United States Drug Patent 5,908,838: Scope, Claims, and Landscape Analysis

What is United States Patent 5,908,838?

United States Patent 5,908,838, titled "Crystalline Forms of Atorvastatin," was granted on June 1, 1999. This patent claims specific crystalline forms of atorvastatin, the active pharmaceutical ingredient in Lipitor®. The patent was filed by Pfizer Inc. and is directed towards improved methods for producing and isolating stable crystalline forms of atorvastatin, which are crucial for drug formulation and bioavailability.

What is the Scope of Patent 5,908,838?

The scope of Patent 5,908,838 is defined by its claims, which specifically delineate the patented inventions. The patent focuses on:

Specific Crystalline Forms: The patent claims distinct crystalline polymorphs of atorvastatin, primarily the anhydrous crystalline form designated as "Form I." This form exhibits desirable physical properties, such as stability and ease of handling, compared to other potential polymorphic forms or amorphous atorvastatin.
Processes for Preparation: The patent also covers processes for preparing these specific crystalline forms. These processes are designed to reproducibly yield the desired polymorph, ensuring consistency in the manufactured drug substance.
Compositions Containing Crystalline Forms: The claims extend to pharmaceutical compositions that incorporate these specific crystalline forms of atorvastatin. This ensures that the patented crystalline forms are protected throughout their use in final drug products.

What are the Key Claims of Patent 5,908,838?

The primary claims of United States Patent 5,908,838 are centered on the unique crystalline structures and their preparation.

Claim 1: This is a foundational claim that defines a specific anhydrous crystalline form of atorvastatin. The claim typically specifies characteristics such as X-ray powder diffraction (XRPD) peaks at particular angles (2θ values) and potentially other physical identifiers like differential scanning calorimetry (DSC) temperatures. This claim is critical as it establishes proprietary control over a specific, stable crystalline polymorph of the active ingredient.

Claim 2-N: Subsequent claims in the patent typically broaden the protection. These may include:

Alternative Crystalline Forms: Claims for other anhydrous or hydrated crystalline forms of atorvastatin that share specific beneficial properties.
Processes for Producing the Crystalline Forms: Claims detailing specific synthetic routes or purification steps that lead to the isolation of the claimed crystalline forms. For instance, a claim might specify a solvent system, temperature range, or a method of crystallization.
Pharmaceutical Compositions: Claims for formulations containing the patented crystalline form of atorvastatin, often in combination with pharmaceutically acceptable excipients. This extends protection to the final dosage form.
Methods of Treatment: While less common for a patent focused on crystalline forms, some patents might include method of treatment claims if the specific crystalline form offers a unique therapeutic advantage. However, for 5,908,838, the focus is primarily on the material science aspect.

The precise wording of these claims, as found in the official patent document, dictates the exact scope of protection and is subject to detailed legal interpretation.

How Has the Patent Landscape for Atorvastatin Evolved?

The patent landscape for atorvastatin is extensive, reflecting its status as a blockbuster drug. Patent 5,908,838 is one of many that have protected various aspects of atorvastatin, from its initial discovery to its manufacturing and formulation.

Early Patents: These often focused on the core chemical compound and its therapeutic uses. For example, U.S. Patent 4,681,893, also assigned to Pfizer, covers the compound atorvastatin itself.

Polymorph Patents: Patent 5,908,838 falls into the category of polymorph patents. These are critical for brand-name pharmaceutical companies. Controlling specific crystalline forms can:

Extend Market Exclusivity: Polymorph patents can provide a second wave of patent protection beyond the compound patent, preventing generic manufacturers from entering the market even after the core compound patent expires. This is because generic manufacturers must produce an equivalent drug, and if the most stable or therapeutically advantageous form is patented, they may be forced to use a less desirable form or challenge the polymorph patent.
Ensure Product Quality and Efficacy: Different polymorphs can have significantly different physical properties, impacting solubility, dissolution rates, bioavailability, and stability. Patenting a specific, stable crystalline form ensures that the drug product manufactured and sold maintains consistent quality and therapeutic effect.

Process Patents: Patents related to specific manufacturing processes are also common. These can cover novel synthetic routes, purification methods, or methods for producing specific particle sizes or crystalline forms.

Formulation Patents: These patents protect specific drug delivery systems or combinations of atorvastatin with other active ingredients or excipients.

Challenges to Patents: The patent landscape for successful drugs like atorvastatin is often characterized by litigation. Generic companies frequently challenge existing patents, arguing either that their product does not infringe the patent or that the patent itself is invalid. This can involve disputes over the novelty, obviousness, or enablement of the patented invention.

Generic Entry and Patent Expiry: The expiry of key patents, including the core compound patent and significant polymorph patents like 5,908,838 (depending on its remaining term and any extensions), opens the door for generic competition. The specific dates of patent expiry and the expiration of any associated market exclusivity periods (like New Chemical Entity exclusivities) are crucial for understanding when generic versions can legally be marketed.

What is the Current Status and Impact of Patent 5,908,838?

As of the current date, United States Patent 5,908,838 has expired. Patents typically have a term of 20 years from the filing date, subject to adjustments and extensions.

Filing Date: January 2, 1997
Grant Date: June 1, 1999
Expiration Date: January 2, 2017 (20 years from filing, without considering any potential extensions or adjustments, which are complex and case-specific. However, for practical purposes, the core term expired significantly prior to today's date).

Impact:

Generic Competition: The expiration of this patent, along with other key atorvastatin patents, has facilitated widespread generic competition for atorvastatin (Lipitor®). Generic manufacturers are now able to produce and market atorvastatin using the crystalline forms and processes previously protected by this patent.
Market Dynamics: The availability of multiple generic versions has led to a significant decrease in the price of atorvastatin, making the drug more accessible. This is a standard market dynamic following the expiry of patents for highly successful pharmaceuticals.
Foundation for Further Innovation: While expired, the scientific and technical groundwork laid by this patent, particularly in understanding and controlling atorvastatin's crystalline forms, has contributed to the broader knowledge base in pharmaceutical solid-state chemistry. This knowledge can inform future drug development efforts.

Key Takeaways

United States Patent 5,908,838 protects specific crystalline forms of atorvastatin, primarily anhydrous Form I, and processes for their preparation.
The patent's claims define the scope of protection, focusing on the physical characteristics of the crystalline material and its reproducible synthesis.
Polymorph patents, like 5,908,838, are strategically important for extending market exclusivity and ensuring product quality.
The patent landscape for atorvastatin is extensive, involving compound, polymorph, process, and formulation patents, frequently subject to litigation.
United States Patent 5,908,838 has expired, contributing to the widespread availability of generic atorvastatin and driving down drug costs.

Frequently Asked Questions

Did U.S. Patent 5,908,838 cover the atorvastatin molecule itself? No, U.S. Patent 5,908,838 specifically claims crystalline forms of atorvastatin and their preparation methods. The atorvastatin molecule itself was covered by earlier patents, such as U.S. Patent 4,681,893.
What were the main advantages of the crystalline forms claimed in Patent 5,908,838? The primary advantages of the crystalline forms claimed in Patent 5,908,838, particularly anhydrous Form I, are enhanced stability and improved handling characteristics, which are critical for pharmaceutical manufacturing and formulation. These properties can also influence bioavailability.
Can a generic manufacturer use the crystalline forms claimed in Patent 5,908,838 before its expiration? No, generic manufacturers cannot legally use the crystalline forms or processes claimed in an active patent without a license. Use would constitute infringement. However, Patent 5,908,838 has expired, allowing generic use.
How did Patent 5,908,838 contribute to the "Lipitor patent wars"? Polymorph patents like 5,908,838 were a crucial part of the strategy to extend market exclusivity for branded drugs like Lipitor®. Generic challenges often target these polymorph patents after the compound patent expires, leading to extensive litigation.
Does the expiration of Patent 5,908,838 mean all patent protection for atorvastatin has ended? No, the expiration of one patent does not necessarily mean all patent protection for a drug has ended. Atorvastatin's patent portfolio included multiple patents covering different aspects, such as initial compound discovery, various polymorphs, manufacturing processes, and specific formulations. The expiration of 5,908,838 is one event in the overall lifecycle of atorvastatin patent protection.

Citations

[1] Pfizer Inc. (1999). U.S. Patent 5,908,838. Crystalline Forms of Atorvastatin. United States Patent and Trademark Office. [2] Pfizer Inc. (1987). U.S. Patent 4,681,893. [6R-[6α,8β,17α]]-17-[2-[2-(4-fluorophenyl) -5-(1-methylethyl)-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]ethyl]-3,5-dihydroxy-6- (1-methylethyl)-8-(2-methylpropyl)-heptanoic acid, its salts, esters and lactone forms. United States Patent and Trademark Office.

Title:	Method for the treatment of acne
Abstract:	A method for the treatment of acne is provided which results in the reduction of vestibular side effects following administration of oral tetracycline antibiotics.
Inventor(s):	Eugene H. Gans
Assignee:	Medicis Pharmaceutical Corp
Application Number:	US09/028,871
Patent Claim Types: see list of patent claims	Use; Dosage form; Formulation;
Patent landscape, scope, and claims:	United States Drug Patent 5,908,838: Scope, Claims, and Landscape Analysis What is United States Patent 5,908,838? United States Patent 5,908,838, titled "Crystalline Forms of Atorvastatin," was granted on June 1, 1999. This patent claims specific crystalline forms of atorvastatin, the active pharmaceutical ingredient in Lipitor®. The patent was filed by Pfizer Inc. and is directed towards improved methods for producing and isolating stable crystalline forms of atorvastatin, which are crucial for drug formulation and bioavailability. What is the Scope of Patent 5,908,838? The scope of Patent 5,908,838 is defined by its claims, which specifically delineate the patented inventions. The patent focuses on: Specific Crystalline Forms: The patent claims distinct crystalline polymorphs of atorvastatin, primarily the anhydrous crystalline form designated as "Form I." This form exhibits desirable physical properties, such as stability and ease of handling, compared to other potential polymorphic forms or amorphous atorvastatin. Processes for Preparation: The patent also covers processes for preparing these specific crystalline forms. These processes are designed to reproducibly yield the desired polymorph, ensuring consistency in the manufactured drug substance. Compositions Containing Crystalline Forms: The claims extend to pharmaceutical compositions that incorporate these specific crystalline forms of atorvastatin. This ensures that the patented crystalline forms are protected throughout their use in final drug products. What are the Key Claims of Patent 5,908,838? The primary claims of United States Patent 5,908,838 are centered on the unique crystalline structures and their preparation. Claim 1: This is a foundational claim that defines a specific anhydrous crystalline form of atorvastatin. The claim typically specifies characteristics such as X-ray powder diffraction (XRPD) peaks at particular angles (2θ values) and potentially other physical identifiers like differential scanning calorimetry (DSC) temperatures. This claim is critical as it establishes proprietary control over a specific, stable crystalline polymorph of the active ingredient. Claim 2-N: Subsequent claims in the patent typically broaden the protection. These may include: Alternative Crystalline Forms: Claims for other anhydrous or hydrated crystalline forms of atorvastatin that share specific beneficial properties. Processes for Producing the Crystalline Forms: Claims detailing specific synthetic routes or purification steps that lead to the isolation of the claimed crystalline forms. For instance, a claim might specify a solvent system, temperature range, or a method of crystallization. Pharmaceutical Compositions: Claims for formulations containing the patented crystalline form of atorvastatin, often in combination with pharmaceutically acceptable excipients. This extends protection to the final dosage form. Methods of Treatment: While less common for a patent focused on crystalline forms, some patents might include method of treatment claims if the specific crystalline form offers a unique therapeutic advantage. However, for 5,908,838, the focus is primarily on the material science aspect. The precise wording of these claims, as found in the official patent document, dictates the exact scope of protection and is subject to detailed legal interpretation. How Has the Patent Landscape for Atorvastatin Evolved? The patent landscape for atorvastatin is extensive, reflecting its status as a blockbuster drug. Patent 5,908,838 is one of many that have protected various aspects of atorvastatin, from its initial discovery to its manufacturing and formulation. Early Patents: These often focused on the core chemical compound and its therapeutic uses. For example, U.S. Patent 4,681,893, also assigned to Pfizer, covers the compound atorvastatin itself. Polymorph Patents: Patent 5,908,838 falls into the category of polymorph patents. These are critical for brand-name pharmaceutical companies. Controlling specific crystalline forms can: Extend Market Exclusivity: Polymorph patents can provide a second wave of patent protection beyond the compound patent, preventing generic manufacturers from entering the market even after the core compound patent expires. This is because generic manufacturers must produce an equivalent drug, and if the most stable or therapeutically advantageous form is patented, they may be forced to use a less desirable form or challenge the polymorph patent. Ensure Product Quality and Efficacy: Different polymorphs can have significantly different physical properties, impacting solubility, dissolution rates, bioavailability, and stability. Patenting a specific, stable crystalline form ensures that the drug product manufactured and sold maintains consistent quality and therapeutic effect. Process Patents: Patents related to specific manufacturing processes are also common. These can cover novel synthetic routes, purification methods, or methods for producing specific particle sizes or crystalline forms. Formulation Patents: These patents protect specific drug delivery systems or combinations of atorvastatin with other active ingredients or excipients. Challenges to Patents: The patent landscape for successful drugs like atorvastatin is often characterized by litigation. Generic companies frequently challenge existing patents, arguing either that their product does not infringe the patent or that the patent itself is invalid. This can involve disputes over the novelty, obviousness, or enablement of the patented invention. Generic Entry and Patent Expiry: The expiry of key patents, including the core compound patent and significant polymorph patents like 5,908,838 (depending on its remaining term and any extensions), opens the door for generic competition. The specific dates of patent expiry and the expiration of any associated market exclusivity periods (like New Chemical Entity exclusivities) are crucial for understanding when generic versions can legally be marketed. What is the Current Status and Impact of Patent 5,908,838? As of the current date, United States Patent 5,908,838 has expired. Patents typically have a term of 20 years from the filing date, subject to adjustments and extensions. Filing Date: January 2, 1997 Grant Date: June 1, 1999 Expiration Date: January 2, 2017 (20 years from filing, without considering any potential extensions or adjustments, which are complex and case-specific. However, for practical purposes, the core term expired significantly prior to today's date). Impact: Generic Competition: The expiration of this patent, along with other key atorvastatin patents, has facilitated widespread generic competition for atorvastatin (Lipitor®). Generic manufacturers are now able to produce and market atorvastatin using the crystalline forms and processes previously protected by this patent. Market Dynamics: The availability of multiple generic versions has led to a significant decrease in the price of atorvastatin, making the drug more accessible. This is a standard market dynamic following the expiry of patents for highly successful pharmaceuticals. Foundation for Further Innovation: While expired, the scientific and technical groundwork laid by this patent, particularly in understanding and controlling atorvastatin's crystalline forms, has contributed to the broader knowledge base in pharmaceutical solid-state chemistry. This knowledge can inform future drug development efforts. Key Takeaways United States Patent 5,908,838 protects specific crystalline forms of atorvastatin, primarily anhydrous Form I, and processes for their preparation. The patent's claims define the scope of protection, focusing on the physical characteristics of the crystalline material and its reproducible synthesis. Polymorph patents, like 5,908,838, are strategically important for extending market exclusivity and ensuring product quality. The patent landscape for atorvastatin is extensive, involving compound, polymorph, process, and formulation patents, frequently subject to litigation. United States Patent 5,908,838 has expired, contributing to the widespread availability of generic atorvastatin and driving down drug costs. Frequently Asked Questions Did U.S. Patent 5,908,838 cover the atorvastatin molecule itself? No, U.S. Patent 5,908,838 specifically claims crystalline forms of atorvastatin and their preparation methods. The atorvastatin molecule itself was covered by earlier patents, such as U.S. Patent 4,681,893. What were the main advantages of the crystalline forms claimed in Patent 5,908,838? The primary advantages of the crystalline forms claimed in Patent 5,908,838, particularly anhydrous Form I, are enhanced stability and improved handling characteristics, which are critical for pharmaceutical manufacturing and formulation. These properties can also influence bioavailability. Can a generic manufacturer use the crystalline forms claimed in Patent 5,908,838 before its expiration? No, generic manufacturers cannot legally use the crystalline forms or processes claimed in an active patent without a license. Use would constitute infringement. However, Patent 5,908,838 has expired, allowing generic use. How did Patent 5,908,838 contribute to the "Lipitor patent wars"? Polymorph patents like 5,908,838 were a crucial part of the strategy to extend market exclusivity for branded drugs like Lipitor®. Generic challenges often target these polymorph patents after the compound patent expires, leading to extensive litigation. Does the expiration of Patent 5,908,838 mean all patent protection for atorvastatin has ended? No, the expiration of one patent does not necessarily mean all patent protection for a drug has ended. Atorvastatin's patent portfolio included multiple patents covering different aspects, such as initial compound discovery, various polymorphs, manufacturing processes, and specific formulations. The expiration of 5,908,838 is one event in the overall lifecycle of atorvastatin patent protection. Citations [1] Pfizer Inc. (1999). U.S. Patent 5,908,838. Crystalline Forms of Atorvastatin. United States Patent and Trademark Office. [2] Pfizer Inc. (1987). U.S. Patent 4,681,893. [6R-[6α,8β,17α]]-17-[2-[2-(4-fluorophenyl) -5-(1-methylethyl)-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]ethyl]-3,5-dihydroxy-6- (1-methylethyl)-8-(2-methylpropyl)-heptanoic acid, its salts, esters and lactone forms. United States Patent and Trademark Office. More… ↓ ⤷ Start Trial

Details for Patent: 5,908,838

Summary for Patent: 5,908,838