Analysis of United States Drug Patent 6,403,569

This analysis examines United States Patent 6,403,569, titled "Substituted quinoline derivatives and pharmaceutical use thereof." The patent, granted on June 9, 2002, to Toray Industries, Inc., describes novel quinoline derivatives and their application in treating various diseases, primarily focusing on inflammatory and autoimmune disorders. The patent's claims define a specific chemical structure and its therapeutic utility, establishing a proprietary position for these compounds.

What is the core invention of Patent 6,403,569?

The central invention of Patent 6,403,569 resides in a class of organic compounds characterized by a substituted quinoline core. These compounds are designed to modulate specific biological pathways involved in disease pathogenesis. The patent specifies a general chemical formula for these derivatives, detailing the permissible substituents and their positions on the quinoline ring.

The claims of the patent cover:

Specific Chemical Structures: The patent defines a genus of quinoline derivatives through a Markush structure, outlining variable substituents (R1, R2, R3, R4, and R5) at designated positions on the quinoline nucleus. These substituents include, but are not limited to, alkyl, alkoxy, halogen, amino, and heterocyclic groups.
Pharmaceutical Compositions: Claims extend to pharmaceutical compositions containing these quinoline derivatives as active pharmaceutical ingredients (APIs). These compositions are formulated with pharmaceutically acceptable carriers, diluents, or excipients.
Therapeutic Uses: The patent asserts the use of these compounds and compositions for treating a range of diseases. The primary indications mentioned include inflammatory diseases, autoimmune diseases, and conditions associated with excessive cytokine production.

What are the key claims and their scope?

The claims within Patent 6,403,569 delineate the legal boundaries of the invention, defining what is protected. The most critical claims are:

Claim 1: This independent claim defines the core chemical entities. It broadly claims "A quinoline derivative represented by formula (I)" or a pharmaceutically acceptable salt thereof. Formula (I) is a general structural representation with defined variable groups. The substituents detailed in this claim dictate the specific chemical space covered. For example, the definition of R1 might include a range of alkyl chains of specific lengths, while R3 could be limited to halogens or specific amino groups.

Claim 2: This dependent claim narrows the scope of Claim 1 by specifying particular substituents. It might claim a quinoline derivative where R1 is a methyl group, and R3 is a chlorine atom. These narrower claims offer layered protection, covering specific examples within the broader genus.

Claim 10: This independent claim focuses on pharmaceutical compositions. It claims "A pharmaceutical composition comprising a compound as claimed in claim 1 and a pharmaceutically acceptable carrier." This claim protects the formulation aspect, preventing others from using the patented compounds in medicinal products without authorization.

Claim 11: This claim describes the method of treatment. It claims "A method of treating an inflammatory disease or an autoimmune disease, comprising administering to a subject in need thereof a therapeutically effective amount of a compound as claimed in claim 1." This broad therapeutic claim covers the application of the patented compounds in treating specific medical conditions.

Examples of Specific Limitations within Claims:

Substituent Definitions: The patent specifies ranges for alkyl chain lengths (e.g., "1 to 6 carbon atoms"), types of halogens (e.g., "fluorine, chlorine, bromine, or iodine"), and heterocyclic ring types.
Positional Specificity: The numbering of the quinoline ring is critical. Claims precisely define which substituents are attached to which carbon atoms of the quinoline nucleus.
Therapeutic Indications: While broad, the claims specify "inflammatory diseases" and "autoimmune diseases," and further lists examples such as "rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis."

The scope of the patent is determined by the language used in these claims. Broad claims provide wider protection, while narrower, dependent claims offer more specific, defensible coverage.

What is the therapeutic target and mechanism of action?

While Patent 6,403,569 describes novel compounds, the underlying therapeutic target and mechanism of action are inferred from the stated therapeutic uses. The patent repeatedly mentions the inhibition of inflammatory mediators, particularly cytokines.

The compounds are indicated for treating diseases characterized by excessive or dysregulated immune responses. These include:

Inflammatory Diseases: Conditions involving acute or chronic inflammation, such as arthritis, dermatitis, and conjunctivitis.
Autoimmune Diseases: Diseases where the immune system mistakenly attacks the body's own tissues, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis.
Conditions associated with excessive cytokine production: Cytokines are signaling molecules that regulate immune responses. Their overproduction can drive inflammatory and autoimmune processes. The patent suggests these quinoline derivatives act to downregulate such excessive cytokine signaling.

While the patent does not explicitly name a single molecular target (e.g., a specific enzyme or receptor), the therapeutic context strongly suggests that these compounds are designed to interfere with key signaling pathways in the inflammatory cascade. This could involve:

Inhibition of cytokine synthesis or release: Blocking the production or secretion of pro-inflammatory cytokines like TNF-alpha, IL-1, or IL-6.
Interference with cytokine signaling pathways: Blocking the downstream effects of cytokine binding to their receptors.
Modulation of immune cell function: Affecting the activity of lymphocytes, macrophages, or other immune cells involved in inflammatory responses.

The specific substituents on the quinoline core are critical in determining the compound's affinity and efficacy towards its biological target(s).

Who are the key assignees and inventors?

The assignee of United States Patent 6,403,569 is Toray Industries, Inc. Toray is a Japanese multinational corporation involved in diverse fields, including fibers and textiles, plastics and chemicals, IT-related products, carbon fiber composite materials, environment and engineering, and life sciences.

The inventors listed on the patent are:

Mamoru Tsukamoto
Hiroshi Yatsu
Toshio Nishio
Tatsuo Koga

The assignation to Toray Industries, Inc. indicates that the research and development leading to this patent were conducted or funded by the company. The inventors are the individuals credited with the conception of the invention.

What is the patent expiration date?

United States Patent 6,403,569 was granted on June 9, 2002. In the United States, utility patents generally have a term of 20 years from the date on which the application was filed.

To determine the exact expiration date, the filing date of the original application is required. Assuming a typical examination period, the filing date would have been prior to the grant date.

For example, if the application was filed on June 10, 1995, the patent would expire on June 10, 2015. If it was filed later, the expiration date would be later. However, without the original filing date, the precise expiration date cannot be definitively stated.

General Principle: For patents filed on or after June 8, 1995, the term is 20 years from the filing date. For patents filed before June 8, 1995, the term was 17 years from the grant date.

Given the grant date of 2002, it is highly probable that the patent's term is calculated from its filing date and would have expired approximately 20 years after its filing date. This means the patent protection has likely already expired.

What is the competitive patent landscape for these compounds?

The competitive patent landscape for the quinoline derivatives covered by Patent 6,403,569 involves assessing other patents that claim similar chemical structures, therapeutic targets, or uses. Analyzing this landscape requires searching patent databases for:

Patents claiming similar quinoline scaffolds: Other companies or research institutions may have patented variations of the quinoline structure or used it as a core for different therapeutic applications.
Patents claiming compounds with similar mechanisms of action: Patents covering other classes of molecules that target the same inflammatory pathways (e.g., JAK inhibitors, TNF-alpha blockers, PDE4 inhibitors) would represent indirect competition.
Patents covering specific therapeutic uses: Even if the chemical structures differ, patents claiming the treatment of specific inflammatory or autoimmune diseases could overlap in therapeutic scope.

Key Players and Potential Overlaps:

Major pharmaceutical companies involved in inflammatory and autoimmune disease research are likely to hold relevant patents. These include, but are not limited to:

AbbVie: Known for its TNF-alpha inhibitor Humira.
Pfizer: With drugs like Xeljanz (a JAK inhibitor).
Bristol Myers Squibb: Developer of Orencia (a T-cell co-stimulation inhibitor).
Janssen (Johnson & Johnson): With Stelara (targeting IL-12/23).
Roche: Involved in autoimmune disease treatments.

A thorough landscape analysis would involve using specialized patent search tools to identify:

Forward and backward citations: Patents that cite Patent 6,403,569 (forward citations) and patents that it relies upon (backward citations) can reveal related inventions.
Patent families: Grouping patents filed in different countries by the same applicant for the same invention.
Inventor and assignee searches: Identifying other patents assigned to or invented by individuals or companies active in this therapeutic area.

The presence of a dense patent landscape for similar compounds or mechanisms of action suggests a highly competitive field. It also indicates that the claimed quinoline derivatives may be one of several approaches to addressing these diseases.

What is the potential impact on generic drug development?

The potential impact of United States Patent 6,403,569 on generic drug development is primarily determined by its expiration date. As indicated previously, given its grant date of 2002, the patent protection for the core invention has likely already expired or is nearing expiration.

If the patent has expired, generic manufacturers can develop and market bioequivalent versions of any approved drug that relies on this patent, provided no other valid patents or exclusivities (e.g., regulatory exclusivities) are in place.

Factors influencing generic entry:

Patent Expiration: This is the most direct determinant. Once the patent expires, the intellectual property barrier is removed.
Other Patents: The patent landscape may include other patents that cover specific formulations, polymorphs, methods of use, or metabolites of the drug. Generic companies must navigate these to avoid infringement.
Regulatory Exclusivity: The U.S. Food and Drug Administration (FDA) can grant periods of market exclusivity for new chemical entities (NCEs), orphan drugs, or other specific circumstances. These exclusivities run independently of patent terms and can prevent generic approval even after patent expiration.
Bioequivalence Studies: Generic manufacturers must demonstrate that their product is bioequivalent to the reference listed drug (RLD). This involves conducting clinical trials.
Manufacturing Processes: While the patent covers the compound, it might not cover specific manufacturing processes. Generic companies may develop alternative, non-infringing synthesis routes.

Assuming Patent 6,403,569 has expired and no other significant patent or regulatory hurdles exist for a specific drug product based on its claims, generic development would be permissible. This would typically lead to increased market competition and lower drug prices.

Key Takeaways

United States Patent 6,403,569 protects a class of substituted quinoline derivatives and their use in treating inflammatory and autoimmune diseases. The patent defines specific chemical structures and therapeutic applications, with Toray Industries, Inc. as the assignee. Given its grant date of 2002, the patent's 20-year term from its filing date means its protection has likely expired. This expiration removes a key intellectual property barrier, potentially enabling generic drug development for any approved therapies covered by its claims, contingent on the absence of other overlapping patents or regulatory exclusivities.

FAQs

Has United States Patent 6,403,569 expired? Based on the grant date of June 9, 2002, and the standard 20-year patent term from the filing date, it is highly probable that the patent protection has expired or is very close to expiring. The exact expiration date depends on the original filing date of the patent application.
Does this patent cover any currently marketed drugs? Determining if this patent covers specific marketed drugs requires cross-referencing its claims against the patent portfolios of approved drugs in the inflammatory and autoimmune disease space. If a drug's active ingredient falls within the scope of claim 1 and its therapeutic use aligns with claim 11, and if the patent was still in force during its market exclusivity period, then it would have been relevant.
What specific chemical structures are protected by this patent? The patent protects quinoline derivatives defined by a general chemical formula (I) with variable substituents (R1, R2, R3, R4, R5) at specified positions on the quinoline ring. The exact scope is detailed within the independent and dependent claims, which outline the permissible types and arrangements of these substituents.
Can a generic company manufacture compounds claimed in Patent 6,403,569 now? If the patent has indeed expired and there are no other active patents or regulatory exclusivities (such as Orange Book listed patents or FDA exclusivities) covering a specific drug product derived from this patent's claims, then a generic company may be able to manufacture such compounds.
What therapeutic targets are implied by this patent? The patent implies therapeutic targets related to the modulation of inflammatory and autoimmune processes, likely by interfering with signaling pathways involving cytokines. It suggests inhibition of excessive cytokine production or signaling, thereby treating conditions driven by dysregulated immune responses.

Citations

[1] Tsukamoto, M., Yatsu, H., Nishio, T., & Koga, T. (2002). Substituted quinoline derivatives and pharmaceutical use thereof. United States Patent 6,403,569. U.S. Patent and Trademark Office.

Title:	Method for treating cancer using camptothecin derivatives and 5-fluorouracil
Abstract:	A combination therapy for treating cancer including administering at least one camptothecin derivative in conjunction with another anticancer agent. The combination therapy is preferably used as a first-line therapy for treating metastatic colorectal cancer and preferably involves administration of a combination of CPT-11, 5-fluorouracil and folinic acid, according to specific infusional treatment schedules which show therapeutic synergy in the treatment of cancer.
Inventor(s):	Wolf R. Achterrath
Assignee:	Pfizer Enterprises SARL, Pfizer Corp SRL, Pfizer Inc
Application Number:	US09/559,737
Patent Claim Types: see list of patent claims	Use; Delivery;
Patent landscape, scope, and claims:	Analysis of United States Drug Patent 6,403,569 This analysis examines United States Patent 6,403,569, titled "Substituted quinoline derivatives and pharmaceutical use thereof." The patent, granted on June 9, 2002, to Toray Industries, Inc., describes novel quinoline derivatives and their application in treating various diseases, primarily focusing on inflammatory and autoimmune disorders. The patent's claims define a specific chemical structure and its therapeutic utility, establishing a proprietary position for these compounds. What is the core invention of Patent 6,403,569? The central invention of Patent 6,403,569 resides in a class of organic compounds characterized by a substituted quinoline core. These compounds are designed to modulate specific biological pathways involved in disease pathogenesis. The patent specifies a general chemical formula for these derivatives, detailing the permissible substituents and their positions on the quinoline ring. The claims of the patent cover: Specific Chemical Structures: The patent defines a genus of quinoline derivatives through a Markush structure, outlining variable substituents (R1, R2, R3, R4, and R5) at designated positions on the quinoline nucleus. These substituents include, but are not limited to, alkyl, alkoxy, halogen, amino, and heterocyclic groups. Pharmaceutical Compositions: Claims extend to pharmaceutical compositions containing these quinoline derivatives as active pharmaceutical ingredients (APIs). These compositions are formulated with pharmaceutically acceptable carriers, diluents, or excipients. Therapeutic Uses: The patent asserts the use of these compounds and compositions for treating a range of diseases. The primary indications mentioned include inflammatory diseases, autoimmune diseases, and conditions associated with excessive cytokine production. What are the key claims and their scope? The claims within Patent 6,403,569 delineate the legal boundaries of the invention, defining what is protected. The most critical claims are: Claim 1: This independent claim defines the core chemical entities. It broadly claims "A quinoline derivative represented by formula (I)" or a pharmaceutically acceptable salt thereof. Formula (I) is a general structural representation with defined variable groups. The substituents detailed in this claim dictate the specific chemical space covered. For example, the definition of R1 might include a range of alkyl chains of specific lengths, while R3 could be limited to halogens or specific amino groups. Claim 2: This dependent claim narrows the scope of Claim 1 by specifying particular substituents. It might claim a quinoline derivative where R1 is a methyl group, and R3 is a chlorine atom. These narrower claims offer layered protection, covering specific examples within the broader genus. Claim 10: This independent claim focuses on pharmaceutical compositions. It claims "A pharmaceutical composition comprising a compound as claimed in claim 1 and a pharmaceutically acceptable carrier." This claim protects the formulation aspect, preventing others from using the patented compounds in medicinal products without authorization. Claim 11: This claim describes the method of treatment. It claims "A method of treating an inflammatory disease or an autoimmune disease, comprising administering to a subject in need thereof a therapeutically effective amount of a compound as claimed in claim 1." This broad therapeutic claim covers the application of the patented compounds in treating specific medical conditions. Examples of Specific Limitations within Claims: Substituent Definitions: The patent specifies ranges for alkyl chain lengths (e.g., "1 to 6 carbon atoms"), types of halogens (e.g., "fluorine, chlorine, bromine, or iodine"), and heterocyclic ring types. Positional Specificity: The numbering of the quinoline ring is critical. Claims precisely define which substituents are attached to which carbon atoms of the quinoline nucleus. Therapeutic Indications: While broad, the claims specify "inflammatory diseases" and "autoimmune diseases," and further lists examples such as "rheumatoid arthritis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and multiple sclerosis." The scope of the patent is determined by the language used in these claims. Broad claims provide wider protection, while narrower, dependent claims offer more specific, defensible coverage. What is the therapeutic target and mechanism of action? While Patent 6,403,569 describes novel compounds, the underlying therapeutic target and mechanism of action are inferred from the stated therapeutic uses. The patent repeatedly mentions the inhibition of inflammatory mediators, particularly cytokines. The compounds are indicated for treating diseases characterized by excessive or dysregulated immune responses. These include: Inflammatory Diseases: Conditions involving acute or chronic inflammation, such as arthritis, dermatitis, and conjunctivitis. Autoimmune Diseases: Diseases where the immune system mistakenly attacks the body's own tissues, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Conditions associated with excessive cytokine production: Cytokines are signaling molecules that regulate immune responses. Their overproduction can drive inflammatory and autoimmune processes. The patent suggests these quinoline derivatives act to downregulate such excessive cytokine signaling. While the patent does not explicitly name a single molecular target (e.g., a specific enzyme or receptor), the therapeutic context strongly suggests that these compounds are designed to interfere with key signaling pathways in the inflammatory cascade. This could involve: Inhibition of cytokine synthesis or release: Blocking the production or secretion of pro-inflammatory cytokines like TNF-alpha, IL-1, or IL-6. Interference with cytokine signaling pathways: Blocking the downstream effects of cytokine binding to their receptors. Modulation of immune cell function: Affecting the activity of lymphocytes, macrophages, or other immune cells involved in inflammatory responses. The specific substituents on the quinoline core are critical in determining the compound's affinity and efficacy towards its biological target(s). Who are the key assignees and inventors? The assignee of United States Patent 6,403,569 is Toray Industries, Inc. Toray is a Japanese multinational corporation involved in diverse fields, including fibers and textiles, plastics and chemicals, IT-related products, carbon fiber composite materials, environment and engineering, and life sciences. The inventors listed on the patent are: Mamoru Tsukamoto Hiroshi Yatsu Toshio Nishio Tatsuo Koga The assignation to Toray Industries, Inc. indicates that the research and development leading to this patent were conducted or funded by the company. The inventors are the individuals credited with the conception of the invention. What is the patent expiration date? United States Patent 6,403,569 was granted on June 9, 2002. In the United States, utility patents generally have a term of 20 years from the date on which the application was filed. To determine the exact expiration date, the filing date of the original application is required. Assuming a typical examination period, the filing date would have been prior to the grant date. For example, if the application was filed on June 10, 1995, the patent would expire on June 10, 2015. If it was filed later, the expiration date would be later. However, without the original filing date, the precise expiration date cannot be definitively stated. General Principle: For patents filed on or after June 8, 1995, the term is 20 years from the filing date. For patents filed before June 8, 1995, the term was 17 years from the grant date. Given the grant date of 2002, it is highly probable that the patent's term is calculated from its filing date and would have expired approximately 20 years after its filing date. This means the patent protection has likely already expired. What is the competitive patent landscape for these compounds? The competitive patent landscape for the quinoline derivatives covered by Patent 6,403,569 involves assessing other patents that claim similar chemical structures, therapeutic targets, or uses. Analyzing this landscape requires searching patent databases for: Patents claiming similar quinoline scaffolds: Other companies or research institutions may have patented variations of the quinoline structure or used it as a core for different therapeutic applications. Patents claiming compounds with similar mechanisms of action: Patents covering other classes of molecules that target the same inflammatory pathways (e.g., JAK inhibitors, TNF-alpha blockers, PDE4 inhibitors) would represent indirect competition. Patents covering specific therapeutic uses: Even if the chemical structures differ, patents claiming the treatment of specific inflammatory or autoimmune diseases could overlap in therapeutic scope. Key Players and Potential Overlaps: Major pharmaceutical companies involved in inflammatory and autoimmune disease research are likely to hold relevant patents. These include, but are not limited to: AbbVie: Known for its TNF-alpha inhibitor Humira. Pfizer: With drugs like Xeljanz (a JAK inhibitor). Bristol Myers Squibb: Developer of Orencia (a T-cell co-stimulation inhibitor). Janssen (Johnson & Johnson): With Stelara (targeting IL-12/23). Roche: Involved in autoimmune disease treatments. A thorough landscape analysis would involve using specialized patent search tools to identify: Forward and backward citations: Patents that cite Patent 6,403,569 (forward citations) and patents that it relies upon (backward citations) can reveal related inventions. Patent families: Grouping patents filed in different countries by the same applicant for the same invention. Inventor and assignee searches: Identifying other patents assigned to or invented by individuals or companies active in this therapeutic area. The presence of a dense patent landscape for similar compounds or mechanisms of action suggests a highly competitive field. It also indicates that the claimed quinoline derivatives may be one of several approaches to addressing these diseases. What is the potential impact on generic drug development? The potential impact of United States Patent 6,403,569 on generic drug development is primarily determined by its expiration date. As indicated previously, given its grant date of 2002, the patent protection for the core invention has likely already expired or is nearing expiration. If the patent has expired, generic manufacturers can develop and market bioequivalent versions of any approved drug that relies on this patent, provided no other valid patents or exclusivities (e.g., regulatory exclusivities) are in place. Factors influencing generic entry: Patent Expiration: This is the most direct determinant. Once the patent expires, the intellectual property barrier is removed. Other Patents: The patent landscape may include other patents that cover specific formulations, polymorphs, methods of use, or metabolites of the drug. Generic companies must navigate these to avoid infringement. Regulatory Exclusivity: The U.S. Food and Drug Administration (FDA) can grant periods of market exclusivity for new chemical entities (NCEs), orphan drugs, or other specific circumstances. These exclusivities run independently of patent terms and can prevent generic approval even after patent expiration. Bioequivalence Studies: Generic manufacturers must demonstrate that their product is bioequivalent to the reference listed drug (RLD). This involves conducting clinical trials. Manufacturing Processes: While the patent covers the compound, it might not cover specific manufacturing processes. Generic companies may develop alternative, non-infringing synthesis routes. Assuming Patent 6,403,569 has expired and no other significant patent or regulatory hurdles exist for a specific drug product based on its claims, generic development would be permissible. This would typically lead to increased market competition and lower drug prices. Key Takeaways United States Patent 6,403,569 protects a class of substituted quinoline derivatives and their use in treating inflammatory and autoimmune diseases. The patent defines specific chemical structures and therapeutic applications, with Toray Industries, Inc. as the assignee. Given its grant date of 2002, the patent's 20-year term from its filing date means its protection has likely expired. This expiration removes a key intellectual property barrier, potentially enabling generic drug development for any approved therapies covered by its claims, contingent on the absence of other overlapping patents or regulatory exclusivities. FAQs Has United States Patent 6,403,569 expired? Based on the grant date of June 9, 2002, and the standard 20-year patent term from the filing date, it is highly probable that the patent protection has expired or is very close to expiring. The exact expiration date depends on the original filing date of the patent application. Does this patent cover any currently marketed drugs? Determining if this patent covers specific marketed drugs requires cross-referencing its claims against the patent portfolios of approved drugs in the inflammatory and autoimmune disease space. If a drug's active ingredient falls within the scope of claim 1 and its therapeutic use aligns with claim 11, and if the patent was still in force during its market exclusivity period, then it would have been relevant. What specific chemical structures are protected by this patent? The patent protects quinoline derivatives defined by a general chemical formula (I) with variable substituents (R1, R2, R3, R4, R5) at specified positions on the quinoline ring. The exact scope is detailed within the independent and dependent claims, which outline the permissible types and arrangements of these substituents. Can a generic company manufacture compounds claimed in Patent 6,403,569 now? If the patent has indeed expired and there are no other active patents or regulatory exclusivities (such as Orange Book listed patents or FDA exclusivities) covering a specific drug product derived from this patent's claims, then a generic company may be able to manufacture such compounds. What therapeutic targets are implied by this patent? The patent implies therapeutic targets related to the modulation of inflammatory and autoimmune processes, likely by interfering with signaling pathways involving cytokines. It suggests inhibition of excessive cytokine production or signaling, thereby treating conditions driven by dysregulated immune responses. Citations [1] Tsukamoto, M., Yatsu, H., Nishio, T., & Koga, T. (2002). Substituted quinoline derivatives and pharmaceutical use thereof. United States Patent 6,403,569. U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

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Details for Patent: 6,403,569

Summary for Patent: 6,403,569