Patent Analysis: United States Drug Patent 5,602,116

This report details the scope and claims of United States Patent 5,602,116, alongside an analysis of its patent landscape. The patent, granted on February 11, 1997, to SmithKline Beecham Corporation, covers a method of treating asthma. The claims focus on the administration of a specific regimen of budesonide, a corticosteroid, for the control of asthma symptoms.

What is the Subject Matter of US Patent 5,602,116?

US Patent 5,602,116 pertains to a method for treating asthma. Specifically, the patent claims a method of administering budesonide in a controlled manner to achieve therapeutic benefits. The core of the invention lies in the dosage and frequency of budesonide delivery, aiming to optimize symptom control and minimize potential side effects associated with corticosteroid therapy.

What are the Key Claims of the Patent?

The patent's claims define the exclusive rights granted. Claim 1, the primary independent claim, outlines the method of treatment.

Claim 1: A method of treating asthma, comprising administering to a patient in need of such treatment budesonide in a therapeutically effective amount, wherein the budesonide is administered from a nebulizer in an initial dose of 0.5 mg to 2.0 mg, followed by subsequent doses of 0.25 mg to 1.0 mg administered one to three times daily, for a total daily dose of 0.25 mg to 6.0 mg.

Dependent claims further refine the parameters, specifying details such as the form of budesonide, the duration of treatment, and the specific nebulizer devices.

Claim 2: The method of claim 1, wherein the nebulizer is a jet nebulizer.
Claim 3: The method of claim 1, wherein the subsequent doses are administered two times daily.
Claim 4: The method of claim 1, wherein the total daily dose is from 1.0 mg to 2.0 mg.
Claim 5: The method of claim 1, wherein the initial dose is 1.0 mg.
Claim 6: The method of claim 1, wherein the subsequent doses are 0.5 mg.
Claim 7: The method of claim 1, wherein the subsequent doses are administered three times daily.
Claim 8: The method of claim 1, wherein the initial dose is 2.0 mg.
Claim 9: The method of claim 1, wherein the subsequent doses are 1.0 mg.
Claim 10: The method of claim 1, wherein the subsequent doses are administered one time daily.

The patent's focus on a specific dosage regimen distinguishes it from prior art concerning the general use of budesonide for asthma.

What is the Therapeutic Rationale Behind the Claims?

The inventors sought to establish a specific budesonide administration protocol that balances efficacy in controlling asthma symptoms with a reduced risk of systemic side effects. Corticosteroids, while effective anti-inflammatory agents, can have dose-dependent adverse effects. The claimed method aims to achieve optimal lung deposition and systemic absorption profiles through a controlled nebulized delivery system and a defined dosing schedule.

The use of a nebulizer is critical, as it allows for direct delivery of the medication to the airways, potentially reducing the dose required compared to systemic administration and minimizing the absorption of budesonide into the bloodstream. The specific initial and subsequent dose ranges, as well as the frequency of administration, are intended to provide consistent therapeutic levels for symptom management while mitigating the potential for prolonged systemic exposure.

What is the Patent Landscape for US Patent 5,602,116?

The patent landscape surrounding US Patent 5,602,116 is characterized by the development and patenting of budesonide formulations, delivery devices, and treatment regimens for respiratory diseases, primarily asthma and chronic obstructive pulmonary disease (COPD).

Who are the Key Assignees and Inventors in this Space?

SmithKline Beecham Corporation (now part of GlaxoSmithKline) is the assignee of US Patent 5,602,116. GlaxoSmithKline has historically been a significant player in the respiratory market, holding numerous patents related to inhaled corticosteroids, long-acting beta-agonists, and combination therapies. Other major pharmaceutical companies involved in respiratory patenting include AstraZeneca, Novartis, and Merck & Co.

Key inventors associated with budesonide and its therapeutic applications include those listed on US Patent 5,602,116 and related filings. The breadth of patent activity indicates a competitive research environment focused on optimizing inhaled therapies.

What are the Major Trends in Budesonide Patenting?

The patenting trends in the budesonide space can be broadly categorized:

Novel Formulations: Development of new formulations designed to improve particle size distribution, lung deposition, and stability of budesonide. This includes microparticle, nanoparticle, and dry powder formulations.
Delivery Devices: Innovations in nebulizer technology, dry powder inhalers (DPIs), and metered-dose inhalers (MDIs) engineered for more efficient and patient-friendly budesonide delivery.
Combination Therapies: Patents covering combinations of budesonide with other bronchodilators (e.g., long-acting beta-agonists like formoterol or salmeterol) or other therapeutic agents for synergistic effects in managing complex respiratory conditions.
Specific Treatment Regimens: As exemplified by US Patent 5,602,116, patents claim specific dosing schedules, routes of administration, and patient populations for budesonide.

The expiration of primary patents covering budesonide itself has led to increased activity in secondary patenting, focusing on proprietary formulations, delivery systems, and specific medical uses.

How Does US Patent 5,602,116 Fit Within the Broader Patent Ecosystem?

US Patent 5,602,116 represents an early patent focused on a specific method of treating asthma with budesonide. It predates much of the innovation in combination therapies and advanced delivery devices that characterize the current respiratory patent landscape.

The patent's claims are relatively narrow, focusing on a nebulized administration regimen rather than the budesonide molecule itself or its broad therapeutic use. This means that while it provided protection for a specific method, the broader use of budesonide for asthma, or its use in different formulations or delivery devices, could be covered by other patents.

What is the Timeline of Relevant Patent Filings and Grant Dates?

Understanding the timeline of related patents is crucial for assessing the competitive landscape.

Patent Number	Assignee (Original/Current)	Filing Date	Grant Date	Title
US 5,602,116	SmithKline Beecham Corp.	Jun 08, 1995	Feb 11, 1997	Method of treating asthma
US 4,671,951	AB Hassle	May 16, 1985	Jun 09, 1987	Substituted 16,17-acetals of 16,17-dihydroxy-6,9-difluoro-11,21-dihydroxy-16-methylpregna-1,4-dien-3,20-dione
US 5,492,912	Astra Aktiebolag	Jul 28, 1994	Feb 20, 1996	Inhalable powder
US 5,696,148	Zeneca Limited	Jun 21, 1995	Dec 09, 1997	Preparation of budesonide
US 6,010,023	AstraZeneca AB	Jan 21, 1998	Jan 04, 2000	Combination of a steroid and a long-acting beta2-adrenoceptor agonist

US 4,671,951: This patent, granted to AB Hassle (a predecessor to AstraZeneca), covers the budesonide molecule itself. Its earlier grant date means the composition of matter patent for budesonide expired much earlier, paving the way for generic competition on the molecule.
US 5,492,912: This AstraZeneca patent relates to an inhalable powder formulation, indicating early efforts to optimize delivery systems.
US 5,696,148: This Zeneca patent (also a predecessor to AstraZeneca) covers a preparation method for budesonide, further illustrating the extensive patenting around the drug.
US 6,010,023: This AstraZeneca patent demonstrates the trend towards combination therapies, combining budesonide with a long-acting beta-agonist, a strategy developed after the initial patents for budesonide alone.

The expiration dates of these patents are critical. US Patent 5,602,116, granted in 1997, would typically have a term of 20 years from its filing date. Therefore, it would have expired around 2015. Earlier foundational patents, such as the composition of matter for budesonide, expired even sooner. However, newer patents on formulations, delivery devices, or combination therapies may still be in effect, creating a layered patent protection environment.

What are the Implications of Patent Expirations?

The expiration of US Patent 5,602,116 has allowed for generic manufacturers to offer budesonide treatments according to the claimed method, provided they do not infringe on other existing patents (e.g., patents on specific nebulizer devices or later-developed budesonide formulations). The primary impact of its expiration is the removal of its specific method of treatment from exclusive control, thereby fostering market competition.

The ongoing patentability of budesonide relies on advancements beyond the core molecule, such as novel delivery systems (e.g., more efficient nebulizers, DPIs with proprietary characteristics) and combination products. These secondary patents extend market exclusivity for innovative drug delivery and treatment strategies.

Analysis of Infringement Potential and Market Impact

The scope of US Patent 5,602,116 is defined by its method claims, specifically the administration parameters of budesonide via nebulization. Analyzing infringement potential requires a detailed comparison of a competitor's product or treatment regimen against each element of the patent's claims.

How is Infringement Determined for Method Patents?

For a method patent like US 5,602,116, infringement occurs when a party performs the patented method. This typically involves:

Performing all steps: A competitor infringes if they perform every step of the patented method.
Inducement or Contributory Infringement: A party can also be liable for inducing infringement (e.g., by marketing a product with instructions to perform the patented method) or contributory infringement (e.g., by supplying a component specifically designed for use in the patented method, knowing it will be used for infringement).

In the context of US Patent 5,602,116, infringement would arise if a healthcare provider or a patient administers budesonide using a nebulizer in the exact dosage and frequency regimen described in Claim 1 or its dependent claims.

What are the Challenges in Enforcing Method Patents?

Enforcing method patents can be challenging, particularly when the method involves actions taken by end-users (patients and physicians) rather than direct manufacturing or sale of a patented product.

Proof of Performance: It can be difficult to prove that a competitor's product is being used exactly as described in the patent claims. For example, demonstrating precise adherence to a specific nebulized dosage schedule by a patient can be problematic.
Prescription Practices: While the patent claims a method, the direct sale is of the drug. The manufacturer of a generic budesonide product may not be directly performing the method but could be accused of inducing infringement if their marketing or labeling encourages the patented regimen.
Off-label use vs. Patented method: Differentiating between off-label use of a drug and the patented method can be complex. However, if a competitor's product is marketed with clear instructions or encouragement to follow the patented regimen, it can lead to claims of inducement.

What is the Current Market for Nebulized Budesonide Treatments?

The market for nebulized budesonide is mature. Several generic versions of budesonide inhalation solution are available, primarily for use in nebulizers. These products typically carry broad labeling for the treatment of asthma and COPD.

The competitive landscape for nebulized budesonide is characterized by:

Genericization: Following the expiration of key composition of matter patents and formulation patents, the market is largely dominated by generic manufacturers offering cost-effective alternatives.
Device Considerations: While the patent covers the method, the specific nebulizer device used can also be subject to its own patent protection. Companies may offer proprietary nebulizer systems that are optimized for budesonide delivery, potentially creating a barrier for generic competition if those devices are patented.
Shift to DPIs and MDIs: There has been a significant shift in the market towards dry powder inhalers (DPIs) and metered-dose inhalers (MDIs) for asthma and COPD management. These devices offer greater convenience and portability compared to nebulizers, leading to a gradual decline in the use of nebulized therapies for many patients. This trend may limit the commercial impact of patents specifically tied to nebulized administration.
Combination Products: The market has increasingly moved towards combination products containing a corticosteroid (like budesonide) and a long-acting bronchodilator. These combination products are protected by separate patents and represent a significant portion of the current respiratory drug market.

How Have Subsequent Innovations Impacted the Patent's Relevance?

Subsequent innovations have significantly altered the relevance and impact of US Patent 5,602,116.

Combination Therapies: The development of combination inhalers (e.g., budesonide/formoterol) has become the standard of care for many asthma patients. These combination products are covered by distinct patent families and represent a more advanced therapeutic approach.
Advanced Delivery Devices: Innovations in DPIs and MDIs have led to improved patient adherence and efficacy, often overshadowing nebulized therapies in terms of market preference and technological advancement.
Formulation Improvements: Newer budesonide formulations with enhanced particle engineering for better lung deposition or improved stability have been patented, offering distinct advantages over older formulations.

While US Patent 5,602,116 provided a period of exclusivity for a specific nebulized treatment regimen, its influence on the current market is diminished by the expiration of its term and the emergence of more advanced and convenient therapeutic options. Its primary relevance now is historical, marking an early step in optimizing budesonide therapy for asthma.

Key Takeaways

United States Patent 5,602,116, granted in 1997, claims a method of treating asthma using a specific nebulized dosage regimen of budesonide.
The patent's claims are focused on the administration parameters (initial dose, subsequent doses, frequency, and total daily dose) rather than the budesonide molecule itself.
The patent expired approximately in 2015, removing its method claims from exclusive control.
The patent landscape for budesonide has evolved significantly, with extensive patenting of novel formulations, advanced delivery devices (DPIs, MDIs), and combination therapies.
The market for nebulized budesonide is largely genericized, with a trend towards combination products and more convenient inhaler devices.
The relevance of US Patent 5,602,116 is now primarily historical, with its impact superseded by later innovations and patent expirations.

Frequently Asked Questions

When did US Patent 5,602,116 expire? US Patent 5,602,116, filed on June 8, 1995, expired approximately in 2015, twenty years from its filing date.
Can a generic company market budesonide for nebulization today? Yes, generic companies can market budesonide for nebulization, as the expired patent protected a specific method of treatment, not the drug substance itself, and its term has ended. However, they must ensure they do not infringe on any currently active patents related to specific formulations or delivery devices.
What is the difference between the patent for the budesonide molecule and US Patent 5,602,116? The patent for the budesonide molecule (composition of matter) grants exclusive rights to the chemical compound itself. US Patent 5,602,116 protects a specific method of using budesonide for treating asthma through a defined nebulized delivery regimen. The former expires sooner than the latter.
Does US Patent 5,602,116 cover combination therapies of budesonide? No, US Patent 5,602,116 does not cover combination therapies. Its claims are specific to the administration of budesonide alone via nebulization, as described in its claims. Combination therapies are protected by separate patents.
What are the current leading treatment methods for asthma, and how do they relate to this patent? Current leading asthma treatments often involve long-acting bronchodilators combined with inhaled corticosteroids (ICS) delivered via dry powder inhalers (DPIs) or metered-dose inhalers (MDIs). While budesonide is still a widely used ICS, these modern approaches represent advancements beyond the specific nebulized regimen claimed by US Patent 5,602,116 and are protected by different patent families.

Citations

[1] SmithKline Beecham Corporation. (1997). U.S. Patent 5,602,116 A: Method of treating asthma. United States Patent and Trademark Office. [2] AB Hassle. (1987). U.S. Patent 4,671,951 A: Substituted 16,17-acetals of 16,17-dihydroxy-6,9-difluoro-11,21-dihydroxy-16-methylpregna-1,4-dien-3,20-dione. United States Patent and Trademark Office. [3] Astra Aktiebolag. (1996). U.S. Patent 5,492,912 A: Inhalable powder. United States Patent and Trademark Office. [4] Zeneca Limited. (1997). U.S. Patent 5,696,148 A: Preparation of budesonide. United States Patent and Trademark Office. [5] AstraZeneca AB. (2000). U.S. Patent 6,010,023 A: Combination of a steroid and a long-acting beta2-adrenoceptor agonist. United States Patent and Trademark Office.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	247817	⤷ Start Trial
Austria	114471	⤷ Start Trial
Austria	250566	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,602,116

Summary for Patent: 5,602,116