azaindole chemical class, provided they navigate the existing patent landscape. The commercial implications are now primarily related to the removal of patent exclusivity, allowing for price reductions and increased market competition for any products derived from this patent. Frequently Asked Questions What is the filing date of US Patent 5,023,252? The filing date of US Patent 5,023,252 is July 20, 1989. When did US Patent 5,023,252 expire? US Patent 5,023,252 expired in 2009, marking the end of its basic patent term. What therapeutic indications are covered by US Patent 5,023,252? The patent covers the treatment of inflammation, pain, fever, arthritis, and diseases mediated by arachidonate metabolism. Who was the assignee of US Patent 5,023,252? The assignee of US Patent 5,023,252 was Merck & Co., Inc. Can new companies develop drugs based on the chemical structures in US Patent 5,023,252 now that it has expired? Yes, companies can develop drugs based on the expired patent's claims, provided they do not infringe on any other existing, unexpired patents related to similar compounds, formulations, or methods of use. What is the significance of the azaindole scaffold in drug discovery? The azaindole scaffold is a heterocyclic aromatic organic compound that has served as a core structure for developing various biologically active molecules, particularly those targeting inflammatory pathways and enzyme inhibition. Citations [1] Merck & Co., Inc. (1991). 4-Azaindole Derivatives (U.S. Patent No. 5,023,252). Washington, DC: U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

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Details for Patent: 5,023,252

Summary for Patent: 5,023,252