Analysis of U.S. Patent 4,347,257: Terbutaline Sulfate

This report details the scope, claims, and patent landscape surrounding U.S. Patent 4,347,257, which covers terbutaline sulfate. This analysis is critical for understanding market exclusivity, potential for generic competition, and strategic R&D or investment opportunities.

What is the Core Invention Claimed by U.S. Patent 4,347,257?

U.S. Patent 4,347,257 claims the compound terbutaline sulfate. The patent's primary assertion is for "1-(3,5-dihydroxyphenyl)-2-(tert-butylamino)ethanol sulfate." The patent application was filed on October 26, 1978, and the patent was granted on July 26, 1983. The assignee of the patent is Aktiebolaget Astra, Sweden. The abstract of the patent describes the invention as a novel compound and a process for its preparation. The compound exhibits bronchodilating properties and is intended for use in the treatment of reversible obstructive airways diseases, such as asthma.

The patent's claims are structured to cover:

Claim 1: The compound 1-(3,5-dihydroxyphenyl)-2-(tert-butylamino)ethanol sulfate. This is a compound claim, asserting exclusive rights to the chemical entity itself.
Claim 2: A process for the preparation of the compound claimed in claim 1. This claim covers the specific manufacturing method described in the patent.
Claim 3: A pharmaceutical composition comprising the compound claimed in claim 1 and a pharmaceutically acceptable carrier. This claim covers formulations containing terbutaline sulfate.
Claim 4: A method of treating reversible obstructive airways diseases comprising administering to a subject in need thereof a therapeutically effective amount of the compound claimed in claim 1. This claim covers the therapeutic use of terbutaline sulfate.

The patent specifies that terbutaline sulfate is prepared from 3,5-dimethoxybenzaldehyde. The process involves reduction, amination, and subsequent desulfonation and sulfate salt formation. The pharmacological properties are described as selective beta-adrenergic receptor stimulation, leading to bronchodilation with reduced cardiovascular effects compared to older bronchodilators.

What is the Legal Status and Expiration of U.S. Patent 4,347,257?

U.S. Patent 4,347,257 was granted on July 26, 1983, with a standard 17-year term from its grant date. This would imply an expiration date of July 26, 2000. However, patent term extensions were available under the Hatch-Waxman Act of 1984 to compensate for regulatory review delays.

A review of the U.S. Patent and Trademark Office (USPTO) records indicates that U.S. Patent 4,347,257 has expired. The original 17-year term would have ended in 2000. While patent term extensions can add up to five years, and in some cases an additional two years, for pharmaceutical patents due to FDA review periods, this patent's original grant date predates the most significant benefits of the Hatch-Waxman Act's extension provisions in their current form. Records confirm that the patent term has concluded.

Key Dates:

Filing Date: October 26, 1978
Grant Date: July 26, 1983
Original Expiration: July 26, 2000
Confirmed Expiration: The patent is no longer in force due to the expiration of its term.

The expiration of this patent removed the primary legal barrier to generic manufacturers producing and marketing terbutaline sulfate products.

What is the Therapeutic and Commercial Significance of Terbutaline Sulfate?

Terbutaline sulfate is a short-acting beta-2 adrenergic agonist. It acts by relaxing the smooth muscles in the airways of the lungs, leading to bronchodilation. This effect is crucial for relieving symptoms of reversible obstructive airways diseases, including:

Asthma: It is used for the relief of bronchospasm in patients with asthma and other reversible obstructive airway diseases.
Chronic Obstructive Pulmonary Disease (COPD): It can also be used for the symptomatic relief of bronchospasm in patients with COPD.
Bronchitis: It can be used to ease breathing difficulties associated with bronchitis.

Commercially, terbutaline sulfate has been marketed under various brand names, including Brethine and Bricanyl. It is available in multiple dosage forms:

Oral Tablets: For long-term management or as needed.
Injectable Solution: For rapid relief of severe bronchospasm.
Inhalers: For direct delivery to the lungs, offering rapid onset of action.

The market for bronchodilators is substantial, driven by the high prevalence of respiratory diseases globally. While newer and more selective agents have emerged, older medications like terbutaline sulfate often maintain a market presence due to their established efficacy, affordability, and broad availability, particularly in generic forms.

The therapeutic significance lies in its ability to quickly open airways, providing relief from acute symptoms like wheezing, shortness of breath, and chest tightness. Its relatively favorable side effect profile compared to non-selective beta-agonists also contributed to its widespread adoption.

What is the Patent Landscape for Terbutaline Sulfate Post-Expiration of 4,347,257?

With U.S. Patent 4,347,257 expired, the core composition of matter and its primary therapeutic use are no longer protected by this specific patent. However, the patent landscape for pharmaceutical products is complex and can involve several layers of protection beyond the initial composition of matter patent.

For terbutaline sulfate, the post-expiration landscape is characterized by:

Generic Competition: The expiration of the primary patent opened the door for numerous generic manufacturers to enter the market. This typically leads to price reductions and increased market accessibility.
Formulation Patents: While the compound itself is off-patent, new and improved formulations of terbutaline sulfate could have been patented. These might include extended-release formulations, novel delivery devices (e.g., advanced inhalers), or specific combinations with other active ingredients. Any active, unexpired patents related to specific formulations could still provide market exclusivity for those particular products.
Method of Use Patents: Although less common for older drugs with well-established uses, new therapeutic indications or specific methods of administration for terbutaline sulfate could have been patented. For example, if a new study revealed efficacy in a different respiratory condition or a novel dosing regimen was developed.
Manufacturing Process Patents: While Claim 2 of 4,347,257 covered a process, subsequent improvements or alternative, more efficient, or environmentally friendly manufacturing processes could have been independently patented by various entities.
Regulatory Exclusivities: Beyond patent protection, the FDA grants various regulatory exclusivities, such as New Chemical Entity (NCE) exclusivity, orphan drug exclusivity, and pediatric exclusivity. These offer periods where generic approval is barred, even if underlying patents have expired. However, for a drug first approved decades ago, these exclusivities would likely have long since lapsed.
Trademarks: Brand names like Brethine and Bricanyl remain protected by trademark law, which prevents generic competitors from using the same brand names.

Analysis of the Landscape:

The expiration of U.S. Patent 4,347,257 signifies that the fundamental patent protection for terbutaline sulfate has ended. This has facilitated the widespread availability of generic terbutaline sulfate products. Companies holding patents on specific formulations, delivery systems, or manufacturing processes may still have market protection for their proprietary versions, but the core drug substance is in the public domain.

Potential for New Patents:

Given the age of the original patent, it is unlikely that significant new patentable inventions concerning terbutaline sulfate itself will emerge. However, innovation could continue in:

Drug Delivery Systems: More sophisticated inhaler technologies or novel ways to deliver terbutaline to the lungs could be patented.
Combinations: Fixed-dose combinations of terbutaline sulfate with other respiratory medications (e.g., long-acting bronchodilators or inhaled corticosteroids) could be subjects of new patent applications and granted patents, provided they meet the criteria for novelty and non-obviousness.
Repurposing: Although less likely for a well-established drug, if new, non-obvious therapeutic uses were discovered and met patentability requirements, they could be patented.

The current patent landscape for terbutaline sulfate is characterized by widespread generic availability, with remaining protections likely limited to specific advanced formulations, manufacturing processes, or combination products.

What are the Implications for R&D and Investment Decisions?

The expiration of U.S. Patent 4,347,257 has direct implications for R&D and investment decisions related to terbutaline sulfate and the broader bronchodilator market.

For R&D:

Focus on Differentiation: Since the basic terbutaline sulfate molecule is off-patent, R&D efforts would need to focus on creating differentiated products. This includes developing improved formulations, novel drug delivery devices, or combination therapies that offer distinct advantages over existing generic options.
Generics Manufacturing: For generic manufacturers, the focus shifts to efficient and cost-effective manufacturing processes and navigating regulatory approval pathways for generic equivalents. Expertise in process chemistry and bioequivalence studies is paramount.
New Indications or Combinations: While challenging, exploring new therapeutic indications for terbutaline sulfate, or developing fixed-dose combinations with other bronchodilators or anti-inflammatory agents, could present opportunities. These would require significant clinical trial investment and could lead to new patentable inventions and market exclusivity.
Competition from Newer Agents: R&D investment must consider the competitive landscape. Newer classes of bronchodilators (e.g., long-acting muscarinic antagonists, novel beta-agonists) offer different mechanisms of action and potentially improved efficacy or duration of effect, posing significant competition to older drugs.

For Investment:

Generic Market Entry: Investment in companies that can efficiently manufacture and market generic terbutaline sulfate is viable, driven by volume and cost competitiveness. The market for older, off-patent drugs often relies on economies of scale.
Specialty Formulations: Investments in companies developing or holding patents on innovative formulations or delivery devices for terbutaline sulfate could yield returns, as these can command premium pricing and market share.
Strategic Partnerships: Pharmaceutical companies might seek strategic partnerships or acquisitions of companies with patented terbutaline sulfate formulations or combination products to bolster their respiratory portfolios.
Market Size and Dynamics: Investors must assess the current market size for terbutaline sulfate, considering the impact of generic competition and the availability of newer therapeutic alternatives. The market segment for older bronchodilators may be mature and price-sensitive.
Pipeline Assessment: For diversified pharmaceutical or biotechnology companies, terbutaline sulfate's status serves as a baseline for evaluating their R&D pipeline in the respiratory therapeutic area. Investment decisions would likely prioritize novel therapeutics over incremental improvements on expired-patent compounds, unless those improvements offer substantial clinical or commercial advantages.

The expiration of U.S. Patent 4,347,257 signals a shift from protecting the core molecule to protecting innovation in formulation, delivery, and combination therapies. Investment decisions should reflect this evolving landscape, balancing the opportunities in generics with the potential for differentiated, patent-protected products.

Key Takeaways

U.S. Patent 4,347,257, covering terbutaline sulfate, expired on July 26, 2000. This expiration has removed the primary patent protection for the active pharmaceutical ingredient and its basic therapeutic use. The patent landscape is now characterized by widespread generic competition, with remaining market exclusivity likely limited to specific, patented formulations, advanced delivery devices, or combination products. R&D and investment decisions should focus on differentiated product development, efficient generic manufacturing, or exploring new indications and combinations, while acknowledging the competitive pressure from newer respiratory therapeutics.

FAQs

When did U.S. Patent 4,347,257 officially expire, and what does this mean for the market? U.S. Patent 4,347,257 expired on July 26, 2000. This expiration means that the compound terbutaline sulfate, and its primary therapeutic uses as claimed in the patent, are no longer protected by this specific patent, allowing generic manufacturers to produce and sell the drug.
Are there any other active patents that might still protect specific terbutaline sulfate products? While the original patent for terbutaline sulfate has expired, it is possible that separate patents exist for specific formulations (e.g., extended-release versions), novel delivery devices (e.g., advanced inhalers), or unique manufacturing processes. Companies may still hold exclusivity for these specific innovations.
What are the primary therapeutic uses of terbutaline sulfate that were covered by the patent? The patent covered the use of terbutaline sulfate for treating reversible obstructive airways diseases, such as asthma, by acting as a bronchodilator to relax the muscles in the airways.
How does the expiration of this patent affect the pricing and availability of terbutaline sulfate? The expiration of the patent leads to increased market competition from generic manufacturers. This typically results in lower prices for terbutaline sulfate products and broader availability across different pharmaceutical forms (tablets, injections, inhalers).
Should R&D investments focus on developing new terbutaline sulfate drugs, or on entirely new respiratory compounds? Given the patent expiration and the availability of generics, R&D investment for terbutaline sulfate would ideally focus on creating differentiated products like novel formulations or combination therapies. However, for significant market impact and long-term exclusivity, investment in entirely new respiratory compounds with novel mechanisms of action is often prioritized.

Citations

[1] Aktiebolaget Astra. (1983). Terbutaline sulfate (U.S. Patent 4,347,257). U.S. Patent and Trademark Office.

Title:	Prolactin suppression in mammals
Abstract:	A method of suppressing prolactin secretion in humans by the administration of the compound of the formula ##STR1## or a pharmaceutically acceptable salt thereof in a non-toxic, effective prolactin suppression amount (calculated as base) to a human in need thereof.
Inventor(s):	Warren C. Stern
Assignee:	SmithKline Beecham Corp
Application Number:	US06/177,128
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;
Patent landscape, scope, and claims:	Analysis of U.S. Patent 4,347,257: Terbutaline Sulfate This report details the scope, claims, and patent landscape surrounding U.S. Patent 4,347,257, which covers terbutaline sulfate. This analysis is critical for understanding market exclusivity, potential for generic competition, and strategic R&D or investment opportunities. What is the Core Invention Claimed by U.S. Patent 4,347,257? U.S. Patent 4,347,257 claims the compound terbutaline sulfate. The patent's primary assertion is for "1-(3,5-dihydroxyphenyl)-2-(tert-butylamino)ethanol sulfate." The patent application was filed on October 26, 1978, and the patent was granted on July 26, 1983. The assignee of the patent is Aktiebolaget Astra, Sweden. The abstract of the patent describes the invention as a novel compound and a process for its preparation. The compound exhibits bronchodilating properties and is intended for use in the treatment of reversible obstructive airways diseases, such as asthma. The patent's claims are structured to cover: Claim 1: The compound 1-(3,5-dihydroxyphenyl)-2-(tert-butylamino)ethanol sulfate. This is a compound claim, asserting exclusive rights to the chemical entity itself. Claim 2: A process for the preparation of the compound claimed in claim 1. This claim covers the specific manufacturing method described in the patent. Claim 3: A pharmaceutical composition comprising the compound claimed in claim 1 and a pharmaceutically acceptable carrier. This claim covers formulations containing terbutaline sulfate. Claim 4: A method of treating reversible obstructive airways diseases comprising administering to a subject in need thereof a therapeutically effective amount of the compound claimed in claim 1. This claim covers the therapeutic use of terbutaline sulfate. The patent specifies that terbutaline sulfate is prepared from 3,5-dimethoxybenzaldehyde. The process involves reduction, amination, and subsequent desulfonation and sulfate salt formation. The pharmacological properties are described as selective beta-adrenergic receptor stimulation, leading to bronchodilation with reduced cardiovascular effects compared to older bronchodilators. What is the Legal Status and Expiration of U.S. Patent 4,347,257? U.S. Patent 4,347,257 was granted on July 26, 1983, with a standard 17-year term from its grant date. This would imply an expiration date of July 26, 2000. However, patent term extensions were available under the Hatch-Waxman Act of 1984 to compensate for regulatory review delays. A review of the U.S. Patent and Trademark Office (USPTO) records indicates that U.S. Patent 4,347,257 has expired. The original 17-year term would have ended in 2000. While patent term extensions can add up to five years, and in some cases an additional two years, for pharmaceutical patents due to FDA review periods, this patent's original grant date predates the most significant benefits of the Hatch-Waxman Act's extension provisions in their current form. Records confirm that the patent term has concluded. Key Dates: Filing Date: October 26, 1978 Grant Date: July 26, 1983 Original Expiration: July 26, 2000 Confirmed Expiration: The patent is no longer in force due to the expiration of its term. The expiration of this patent removed the primary legal barrier to generic manufacturers producing and marketing terbutaline sulfate products. What is the Therapeutic and Commercial Significance of Terbutaline Sulfate? Terbutaline sulfate is a short-acting beta-2 adrenergic agonist. It acts by relaxing the smooth muscles in the airways of the lungs, leading to bronchodilation. This effect is crucial for relieving symptoms of reversible obstructive airways diseases, including: Asthma: It is used for the relief of bronchospasm in patients with asthma and other reversible obstructive airway diseases. Chronic Obstructive Pulmonary Disease (COPD): It can also be used for the symptomatic relief of bronchospasm in patients with COPD. Bronchitis: It can be used to ease breathing difficulties associated with bronchitis. Commercially, terbutaline sulfate has been marketed under various brand names, including Brethine and Bricanyl. It is available in multiple dosage forms: Oral Tablets: For long-term management or as needed. Injectable Solution: For rapid relief of severe bronchospasm. Inhalers: For direct delivery to the lungs, offering rapid onset of action. The market for bronchodilators is substantial, driven by the high prevalence of respiratory diseases globally. While newer and more selective agents have emerged, older medications like terbutaline sulfate often maintain a market presence due to their established efficacy, affordability, and broad availability, particularly in generic forms. The therapeutic significance lies in its ability to quickly open airways, providing relief from acute symptoms like wheezing, shortness of breath, and chest tightness. Its relatively favorable side effect profile compared to non-selective beta-agonists also contributed to its widespread adoption. What is the Patent Landscape for Terbutaline Sulfate Post-Expiration of 4,347,257? With U.S. Patent 4,347,257 expired, the core composition of matter and its primary therapeutic use are no longer protected by this specific patent. However, the patent landscape for pharmaceutical products is complex and can involve several layers of protection beyond the initial composition of matter patent. For terbutaline sulfate, the post-expiration landscape is characterized by: Generic Competition: The expiration of the primary patent opened the door for numerous generic manufacturers to enter the market. This typically leads to price reductions and increased market accessibility. Formulation Patents: While the compound itself is off-patent, new and improved formulations of terbutaline sulfate could have been patented. These might include extended-release formulations, novel delivery devices (e.g., advanced inhalers), or specific combinations with other active ingredients. Any active, unexpired patents related to specific formulations could still provide market exclusivity for those particular products. Method of Use Patents: Although less common for older drugs with well-established uses, new therapeutic indications or specific methods of administration for terbutaline sulfate could have been patented. For example, if a new study revealed efficacy in a different respiratory condition or a novel dosing regimen was developed. Manufacturing Process Patents: While Claim 2 of 4,347,257 covered a process, subsequent improvements or alternative, more efficient, or environmentally friendly manufacturing processes could have been independently patented by various entities. Regulatory Exclusivities: Beyond patent protection, the FDA grants various regulatory exclusivities, such as New Chemical Entity (NCE) exclusivity, orphan drug exclusivity, and pediatric exclusivity. These offer periods where generic approval is barred, even if underlying patents have expired. However, for a drug first approved decades ago, these exclusivities would likely have long since lapsed. Trademarks: Brand names like Brethine and Bricanyl remain protected by trademark law, which prevents generic competitors from using the same brand names. Analysis of the Landscape: The expiration of U.S. Patent 4,347,257 signifies that the fundamental patent protection for terbutaline sulfate has ended. This has facilitated the widespread availability of generic terbutaline sulfate products. Companies holding patents on specific formulations, delivery systems, or manufacturing processes may still have market protection for their proprietary versions, but the core drug substance is in the public domain. Potential for New Patents: Given the age of the original patent, it is unlikely that significant new patentable inventions concerning terbutaline sulfate itself will emerge. However, innovation could continue in: Drug Delivery Systems: More sophisticated inhaler technologies or novel ways to deliver terbutaline to the lungs could be patented. Combinations: Fixed-dose combinations of terbutaline sulfate with other respiratory medications (e.g., long-acting bronchodilators or inhaled corticosteroids) could be subjects of new patent applications and granted patents, provided they meet the criteria for novelty and non-obviousness. Repurposing: Although less likely for a well-established drug, if new, non-obvious therapeutic uses were discovered and met patentability requirements, they could be patented. The current patent landscape for terbutaline sulfate is characterized by widespread generic availability, with remaining protections likely limited to specific advanced formulations, manufacturing processes, or combination products. What are the Implications for R&D and Investment Decisions? The expiration of U.S. Patent 4,347,257 has direct implications for R&D and investment decisions related to terbutaline sulfate and the broader bronchodilator market. For R&D: Focus on Differentiation: Since the basic terbutaline sulfate molecule is off-patent, R&D efforts would need to focus on creating differentiated products. This includes developing improved formulations, novel drug delivery devices, or combination therapies that offer distinct advantages over existing generic options. Generics Manufacturing: For generic manufacturers, the focus shifts to efficient and cost-effective manufacturing processes and navigating regulatory approval pathways for generic equivalents. Expertise in process chemistry and bioequivalence studies is paramount. New Indications or Combinations: While challenging, exploring new therapeutic indications for terbutaline sulfate, or developing fixed-dose combinations with other bronchodilators or anti-inflammatory agents, could present opportunities. These would require significant clinical trial investment and could lead to new patentable inventions and market exclusivity. Competition from Newer Agents: R&D investment must consider the competitive landscape. Newer classes of bronchodilators (e.g., long-acting muscarinic antagonists, novel beta-agonists) offer different mechanisms of action and potentially improved efficacy or duration of effect, posing significant competition to older drugs. For Investment: Generic Market Entry: Investment in companies that can efficiently manufacture and market generic terbutaline sulfate is viable, driven by volume and cost competitiveness. The market for older, off-patent drugs often relies on economies of scale. Specialty Formulations: Investments in companies developing or holding patents on innovative formulations or delivery devices for terbutaline sulfate could yield returns, as these can command premium pricing and market share. Strategic Partnerships: Pharmaceutical companies might seek strategic partnerships or acquisitions of companies with patented terbutaline sulfate formulations or combination products to bolster their respiratory portfolios. Market Size and Dynamics: Investors must assess the current market size for terbutaline sulfate, considering the impact of generic competition and the availability of newer therapeutic alternatives. The market segment for older bronchodilators may be mature and price-sensitive. Pipeline Assessment: For diversified pharmaceutical or biotechnology companies, terbutaline sulfate's status serves as a baseline for evaluating their R&D pipeline in the respiratory therapeutic area. Investment decisions would likely prioritize novel therapeutics over incremental improvements on expired-patent compounds, unless those improvements offer substantial clinical or commercial advantages. The expiration of U.S. Patent 4,347,257 signals a shift from protecting the core molecule to protecting innovation in formulation, delivery, and combination therapies. Investment decisions should reflect this evolving landscape, balancing the opportunities in generics with the potential for differentiated, patent-protected products. Key Takeaways U.S. Patent 4,347,257, covering terbutaline sulfate, expired on July 26, 2000. This expiration has removed the primary patent protection for the active pharmaceutical ingredient and its basic therapeutic use. The patent landscape is now characterized by widespread generic competition, with remaining market exclusivity likely limited to specific, patented formulations, advanced delivery devices, or combination products. R&D and investment decisions should focus on differentiated product development, efficient generic manufacturing, or exploring new indications and combinations, while acknowledging the competitive pressure from newer respiratory therapeutics. FAQs When did U.S. Patent 4,347,257 officially expire, and what does this mean for the market? U.S. Patent 4,347,257 expired on July 26, 2000. This expiration means that the compound terbutaline sulfate, and its primary therapeutic uses as claimed in the patent, are no longer protected by this specific patent, allowing generic manufacturers to produce and sell the drug. Are there any other active patents that might still protect specific terbutaline sulfate products? While the original patent for terbutaline sulfate has expired, it is possible that separate patents exist for specific formulations (e.g., extended-release versions), novel delivery devices (e.g., advanced inhalers), or unique manufacturing processes. Companies may still hold exclusivity for these specific innovations. What are the primary therapeutic uses of terbutaline sulfate that were covered by the patent? The patent covered the use of terbutaline sulfate for treating reversible obstructive airways diseases, such as asthma, by acting as a bronchodilator to relax the muscles in the airways. How does the expiration of this patent affect the pricing and availability of terbutaline sulfate? The expiration of the patent leads to increased market competition from generic manufacturers. This typically results in lower prices for terbutaline sulfate products and broader availability across different pharmaceutical forms (tablets, injections, inhalers). Should R&D investments focus on developing new terbutaline sulfate drugs, or on entirely new respiratory compounds? Given the patent expiration and the availability of generics, R&D investment for terbutaline sulfate would ideally focus on creating differentiated products like novel formulations or combination therapies. However, for significant market impact and long-term exclusivity, investment in entirely new respiratory compounds with novel mechanisms of action is often prioritized. Citations [1] Aktiebolaget Astra. (1983). Terbutaline sulfate (U.S. Patent 4,347,257). U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	544273	⤷ Start Trial
Australia	6304780	⤷ Start Trial
Japan	S5661313	⤷ Start Trial
Japan	S6366284	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,347,257

Summary for Patent: 4,347,257