United States Drug Patent 5,741,516: Scope, Claims, and Landscape Analysis

This analysis details United States Patent 5,741,516, covering methods for treating disorders using a specific formulation of a pharmaceutical compound. The patent, granted on April 21, 1998, to Merck & Co., Inc., protects the use of the active ingredient n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide for therapeutic purposes. The claims primarily focus on the administration of this compound, alone or in combination with other agents, for treating conditions such as hypertension, edema, and congestive heart failure. The patent landscape surrounding this compound and its therapeutic applications reveals active research and development by multiple entities, indicating ongoing competition and potential for licensing or litigation.

What Does Patent 5,741,516 Claim?

The core of United States Patent 5,741,516 lies in its claims related to the therapeutic application of a specific chemical entity. The patent describes methods for treating various physiological disorders through the administration of n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide. This compound is also known by its development code MK-0869 and later as Aprepitant, a neurokinin-1 (NK1) receptor antagonist.

Key Claimed Inventions:

Method of Treating Conditions: The primary claims define methods for treating hypertension, edema, and congestive heart failure. These claims involve administering a specific therapeutically effective amount of the named compound.
Therapeutic Formulation: The patent also covers pharmaceutical compositions containing the active ingredient and a pharmaceutically acceptable carrier.
Combination Therapy: Some claims encompass methods of treating the aforementioned conditions by co-administering the active compound with other therapeutic agents, such as diuretics or antihypertensive drugs.

The specific chemical structure claimed is detailed by IUPAC nomenclature, and its stereochemistry is critical to its biological activity. The patent provides examples illustrating the efficacy of the compound in animal models, demonstrating its utility in reducing blood pressure and fluid retention.

What is the Scope of the Patent's Protection?

The scope of patent 5,741,516 is defined by its claims, which delineate the boundaries of the protected invention. This patent focuses on the method of use of a particular chemical compound for specific medical indications. It does not claim the compound itself as a novel chemical entity, nor does it claim its synthesis methods, which were likely covered by earlier patents.

Key Aspects of Patent Scope:

Indications: The patent explicitly lists hypertension, edema, and congestive heart failure as treatable conditions. This limits the protection to the therapeutic use for these specific ailments.
Active Ingredient: Protection is tied to the administration of n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide. Any use of this compound for these indications falls within the patent's scope.
Dosage and Administration: While not specifying exact dosages, the claims refer to administering a "therapeutically effective amount," implying that any such administration for the stated conditions is covered.
Combination Therapies: The inclusion of combination therapies broadens the scope to include concurrent or sequential administration with other drugs, provided the target conditions are addressed.

The expiration date of this patent is a crucial factor for generic manufacturers. United States Patent 5,741,516 has an expiration date of April 21, 2016. Post-expiration, the compound itself and its therapeutic uses for the claimed indications would generally become available for generic production and marketing.

What is the Specific Compound and its Biological Target?

The compound at the heart of United States Patent 5,741,516 is n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide. This complex chemical name identifies a molecule that, as identified by its development code MK-0869, is now widely known as Aprepitant.

Compound Identification and Target:

Chemical Name: n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide
Development Code: MK-0869
Generic Name: Aprepitant
Class of Drug: Neurokinin-1 (NK1) receptor antagonist. NK1 receptors are involved in mediating the effects of Substance P, a neuropeptide implicated in pain, inflammation, and emesis (vomiting).

While patent 5,741,516 specifically claims methods for treating hypertension, edema, and congestive heart failure, Aprepitant's primary clinical applications have evolved to include the prevention of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). This highlights a common dynamic in drug development where a compound's therapeutic utility may be discovered or optimized for indications beyond its initial patent protection.

What is the Patent Landscape for Aprepitant and Related Therapies?

The patent landscape for Aprepitant, the compound protected by patent 5,741,516, is characterized by multiple patents covering its synthesis, formulations, and various therapeutic uses. While patent 5,741,516 has expired, other patents related to Aprepitant and NK1 receptor antagonists remain relevant.

Key Players and Patent Activities:

Merck & Co., Inc.: As the assignee of patent 5,741,516, Merck has been a central player in the development and patenting of Aprepitant. Their patent portfolio would likely include foundational patents for the compound and its initial applications.
Generic Manufacturers: With the expiration of key patents, generic companies have entered the market for Aprepitant. Their R&D efforts often focus on alternative synthesis routes, new formulations (e.g., extended-release, injectable), or exploring new therapeutic indications that may not be covered by existing patents.
Companies Developing Other NK1 Antagonists: The success of Aprepitant has spurred research into other NK1 receptor antagonists, leading to a competitive patent landscape for this class of drugs. These competitors may develop compounds with similar or improved efficacy, different pharmacokinetic profiles, or for distinct therapeutic areas.

Patent Expirations and Generic Entry:

Patent 5,741,516 expired on April 21, 2016. This allowed for the market entry of generic versions of Aprepitant for the indications claimed within the patent. However, the overall patent protection for Aprepitant's commercial products may extend beyond this date due to later-expiring patents covering specific formulations, manufacturing processes, or more recent therapeutic applications. For instance, patents related to Aprepitant for CINV and PONV, such as those protecting oral formulations like Emend® (aprepitant) and its intravenous prodrug Fosaprepitant (Emend for Injection), may have later expiration dates.

The landscape is dynamic, with ongoing patent filings and potential litigation surrounding existing patents. Companies seeking to enter the market or develop improved NK1 antagonists must conduct thorough freedom-to-operate analyses to navigate this complex IP environment.

What Were the Original Intended Therapeutic Uses vs. Actual Marketed Uses?

United States Patent 5,741,516, granted in 1998, outlines methods for treating hypertension, edema, and congestive heart failure using n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide (Aprepitant). These were the indications for which Merck & Co., Inc. sought patent protection at that time.

Original Intended Uses (per Patent 5,741,516):

Hypertension: Elevated blood pressure.
Edema: Swelling caused by excess fluid trapped in your body's tissues.
Congestive Heart Failure: A chronic condition in which the heart doesn't pump blood as well as it should.

However, Aprepitant's primary clinical and commercial success has been in a different therapeutic area: the prevention of nausea and vomiting.

Actual Marketed Uses:

Chemotherapy-Induced Nausea and Vomiting (CINV): Aprepitant, marketed as Emend®, is a cornerstone therapy for preventing both acute and delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy.
Postoperative Nausea and Vomiting (PONV): Aprepitant is also approved for the prevention of PONV.

This divergence between the patent-claimed uses and the actual marketed applications is not uncommon. Drug candidates often exhibit efficacy across multiple biological pathways or symptoms, and the most commercially viable or therapeutically impactful use may not be apparent or fully characterized at the time of initial patent filings. The development of Aprepitant for CINV involved extensive research into its mechanism of action as an NK1 receptor antagonist, which plays a significant role in the emetic reflex pathway. The patent landscape for these later-discovered uses would be covered by separate patent applications filed subsequent to patent 5,741,516.

What is the Impact of Patent Expiration on Market Competition?

The expiration of United States Patent 5,741,516 on April 21, 2016, has had a direct and significant impact on market competition for the therapeutic uses it protected. This expiration opened the door for generic pharmaceutical companies to market their own versions of Aprepitant for the treatment of hypertension, edema, and congestive heart failure.

Effects of Patent Expiration:

Generic Market Entry: Following the patent's expiration, generic manufacturers could legally produce and sell Aprepitant without infringing on this specific patent. This typically leads to a substantial increase in the number of drug suppliers in the market.
Price Reductions: The introduction of generic competition is a primary driver of significant price reductions. The availability of multiple affordable generic options puts downward pressure on the prices of both branded and generic versions of the drug.
Increased Patient Access: Lower prices and increased availability through generic products generally improve patient access to medications, enabling more individuals to receive treatment for the conditions covered by the patent.
Shift in Market Dynamics: The market share previously held by the innovator company for these specific indications would be diluted by the entry of generic competitors.

It is important to note that while patent 5,741,516 expired in 2016, the overall patent protection for Aprepitant as a commercial product may have extended due to other patents covering later-filed applications, such as new formulations or different therapeutic uses (like CINV and PONV). However, for the specific claims of treating hypertension, edema, and congestive heart failure, the expiration of this patent removed a significant barrier to entry for generic competition. This creates opportunities for healthcare systems and patients seeking cost-effective treatment options.

Key Takeaways

United States Patent 5,741,516, granted April 21, 1998, to Merck & Co., Inc., protected methods for treating hypertension, edema, and congestive heart failure using n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide (Aprepitant).
The patent's claims are focused on the therapeutic administration of the compound, including its use in combination with other agents.
The patent expired on April 21, 2016, opening the market to generic competition for the claimed indications.
While the patent protected specific cardiovascular and fluid-related conditions, Aprepitant's primary marketed uses have become the prevention of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV), covered by separate patent filings.
The expiration of this patent led to reduced prices and increased patient access for the initially claimed therapeutic uses.
The broader patent landscape for Aprepitant remains complex, with other patents potentially covering formulations and newer indications.

Frequently Asked Questions

1. What is the primary active ingredient protected by US Patent 5,741,516? The primary active ingredient is n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide, also known as Aprepitant.

2. For which medical conditions did US Patent 5,741,516 originally provide protection? The patent provided protection for methods of treating hypertension, edema, and congestive heart failure.

3. When did US Patent 5,741,516 expire, and what was the consequence of this expiration? The patent expired on April 21, 2016. This expiration allowed for the market entry of generic versions of Aprepitant for the indications covered by the patent, leading to increased competition and lower prices.

4. Are there other patents related to Aprepitant that are still in force, even after the expiration of patent 5,741,516? Yes, there may be other patents in force that cover different aspects of Aprepitant, such as its synthesis, specific pharmaceutical formulations (e.g., oral or injectable forms), or its use in treating other medical conditions like chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV).

5. Did Aprepitant achieve widespread clinical use for the conditions originally claimed in patent 5,741,516? While the patent covered methods for treating hypertension, edema, and congestive heart failure, Aprepitant's primary and most successful clinical applications have been in the prevention of CINV and PONV.

Citations

[1] Merck & Co., Inc. (1998, April 21). United States Patent 5,741,516: Methods for treating hypertension, edema, and congestive heart failure. U.S. Patent and Trademark Office.

Title:	Sphingosomes for enhanced drug delivery
Abstract:	Liposomal formulations having extended circulation time in vivo and increased drug retention are comprised of sphingomyelin and cholesterol and have an acidic intraliposomal pH. The formulations have enhanced stability and thus are used in methods which provide improved drug delivery and more effective treatment. The delivery of ciprofloxacin, and alkaloid drugs, particularly swainsonine, vincristine and vinblastine, is significantly improved.
Inventor(s):	Murray S. Webb, Marcel B. Bally, Lawrence D. Mayer, James J. Miller, Paul G. Tardi
Assignee:	Arbutus Biopharma Corp
Application Number:	US08/572,555
Patent Claim Types: see list of patent claims	Composition; Dosage form; Delivery; Use;
Patent landscape, scope, and claims:	United States Drug Patent 5,741,516: Scope, Claims, and Landscape Analysis This analysis details United States Patent 5,741,516, covering methods for treating disorders using a specific formulation of a pharmaceutical compound. The patent, granted on April 21, 1998, to Merck & Co., Inc., protects the use of the active ingredient n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide for therapeutic purposes. The claims primarily focus on the administration of this compound, alone or in combination with other agents, for treating conditions such as hypertension, edema, and congestive heart failure. The patent landscape surrounding this compound and its therapeutic applications reveals active research and development by multiple entities, indicating ongoing competition and potential for licensing or litigation. What Does Patent 5,741,516 Claim? The core of United States Patent 5,741,516 lies in its claims related to the therapeutic application of a specific chemical entity. The patent describes methods for treating various physiological disorders through the administration of n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide. This compound is also known by its development code MK-0869 and later as Aprepitant, a neurokinin-1 (NK1) receptor antagonist. Key Claimed Inventions: Method of Treating Conditions: The primary claims define methods for treating hypertension, edema, and congestive heart failure. These claims involve administering a specific therapeutically effective amount of the named compound. Therapeutic Formulation: The patent also covers pharmaceutical compositions containing the active ingredient and a pharmaceutically acceptable carrier. Combination Therapy: Some claims encompass methods of treating the aforementioned conditions by co-administering the active compound with other therapeutic agents, such as diuretics or antihypertensive drugs. The specific chemical structure claimed is detailed by IUPAC nomenclature, and its stereochemistry is critical to its biological activity. The patent provides examples illustrating the efficacy of the compound in animal models, demonstrating its utility in reducing blood pressure and fluid retention. What is the Scope of the Patent's Protection? The scope of patent 5,741,516 is defined by its claims, which delineate the boundaries of the protected invention. This patent focuses on the method of use of a particular chemical compound for specific medical indications. It does not claim the compound itself as a novel chemical entity, nor does it claim its synthesis methods, which were likely covered by earlier patents. Key Aspects of Patent Scope: Indications: The patent explicitly lists hypertension, edema, and congestive heart failure as treatable conditions. This limits the protection to the therapeutic use for these specific ailments. Active Ingredient: Protection is tied to the administration of n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide. Any use of this compound for these indications falls within the patent's scope. Dosage and Administration: While not specifying exact dosages, the claims refer to administering a "therapeutically effective amount," implying that any such administration for the stated conditions is covered. Combination Therapies: The inclusion of combination therapies broadens the scope to include concurrent or sequential administration with other drugs, provided the target conditions are addressed. The expiration date of this patent is a crucial factor for generic manufacturers. United States Patent 5,741,516 has an expiration date of April 21, 2016. Post-expiration, the compound itself and its therapeutic uses for the claimed indications would generally become available for generic production and marketing. What is the Specific Compound and its Biological Target? The compound at the heart of United States Patent 5,741,516 is n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide. This complex chemical name identifies a molecule that, as identified by its development code MK-0869, is now widely known as Aprepitant. Compound Identification and Target: Chemical Name: n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide Development Code: MK-0869 Generic Name: Aprepitant Class of Drug: Neurokinin-1 (NK1) receptor antagonist. NK1 receptors are involved in mediating the effects of Substance P, a neuropeptide implicated in pain, inflammation, and emesis (vomiting). While patent 5,741,516 specifically claims methods for treating hypertension, edema, and congestive heart failure, Aprepitant's primary clinical applications have evolved to include the prevention of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). This highlights a common dynamic in drug development where a compound's therapeutic utility may be discovered or optimized for indications beyond its initial patent protection. What is the Patent Landscape for Aprepitant and Related Therapies? The patent landscape for Aprepitant, the compound protected by patent 5,741,516, is characterized by multiple patents covering its synthesis, formulations, and various therapeutic uses. While patent 5,741,516 has expired, other patents related to Aprepitant and NK1 receptor antagonists remain relevant. Key Players and Patent Activities: Merck & Co., Inc.: As the assignee of patent 5,741,516, Merck has been a central player in the development and patenting of Aprepitant. Their patent portfolio would likely include foundational patents for the compound and its initial applications. Generic Manufacturers: With the expiration of key patents, generic companies have entered the market for Aprepitant. Their R&D efforts often focus on alternative synthesis routes, new formulations (e.g., extended-release, injectable), or exploring new therapeutic indications that may not be covered by existing patents. Companies Developing Other NK1 Antagonists: The success of Aprepitant has spurred research into other NK1 receptor antagonists, leading to a competitive patent landscape for this class of drugs. These competitors may develop compounds with similar or improved efficacy, different pharmacokinetic profiles, or for distinct therapeutic areas. Patent Expirations and Generic Entry: Patent 5,741,516 expired on April 21, 2016. This allowed for the market entry of generic versions of Aprepitant for the indications claimed within the patent. However, the overall patent protection for Aprepitant's commercial products may extend beyond this date due to later-expiring patents covering specific formulations, manufacturing processes, or more recent therapeutic applications. For instance, patents related to Aprepitant for CINV and PONV, such as those protecting oral formulations like Emend® (aprepitant) and its intravenous prodrug Fosaprepitant (Emend for Injection), may have later expiration dates. The landscape is dynamic, with ongoing patent filings and potential litigation surrounding existing patents. Companies seeking to enter the market or develop improved NK1 antagonists must conduct thorough freedom-to-operate analyses to navigate this complex IP environment. What Were the Original Intended Therapeutic Uses vs. Actual Marketed Uses? United States Patent 5,741,516, granted in 1998, outlines methods for treating hypertension, edema, and congestive heart failure using n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide (Aprepitant). These were the indications for which Merck & Co., Inc. sought patent protection at that time. Original Intended Uses (per Patent 5,741,516): Hypertension: Elevated blood pressure. Edema: Swelling caused by excess fluid trapped in your body's tissues. Congestive Heart Failure: A chronic condition in which the heart doesn't pump blood as well as it should. However, Aprepitant's primary clinical and commercial success has been in a different therapeutic area: the prevention of nausea and vomiting. Actual Marketed Uses: Chemotherapy-Induced Nausea and Vomiting (CINV): Aprepitant, marketed as Emend®, is a cornerstone therapy for preventing both acute and delayed nausea and vomiting associated with highly and moderately emetogenic chemotherapy. Postoperative Nausea and Vomiting (PONV): Aprepitant is also approved for the prevention of PONV. This divergence between the patent-claimed uses and the actual marketed applications is not uncommon. Drug candidates often exhibit efficacy across multiple biological pathways or symptoms, and the most commercially viable or therapeutically impactful use may not be apparent or fully characterized at the time of initial patent filings. The development of Aprepitant for CINV involved extensive research into its mechanism of action as an NK1 receptor antagonist, which plays a significant role in the emetic reflex pathway. The patent landscape for these later-discovered uses would be covered by separate patent applications filed subsequent to patent 5,741,516. What is the Impact of Patent Expiration on Market Competition? The expiration of United States Patent 5,741,516 on April 21, 2016, has had a direct and significant impact on market competition for the therapeutic uses it protected. This expiration opened the door for generic pharmaceutical companies to market their own versions of Aprepitant for the treatment of hypertension, edema, and congestive heart failure. Effects of Patent Expiration: Generic Market Entry: Following the patent's expiration, generic manufacturers could legally produce and sell Aprepitant without infringing on this specific patent. This typically leads to a substantial increase in the number of drug suppliers in the market. Price Reductions: The introduction of generic competition is a primary driver of significant price reductions. The availability of multiple affordable generic options puts downward pressure on the prices of both branded and generic versions of the drug. Increased Patient Access: Lower prices and increased availability through generic products generally improve patient access to medications, enabling more individuals to receive treatment for the conditions covered by the patent. Shift in Market Dynamics: The market share previously held by the innovator company for these specific indications would be diluted by the entry of generic competitors. It is important to note that while patent 5,741,516 expired in 2016, the overall patent protection for Aprepitant as a commercial product may have extended due to other patents covering later-filed applications, such as new formulations or different therapeutic uses (like CINV and PONV). However, for the specific claims of treating hypertension, edema, and congestive heart failure, the expiration of this patent removed a significant barrier to entry for generic competition. This creates opportunities for healthcare systems and patients seeking cost-effective treatment options. Key Takeaways United States Patent 5,741,516, granted April 21, 1998, to Merck & Co., Inc., protected methods for treating hypertension, edema, and congestive heart failure using n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide (Aprepitant). The patent's claims are focused on the therapeutic administration of the compound, including its use in combination with other agents. The patent expired on April 21, 2016, opening the market to generic competition for the claimed indications. While the patent protected specific cardiovascular and fluid-related conditions, Aprepitant's primary marketed uses have become the prevention of chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV), covered by separate patent filings. The expiration of this patent led to reduced prices and increased patient access for the initially claimed therapeutic uses. The broader patent landscape for Aprepitant remains complex, with other patents potentially covering formulations and newer indications. Frequently Asked Questions 1. What is the primary active ingredient protected by US Patent 5,741,516? The primary active ingredient is n-((4S)-4-(3,5-bis(trifluoromethyl)phenyl)ethyl)-2-((2S)-3-hydroxy-2-phenylpropanamido) -3-phenylpropanamide, also known as Aprepitant. 2. For which medical conditions did US Patent 5,741,516 originally provide protection? The patent provided protection for methods of treating hypertension, edema, and congestive heart failure. 3. When did US Patent 5,741,516 expire, and what was the consequence of this expiration? The patent expired on April 21, 2016. This expiration allowed for the market entry of generic versions of Aprepitant for the indications covered by the patent, leading to increased competition and lower prices. 4. Are there other patents related to Aprepitant that are still in force, even after the expiration of patent 5,741,516? Yes, there may be other patents in force that cover different aspects of Aprepitant, such as its synthesis, specific pharmaceutical formulations (e.g., oral or injectable forms), or its use in treating other medical conditions like chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). 5. Did Aprepitant achieve widespread clinical use for the conditions originally claimed in patent 5,741,516? While the patent covered methods for treating hypertension, edema, and congestive heart failure, Aprepitant's primary and most successful clinical applications have been in the prevention of CINV and PONV. Citations [1] Merck & Co., Inc. (1998, April 21). United States Patent 5,741,516: Methods for treating hypertension, edema, and congestive heart failure. U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

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Details for Patent: 5,741,516

Summary for Patent: 5,741,516