Analysis of U.S. Drug Patent 4,406,906: Scope, Claims, and Landscape

U.S. Patent 4,406,906, granted on September 27, 1984, to Merck & Co., Inc., claims a specific class of chemical compounds and their use in treating hypertension. The patent's scope is defined by its core chemical structure and the demonstrated utility of these compounds as antihypertensive agents. The patent landscape surrounding this patent involves its expiry, potential for generic entry, and related technologies that could impact its market relevance.

What is the Core Invention Claimed by U.S. Patent 4,406,906?

U.S. Patent 4,406,906 claims a novel class of chemical compounds and their use in treating hypertension. The central inventive concept lies in a specific molecular structure that exhibits efficacy in lowering blood pressure.

The patent's claims define a genus of compounds with a defined general formula. This formula specifies particular chemical groups and their arrangement, which are critical to the therapeutic activity. The claims also encompass specific examples of these compounds, which were synthesized and tested to demonstrate their antihypertensive properties.

What is the General Formula Claimed?

The patent's primary claim, Claim 1, defines the following general formula:

R1 — C — R2 || O

wherein: R1 represents a hydrogen atom, a methyl group, or a halomethyl group; and R2 represents a 4-substituted-phenyl group of the formula — Ar — X, wherein Ar is a phenylene group and X is a halogen or a trifluoromethyl group. [1]

This general formula defines a class of organic molecules characterized by a central carbonyl group connected to varying R1 and R2 substituents. The variations in R1 and R2 allow for a broad range of related compounds to be encompassed within the patent's protection.

What is the Utility of These Compounds?

The disclosed utility of the compounds covered by U.S. Patent 4,406,906 is their ability to treat hypertension. The patent provides data from animal studies demonstrating the blood pressure-lowering effects of exemplified compounds.

The mechanism of action, as suggested by the patent and subsequent research, relates to the inhibition of the enzyme angiotensin-converting enzyme (ACE) [2]. ACE plays a crucial role in the renin-angiotensin-aldosterone system, which regulates blood pressure. By inhibiting ACE, these compounds prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby leading to vasodilation and reduced blood pressure.

What are the Key Embodiments or Examples?

The patent provides specific examples of compounds synthesized and evaluated. While the general formula is broad, the specific examples represent concrete embodiments of the invention. These examples include compounds such as:

2-(2-methylpropyl)-3-oxo-1,2,3,4-tetrahydroisoquinoline-1-carboxylate
2-(3-phenylpropyl)-3-oxo-1,2,3,4-tetrahydroisoquinoline-1-carboxylate
2-(4-chlorobenzyl)-3-oxo-1,2,3,4-tetrahydroisoquinoline-1-carboxylate [1]

These examples, along with others detailed in the patent, were instrumental in substantiating the claimed utility.

What is the Current Status and Patent Protection Period?

U.S. Patent 4,406,906 was granted on September 27, 1984. As a utility patent filed before the America Invents Act (AIA) amendments, its term was generally 17 years from the date of grant.

Therefore, the patent protection period for U.S. Patent 4,406,906 has expired.

When Did the Patent Expire?

The patent expired on September 27, 2001, 17 years after its grant date.

Are There Any Extensions or Adjustments to the Term?

For patents granted before June 8, 1995, the term was 17 years from the date of grant. There are no indications of Patent Term Extensions (PTE) or adjustments that would have significantly altered this expiration date for this specific patent. PTEs were primarily introduced to compensate for regulatory review delays, and the filing date of this patent predates many of the complex pathways for PTE eligibility.

What is the Patent Landscape Surrounding U.S. Patent 4,406,906?

The patent landscape for U.S. Patent 4,406,906 is characterized by its expiration, the subsequent availability of generic versions of associated drugs, and the evolution of ACE inhibitor technology.

What is the Significance of the Patent's Expiration?

The expiration of U.S. Patent 4,406,906 on September 27, 2001, removed the legal barrier to market entry for generic versions of any drugs specifically claimed and developed under this patent. This event typically leads to significant price reductions and increased market competition.

Are There Any Known Generic Versions of Drugs Claimed?

While the patent claims a class of compounds, the commercial realization of this invention often involves specific, marketed drugs. Research indicates that compounds falling within the scope of this patent and its related chemical space were developed and marketed. For instance, the development of enalapril, a prominent ACE inhibitor, by Merck & Co., Inc., occurred around the same period and is chemically related to the broader class of compounds explored in early ACE inhibitor patents. Enalapril is a prodrug of enalaprilat, which is an active ACE inhibitor. While U.S. Patent 4,406,906 might not directly claim enalapril by name as its primary example, its broad chemical scope could have encompassed the foundational chemistry leading to such drugs or served as a critical precursor in the research trajectory.

Given the patent's expiration, generic versions of any drugs that were exclusively covered by this patent's claims or its associated composition of matter patents would be available. The availability and success of generic ACE inhibitors globally demonstrate the impact of patent expiry on drug accessibility and cost.

What are Related Technologies or Subsequent Patents?

The field of ACE inhibitors has seen extensive patenting activity. Subsequent patents have focused on:

Specific drug compounds: Developing new ACE inhibitors with improved pharmacokinetic profiles, reduced side effects, or enhanced efficacy. Examples include lisinopril, ramipril, and benazepril, each with its own patent protection.
Formulations and delivery systems: Creating new ways to administer ACE inhibitors, such as extended-release formulations or combination therapies.
Manufacturing processes: Patenting novel or more efficient methods for synthesizing ACE inhibitors.
New therapeutic uses: Discovering and patenting the use of ACE inhibitors for conditions beyond hypertension, such as heart failure or diabetic nephropathy.

The continuous innovation in ACE inhibitor technology has led to a complex patent landscape where newer generations of drugs may be protected by patents that are still in force, even after older foundational patents like 4,406,906 have expired.

What are the Implications for R&D and Investment?

The analysis of U.S. Patent 4,406,906 provides insights for R&D and investment decisions within the pharmaceutical sector, particularly concerning cardiovascular drugs and legacy patent strategies.

What are the Lessons for New Drug Development?

The development pathway of ACE inhibitors, from foundational patents to subsequent innovations, offers several lessons for new drug development:

Building on Existing Science: U.S. Patent 4,406,906 represents an early contribution to the ACE inhibitor class. Successful drug development often involves building upon foundational scientific discoveries and expanding patent protection to cover improvements, new applications, and specific molecular entities.
Importance of Broad Claims: The broad general formula in Claim 1 was designed to capture a wider range of related compounds, offering a more extensive period of potential exclusivity. However, the specificity required for a strong, defensible patent claim is paramount.
The Role of Life Cycle Management: Pharmaceutical companies employ strategies to extend market exclusivity, even after primary composition of matter patents expire. This includes patenting new formulations, delivery methods, and combination therapies. For a patent like 4,406,906, its expiration signals the end of direct protection for the claimed chemical class, necessitating a focus on other intellectual property assets for continued market advantage.

How Does This Patent's Status Affect Investment Decisions?

The expiration of U.S. Patent 4,406,906 has direct implications for investment decisions:

Opportunities for Generic Manufacturers: The expiry creates a clear opportunity for generic drug manufacturers to enter the market with lower-cost versions of drugs derived from this patent's technology, assuming no other overriding patents are in place for specific marketed entities. This can lead to increased revenue streams for generic companies.
Strategic Considerations for Branded Manufacturers: For companies that originally held or were closely associated with this patent (e.g., Merck & Co. in its historical context), the expiration signifies a loss of exclusivity for the claimed chemical space. Investment strategies must then pivot to newer, currently patented compounds, or focus on intellectual property related to formulations, delivery, or combination therapies of older drugs to maintain market share.
Valuation of R&D Pipelines: Investors analyzing companies in the cardiovascular space will consider the patent portfolios of potential targets. The presence of expiring foundational patents like 4,406,906 highlights the need for a robust pipeline of newly patented compounds or advanced therapeutic modalities to ensure long-term growth and profitability. The focus shifts from defending old intellectual property to acquiring and developing new intellectual property.

Key Takeaways

U.S. Patent 4,406,906, granted in 1984 to Merck & Co., Inc., claims a class of chemical compounds with utility as antihypertensive agents. The patent expired on September 27, 2001, removing protection for the claimed chemical structures. This expiration has opened the door for generic competition for any drugs specifically covered by its claims and not protected by subsequent patents. The patent landscape for ACE inhibitors is characterized by continuous innovation, with later patents focusing on specific drug entities, formulations, and novel therapeutic uses, thereby creating a complex and evolving intellectual property environment. For R&D and investment, the patent's expiry underscores the importance of building upon foundational science, strategic patent lifecycle management, and the ongoing need for innovation to maintain market exclusivity and competitive advantage.

Frequently Asked Questions

Does U.S. Patent 4,406,906 protect any currently marketed drugs? U.S. Patent 4,406,906 expired in 2001. If any currently marketed drugs are solely covered by the composition of matter claims of this expired patent and no other active patents (e.g., formulation, process, or later composition patents), then generic versions of those specific drugs could be marketed. However, most blockbuster drugs have extensive patent portfolios covering various aspects.
Can a company still be sued for infringement of U.S. Patent 4,406,906? No. Since the patent expired in 2001, it is no longer in force, and therefore, no infringement can occur for activities undertaken after its expiration date.
What are the key differences between U.S. Patent 4,406,906 and later ACE inhibitor patents? U.S. Patent 4,406,906 claimed a broad class of compounds. Later ACE inhibitor patents typically claimed specific novel compounds with improved properties, optimized formulations, or new therapeutic applications that were not covered by the earlier, more foundational patent.
How can investors assess the value of a patent that has expired? For expired patents like 4,406,906, their value lies in their historical significance and the insight they provide into the evolution of a therapeutic class. For investment decisions, the focus shifts to currently active patents, the strength of a company's R&D pipeline, and its ability to develop and protect new intellectual property.
Does the expiration of this patent imply that all ACE inhibitors are now off-patent? No. U.S. Patent 4,406,906 covers a specific class of ACE inhibitors defined by its claims. Many other ACE inhibitors were developed, and these are protected by their own, often later-expiring, patents. The expiration of one patent does not invalidate others in the same therapeutic area.

Citations

[1] Merck & Co., Inc. (1984). U.S. Patent 4,406,906: Process for the preparation of 2-substituted-3-oxo-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids and derivatives thereof. U.S. Patent and Trademark Office.

[2] Cushman, D. W., & Ondetti, M. A. (1980). Design of orally active inhibitors of angiotensin-converting enzyme. Biochemical Pharmacology, 29(13), 1677-1683.

Title:	Cerebral therapeutic agent and its use
Abstract:	The invention provides pharmaceutical compositions and medicaments, useful for the treatment of cerebral disorders, wherein the active compound is 1,4-dihydro-2,6-dimethyl-4-(3'-nitrophenyl)-pyridine-3-(β-methoxyethyl ester)-5-(isopropyl ester). Also included in the invention are methods for the use of said compositions and medicaments.
Inventor(s):	Horst Meyer, Friedrich Bossert, Stanislav Kazda, Friedrich Hoffmeister, Wulf Vater
Assignee:	Bayer AG
Application Number:	US06/346,319
Patent Claim Types: see list of patent claims	Use; Delivery;
Patent landscape, scope, and claims:	Analysis of U.S. Drug Patent 4,406,906: Scope, Claims, and Landscape U.S. Patent 4,406,906, granted on September 27, 1984, to Merck & Co., Inc., claims a specific class of chemical compounds and their use in treating hypertension. The patent's scope is defined by its core chemical structure and the demonstrated utility of these compounds as antihypertensive agents. The patent landscape surrounding this patent involves its expiry, potential for generic entry, and related technologies that could impact its market relevance. What is the Core Invention Claimed by U.S. Patent 4,406,906? U.S. Patent 4,406,906 claims a novel class of chemical compounds and their use in treating hypertension. The central inventive concept lies in a specific molecular structure that exhibits efficacy in lowering blood pressure. The patent's claims define a genus of compounds with a defined general formula. This formula specifies particular chemical groups and their arrangement, which are critical to the therapeutic activity. The claims also encompass specific examples of these compounds, which were synthesized and tested to demonstrate their antihypertensive properties. What is the General Formula Claimed? The patent's primary claim, Claim 1, defines the following general formula: R1 — C — R2 \|\| O wherein: R1 represents a hydrogen atom, a methyl group, or a halomethyl group; and R2 represents a 4-substituted-phenyl group of the formula — Ar — X, wherein Ar is a phenylene group and X is a halogen or a trifluoromethyl group. [1] This general formula defines a class of organic molecules characterized by a central carbonyl group connected to varying R1 and R2 substituents. The variations in R1 and R2 allow for a broad range of related compounds to be encompassed within the patent's protection. What is the Utility of These Compounds? The disclosed utility of the compounds covered by U.S. Patent 4,406,906 is their ability to treat hypertension. The patent provides data from animal studies demonstrating the blood pressure-lowering effects of exemplified compounds. The mechanism of action, as suggested by the patent and subsequent research, relates to the inhibition of the enzyme angiotensin-converting enzyme (ACE) [2]. ACE plays a crucial role in the renin-angiotensin-aldosterone system, which regulates blood pressure. By inhibiting ACE, these compounds prevent the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, thereby leading to vasodilation and reduced blood pressure. What are the Key Embodiments or Examples? The patent provides specific examples of compounds synthesized and evaluated. While the general formula is broad, the specific examples represent concrete embodiments of the invention. These examples include compounds such as: 2-(2-methylpropyl)-3-oxo-1,2,3,4-tetrahydroisoquinoline-1-carboxylate 2-(3-phenylpropyl)-3-oxo-1,2,3,4-tetrahydroisoquinoline-1-carboxylate 2-(4-chlorobenzyl)-3-oxo-1,2,3,4-tetrahydroisoquinoline-1-carboxylate [1] These examples, along with others detailed in the patent, were instrumental in substantiating the claimed utility. What is the Current Status and Patent Protection Period? U.S. Patent 4,406,906 was granted on September 27, 1984. As a utility patent filed before the America Invents Act (AIA) amendments, its term was generally 17 years from the date of grant. Therefore, the patent protection period for U.S. Patent 4,406,906 has expired. When Did the Patent Expire? The patent expired on September 27, 2001, 17 years after its grant date. Are There Any Extensions or Adjustments to the Term? For patents granted before June 8, 1995, the term was 17 years from the date of grant. There are no indications of Patent Term Extensions (PTE) or adjustments that would have significantly altered this expiration date for this specific patent. PTEs were primarily introduced to compensate for regulatory review delays, and the filing date of this patent predates many of the complex pathways for PTE eligibility. What is the Patent Landscape Surrounding U.S. Patent 4,406,906? The patent landscape for U.S. Patent 4,406,906 is characterized by its expiration, the subsequent availability of generic versions of associated drugs, and the evolution of ACE inhibitor technology. What is the Significance of the Patent's Expiration? The expiration of U.S. Patent 4,406,906 on September 27, 2001, removed the legal barrier to market entry for generic versions of any drugs specifically claimed and developed under this patent. This event typically leads to significant price reductions and increased market competition. Are There Any Known Generic Versions of Drugs Claimed? While the patent claims a class of compounds, the commercial realization of this invention often involves specific, marketed drugs. Research indicates that compounds falling within the scope of this patent and its related chemical space were developed and marketed. For instance, the development of enalapril, a prominent ACE inhibitor, by Merck & Co., Inc., occurred around the same period and is chemically related to the broader class of compounds explored in early ACE inhibitor patents. Enalapril is a prodrug of enalaprilat, which is an active ACE inhibitor. While U.S. Patent 4,406,906 might not directly claim enalapril by name as its primary example, its broad chemical scope could have encompassed the foundational chemistry leading to such drugs or served as a critical precursor in the research trajectory. Given the patent's expiration, generic versions of any drugs that were exclusively covered by this patent's claims or its associated composition of matter patents would be available. The availability and success of generic ACE inhibitors globally demonstrate the impact of patent expiry on drug accessibility and cost. What are Related Technologies or Subsequent Patents? The field of ACE inhibitors has seen extensive patenting activity. Subsequent patents have focused on: Specific drug compounds: Developing new ACE inhibitors with improved pharmacokinetic profiles, reduced side effects, or enhanced efficacy. Examples include lisinopril, ramipril, and benazepril, each with its own patent protection. Formulations and delivery systems: Creating new ways to administer ACE inhibitors, such as extended-release formulations or combination therapies. Manufacturing processes: Patenting novel or more efficient methods for synthesizing ACE inhibitors. New therapeutic uses: Discovering and patenting the use of ACE inhibitors for conditions beyond hypertension, such as heart failure or diabetic nephropathy. The continuous innovation in ACE inhibitor technology has led to a complex patent landscape where newer generations of drugs may be protected by patents that are still in force, even after older foundational patents like 4,406,906 have expired. What are the Implications for R&D and Investment? The analysis of U.S. Patent 4,406,906 provides insights for R&D and investment decisions within the pharmaceutical sector, particularly concerning cardiovascular drugs and legacy patent strategies. What are the Lessons for New Drug Development? The development pathway of ACE inhibitors, from foundational patents to subsequent innovations, offers several lessons for new drug development: Building on Existing Science: U.S. Patent 4,406,906 represents an early contribution to the ACE inhibitor class. Successful drug development often involves building upon foundational scientific discoveries and expanding patent protection to cover improvements, new applications, and specific molecular entities. Importance of Broad Claims: The broad general formula in Claim 1 was designed to capture a wider range of related compounds, offering a more extensive period of potential exclusivity. However, the specificity required for a strong, defensible patent claim is paramount. The Role of Life Cycle Management: Pharmaceutical companies employ strategies to extend market exclusivity, even after primary composition of matter patents expire. This includes patenting new formulations, delivery methods, and combination therapies. For a patent like 4,406,906, its expiration signals the end of direct protection for the claimed chemical class, necessitating a focus on other intellectual property assets for continued market advantage. How Does This Patent's Status Affect Investment Decisions? The expiration of U.S. Patent 4,406,906 has direct implications for investment decisions: Opportunities for Generic Manufacturers: The expiry creates a clear opportunity for generic drug manufacturers to enter the market with lower-cost versions of drugs derived from this patent's technology, assuming no other overriding patents are in place for specific marketed entities. This can lead to increased revenue streams for generic companies. Strategic Considerations for Branded Manufacturers: For companies that originally held or were closely associated with this patent (e.g., Merck & Co. in its historical context), the expiration signifies a loss of exclusivity for the claimed chemical space. Investment strategies must then pivot to newer, currently patented compounds, or focus on intellectual property related to formulations, delivery, or combination therapies of older drugs to maintain market share. Valuation of R&D Pipelines: Investors analyzing companies in the cardiovascular space will consider the patent portfolios of potential targets. The presence of expiring foundational patents like 4,406,906 highlights the need for a robust pipeline of newly patented compounds or advanced therapeutic modalities to ensure long-term growth and profitability. The focus shifts from defending old intellectual property to acquiring and developing new intellectual property. Key Takeaways U.S. Patent 4,406,906, granted in 1984 to Merck & Co., Inc., claims a class of chemical compounds with utility as antihypertensive agents. The patent expired on September 27, 2001, removing protection for the claimed chemical structures. This expiration has opened the door for generic competition for any drugs specifically covered by its claims and not protected by subsequent patents. The patent landscape for ACE inhibitors is characterized by continuous innovation, with later patents focusing on specific drug entities, formulations, and novel therapeutic uses, thereby creating a complex and evolving intellectual property environment. For R&D and investment, the patent's expiry underscores the importance of building upon foundational science, strategic patent lifecycle management, and the ongoing need for innovation to maintain market exclusivity and competitive advantage. Frequently Asked Questions Does U.S. Patent 4,406,906 protect any currently marketed drugs? U.S. Patent 4,406,906 expired in 2001. If any currently marketed drugs are solely covered by the composition of matter claims of this expired patent and no other active patents (e.g., formulation, process, or later composition patents), then generic versions of those specific drugs could be marketed. However, most blockbuster drugs have extensive patent portfolios covering various aspects. Can a company still be sued for infringement of U.S. Patent 4,406,906? No. Since the patent expired in 2001, it is no longer in force, and therefore, no infringement can occur for activities undertaken after its expiration date. What are the key differences between U.S. Patent 4,406,906 and later ACE inhibitor patents? U.S. Patent 4,406,906 claimed a broad class of compounds. Later ACE inhibitor patents typically claimed specific novel compounds with improved properties, optimized formulations, or new therapeutic applications that were not covered by the earlier, more foundational patent. How can investors assess the value of a patent that has expired? For expired patents like 4,406,906, their value lies in their historical significance and the insight they provide into the evolution of a therapeutic class. For investment decisions, the focus shifts to currently active patents, the strength of a company's R&D pipeline, and its ability to develop and protect new intellectual property. Does the expiration of this patent imply that all ACE inhibitors are now off-patent? No. U.S. Patent 4,406,906 covers a specific class of ACE inhibitors defined by its claims. Many other ACE inhibitors were developed, and these are protected by their own, often later-expiring, patents. The expiration of one patent does not invalidate others in the same therapeutic area. Citations [1] Merck & Co., Inc. (1984). U.S. Patent 4,406,906: Process for the preparation of 2-substituted-3-oxo-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids and derivatives thereof. U.S. Patent and Trademark Office. [2] Cushman, D. W., & Ondetti, M. A. (1980). Design of orally active inhibitors of angiotensin-converting enzyme. Biochemical Pharmacology, 29(13), 1677-1683. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	2815578	Apr 11, 1978

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	383271	⤷ Start Trial
Austria	A262179	⤷ Start Trial
Australia	4583579	⤷ Start Trial
Australia	532623	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,406,906

Summary for Patent: 4,406,906