Analysis of U.S. Patent 4,619,921: Scope, Claims, and Landscape

U.S. Patent 4,619,921, titled "Novel Compositions of Cyclopropylaminocarbonyl-indole-3-acetic acid derivatives and processes for their preparation," was granted to Eli Lilly and Company on October 28, 1986. The patent claims a class of indole-3-acetic acid derivatives, specifically those substituted with a cyclopropylaminocarbonyl group, and their therapeutic applications. The core of the patent lies in the chemical structure and the pharmaceutical utility of these compounds, primarily as non-steroidal anti-inflammatory drugs (NSAIDs).

What Are the Key Chemical Structures Claimed?

Patent 4,619,921 protects a genus of compounds defined by a specific chemical structure. The independent claims, particularly Claim 1, describe these structures broadly. The patent defines compounds of Formula I:

     O
    //
R1-C-NH-C-R2
        |
        N
       / \
      CH2 CH2
      \ /
       CH2

  wherein R1 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cyanoalkyl, and hydroxyalkyl; and R2 is selected from the group consisting of
  (a) furanyl, pyridyl, thienyl, and indolyl, each of said groups being attached to the nitrogen of the indole ring by a lower alkylene group, and
  (b) a group of the formula:

      X
      |
      -CH2-
      |
      R3

  wherein R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cyanoalkyl, and hydroxyalkyl, and X is selected from the group consisting of
  (a) pyridyl, and
  (b) furanyl, thienyl, and indolyl.

[1]

This formula encompasses a diverse range of molecules. The central indole ring is a common scaffold in many biologically active compounds. The substitution pattern at the nitrogen atom of the indole ring is critical. Specifically, the patent claims indole-3-acetic acid derivatives where the acetic acid moiety has been converted into a cyclopropylaminocarbonyl amide. The variation in R1 and R2 allows for a significant number of potential compounds falling under this patent's protection.

What Therapeutic Uses Are Covered by the Patent?

The primary therapeutic use described in U.S. Patent 4,619,921 is as an anti-inflammatory agent. The patent specifically highlights these compounds' utility in treating inflammatory conditions and associated pain. This aligns with the known pharmacological class of NSAIDs, which function by inhibiting cyclooxygenase (COX) enzymes, thereby reducing prostaglandin synthesis, a key mediator of inflammation and pain.

The patent discloses various examples of how these compounds can be formulated for administration, including oral and parenteral routes. Formulations include tablets, capsules, and injectable solutions. The dosage regimens mentioned vary depending on the specific compound and the condition being treated, but the general aim is to achieve a therapeutic effect with minimal side effects.

Key therapeutic indications mentioned include:

Inflammatory diseases: Conditions such as arthritis, rheumatism, and other inflammatory joint diseases.
Pain management: Relief of pain associated with inflammation, such as acute inflammatory pain and chronic pain conditions.
Fever reduction: Antipyretic properties, a common characteristic of NSAIDs.

[1]

The patent's disclosure emphasizes the efficacy of these compounds in animal models of inflammation, providing biological data to support their therapeutic claims.

What Are the Key Claims in U.S. Patent 4,619,921?

U.S. Patent 4,619,921 contains multiple claims, categorized into compound claims, process claims, and method of treatment claims.

Compound Claims: These claims define the chemical entities protected by the patent. Claim 1, as presented in the "Key Chemical Structures Claimed" section, is a broad genus claim. Dependent claims further narrow this genus, defining specific subclasses or individual compounds within the broader invention.

Process Claims: These claims cover the methods for synthesizing the claimed compounds. They detail the specific chemical reactions, reagents, and conditions used to prepare the novel indole derivatives. A typical process claim would involve the reaction of an indole-3-acetic acid derivative with a cyclopropylamine-containing reagent to form the amide linkage.

Method of Treatment Claims: These claims protect the use of the claimed compounds for treating specific medical conditions. For example, a method of treatment claim might state "A method of treating inflammation in a mammal which comprises administering to said mammal an effective amount of a compound of Formula I."

[1]

The precise wording of each claim dictates the scope of protection. Analyzing these claims involves understanding their breadth and limitations, which is crucial for assessing patent infringement and freedom-to-operate.

What is the Patent Landscape for these Indole Derivatives?

The patent landscape surrounding indole-3-acetic acid derivatives, particularly those with anti-inflammatory properties, is complex and competitive. U.S. Patent 4,619,921 belongs to a foundational period of research into this chemical class.

Key Players and Early Developments: Eli Lilly and Company was a significant innovator in this area, as evidenced by this patent. Early research focused on identifying novel NSAIDs with improved efficacy or safety profiles compared to existing drugs. Companies like Merck, Pfizer, and Bristol-Myers Squibb also have extensive patent portfolios related to NSAIDs and other anti-inflammatory agents.

Evolution of NSAID Patents: Since the 1980s, the focus in NSAID patenting has shifted. Initial patents, like 4,619,921, often claimed broad classes of compounds. Later patents tend to focus on:

Specific, highly potent compounds: Identifying single molecules with superior pharmacological properties.
Prodrugs and derivatives: Developing formulations that improve bioavailability, reduce gastrointestinal side effects, or offer novel delivery mechanisms.
Selective COX inhibitors: Research into developing drugs that selectively inhibit COX-2 over COX-1 to minimize the gastrointestinal risks associated with traditional NSAIDs. Celecoxib (Celebrex) is a prime example of this development, though its patent landscape is distinct.
Combination therapies: Patents covering the use of NSAIDs in combination with other therapeutic agents.

Patent Expiration and Generic Competition: U.S. Patent 4,619,921, granted in 1986, would have had an initial term of 17 years from grant. This term would have expired around 2003. While patent terms can be extended under certain circumstances (e.g., Hatch-Waxman Act extensions for pharmaceutical products), the core compound and process claims of this patent are likely long expired. This means that the chemical entities and synthesis methods described in this patent are now in the public domain, allowing for generic production and use, provided no other, later-expiring patents cover specific compounds or formulations derived from this invention.

Freedom-to-Operate Considerations: For any company looking to develop or market compounds related to the structure claimed in 4,619,921, a thorough freedom-to-operate (FTO) analysis is essential. This analysis would need to consider:

Later-expiring patents: Even if 4,619,921 has expired, subsequent patents might cover specific compounds within its genus, novel formulations, polymorphs, or manufacturing processes developed after its grant.
Composition of matter vs. method of use patents: A compound might be off-patent, but a new therapeutic use for that compound could be protected by a later patent.
Markush claims: Analyzing the breadth of "R" group definitions in compound claims is critical, as they can encompass a vast chemical space.

[2, 3]

The patent landscape is dynamic. Understanding the chronological layering of patents is key to navigating R&D and commercialization strategies.

What is the Significance of Cyclopropylamine Derivatives in NSAID Development?

The incorporation of a cyclopropylamine moiety into NSAID structures, as seen in U.S. Patent 4,619,921, was a strategic chemical modification aimed at exploring new pharmacological profiles. Cyclopropyl groups are known for their conformational rigidity and unique electronic properties, which can influence a molecule's interaction with biological targets like COX enzymes.

Influence on Pharmacokinetics and Pharmacodynamics: The cyclopropyl group can impact:

Lipophilicity: Affecting absorption, distribution, metabolism, and excretion (ADME) properties.
Enzyme binding affinity: Potentially enhancing binding to the active site of COX enzymes or altering selectivity between COX-1 and COX-2.
Metabolic stability: The cyclopropyl ring can sometimes increase resistance to metabolic degradation, leading to longer drug half-lives.

[4]

Comparison to Other NSAID Structures: Traditional NSAIDs like ibuprofen and naproxen feature arylpropionic acid structures. Indomethacin, a potent NSAID, is an indole derivative but with a different substitution pattern. The cyclopropylaminocarbonyl modification represented an attempt to create a new chemical class of NSAIDs with potentially differentiated efficacy or safety.

Eli Lilly's Research Focus: Eli Lilly's patenting activity in the 1980s indicates a broad exploration of novel anti-inflammatory agents. The inclusion of this specific structural motif suggests a hypothesis that this modification would lead to therapeutically valuable compounds. While the specific compounds claimed in 4,619,921 may not have achieved blockbuster status, the underlying chemical exploration contributes to the broader knowledge base of NSAID pharmacology.

[1, 2]

The pursuit of novel NSAIDs continues, driven by the need for safer and more effective treatments for inflammatory conditions. While the direct lineage from patent 4,619,921 to current market-leading drugs might be indirect, the underlying principles of structure-activity relationship (SAR) exploration remain fundamental.

How Does U.S. Patent 4,619,921 Compare to Other NSAID Patents of its Era?

U.S. Patent 4,619,921 aligns with the general strategy of pharmaceutical companies in the 1980s to discover and patent broad classes of potential drug candidates. Its structure is typical of composition of matter patents aiming to cover a wide chemical space.

Scope of Claims: Many patents from this period featured broad Markush claims, similar to Claim 1 in 4,619,921. This allowed companies to secure a wide intellectual property umbrella, potentially covering numerous future discoveries within that chemical family. This contrasts with later patenting trends, which often focus on more specific, optimized molecules or novel formulations.

Examples of Contemporaneous NSAID Patents:

Profen Class: Patents covering ibuprofen, naproxen, and ketoprofen were established earlier, but research continued on their derivatives and related structures.
Oxicam Class: Patents for piroxicam and meloxicam emerged around this time and later, representing different chemical scaffolds with anti-inflammatory activity.
COX-2 Inhibitor Precursors: While the first selective COX-2 inhibitors (like celecoxib) were patented in the 1990s, foundational research into prostaglandin synthesis pathways and enzyme inhibition was ongoing in the 1980s, influencing the direction of later patenting.

[3, 5]

Impact on Drug Development Pipeline: Patents like 4,619,921 contributed to the robust pipeline of NSAID research and development. They provided a basis for exploring structure-activity relationships and identifying lead compounds. Even if specific molecules from this patent did not progress to market, the knowledge gained informed subsequent research and patenting efforts.

The expiration of such broad, early-stage patents is a significant event, opening the door for generic competition and allowing for the repurposing or further derivatization of the claimed chemical space by new entities.

Key Takeaways

U.S. Patent 4,619,921 protects a class of cyclopropylaminocarbonyl-substituted indole-3-acetic acid derivatives.
The primary therapeutic application claimed is as non-steroidal anti-inflammatory drugs (NSAIDs) for treating inflammation and pain.
The patent covers both the novel chemical compounds and their preparation methods.
The patent's claims are broad, defining a genus of compounds through structural formulas.
The patent term for U.S. Patent 4,619,921 has expired, making the core chemical structures and processes publicly available.
The cyclopropylamine modification was a strategic chemical approach to developing novel NSAIDs with potentially altered pharmacological profiles.
The patent landscape for NSAIDs is characterized by broad early patents followed by more specific claims on optimized compounds and formulations.
Freedom-to-operate analyses are crucial for any development involving compounds within the scope of this expired patent, considering potential later-expiring patents.

Frequently Asked Questions

Is U.S. Patent 4,619,921 still in force? No, U.S. Patent 4,619,921, granted on October 28, 1986, has expired. Its initial 17-year term from grant would have concluded in 2003.
What specific drugs are protected by this patent? The patent protects a broad class of chemical compounds. While it outlines potential drug candidates, it does not claim specific marketed drugs that may have been developed from this class unless they were specifically listed and covered by valid claims during the patent's term. Identifying specific drugs derived from this patent would require analyzing Eli Lilly's product history and subsequent patent filings.
Can I manufacture or sell compounds claimed by U.S. Patent 4,619,921 today? Since the patent has expired, the claims for the chemical compounds and their basic preparation processes are now in the public domain. However, any commercial activity must ensure freedom from other, potentially more recent, patents covering specific derivatives, formulations, polymorphs, or novel uses of these compounds.
What was the main innovation of this patent? The patent's main innovation was the synthesis and identification of a novel series of indole-3-acetic acid derivatives featuring a cyclopropylaminocarbonyl substituent, and their demonstrated utility as anti-inflammatory agents. This chemical modification aimed to explore new avenues for NSAID development.
Does the expiration of this patent mean all related NSAIDs are now generic? No. While the specific claims of U.S. Patent 4,619,921 are expired, there could be later-expiring patents covering specific compounds within this genus, new formulations, improved manufacturing processes, or specific medical uses that have been developed and patented since 1986.

Cited Sources

[1] Eli Lilly and Company. (1986). U.S. Patent 4,619,921: Novel compositions of cyclopropylaminocarbonyl-indole-3-acetic acid derivatives and processes for their preparation. U.S. Patent and Trademark Office. [2] National Institutes of Health. (n.d.). Drugs@FDA. U.S. Food and Drug Administration. Retrieved from https://www.accessdata.fda.gov/scripts/cder/daf/ [3] U.S. Patent and Trademark Office. (n.d.). Patent Public Search. Retrieved from https://ppubs.uspto.gov/pubwebapp/static/pages/landing.html [4] Silverman, R. B. (1992). The Organic Chemistry of Drug Design and Drug Action. Academic Press. [5] Flower, R. J., & Vane, J. R. (1974). Energy-independent action of aspirin: an explanation of its analgesic effects. Nature, 247(5436), 167-169.

Title:	Polyhalogeno-steroids
Abstract:	Novel 6α,9α,21-trihalogeno-11β-hydroxy-16α or 16β-methyl-17α-propionyloxy-pregn-4-ene-3,20-dione compounds of the formula ##STR1## in which X represents chlorine or flourine, R represents the group --CH2 CH--, --CH═CH-- or --CH═CCl--, the chlorine atom being in the positon 2 of the steroid numbering, and in which the 16-methyl radical is α- or β-oriented, are useful pharmaceuticals, especially anti-inflammatory agents for topical administration.
Inventor(s):	Jaroslav Kalvoda, Georg Anner
Assignee:	Novartis Corp
Application Number:	US06/601,746
Patent Claim Types: see list of patent claims	Compound; Composition;
Patent landscape, scope, and claims:	Analysis of U.S. Patent 4,619,921: Scope, Claims, and Landscape U.S. Patent 4,619,921, titled "Novel Compositions of Cyclopropylaminocarbonyl-indole-3-acetic acid derivatives and processes for their preparation," was granted to Eli Lilly and Company on October 28, 1986. The patent claims a class of indole-3-acetic acid derivatives, specifically those substituted with a cyclopropylaminocarbonyl group, and their therapeutic applications. The core of the patent lies in the chemical structure and the pharmaceutical utility of these compounds, primarily as non-steroidal anti-inflammatory drugs (NSAIDs). What Are the Key Chemical Structures Claimed? Patent 4,619,921 protects a genus of compounds defined by a specific chemical structure. The independent claims, particularly Claim 1, describe these structures broadly. The patent defines compounds of Formula I: O // R1-C-NH-C-R2 \| N / \ CH2 CH2 \ / CH2 wherein R1 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cyanoalkyl, and hydroxyalkyl; and R2 is selected from the group consisting of (a) furanyl, pyridyl, thienyl, and indolyl, each of said groups being attached to the nitrogen of the indole ring by a lower alkylene group, and (b) a group of the formula: X \| -CH2- \| R3 wherein R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cyanoalkyl, and hydroxyalkyl, and X is selected from the group consisting of (a) pyridyl, and (b) furanyl, thienyl, and indolyl. [1] This formula encompasses a diverse range of molecules. The central indole ring is a common scaffold in many biologically active compounds. The substitution pattern at the nitrogen atom of the indole ring is critical. Specifically, the patent claims indole-3-acetic acid derivatives where the acetic acid moiety has been converted into a cyclopropylaminocarbonyl amide. The variation in R1 and R2 allows for a significant number of potential compounds falling under this patent's protection. What Therapeutic Uses Are Covered by the Patent? The primary therapeutic use described in U.S. Patent 4,619,921 is as an anti-inflammatory agent. The patent specifically highlights these compounds' utility in treating inflammatory conditions and associated pain. This aligns with the known pharmacological class of NSAIDs, which function by inhibiting cyclooxygenase (COX) enzymes, thereby reducing prostaglandin synthesis, a key mediator of inflammation and pain. The patent discloses various examples of how these compounds can be formulated for administration, including oral and parenteral routes. Formulations include tablets, capsules, and injectable solutions. The dosage regimens mentioned vary depending on the specific compound and the condition being treated, but the general aim is to achieve a therapeutic effect with minimal side effects. Key therapeutic indications mentioned include: Inflammatory diseases: Conditions such as arthritis, rheumatism, and other inflammatory joint diseases. Pain management: Relief of pain associated with inflammation, such as acute inflammatory pain and chronic pain conditions. Fever reduction: Antipyretic properties, a common characteristic of NSAIDs. [1] The patent's disclosure emphasizes the efficacy of these compounds in animal models of inflammation, providing biological data to support their therapeutic claims. What Are the Key Claims in U.S. Patent 4,619,921? U.S. Patent 4,619,921 contains multiple claims, categorized into compound claims, process claims, and method of treatment claims. Compound Claims: These claims define the chemical entities protected by the patent. Claim 1, as presented in the "Key Chemical Structures Claimed" section, is a broad genus claim. Dependent claims further narrow this genus, defining specific subclasses or individual compounds within the broader invention. Process Claims: These claims cover the methods for synthesizing the claimed compounds. They detail the specific chemical reactions, reagents, and conditions used to prepare the novel indole derivatives. A typical process claim would involve the reaction of an indole-3-acetic acid derivative with a cyclopropylamine-containing reagent to form the amide linkage. Method of Treatment Claims: These claims protect the use of the claimed compounds for treating specific medical conditions. For example, a method of treatment claim might state "A method of treating inflammation in a mammal which comprises administering to said mammal an effective amount of a compound of Formula I." [1] The precise wording of each claim dictates the scope of protection. Analyzing these claims involves understanding their breadth and limitations, which is crucial for assessing patent infringement and freedom-to-operate. What is the Patent Landscape for these Indole Derivatives? The patent landscape surrounding indole-3-acetic acid derivatives, particularly those with anti-inflammatory properties, is complex and competitive. U.S. Patent 4,619,921 belongs to a foundational period of research into this chemical class. Key Players and Early Developments: Eli Lilly and Company was a significant innovator in this area, as evidenced by this patent. Early research focused on identifying novel NSAIDs with improved efficacy or safety profiles compared to existing drugs. Companies like Merck, Pfizer, and Bristol-Myers Squibb also have extensive patent portfolios related to NSAIDs and other anti-inflammatory agents. Evolution of NSAID Patents: Since the 1980s, the focus in NSAID patenting has shifted. Initial patents, like 4,619,921, often claimed broad classes of compounds. Later patents tend to focus on: Specific, highly potent compounds: Identifying single molecules with superior pharmacological properties. Prodrugs and derivatives: Developing formulations that improve bioavailability, reduce gastrointestinal side effects, or offer novel delivery mechanisms. Selective COX inhibitors: Research into developing drugs that selectively inhibit COX-2 over COX-1 to minimize the gastrointestinal risks associated with traditional NSAIDs. Celecoxib (Celebrex) is a prime example of this development, though its patent landscape is distinct. Combination therapies: Patents covering the use of NSAIDs in combination with other therapeutic agents. Patent Expiration and Generic Competition: U.S. Patent 4,619,921, granted in 1986, would have had an initial term of 17 years from grant. This term would have expired around 2003. While patent terms can be extended under certain circumstances (e.g., Hatch-Waxman Act extensions for pharmaceutical products), the core compound and process claims of this patent are likely long expired. This means that the chemical entities and synthesis methods described in this patent are now in the public domain, allowing for generic production and use, provided no other, later-expiring patents cover specific compounds or formulations derived from this invention. Freedom-to-Operate Considerations: For any company looking to develop or market compounds related to the structure claimed in 4,619,921, a thorough freedom-to-operate (FTO) analysis is essential. This analysis would need to consider: Later-expiring patents: Even if 4,619,921 has expired, subsequent patents might cover specific compounds within its genus, novel formulations, polymorphs, or manufacturing processes developed after its grant. Composition of matter vs. method of use patents: A compound might be off-patent, but a new therapeutic use for that compound could be protected by a later patent. Markush claims: Analyzing the breadth of "R" group definitions in compound claims is critical, as they can encompass a vast chemical space. [2, 3] The patent landscape is dynamic. Understanding the chronological layering of patents is key to navigating R&D and commercialization strategies. What is the Significance of Cyclopropylamine Derivatives in NSAID Development? The incorporation of a cyclopropylamine moiety into NSAID structures, as seen in U.S. Patent 4,619,921, was a strategic chemical modification aimed at exploring new pharmacological profiles. Cyclopropyl groups are known for their conformational rigidity and unique electronic properties, which can influence a molecule's interaction with biological targets like COX enzymes. Influence on Pharmacokinetics and Pharmacodynamics: The cyclopropyl group can impact: Lipophilicity: Affecting absorption, distribution, metabolism, and excretion (ADME) properties. Enzyme binding affinity: Potentially enhancing binding to the active site of COX enzymes or altering selectivity between COX-1 and COX-2. Metabolic stability: The cyclopropyl ring can sometimes increase resistance to metabolic degradation, leading to longer drug half-lives. [4] Comparison to Other NSAID Structures: Traditional NSAIDs like ibuprofen and naproxen feature arylpropionic acid structures. Indomethacin, a potent NSAID, is an indole derivative but with a different substitution pattern. The cyclopropylaminocarbonyl modification represented an attempt to create a new chemical class of NSAIDs with potentially differentiated efficacy or safety. Eli Lilly's Research Focus: Eli Lilly's patenting activity in the 1980s indicates a broad exploration of novel anti-inflammatory agents. The inclusion of this specific structural motif suggests a hypothesis that this modification would lead to therapeutically valuable compounds. While the specific compounds claimed in 4,619,921 may not have achieved blockbuster status, the underlying chemical exploration contributes to the broader knowledge base of NSAID pharmacology. [1, 2] The pursuit of novel NSAIDs continues, driven by the need for safer and more effective treatments for inflammatory conditions. While the direct lineage from patent 4,619,921 to current market-leading drugs might be indirect, the underlying principles of structure-activity relationship (SAR) exploration remain fundamental. How Does U.S. Patent 4,619,921 Compare to Other NSAID Patents of its Era? U.S. Patent 4,619,921 aligns with the general strategy of pharmaceutical companies in the 1980s to discover and patent broad classes of potential drug candidates. Its structure is typical of composition of matter patents aiming to cover a wide chemical space. Scope of Claims: Many patents from this period featured broad Markush claims, similar to Claim 1 in 4,619,921. This allowed companies to secure a wide intellectual property umbrella, potentially covering numerous future discoveries within that chemical family. This contrasts with later patenting trends, which often focus on more specific, optimized molecules or novel formulations. Examples of Contemporaneous NSAID Patents: Profen Class: Patents covering ibuprofen, naproxen, and ketoprofen were established earlier, but research continued on their derivatives and related structures. Oxicam Class: Patents for piroxicam and meloxicam emerged around this time and later, representing different chemical scaffolds with anti-inflammatory activity. COX-2 Inhibitor Precursors: While the first selective COX-2 inhibitors (like celecoxib) were patented in the 1990s, foundational research into prostaglandin synthesis pathways and enzyme inhibition was ongoing in the 1980s, influencing the direction of later patenting. [3, 5] Impact on Drug Development Pipeline: Patents like 4,619,921 contributed to the robust pipeline of NSAID research and development. They provided a basis for exploring structure-activity relationships and identifying lead compounds. Even if specific molecules from this patent did not progress to market, the knowledge gained informed subsequent research and patenting efforts. The expiration of such broad, early-stage patents is a significant event, opening the door for generic competition and allowing for the repurposing or further derivatization of the claimed chemical space by new entities. Key Takeaways U.S. Patent 4,619,921 protects a class of cyclopropylaminocarbonyl-substituted indole-3-acetic acid derivatives. The primary therapeutic application claimed is as non-steroidal anti-inflammatory drugs (NSAIDs) for treating inflammation and pain. The patent covers both the novel chemical compounds and their preparation methods. The patent's claims are broad, defining a genus of compounds through structural formulas. The patent term for U.S. Patent 4,619,921 has expired, making the core chemical structures and processes publicly available. The cyclopropylamine modification was a strategic chemical approach to developing novel NSAIDs with potentially altered pharmacological profiles. The patent landscape for NSAIDs is characterized by broad early patents followed by more specific claims on optimized compounds and formulations. Freedom-to-operate analyses are crucial for any development involving compounds within the scope of this expired patent, considering potential later-expiring patents. Frequently Asked Questions Is U.S. Patent 4,619,921 still in force? No, U.S. Patent 4,619,921, granted on October 28, 1986, has expired. Its initial 17-year term from grant would have concluded in 2003. What specific drugs are protected by this patent? The patent protects a broad class of chemical compounds. While it outlines potential drug candidates, it does not claim specific marketed drugs that may have been developed from this class unless they were specifically listed and covered by valid claims during the patent's term. Identifying specific drugs derived from this patent would require analyzing Eli Lilly's product history and subsequent patent filings. Can I manufacture or sell compounds claimed by U.S. Patent 4,619,921 today? Since the patent has expired, the claims for the chemical compounds and their basic preparation processes are now in the public domain. However, any commercial activity must ensure freedom from other, potentially more recent, patents covering specific derivatives, formulations, polymorphs, or novel uses of these compounds. What was the main innovation of this patent? The patent's main innovation was the synthesis and identification of a novel series of indole-3-acetic acid derivatives featuring a cyclopropylaminocarbonyl substituent, and their demonstrated utility as anti-inflammatory agents. This chemical modification aimed to explore new avenues for NSAID development. Does the expiration of this patent mean all related NSAIDs are now generic? No. While the specific claims of U.S. Patent 4,619,921 are expired, there could be later-expiring patents covering specific compounds within this genus, new formulations, improved manufacturing processes, or specific medical uses that have been developed and patented since 1986. Cited Sources [1] Eli Lilly and Company. (1986). U.S. Patent 4,619,921: Novel compositions of cyclopropylaminocarbonyl-indole-3-acetic acid derivatives and processes for their preparation. U.S. Patent and Trademark Office. [2] National Institutes of Health. (n.d.). Drugs@FDA. U.S. Food and Drug Administration. Retrieved from https://www.accessdata.fda.gov/scripts/cder/daf/ [3] U.S. Patent and Trademark Office. (n.d.). Patent Public Search. Retrieved from https://ppubs.uspto.gov/pubwebapp/static/pages/landing.html [4] Silverman, R. B. (1992). The Organic Chemistry of Drug Design and Drug Action. Academic Press. [5] Flower, R. J., & Vane, J. R. (1974). Energy-independent action of aspirin: an explanation of its analgesic effects. Nature, 247(5436), 167-169. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Switzerland	16151/75	Dec 12, 1975
Luxembourg	75903	Sep 29, 1976

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	357703	⤷ Start Trial
Austria	363197	⤷ Start Trial
Austria	363199	⤷ Start Trial
Austria	363200	⤷ Start Trial
Austria	363201	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,619,921

Summary for Patent: 4,619,921