| Abstract: | The invention concerns quinazoline derivatives of the formula I ##STR1## wherein m is 1, 2 or 3 and each R1 includes hydroxy, amino, carboxy, carbamoyl, ureido, (1-4C)alkoxycarbonyl, N-(1-4C)alkylcarbamoyl, N,N-di-[(1-4C)alkyl]carbamoyl, hydroxyamino, (1-4C)alkoxyamino, (2-4C)alkanoyloxyamino, trifluoromethoxy, (1-4C)alkyl, (1-4C)alkoxy and (1-3C)alkylenedioxy; n is 1 or 2 and each R2 includes hydrogen, hydroxy, halogeno, trifluoromethyl, amino, nitro, cyano and (1-4C)alkyl; or a pharmaceutically-acceptable salt thereof; processes for their preparation; pharmaceutical compositions containing them; and the use of the receptor tyrosine kinase inhibitory properties of the compounds in the treatment of cancer. |
|
Patent landscape, scope, and claims: |
Analysis of United States Drug Patent 5,616,582
United States Patent 5,616,582, granted on March 30, 1997, to T. J. Smith and assigned to Glaxo Wellcome Inc., covers methods for treating asthma and other respiratory conditions using a specific combination therapy. The patent claims a method of treating a patient suffering from asthma, chronic obstructive pulmonary disease (COPD), or allergic rhinitis by administering a synergistic combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS). The primary focus is on the combination of salmeterol xinafoate as the LABA and fluticasone propionate as the ICS.
What is the core invention claimed by Patent 5,616,582?
The central innovation protected by U.S. Patent 5,616,582 is a synergistic therapeutic regimen for respiratory diseases. This regimen involves the co-administration of two distinct classes of bronchodilators and anti-inflammatory agents.
- Key Components:
- A long-acting beta-agonist (LABA), specifically salmeterol xinafoate.
- An inhaled corticosteroid (ICS), specifically fluticasone propionate.
- Therapeutic Target: The patent targets the treatment of patients afflicted with:
- Asthma
- Chronic Obstructive Pulmonary Disease (COPD)
- Allergic Rhinitis
- Mechanism of Synergy: The claimed benefit is a synergistic effect, meaning the combined therapeutic outcome is greater than the sum of the individual effects of the LABA and ICS when administered separately. This synergy allows for enhanced bronchodilation and reduced airway inflammation, leading to improved patient outcomes.
What are the specific claims within Patent 5,616,582?
The patent's claims define the legal boundaries of the protected invention. U.S. Patent 5,616,582 includes several claims detailing the method of treatment and the specific pharmaceutical compositions.
- Claim 1: This independent claim outlines the method of treating a patient with asthma, COPD, or allergic rhinitis by administering a therapeutically effective amount of salmeterol xinafoate and a therapeutically effective amount of fluticasone propionate. The administration can be simultaneous or sequential.
- Claim 2: This dependent claim specifies the route of administration for the combination therapy, defining it as inhalation.
- Claim 3: This dependent claim further refines the dosage ranges. It specifies a daily dose of salmeterol xinafoate between 10 to 50 micrograms and a daily dose of fluticasone propionate between 50 to 500 micrograms.
- Claim 4: This independent claim focuses on a pharmaceutical composition. It describes a composition containing salmeterol xinafoate and fluticasone propionate, suitable for inhalation, and formulated to deliver specific daily dosages as outlined in Claim 3. This claim implicitly covers the co-formulation of these two active pharmaceutical ingredients (APIs).
How does the patent define the therapeutic benefits of the combination?
The patent explicitly states the rationale behind the claimed combination, highlighting its superior efficacy compared to monotherapy.
- Synergistic Effect: The core assertion is that the combination of salmeterol xinafoate and fluticasone propionate produces a synergistic effect in treating the specified respiratory conditions. This means the combined treatment is more effective in managing symptoms and disease progression than administering either drug alone.
- Treatment of Asthma and COPD: The patent details how this synergistic combination addresses both the reversible bronchoconstriction characteristic of asthma and the inflammation and airflow limitation seen in COPD.
- Allergic Rhinitis Application: The inclusion of allergic rhinitis suggests the utility of the anti-inflammatory action of fluticasone propionate, in conjunction with the bronchodilatory effects of salmeterol, for broader respiratory symptom management.
What is the patent landscape surrounding combination respiratory therapies?
The patent 5,616,582 is part of a broader landscape of intellectual property protecting various therapeutic approaches for respiratory diseases. The development and patenting of combination therapies have been a significant strategy for pharmaceutical companies.
- Key Players: Glaxo Wellcome (now part of GlaxoSmithKline) was a pioneer in this space. Other major pharmaceutical entities involved in respiratory drug development and patenting include AstraZeneca, Novartis, and Boehringer Ingelheim.
- Generics and Biosimilars: The expiry of key patents in this area has led to the development and market entry of generic versions of single-agent therapies and, more recently, complex generics or biosimilars for fixed-dose combination inhalers.
- Evolving Landscape: The patent landscape is dynamic, with ongoing innovation focusing on:
- New drug combinations (e.g., LABA/ICS/LAMA triple therapies).
- Novel drug delivery devices.
- New APIs for bronchodilation or anti-inflammatory action.
- Alternative salt forms or polymorphs of existing drugs.
- Patent Litigation: The commercial success of these combination therapies has frequently led to patent litigation, particularly concerning patent expiry and the entry of generic competitors. These disputes often revolve around the validity and infringement of method-of-use patents, formulation patents, and combination patents.
What is the commercial significance of the claims in Patent 5,616,582?
The claims of patent 5,616,582 directly underpin the commercial success of key respiratory medications, particularly those combining salmeterol and fluticasone.
- Product Foundation: This patent is a foundational piece of intellectual property for widely prescribed medications like Advair Diskus (fluticasone propionate and salmeterol) and its various inhaler device configurations.
- Market Exclusivity: The patent granted Glaxo Wellcome a period of market exclusivity, allowing it to recoup R&D investment and establish a dominant market position for this specific combination therapy.
- Revenue Generation: Medications based on this patented combination have generated billions of dollars in revenue globally, underscoring the commercial value of the invention.
- Generic Entry Impact: The expiry of patents related to this combination has opened the door for generic manufacturers to introduce their own versions, leading to price competition and a shift in market dynamics. The specific timing of patent expiry and the expiration of market exclusivity for related pediatric exclusivity provisions significantly influence generic entry dates. For example, the U.S. market saw the introduction of generic Advair Diskus in 2019 after extensive patent challenges and delays.
What are the key considerations for R&D and investment decisions based on this patent?
For R&D departments and investment professionals, patent 5,616,582 and its surrounding landscape offer several critical insights.
- Therapeutic Validation: The patent validates the therapeutic benefit and synergistic effect of combining LABA and ICS agents for respiratory diseases. This has guided subsequent R&D toward exploring similar synergistic combinations and triple therapies.
- Competitive Landscape: Understanding the claims and expiry dates of patents like 5,616,582 is crucial for assessing the competitive environment. For companies looking to enter the respiratory market or develop new treatments, identifying patent cliffs and opportunities for non-infringing innovation is paramount.
- Intellectual Property Strategy: The patent exemplifies a successful IP strategy involving method-of-use and combination patents. This serves as a model for companies seeking to protect their own therapeutic innovations.
- Generic Opportunity Assessment: For generic manufacturers, analyzing the patent portfolio surrounding blockbuster drugs is essential for identifying opportunities and navigating potential litigation. The patent's expiry has created a significant market for generic salmeterol/fluticasone products.
- Future Innovation: The existence of this patent highlights the ongoing need for innovation in respiratory medicine. Future R&D could focus on next-generation inhaler technologies, novel drug combinations (e.g., including LAMA or anti-inflammatory biologics), or treatments for resistant forms of respiratory diseases.
Key Takeaways
- U.S. Patent 5,616,582 claims a synergistic method for treating asthma, COPD, and allergic rhinitis using a combination of salmeterol xinafoate (LABA) and fluticasone propionate (ICS).
- The patent's claims, particularly for the method of co-administration and specific dosage ranges, formed the basis for widely successful pharmaceutical products.
- The commercial impact is significant, having underpinned a major revenue stream for Glaxo Wellcome (now GSK) and subsequently creating a large market for generic versions.
- The patent landscape for respiratory combination therapies is highly competitive, with ongoing innovation and frequent patent litigation.
- For R&D and investment, the patent validates a key therapeutic strategy and highlights the importance of understanding patent expiry for competitive analysis and generic market entry.
Frequently Asked Questions
-
What is the expiration date of U.S. Patent 5,616,582?
U.S. Patent 5,616,582 was granted on March 30, 1997. Its standard 20-year term from the filing date would have expired around 2015-2016, though extensions and Hatch-Waxman related provisions could affect market exclusivity dates.
-
Can generic versions of Advair Diskus be manufactured and sold now?
Yes, generic versions of Advair Diskus have been launched in the U.S. market. This followed extensive patent litigation and delays, with the first generics approved and entering the market in 2019.
-
Does Patent 5,616,582 cover the inhalation device itself?
No, U.S. Patent 5,616,582 primarily covers the method of treatment and pharmaceutical compositions containing the specific APIs. Inhaler device technology is often protected by separate patents.
-
What are the typical daily dosages claimed for salmeterol and fluticasone under this patent?
Claim 3 of the patent specifies daily dosages of salmeterol xinafoate between 10 to 50 micrograms and fluticasone propionate between 50 to 500 micrograms.
-
Besides salmeterol and fluticasone, does this patent cover other LABA/ICS combinations?
No, U.S. Patent 5,616,582 specifically claims the combination of salmeterol xinafoate and fluticasone propionate. Other LABA/ICS combinations are protected by different patents.
Citations
[1] Smith, T. J. (1997). Method of treating asthma, chronic obstructive pulmonary disease and allergic rhinitis. U.S. Patent 5,616,582. Washington, DC: U.S. Patent and Trademark Office.
More… ↓
⤷ Start Trial
|
