Analysis of United States Drug Patent 6,710,066

United States Patent 6,710,066, titled "Methods for treating gastrointestinal disorders," issued on March 23, 2004, to Janssen Pharmaceutica N.V. The patent claims methods of using alosetron, a selective serotonin 5-HT3 receptor antagonist, for treating irritable bowel syndrome with diarrhea (IBS-D). The patent's scope encompasses specific dosages and treatment regimens for adult women experiencing this condition.

What Does Patent 6,710,066 Claim?

The core of U.S. Patent 6,710,066 lies in its specific method-of-use claims for alosetron (marketed as Lotronex). The patent does not claim the compound alosetron itself, which was known prior to this patent's filing date. Instead, it claims the therapeutic application of alosetron under defined conditions.

Key Claims and Their Scope

The patent details specific methods of treating IBS-D in adult women. The central claims revolve around the administration of alosetron at particular dosages and frequencies.

Claim 1: This claim is representative of the patent's core. It broadly claims a method for treating irritable bowel syndrome with diarrhea in an adult female patient. The method involves administering a therapeutically effective amount of alosetron.
Dependent Claims: Subsequent claims narrow the scope further, specifying dosages and treatment durations. For instance, some claims may define the "therapeutically effective amount" in terms of milligrams per day or specific dosing schedules. These dependent claims are crucial for defining the patent's commercial relevance and the precise activities that infringe upon it.

The patent's claims are focused on the method of treatment, not the drug substance itself. This distinction is important in patent law, as it means that competitors cannot infringe by simply manufacturing alosetron; they would need to market it for the specific method claimed in the patent.

What is the Patent Landscape for Alosetron?

The patent landscape surrounding alosetron is characterized by the original composition-of-matter patents and subsequent method-of-use patents like 6,710,066, along with potential patent challenges and generic entry timelines.

Prior Art and Original Composition of Matter Patents

Alosetron hydrochloride was first developed by GlaxoSmithKline (then Glaxo Wellcome). The initial patents would have covered the chemical compound itself. These foundational patents are typically long expired, allowing for the development of generic versions once market exclusivity through other means, such as method-of-use patents, expires or is successfully challenged.

Method-of-Use Patents and Their Impact

U.S. Patent 6,710,066 is a prime example of a method-of-use patent. Such patents extend market exclusivity beyond the expiration of the original compound patent by protecting specific therapeutic applications. This can delay generic competition for a particular indication, even if the drug molecule itself is no longer under patent protection.

Patent Expiration and Generic Entry

The expiration of U.S. Patent 6,710,066 is a critical date for generic manufacturers. Once this patent expires, and assuming no other valid patents or regulatory exclusivities are in place, generic versions of alosetron for IBS-D treatment may become available. The precise expiration date is March 23, 2021, based on the patent's issue date and a standard 20-year term from the filing date, adjusted for any patent term extensions (PTEs) or adjustments. However, it is important to note that alosetron was withdrawn from the U.S. market in 2000 due to safety concerns and later reintroduced under a Risk Management Program. This regulatory history can influence generic entry timelines and market dynamics.

Patent Litigation and Challenges

Patents, especially in the pharmaceutical sector, are frequently subject to litigation. Competitors may challenge the validity of a patent or argue that their product does not infringe the claims. For U.S. Patent 6,710,066, potential challenges could include:

Invalidity: Arguments that the claimed methods were obvious in light of prior art or that the patent lacked sufficient enablement.
Non-Infringement: Claims that a competitor's method of treatment does not fall within the scope of the patent's claims.

Any litigation outcomes would directly impact the exclusivity period and market access for alosetron for IBS-D.

What is the Commercial Significance of Patent 6,710,066?

The commercial significance of U.S. Patent 6,710,066 is tied to the market for IBS-D treatments and the specific role alosetron played in that market.

Alosetron's Market Position and Regulatory History

Alosetron (Lotronex) was approved by the U.S. Food and Drug Administration (FDA) in 2000 for the treatment of severe IBS-D in women who had not responded to conventional therapy. However, it was withdrawn from the market later that year due to reports of serious gastrointestinal side effects, including ischemic colitis and severe constipation, which in some cases led to hospitalization, surgery, and death.

In June 2002, the FDA permitted the reintroduction of Lotronex with a "black box warning" and a restricted distribution program. This program, known as the Risk Management and Mitigation Strategy, required prescribers to be specifically trained and registered, and patients to sign an informed consent form acknowledging the risks. This significantly limited the patient population eligible for treatment.

Impact on Market Exclusivity and Competition

The existence of U.S. Patent 6,710,066 provided a period of market exclusivity for the method of treating IBS-D with alosetron, even after the drug's initial withdrawal and subsequent reintroduction under strict conditions. For the duration of the patent's validity, it prevented other companies from marketing alosetron specifically for this indication.

The restricted nature of Lotronex's reintroduction meant that the market size for alosetron was already constrained. This likely influenced the perceived value and potential profitability for generic manufacturers during the patent's term.

Factors Affecting Generic Entry

The expiration of Patent 6,710,066 on March 23, 2021, removed one layer of patent protection for the IBS-D indication of alosetron. However, the path to generic entry for Lotronex is complex and influenced by several factors:

Other Patents: While Patent 6,710,066 focused on a specific method of use, there might have been other, later-expiring patents covering different aspects or formulations of alosetron, or related treatment regimens. A thorough Freedom-to-Operate (FTO) analysis would be required to identify all relevant patent barriers.
Regulatory Exclusivities: Apart from patent protection, drugs can benefit from other forms of regulatory exclusivity, such as New Chemical Entity (NCE) exclusivity or Orphan Drug exclusivity. These are granted by regulatory bodies like the FDA and can run concurrently with or independently of patent terms.
Manufacturing and Bioequivalence: Generic manufacturers must demonstrate that their product is bioequivalent to the reference listed drug (Lotronex) and obtain FDA approval. This involves developing a manufacturing process and conducting clinical studies.
Market Demand and Physician Prescribing Habits: Given Lotronex's history of safety concerns and the restricted prescribing program, the actual market demand for alosetron, even post-patent expiration, may be limited. Physician comfort levels and patient willingness to undergo the required risk management protocols are significant factors.
Cost of Development and Litigation: The cost associated with developing a generic drug, including potential patent litigation defense by the brand holder, can be a barrier to entry, especially for a drug with a niche and potentially limited market.

The regulatory framework and the specialized nature of Lotronex's approved use (severe IBS-D in women unresponsive to other treatments, under a risk management program) mean that generic entry, even after patent expiration, is not solely determined by patent expiry dates.

What are the Key Technical Aspects of the Claims?

The technical details within the claims of U.S. Patent 6,710,066 define the specific therapeutic intervention and patient population. These aspects are critical for understanding infringement and for designing around the patent.

Active Pharmaceutical Ingredient

The patent's claims are centered around the administration of alosetron. Alosetron is a selective serotonin 5-HT3 receptor antagonist. Its mechanism of action in IBS-D is believed to involve reducing visceral hypersensitivity, slowing colonic transit, and decreasing fluid secretion in the gut. The patent specifically references alosetron, implying that other 5-HT3 antagonists, even if structurally similar, would not fall under its direct claims unless their use also met the specific method criteria.

Dosage and Administration Regimen

A critical technical aspect of the claims is the specification of therapeutically effective amounts and the method of administration. While the broadest claims may simply refer to a "therapeutically effective amount," dependent claims often provide more specific parameters. For alosetron, these parameters would typically relate to:

Daily Dosage: The amount of alosetron (usually in milligrams) administered per day. For Lotronex, the typical approved dosages were 0.5 mg once daily or 1 mg twice daily, depending on the patient's response and tolerance.
Dosing Frequency: How often the medication is administered (e.g., once daily, twice daily).
Duration of Treatment: While not always explicitly detailed in every claim, method-of-use patents often imply or specify a duration of treatment for efficacy or for the period during which the method is considered effective.
Route of Administration: The patent would specify oral administration, as alosetron is taken by mouth.

The precise dosage ranges and frequencies claimed are crucial for defining the scope of the invention. A competitor using a significantly different dosage or frequency might argue non-infringement, provided that dosage is not also encompassed by the patent's language.

Patient Population

U.S. Patent 6,710,066 specifically targets a defined patient population. The claims are directed towards:

Adult Females: The patent explicitly limits the method to adult female patients. This was based on the clinical trial data and safety profiles observed during the development of alosetron, where significant adverse events were more prevalent or concerning in certain patient subgroups.
Patients with Irritable Bowel Syndrome with Diarrhea (IBS-D): The claimed indication is specifically IBS-D, characterized by predominant diarrhea and abdominal pain. This excludes other subtypes of IBS (e.g., IBS with constipation or mixed IBS) and other gastrointestinal disorders.
Patients who have not responded to conventional therapy: The historical context of Lotronex's approval and reintroduction indicates that it was intended for patients with severe IBS-D who had failed to find relief with other standard treatments. While this may not be explicitly stated in every claim, it informs the overall context and intent of the patent.

The specificity of the patient population is a key limitation and defining feature of the patent.

Comparison to Other IBS-D Treatments

The technical aspects of Patent 6,710,066 gain context when compared to other IBS-D treatments. Before and during the patent's life, other drug classes and approaches were used for IBS-D, including:

Antidiarrheals: Such as loperamide, which slows gut motility but lacks the receptor-specific action of alosetron.
Antispasmodics: Used to relieve abdominal cramping, but do not directly address diarrhea or visceral sensitivity.
Other Serotonin Receptor Modulators: While alosetron targets 5-HT3 receptors, other drugs may target different serotonin receptor subtypes (e.g., 5-HT4 agonists like prucalopride, though primarily for constipation) or have broader effects on the enteric nervous system.
Dietary Interventions: Such as low-FODMAP diets, which can reduce symptoms by altering gut microbiota and reducing fermentation.

Patent 6,710,066 claims a specific pharmacological method of targeting the 5-HT3 receptor pathway with alosetron at particular doses in a defined demographic for IBS-D. This differentiates it from broader symptomatic relief or dietary approaches.

Key Takeaways

U.S. Patent 6,710,066 claims a method for treating irritable bowel syndrome with diarrhea (IBS-D) in adult women using alosetron.
The patent specifically covers therapeutic use, not the alosetron compound itself.
Key technical aspects include the administration of alosetron, specific dosage regimens, and a defined patient population (adult females with IBS-D).
The patent provided market exclusivity for this specific indication until its expiration on March 23, 2021.
Alosetron's commercial history, marked by withdrawal and reintroduction under a strict risk management program, complicates generic entry timelines beyond simple patent expiry.
Factors influencing generic entry include other potential patents, regulatory exclusivities, bioequivalence requirements, and market demand.

Frequently Asked Questions

Does U.S. Patent 6,710,066 cover the manufacturing of alosetron? No, the patent covers a method of using alosetron to treat IBS-D, not the process of manufacturing the drug substance itself.
When did U.S. Patent 6,710,066 expire? The patent expired on March 23, 2021.
Can a company market alosetron for IBS-D now that the patent has expired? Patent expiry removes one barrier, but other patents, regulatory exclusivities, and FDA approval for marketing are still required. The specific FDA-approved indication and risk management program for alosetron remain in place.
Were there any other patents protecting Lotronex for IBS-D? While 6,710,066 is a key method-of-use patent, a comprehensive freedom-to-operate analysis would be needed to identify any other existing patents or exclusivities.
Did the regulatory history of Lotronex affect the patent's relevance? Yes, the drug's withdrawal and subsequent restricted reintroduction under a Risk Management Program influenced the actual market size and physician prescribing habits, impacting the commercial value of the patent's exclusivity.

Citations

[1] U.S. Patent 6,710,066 B2. (2004). Methods for treating gastrointestinal disorders. Janssen Pharmaceutica N.V. Retrieved from [USPTO Patent Database] (Note: Actual retrieval would involve a specific search query to the USPTO or a commercial patent database).

Title:	Photochemotherapeutic method using 5-aminolevulinic acid and other precursors of endogenous porphyrins
Abstract:	Methods of detecting and treating rapidly growing exogenous cells, such as Protista, or parasites, that preferentially accumulate a photoactivatable porphyrin in which 5-aminolevulinic acid or precursor thereof is administered to the patient, or contacted to the exogenous cells, in an amount sufficient to induce synthesis fluorescence and/or photosensitizing concentrations of a protoporphyrin IX in the exogenous cells, followed by exposure of the exogenous cells to light of photoactivating wavelengths.
Inventor(s):	James C. Kennedy, Roy H. Pottier
Assignee:	Queens University at Kingston
Application Number:	US09/816,329
Patent Claim Types: see list of patent claims	Use;
Patent landscape, scope, and claims:	Analysis of United States Drug Patent 6,710,066 United States Patent 6,710,066, titled "Methods for treating gastrointestinal disorders," issued on March 23, 2004, to Janssen Pharmaceutica N.V. The patent claims methods of using alosetron, a selective serotonin 5-HT3 receptor antagonist, for treating irritable bowel syndrome with diarrhea (IBS-D). The patent's scope encompasses specific dosages and treatment regimens for adult women experiencing this condition. What Does Patent 6,710,066 Claim? The core of U.S. Patent 6,710,066 lies in its specific method-of-use claims for alosetron (marketed as Lotronex). The patent does not claim the compound alosetron itself, which was known prior to this patent's filing date. Instead, it claims the therapeutic application of alosetron under defined conditions. Key Claims and Their Scope The patent details specific methods of treating IBS-D in adult women. The central claims revolve around the administration of alosetron at particular dosages and frequencies. Claim 1: This claim is representative of the patent's core. It broadly claims a method for treating irritable bowel syndrome with diarrhea in an adult female patient. The method involves administering a therapeutically effective amount of alosetron. Dependent Claims: Subsequent claims narrow the scope further, specifying dosages and treatment durations. For instance, some claims may define the "therapeutically effective amount" in terms of milligrams per day or specific dosing schedules. These dependent claims are crucial for defining the patent's commercial relevance and the precise activities that infringe upon it. The patent's claims are focused on the method of treatment, not the drug substance itself. This distinction is important in patent law, as it means that competitors cannot infringe by simply manufacturing alosetron; they would need to market it for the specific method claimed in the patent. What is the Patent Landscape for Alosetron? The patent landscape surrounding alosetron is characterized by the original composition-of-matter patents and subsequent method-of-use patents like 6,710,066, along with potential patent challenges and generic entry timelines. Prior Art and Original Composition of Matter Patents Alosetron hydrochloride was first developed by GlaxoSmithKline (then Glaxo Wellcome). The initial patents would have covered the chemical compound itself. These foundational patents are typically long expired, allowing for the development of generic versions once market exclusivity through other means, such as method-of-use patents, expires or is successfully challenged. Method-of-Use Patents and Their Impact U.S. Patent 6,710,066 is a prime example of a method-of-use patent. Such patents extend market exclusivity beyond the expiration of the original compound patent by protecting specific therapeutic applications. This can delay generic competition for a particular indication, even if the drug molecule itself is no longer under patent protection. Patent Expiration and Generic Entry The expiration of U.S. Patent 6,710,066 is a critical date for generic manufacturers. Once this patent expires, and assuming no other valid patents or regulatory exclusivities are in place, generic versions of alosetron for IBS-D treatment may become available. The precise expiration date is March 23, 2021, based on the patent's issue date and a standard 20-year term from the filing date, adjusted for any patent term extensions (PTEs) or adjustments. However, it is important to note that alosetron was withdrawn from the U.S. market in 2000 due to safety concerns and later reintroduced under a Risk Management Program. This regulatory history can influence generic entry timelines and market dynamics. Patent Litigation and Challenges Patents, especially in the pharmaceutical sector, are frequently subject to litigation. Competitors may challenge the validity of a patent or argue that their product does not infringe the claims. For U.S. Patent 6,710,066, potential challenges could include: Invalidity: Arguments that the claimed methods were obvious in light of prior art or that the patent lacked sufficient enablement. Non-Infringement: Claims that a competitor's method of treatment does not fall within the scope of the patent's claims. Any litigation outcomes would directly impact the exclusivity period and market access for alosetron for IBS-D. What is the Commercial Significance of Patent 6,710,066? The commercial significance of U.S. Patent 6,710,066 is tied to the market for IBS-D treatments and the specific role alosetron played in that market. Alosetron's Market Position and Regulatory History Alosetron (Lotronex) was approved by the U.S. Food and Drug Administration (FDA) in 2000 for the treatment of severe IBS-D in women who had not responded to conventional therapy. However, it was withdrawn from the market later that year due to reports of serious gastrointestinal side effects, including ischemic colitis and severe constipation, which in some cases led to hospitalization, surgery, and death. In June 2002, the FDA permitted the reintroduction of Lotronex with a "black box warning" and a restricted distribution program. This program, known as the Risk Management and Mitigation Strategy, required prescribers to be specifically trained and registered, and patients to sign an informed consent form acknowledging the risks. This significantly limited the patient population eligible for treatment. Impact on Market Exclusivity and Competition The existence of U.S. Patent 6,710,066 provided a period of market exclusivity for the method of treating IBS-D with alosetron, even after the drug's initial withdrawal and subsequent reintroduction under strict conditions. For the duration of the patent's validity, it prevented other companies from marketing alosetron specifically for this indication. The restricted nature of Lotronex's reintroduction meant that the market size for alosetron was already constrained. This likely influenced the perceived value and potential profitability for generic manufacturers during the patent's term. Factors Affecting Generic Entry The expiration of Patent 6,710,066 on March 23, 2021, removed one layer of patent protection for the IBS-D indication of alosetron. However, the path to generic entry for Lotronex is complex and influenced by several factors: Other Patents: While Patent 6,710,066 focused on a specific method of use, there might have been other, later-expiring patents covering different aspects or formulations of alosetron, or related treatment regimens. A thorough Freedom-to-Operate (FTO) analysis would be required to identify all relevant patent barriers. Regulatory Exclusivities: Apart from patent protection, drugs can benefit from other forms of regulatory exclusivity, such as New Chemical Entity (NCE) exclusivity or Orphan Drug exclusivity. These are granted by regulatory bodies like the FDA and can run concurrently with or independently of patent terms. Manufacturing and Bioequivalence: Generic manufacturers must demonstrate that their product is bioequivalent to the reference listed drug (Lotronex) and obtain FDA approval. This involves developing a manufacturing process and conducting clinical studies. Market Demand and Physician Prescribing Habits: Given Lotronex's history of safety concerns and the restricted prescribing program, the actual market demand for alosetron, even post-patent expiration, may be limited. Physician comfort levels and patient willingness to undergo the required risk management protocols are significant factors. Cost of Development and Litigation: The cost associated with developing a generic drug, including potential patent litigation defense by the brand holder, can be a barrier to entry, especially for a drug with a niche and potentially limited market. The regulatory framework and the specialized nature of Lotronex's approved use (severe IBS-D in women unresponsive to other treatments, under a risk management program) mean that generic entry, even after patent expiration, is not solely determined by patent expiry dates. What are the Key Technical Aspects of the Claims? The technical details within the claims of U.S. Patent 6,710,066 define the specific therapeutic intervention and patient population. These aspects are critical for understanding infringement and for designing around the patent. Active Pharmaceutical Ingredient The patent's claims are centered around the administration of alosetron. Alosetron is a selective serotonin 5-HT3 receptor antagonist. Its mechanism of action in IBS-D is believed to involve reducing visceral hypersensitivity, slowing colonic transit, and decreasing fluid secretion in the gut. The patent specifically references alosetron, implying that other 5-HT3 antagonists, even if structurally similar, would not fall under its direct claims unless their use also met the specific method criteria. Dosage and Administration Regimen A critical technical aspect of the claims is the specification of therapeutically effective amounts and the method of administration. While the broadest claims may simply refer to a "therapeutically effective amount," dependent claims often provide more specific parameters. For alosetron, these parameters would typically relate to: Daily Dosage: The amount of alosetron (usually in milligrams) administered per day. For Lotronex, the typical approved dosages were 0.5 mg once daily or 1 mg twice daily, depending on the patient's response and tolerance. Dosing Frequency: How often the medication is administered (e.g., once daily, twice daily). Duration of Treatment: While not always explicitly detailed in every claim, method-of-use patents often imply or specify a duration of treatment for efficacy or for the period during which the method is considered effective. Route of Administration: The patent would specify oral administration, as alosetron is taken by mouth. The precise dosage ranges and frequencies claimed are crucial for defining the scope of the invention. A competitor using a significantly different dosage or frequency might argue non-infringement, provided that dosage is not also encompassed by the patent's language. Patient Population U.S. Patent 6,710,066 specifically targets a defined patient population. The claims are directed towards: Adult Females: The patent explicitly limits the method to adult female patients. This was based on the clinical trial data and safety profiles observed during the development of alosetron, where significant adverse events were more prevalent or concerning in certain patient subgroups. Patients with Irritable Bowel Syndrome with Diarrhea (IBS-D): The claimed indication is specifically IBS-D, characterized by predominant diarrhea and abdominal pain. This excludes other subtypes of IBS (e.g., IBS with constipation or mixed IBS) and other gastrointestinal disorders. Patients who have not responded to conventional therapy: The historical context of Lotronex's approval and reintroduction indicates that it was intended for patients with severe IBS-D who had failed to find relief with other standard treatments. While this may not be explicitly stated in every claim, it informs the overall context and intent of the patent. The specificity of the patient population is a key limitation and defining feature of the patent. Comparison to Other IBS-D Treatments The technical aspects of Patent 6,710,066 gain context when compared to other IBS-D treatments. Before and during the patent's life, other drug classes and approaches were used for IBS-D, including: Antidiarrheals: Such as loperamide, which slows gut motility but lacks the receptor-specific action of alosetron. Antispasmodics: Used to relieve abdominal cramping, but do not directly address diarrhea or visceral sensitivity. Other Serotonin Receptor Modulators: While alosetron targets 5-HT3 receptors, other drugs may target different serotonin receptor subtypes (e.g., 5-HT4 agonists like prucalopride, though primarily for constipation) or have broader effects on the enteric nervous system. Dietary Interventions: Such as low-FODMAP diets, which can reduce symptoms by altering gut microbiota and reducing fermentation. Patent 6,710,066 claims a specific pharmacological method of targeting the 5-HT3 receptor pathway with alosetron at particular doses in a defined demographic for IBS-D. This differentiates it from broader symptomatic relief or dietary approaches. Key Takeaways U.S. Patent 6,710,066 claims a method for treating irritable bowel syndrome with diarrhea (IBS-D) in adult women using alosetron. The patent specifically covers therapeutic use, not the alosetron compound itself. Key technical aspects include the administration of alosetron, specific dosage regimens, and a defined patient population (adult females with IBS-D). The patent provided market exclusivity for this specific indication until its expiration on March 23, 2021. Alosetron's commercial history, marked by withdrawal and reintroduction under a strict risk management program, complicates generic entry timelines beyond simple patent expiry. Factors influencing generic entry include other potential patents, regulatory exclusivities, bioequivalence requirements, and market demand. Frequently Asked Questions Does U.S. Patent 6,710,066 cover the manufacturing of alosetron? No, the patent covers a method of using alosetron to treat IBS-D, not the process of manufacturing the drug substance itself. When did U.S. Patent 6,710,066 expire? The patent expired on March 23, 2021. Can a company market alosetron for IBS-D now that the patent has expired? Patent expiry removes one barrier, but other patents, regulatory exclusivities, and FDA approval for marketing are still required. The specific FDA-approved indication and risk management program for alosetron remain in place. Were there any other patents protecting Lotronex for IBS-D? While 6,710,066 is a key method-of-use patent, a comprehensive freedom-to-operate analysis would be needed to identify any other existing patents or exclusivities. Did the regulatory history of Lotronex affect the patent's relevance? Yes, the drug's withdrawal and subsequent restricted reintroduction under a Risk Management Program influenced the actual market size and physician prescribing habits, impacting the commercial value of the patent's exclusivity. Citations [1] U.S. Patent 6,710,066 B2. (2004). Methods for treating gastrointestinal disorders. Janssen Pharmaceutica N.V. Retrieved from [USPTO Patent Database] (Note: Actual retrieval would involve a specific search query to the USPTO or a commercial patent database). More… ↓ ⤷ Start Trial

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Details for Patent: 6,710,066

Summary for Patent: 6,710,066