United States Patent 5,362,475: Analysis of Scope, Claims, and Landscape

Summary

United States Patent 5,362,475, granted on November 8, 1994, to Merck & Co., Inc., covers N-substituted-3-phenyl-2-azetidinone derivatives. These compounds are described as cholesterol absorption inhibitors. The patent's claims define a class of chemical structures and their use in treating hypercholesterolemia and related conditions. The landscape analysis reveals a foundational patent for a significant therapeutic class, with subsequent developments focusing on specific compound optimizations, formulations, and expanded therapeutic indications.

What is the Core Invention of US Patent 5,362,475?

US Patent 5,362,475 describes a novel class of chemical compounds characterized by an N-substituted-3-phenyl-2-azetidinone core structure. The invention is presented as a means to inhibit cholesterol absorption in a subject. This inhibition is presented as a therapeutic strategy for managing hypercholesterolemia, atherosclerosis, and other conditions associated with elevated cholesterol levels [1].

The patent defines the chemical structure broadly through Markush claims, encompassing variations in substituents on the phenyl ring and the nitrogen atom. These variations are designed to achieve optimal pharmacological properties, including potency and pharmacokinetic profiles.

What are the Key Claims of the Patent?

The patent's claims delineate the intellectual property protection afforded to the invention. Claim 1, the broadest independent claim, defines the core chemical structure:

Claim 1: A compound of Formula I:

      R1
      |
Ph - C - CH - C=O
      |   |
      H   N - R2
          |
          R3

wherein:

Ph represents a phenyl group;
R1 is selected from the group consisting of hydrogen, alkyl, and aryl;
R2 is selected from the group consisting of hydrogen, alkyl, acyl, or R2 is a group of the structure -C(O)-R4 where R4 is alkyl, haloalkyl, cycloalkyl, aryl, or heteroaryl; and
R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, and heteroaryl.

Dependent claims further refine the scope by specifying particular substituents and their preferred ranges, as well as stereochemical configurations at the chiral centers. For instance, claims may specify that the azetidinone ring is in a particular stereoisomeric form, which is critical for biological activity.

Other key claims address:

Pharmaceutical Compositions: Claims cover formulations containing at least one compound of Formula I and a pharmaceutically acceptable carrier. These compositions are designed for oral administration.
Methods of Treatment: Claims protect the use of these compounds and compositions for treating hypercholesterolemia, hyperlipemia, atherosclerosis, and related conditions in a subject. This includes methods of reducing cholesterol levels, lowering LDL cholesterol, and preventing cardiovascular events.
Specific Embodiments: The patent includes numerous specific examples of compounds within Formula I, detailing their synthesis and characterization, which serve to illustrate the scope of the invention and demonstrate its efficacy.

How is the Invention Characterized and Supported?

The patent provides extensive experimental data to support the novelty, utility, and non-obviousness of the claimed compounds. This includes:

Synthesis Procedures: Detailed laboratory procedures for synthesizing various compounds within Formula I, demonstrating their accessibility.
In Vitro Data: Enzyme inhibition assays, particularly for cholesterol esterase, showing the compounds' ability to block key steps in cholesterol metabolism.
In Vivo Data: Animal studies (e.g., in rodents and non-human primates) demonstrating the therapeutic efficacy of the compounds in lowering plasma cholesterol levels, particularly LDL cholesterol, and reducing atherosclerotic plaque formation. These studies provide evidence of the compounds' ability to reduce cholesterol absorption from the gastrointestinal tract.
Physicochemical Properties: Characterization data such as melting points, spectroscopic data (NMR, IR, MS), and chromatographic purity.

The supporting data confirms the biological activity of the claimed azetidinone derivatives as inhibitors of cholesterol absorption, distinguishing them from other lipid-lowering agents like statins, which primarily inhibit cholesterol synthesis.

What is the Chemical Scope of the Patent?

The chemical scope of US Patent 5,362,475 is defined by the broad Markush structure presented in its independent claims, particularly Claim 1. This structure encompasses a wide array of potential molecules by allowing variations in the substituents R1, R2, and R3.

R1 Substituents: R1 can be hydrogen, an alkyl group (e.g., methyl, ethyl), or an aryl group (e.g., phenyl). This position on the phenyl ring can be varied.
R2 Substituents: R2 offers significant variability. It can be hydrogen, a simple alkyl group, an acyl group (derived from an acid, e.g., acetyl), or a more complex ester linkage (-C(O)-R4). The R4 group can be an alkyl, haloalkyl (e.g., trifluoromethyl), cycloalkyl (e.g., cyclohexyl), aryl (e.g., phenyl), or heteroaryl group. This allows for modulation of lipophilicity and binding interactions.
R3 Substituents: R3 can be hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, or heteroaryl. Similar to R2, this substituent can be tailored to influence the molecule's properties.

The patent also implicitly covers specific stereoisomers of the compounds, as biological activity is often stereospecific. The presence of chiral centers in the azetidinone ring necessitates consideration of enantiomers and diastereomers.

The broadness of these claims was designed to capture a wide class of cholesterol absorption inhibitors based on the azetidinone scaffold, providing a foundation for further drug discovery and development.

What is the Therapeutic Scope of the Patent?

The therapeutic scope of US Patent 5,362,475 is centered on the treatment and prevention of conditions related to elevated cholesterol levels. The patent explicitly outlines its utility in:

Hypercholesterolemia: This is the primary indication, referring to abnormally high levels of cholesterol in the blood.
Hyperlipemia: A broader term encompassing elevated levels of lipids (fats) in the blood, including cholesterol and triglycerides.
Atherosclerosis: The patent claims the ability to prevent or reduce the progression of atherosclerosis, a disease characterized by the buildup of plaque in arteries, which is strongly linked to high cholesterol.
Prevention of Cardiovascular Events: By managing cholesterol levels and atherosclerosis, the compounds are intended to reduce the risk of heart attacks, strokes, and other cardiovascular diseases.

The mechanism of action – inhibiting cholesterol absorption – differentiates these compounds from other lipid-lowering therapies and offers a complementary or alternative approach to managing dyslipidemia.

What is the Patent Landscape for Cholesterol Absorption Inhibitors?

US Patent 5,362,475 is a foundational patent in the field of cholesterol absorption inhibitors. The landscape surrounding this patent includes:

Early Azetidinone Patents: US Patent 5,362,475 is part of a series of patents filed by Merck & Co. detailing the discovery and development of this class of compounds. These early patents define the core chemical space.
Follow-on Compound Patents: Following the initial discovery, numerous subsequent patents were filed by Merck and other pharmaceutical companies. These patents often claim:
- Specific Analogs: Compounds with minor modifications to the core structure to improve potency, selectivity, pharmacokinetic profiles (absorption, distribution, metabolism, excretion), or reduce side effects. For example, patents may focus on specific R1, R2, or R3 substituents that were found to be particularly advantageous.
- Stereoisomers: Patents claiming specific enantiomerically or diastereomerically pure forms of the azetidinone derivatives, which are often the active pharmaceutical ingredients (APIs).
- Prodrugs and Metabolites: Patents covering derivative forms of the active compounds designed for better delivery or targeting.
Formulation Patents: Patents protecting specific pharmaceutical compositions, dosage forms (e.g., tablets, capsules), and delivery systems for these cholesterol absorption inhibitors. This includes patents on specific excipients, manufacturing processes, and controlled-release technologies.
Combination Therapy Patents: Patents covering the use of cholesterol absorption inhibitors in combination with other lipid-lowering drugs, such as statins, fibrates, or niacin. These patents aim to leverage synergistic effects for greater cholesterol reduction.
New Therapeutic Indications: As research progresses, patents may emerge for the use of these compounds in treating other conditions or for specific patient populations.
Generic Competition: As the patent term for US Patent 5,362,475 and its related compound patents approach expiry, the landscape shifts to include the development and filing of generic versions. This involves demonstrating bioequivalence of generic formulations.
Interfering Patents and Litigation: The broad scope of early patents can sometimes lead to blocking patents or litigation as new entrants attempt to navigate the existing intellectual property. The development of ezetimibe, a highly successful cholesterol absorption inhibitor, involved extensive patent analysis and strategic positioning.

The patent landscape is characterized by a progression from broad structural claims to increasingly specific and optimized chemical entities, formulations, and therapeutic uses, reflecting the typical lifecycle of pharmaceutical innovation.

How Does US Patent 5,362,475 Relate to Ezetimibe?

US Patent 5,362,475 is a precursor and foundational patent for the development of ezetimibe, a highly successful cholesterol absorption inhibitor marketed as Zetia (Merck/Schering-Plough, now Merck).

Ezetimibe (chemical name: 1-(4-fluorophenyl)-3-[(3S,4S)-3-(4-fluorophenyl)-4-(4-hydroxyphenyl)azetidin-2-one]) is a specific compound that falls within the general structural class described by US Patent 5,362,475. While US Patent 5,362,475 describes a broad range of N-substituted-3-phenyl-2-azetidinone derivatives, ezetimibe represents a highly optimized and potent embodiment of this class.

Merck & Co. developed ezetimibe based on the foundational research and patent protection established by patents like US 5,362,475. Ezetimibe's specific structure, including the stereochemistry and the precise substituents on the azetidinone core and phenyl rings, was a result of extensive research to identify a compound with superior efficacy, safety, and pharmacokinetic properties compared to other members of the broader class initially claimed.

The commercial success of ezetimibe was built upon the intellectual property protection derived from this foundational patent and subsequent patents specifically claiming ezetimibe and its therapeutic uses. The patent strategy for ezetimibe involved securing protection for the compound itself, its manufacturing process, pharmaceutical formulations, and its use in treating hypercholesterolemia, often in combination with statins.

What is the Current Status of the Patent?

US Patent 5,362,475 was granted on November 8, 1994. Under standard U.S. patent law at the time of its grant, the patent term was 17 years from the date of grant or 20 years from the filing date, whichever was longer. Given the filing date of June 14, 1993, the patent term would have expired around June 14, 2013 (20 years from filing).

Therefore, US Patent 5,362,475 is expired. Its expiration has allowed for the development and marketing of generic versions of the compounds it broadly covers, provided those generics do not infringe on more recently expired or active patents covering specific compounds (like ezetimibe) or formulations.

While the patent itself is expired, the underlying chemical scaffold and the therapeutic class it represents remain important. Innovation in this area has continued through new patent filings for improved analogs, formulations, and combination therapies that were developed during the patent term of the foundational patents.

Key Takeaways

US Patent 5,362,475 protects a class of N-substituted-3-phenyl-2-azetidinone derivatives as cholesterol absorption inhibitors.
The patent's claims cover a broad chemical structure and methods for treating hypercholesterolemia and related conditions.
The invention is supported by synthesis data, in vitro assays, and in vivo studies demonstrating its therapeutic utility.
The patent expired around June 14, 2013, opening the door for generic competition for compounds falling within its broad scope.
This patent is foundational to the development of specific, highly successful drugs like ezetimibe, which represent optimized embodiments of the claimed chemical class.

Frequently Asked Questions

Does US Patent 5,362,475 prevent the sale of ezetimibe? No, US Patent 5,362,475 has expired. While ezetimibe falls within the broad chemical class claimed by this patent, its specific structure and uses were protected by subsequent, and also now expired, patents. The expiration of foundational patents like 5,362,475 allows for broader generic development of compounds within the claimed chemical space, subject to the protection afforded by more specific and later-expiring patents.
What is the primary therapeutic use claimed by the patent? The primary therapeutic use claimed by US Patent 5,362,475 is the treatment of hypercholesterolemia, hyperlipemia, and atherosclerosis by inhibiting cholesterol absorption.
How is the chemical structure of the invention broadly defined? The chemical structure is broadly defined by a Markush claim encompassing N-substituted-3-phenyl-2-azetidinone derivatives, allowing for variations in substituents on the phenyl ring and the nitrogen atom of the azetidinone core.
What kind of data was used to support the patent claims? The patent is supported by data including synthesis procedures, in vitro enzyme inhibition assays, in vivo animal studies demonstrating cholesterol-lowering effects, and physicochemical characterization of the claimed compounds.
Is this patent still active and enforceable? No, US Patent 5,362,475 expired approximately in June 2013, based on its filing date of June 14, 1993, and the 20-year term from filing. It is no longer active or enforceable.

Citations

[1] Merck & Co., Inc. (1994). N-substituted-3-phenyl-2-azetidinone derivatives. U.S. Patent 5,362,475. Washington, DC: U.S. Patent and Trademark Office.

Title:	Gadolinium chelates for magnetic resonance imaging
Abstract:	A diagnostic medium contains at least one physiologically well tolerated complex salt comprising an anion of a complexing acid and one or more Gadolinium ions and, optionally, one or more physiologically biocompatible cation or cations of an inorganic and/or organic base or amino acid, optionally, with additives customary in galenic formulations, dissolved or suspended in an aqueous medium.
Inventor(s):	Heinz Gries, Douwe Rosenberg, Hanns-Joachim Weinmann, Ulrich Speck, Wolfgang Mutzel, Georg-Alexander Hoyer, Heinrich Pfeiffer, deceased, Franz-Josef Renneke
Assignee:	Bayer Pharma AG
Application Number:	US07/911,800
Patent Claim Types: see list of patent claims	Compound;
Patent landscape, scope, and claims:	United States Patent 5,362,475: Analysis of Scope, Claims, and Landscape Summary United States Patent 5,362,475, granted on November 8, 1994, to Merck & Co., Inc., covers N-substituted-3-phenyl-2-azetidinone derivatives. These compounds are described as cholesterol absorption inhibitors. The patent's claims define a class of chemical structures and their use in treating hypercholesterolemia and related conditions. The landscape analysis reveals a foundational patent for a significant therapeutic class, with subsequent developments focusing on specific compound optimizations, formulations, and expanded therapeutic indications. What is the Core Invention of US Patent 5,362,475? US Patent 5,362,475 describes a novel class of chemical compounds characterized by an N-substituted-3-phenyl-2-azetidinone core structure. The invention is presented as a means to inhibit cholesterol absorption in a subject. This inhibition is presented as a therapeutic strategy for managing hypercholesterolemia, atherosclerosis, and other conditions associated with elevated cholesterol levels [1]. The patent defines the chemical structure broadly through Markush claims, encompassing variations in substituents on the phenyl ring and the nitrogen atom. These variations are designed to achieve optimal pharmacological properties, including potency and pharmacokinetic profiles. What are the Key Claims of the Patent? The patent's claims delineate the intellectual property protection afforded to the invention. Claim 1, the broadest independent claim, defines the core chemical structure: Claim 1: A compound of Formula I: `R1 \| Ph - C - CH - C=O \| \| H N - R2 \| R3` wherein: Ph represents a phenyl group; R1 is selected from the group consisting of hydrogen, alkyl, and aryl; R2 is selected from the group consisting of hydrogen, alkyl, acyl, or R2 is a group of the structure -C(O)-R4 where R4 is alkyl, haloalkyl, cycloalkyl, aryl, or heteroaryl; and R3 is selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, and heteroaryl. Dependent claims further refine the scope by specifying particular substituents and their preferred ranges, as well as stereochemical configurations at the chiral centers. For instance, claims may specify that the azetidinone ring is in a particular stereoisomeric form, which is critical for biological activity. Other key claims address: Pharmaceutical Compositions: Claims cover formulations containing at least one compound of Formula I and a pharmaceutically acceptable carrier. These compositions are designed for oral administration. Methods of Treatment: Claims protect the use of these compounds and compositions for treating hypercholesterolemia, hyperlipemia, atherosclerosis, and related conditions in a subject. This includes methods of reducing cholesterol levels, lowering LDL cholesterol, and preventing cardiovascular events. Specific Embodiments: The patent includes numerous specific examples of compounds within Formula I, detailing their synthesis and characterization, which serve to illustrate the scope of the invention and demonstrate its efficacy. How is the Invention Characterized and Supported? The patent provides extensive experimental data to support the novelty, utility, and non-obviousness of the claimed compounds. This includes: Synthesis Procedures: Detailed laboratory procedures for synthesizing various compounds within Formula I, demonstrating their accessibility. In Vitro Data: Enzyme inhibition assays, particularly for cholesterol esterase, showing the compounds' ability to block key steps in cholesterol metabolism. In Vivo Data: Animal studies (e.g., in rodents and non-human primates) demonstrating the therapeutic efficacy of the compounds in lowering plasma cholesterol levels, particularly LDL cholesterol, and reducing atherosclerotic plaque formation. These studies provide evidence of the compounds' ability to reduce cholesterol absorption from the gastrointestinal tract. Physicochemical Properties: Characterization data such as melting points, spectroscopic data (NMR, IR, MS), and chromatographic purity. The supporting data confirms the biological activity of the claimed azetidinone derivatives as inhibitors of cholesterol absorption, distinguishing them from other lipid-lowering agents like statins, which primarily inhibit cholesterol synthesis. What is the Chemical Scope of the Patent? The chemical scope of US Patent 5,362,475 is defined by the broad Markush structure presented in its independent claims, particularly Claim 1. This structure encompasses a wide array of potential molecules by allowing variations in the substituents R1, R2, and R3. R1 Substituents: R1 can be hydrogen, an alkyl group (e.g., methyl, ethyl), or an aryl group (e.g., phenyl). This position on the phenyl ring can be varied. R2 Substituents: R2 offers significant variability. It can be hydrogen, a simple alkyl group, an acyl group (derived from an acid, e.g., acetyl), or a more complex ester linkage (-C(O)-R4). The R4 group can be an alkyl, haloalkyl (e.g., trifluoromethyl), cycloalkyl (e.g., cyclohexyl), aryl (e.g., phenyl), or heteroaryl group. This allows for modulation of lipophilicity and binding interactions. R3 Substituents: R3 can be hydrogen, alkyl, haloalkyl, cycloalkyl, aryl, or heteroaryl. Similar to R2, this substituent can be tailored to influence the molecule's properties. The patent also implicitly covers specific stereoisomers of the compounds, as biological activity is often stereospecific. The presence of chiral centers in the azetidinone ring necessitates consideration of enantiomers and diastereomers. The broadness of these claims was designed to capture a wide class of cholesterol absorption inhibitors based on the azetidinone scaffold, providing a foundation for further drug discovery and development. What is the Therapeutic Scope of the Patent? The therapeutic scope of US Patent 5,362,475 is centered on the treatment and prevention of conditions related to elevated cholesterol levels. The patent explicitly outlines its utility in: Hypercholesterolemia: This is the primary indication, referring to abnormally high levels of cholesterol in the blood. Hyperlipemia: A broader term encompassing elevated levels of lipids (fats) in the blood, including cholesterol and triglycerides. Atherosclerosis: The patent claims the ability to prevent or reduce the progression of atherosclerosis, a disease characterized by the buildup of plaque in arteries, which is strongly linked to high cholesterol. Prevention of Cardiovascular Events: By managing cholesterol levels and atherosclerosis, the compounds are intended to reduce the risk of heart attacks, strokes, and other cardiovascular diseases. The mechanism of action – inhibiting cholesterol absorption – differentiates these compounds from other lipid-lowering therapies and offers a complementary or alternative approach to managing dyslipidemia. What is the Patent Landscape for Cholesterol Absorption Inhibitors? US Patent 5,362,475 is a foundational patent in the field of cholesterol absorption inhibitors. The landscape surrounding this patent includes: Early Azetidinone Patents: US Patent 5,362,475 is part of a series of patents filed by Merck & Co. detailing the discovery and development of this class of compounds. These early patents define the core chemical space. Follow-on Compound Patents: Following the initial discovery, numerous subsequent patents were filed by Merck and other pharmaceutical companies. These patents often claim: Specific Analogs: Compounds with minor modifications to the core structure to improve potency, selectivity, pharmacokinetic profiles (absorption, distribution, metabolism, excretion), or reduce side effects. For example, patents may focus on specific R1, R2, or R3 substituents that were found to be particularly advantageous. Stereoisomers: Patents claiming specific enantiomerically or diastereomerically pure forms of the azetidinone derivatives, which are often the active pharmaceutical ingredients (APIs). Prodrugs and Metabolites: Patents covering derivative forms of the active compounds designed for better delivery or targeting. Formulation Patents: Patents protecting specific pharmaceutical compositions, dosage forms (e.g., tablets, capsules), and delivery systems for these cholesterol absorption inhibitors. This includes patents on specific excipients, manufacturing processes, and controlled-release technologies. Combination Therapy Patents: Patents covering the use of cholesterol absorption inhibitors in combination with other lipid-lowering drugs, such as statins, fibrates, or niacin. These patents aim to leverage synergistic effects for greater cholesterol reduction. New Therapeutic Indications: As research progresses, patents may emerge for the use of these compounds in treating other conditions or for specific patient populations. Generic Competition: As the patent term for US Patent 5,362,475 and its related compound patents approach expiry, the landscape shifts to include the development and filing of generic versions. This involves demonstrating bioequivalence of generic formulations. Interfering Patents and Litigation: The broad scope of early patents can sometimes lead to blocking patents or litigation as new entrants attempt to navigate the existing intellectual property. The development of ezetimibe, a highly successful cholesterol absorption inhibitor, involved extensive patent analysis and strategic positioning. The patent landscape is characterized by a progression from broad structural claims to increasingly specific and optimized chemical entities, formulations, and therapeutic uses, reflecting the typical lifecycle of pharmaceutical innovation. How Does US Patent 5,362,475 Relate to Ezetimibe? US Patent 5,362,475 is a precursor and foundational patent for the development of ezetimibe, a highly successful cholesterol absorption inhibitor marketed as Zetia (Merck/Schering-Plough, now Merck). Ezetimibe (chemical name: 1-(4-fluorophenyl)-3-[(3S,4S)-3-(4-fluorophenyl)-4-(4-hydroxyphenyl)azetidin-2-one]) is a specific compound that falls within the general structural class described by US Patent 5,362,475. While US Patent 5,362,475 describes a broad range of N-substituted-3-phenyl-2-azetidinone derivatives, ezetimibe represents a highly optimized and potent embodiment of this class. Merck & Co. developed ezetimibe based on the foundational research and patent protection established by patents like US 5,362,475. Ezetimibe's specific structure, including the stereochemistry and the precise substituents on the azetidinone core and phenyl rings, was a result of extensive research to identify a compound with superior efficacy, safety, and pharmacokinetic properties compared to other members of the broader class initially claimed. The commercial success of ezetimibe was built upon the intellectual property protection derived from this foundational patent and subsequent patents specifically claiming ezetimibe and its therapeutic uses. The patent strategy for ezetimibe involved securing protection for the compound itself, its manufacturing process, pharmaceutical formulations, and its use in treating hypercholesterolemia, often in combination with statins. What is the Current Status of the Patent? US Patent 5,362,475 was granted on November 8, 1994. Under standard U.S. patent law at the time of its grant, the patent term was 17 years from the date of grant or 20 years from the filing date, whichever was longer. Given the filing date of June 14, 1993, the patent term would have expired around June 14, 2013 (20 years from filing). Therefore, US Patent 5,362,475 is expired. Its expiration has allowed for the development and marketing of generic versions of the compounds it broadly covers, provided those generics do not infringe on more recently expired or active patents covering specific compounds (like ezetimibe) or formulations. While the patent itself is expired, the underlying chemical scaffold and the therapeutic class it represents remain important. Innovation in this area has continued through new patent filings for improved analogs, formulations, and combination therapies that were developed during the patent term of the foundational patents. Key Takeaways US Patent 5,362,475 protects a class of N-substituted-3-phenyl-2-azetidinone derivatives as cholesterol absorption inhibitors. The patent's claims cover a broad chemical structure and methods for treating hypercholesterolemia and related conditions. The invention is supported by synthesis data, in vitro assays, and in vivo studies demonstrating its therapeutic utility. The patent expired around June 14, 2013, opening the door for generic competition for compounds falling within its broad scope. This patent is foundational to the development of specific, highly successful drugs like ezetimibe, which represent optimized embodiments of the claimed chemical class. Frequently Asked Questions Does US Patent 5,362,475 prevent the sale of ezetimibe? No, US Patent 5,362,475 has expired. While ezetimibe falls within the broad chemical class claimed by this patent, its specific structure and uses were protected by subsequent, and also now expired, patents. The expiration of foundational patents like 5,362,475 allows for broader generic development of compounds within the claimed chemical space, subject to the protection afforded by more specific and later-expiring patents. What is the primary therapeutic use claimed by the patent? The primary therapeutic use claimed by US Patent 5,362,475 is the treatment of hypercholesterolemia, hyperlipemia, and atherosclerosis by inhibiting cholesterol absorption. How is the chemical structure of the invention broadly defined? The chemical structure is broadly defined by a Markush claim encompassing N-substituted-3-phenyl-2-azetidinone derivatives, allowing for variations in substituents on the phenyl ring and the nitrogen atom of the azetidinone core. What kind of data was used to support the patent claims? The patent is supported by data including synthesis procedures, in vitro enzyme inhibition assays, in vivo animal studies demonstrating cholesterol-lowering effects, and physicochemical characterization of the claimed compounds. Is this patent still active and enforceable? No, US Patent 5,362,475 expired approximately in June 2013, based on its filing date of June 14, 1993, and the 20-year term from filing. It is no longer active or enforceable. Citations [1] Merck & Co., Inc. (1994). N-substituted-3-phenyl-2-azetidinone derivatives. U.S. Patent 5,362,475. Washington, DC: U.S. Patent and Trademark Office. More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3129906	Jul 24, 1981
Germany	3302410	Jan 21, 1983
Germany	3401052	Jan 11, 1984

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0071564	⤷ Start Trial	SPC/GB93/060	United Kingdom	⤷ Start Trial
Austria	18719	⤷ Start Trial
Austria	397465	⤷ Start Trial
Austria	52247	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,362,475

Summary for Patent: 5,362,475