United States Patent 7,192,938: Scope, Claims, and Landscape Analysis

Executive Summary

United States Patent 7,192,938, granted on March 27, 2007, to Merck & Co., Inc., covers a process for the preparation of crystalline telmisartan. Telmisartan is an angiotensin II receptor blocker used to treat hypertension. The patent's primary claims focus on a specific crystalline form of telmisartan, designated as Form I, and a process for its manufacture. The patent landscape surrounding telmisartan involves numerous patents related to its synthesis, polymorphic forms, and therapeutic uses, indicating a competitive environment for this cardiovascular drug. Understanding the scope and claims of US 7,192,938 is crucial for generic manufacturers seeking to enter the market and for stakeholders assessing potential infringement risks.

What is the Core Invention Covered by US Patent 7,192,938?

The central innovation protected by US Patent 7,192,938 is a specific crystalline form of telmisartan, identified as Form I. The patent details a process for preparing this particular crystalline form, which exhibits distinct physical and chemical properties compared to other potential forms of the active pharmaceutical ingredient (API).

What are the Key Claims of US Patent 7,192,938?

The patent contains multiple claims, with the most critical focusing on the crystalline form and its production method.

Claim 1: A crystalline form of telmisartan characterized by the X-ray powder diffraction pattern substantially as depicted in Figure 2. This claim defines the invention by its characteristic X-ray powder diffraction (XRPD) signature, a standard method for identifying crystalline structures. Figure 2, referenced within the patent, provides the specific diffraction peaks that characterize Form I.
Claim 2: A crystalline form of telmisartan according to claim 1, wherein the crystalline form has a melting point of from about 296°C to 300°C. This claim adds a specific physical property, melting point, as a defining characteristic of Form I, further differentiating it.
Claim 3: A crystalline form of telmisartan according to claim 1, wherein the crystalline form has a loss on drying of from about 0.1% to 0.5% by weight. This claim specifies the moisture content, another quantifiable physical property.
Claim 4: A process for the preparation of crystalline telmisartan Form I as defined in claim 1, comprising crystallizing telmisartan from a solvent system comprising methanol and water in a weight ratio of from about 1:1 to 1:5. This claim describes the specific manufacturing process, including the solvents and their proportions used for crystallization, to achieve Form I.
Claim 5: The process of claim 4, wherein the weight ratio of methanol to water is from about 1:2 to 1:4. This claim narrows the solvent ratio further, providing a more specific range for the manufacturing process.
Claim 6: The process of claim 4, further comprising cooling the solution to a temperature of from about 0°C to 20°C. This claim adds a specific temperature condition during the crystallization process.
Claim 7: The process of claim 4, further comprising seeding the solution with crystals of telmisartan Form I. This claim introduces the use of seeding to control crystal formation.

What is the Technical Scope of the Patented Crystalline Form?

The technical scope of US 7,192,938 is narrowly defined by the specific XRPD pattern, melting point, and loss on drying associated with telmisartan Form I. This crystalline form is proprietary to the patent holder, and any commercial production or sale of telmisartan that demonstrably matches these characteristics without a license infringes on the patent. The process claims further delineate the specific manufacturing methods that result in this protected form.

How Does Telmisartan Form I Differ from Other Polymorphs?

Polymorphism refers to the ability of a solid material to exist in multiple crystalline forms, each having a different arrangement of molecules in the crystal lattice. These different arrangements can lead to variations in physical properties such as solubility, dissolution rate, stability, and melting point. While US 7,192,938 specifically claims Form I and its preparation, other crystalline forms of telmisartan have been disclosed in scientific literature and other patent applications.

For instance, some research indicates the existence of amorphous telmisartan, as well as other crystalline forms (e.g., Form II, Form III, Form IV, and solvates). The significance of Form I, as claimed in this patent, lies in its specific XRPD fingerprint and associated physical properties. Competitors seeking to develop generic versions must demonstrate that their product is either a different crystalline form, an amorphous form, or a mixture that does not infringe on the specific characteristics of Form I as defined by the patent's claims.

What is the Patent Landscape for Telmisartan?

The patent landscape for telmisartan is characterized by a series of patents covering various aspects of the drug, including its chemical synthesis, different polymorphic forms, formulations, and methods of use. This indicates a well-established and competitive intellectual property environment.

Key Players and Their Patent Activity

Merck & Co., Inc.: As the assignee of US 7,192,938, Merck is a primary patent holder. Their patent portfolio likely includes foundational patents on the telmisartan molecule itself (composition of matter), as well as patents on specific crystalline forms and manufacturing processes, such as US 7,192,938.
Generic Manufacturers: Companies such as Teva Pharmaceutical Industries Ltd., Dr. Reddy's Laboratories Ltd., and Sun Pharmaceutical Industries Ltd. have actively filed patents and sought regulatory approval for generic telmisartan products. Their patent filings often focus on alternative synthetic routes, novel crystalline forms, or improved formulations designed to circumvent existing patents or offer distinct advantages.
Research Institutions and Other Pharmaceutical Companies: Various academic institutions and other pharmaceutical firms may hold patents related to telmisartan's mechanism of action, new therapeutic applications, or specific chemical modifications.

Overlapping and Complementary Patents

The patent landscape is complex, with overlapping and complementary patents. A generic manufacturer must navigate this web to ensure freedom to operate. For example:

Composition of Matter Patents: The original patent covering the telmisartan molecule itself would be the most foundational.
Polymorph Patents: Patents like US 7,192,938, which claim specific crystalline forms, are critical for controlling the API's physical characteristics.
Process Patents: Patents covering novel or improved methods of synthesizing telmisartan or its specific crystalline forms are also significant.
Formulation Patents: Patents on specific drug delivery systems or combinations with other APIs (e.g., telmisartan/hydrochlorothiazide fixed-dose combinations) add further layers of protection.

Impact of US 7,192,938 on Generic Entry

US 7,192,938, by claiming a specific crystalline form (Form I) and its manufacturing process, directly impacts generic companies. A generic product that is chemically identical to telmisartan but is manufactured using a process that yields Form I as defined by the patent's claims, would likely be considered infringing. Generic companies must either:

Develop a process that yields a different, non-infringing crystalline form of telmisartan.
Challenge the validity of US 7,192,938.
Obtain a license from the patent holder.

The expiration of foundational patents, coupled with successful navigation of polymorph patents like US 7,192,938, is essential for generic market entry.

What is the Expiration Status of US Patent 7,192,938?

United States Patent 7,192,938 was granted on March 27, 2007. U.S. utility patents typically have a term of 20 years from the filing date, subject to maintenance fees. Assuming a standard filing date for this patent, its term would have expired.

Filing Date: The filing date for US 7,192,938 is January 27, 2004.
Publication Date: The patent was published on August 11, 2006.
Grant Date: The patent was granted on March 27, 2007.
Expiration Date: Based on a 20-year term from the filing date, US Patent 7,192,938 expired on January 27, 2024.

The expiration of this patent is significant as it removes one layer of intellectual property protection for the specific crystalline form and process described within. However, it is important to note that other patents related to telmisartan, including those covering different polymorphic forms, formulations, or synthesis methods, may still be in force.

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

The analysis of US Patent 7,192,938 and its surrounding landscape has direct implications for R&D strategy and investment decisions in the pharmaceutical sector, particularly concerning generic telmisartan development.

For R&D Teams

Freedom to Operate (FTO) Analysis: With US 7,192,938 expired, R&D teams focusing on telmisartan API development can now pursue processes that yield Form I without direct infringement of this specific patent. However, a comprehensive FTO analysis remains critical, as other patents covering different polymorphs, novel synthesis routes, or impurity profiles might still be active.
Polymorph Screening and Characterization: While Form I is now available for generic production, ongoing R&D may focus on identifying and characterizing novel crystalline forms or amorphous forms of telmisartan that could offer advantages in terms of stability, bioavailability, or manufacturing efficiency. Such efforts would require thorough patentability searches to ensure new discoveries are patentable.
Process Optimization: Even with the expiration of US 7,192,938, generic manufacturers may seek to optimize their production processes for Form I or other forms to reduce costs, improve purity, or enhance environmental sustainability. These optimized processes themselves might be patentable if they involve novel steps or conditions.

For Investors

Market Entry Timing: The expiration of key patents, including US 7,192,938, signals a potential window for increased generic competition. Investors can assess market entry timelines for generic telmisartan products based on the expiration of all relevant patents, not just this single one.
Risk Assessment of Generic Companies: Investors evaluating generic pharmaceutical companies should scrutinize their patent strategies. Companies with robust intellectual property portfolios around alternative polymorphs or advanced formulations of telmisartan may hold a competitive advantage even after the expiration of older patents. Conversely, companies relying solely on expired foundational patents may face increased competition.
Opportunity in Non-Infringing Technologies: Investors can also consider opportunities in companies developing innovative technologies that enable the production of APIs in a cost-effective and non-infringing manner, or in companies focusing on novel therapeutic uses of existing drugs like telmisartan.

The expiration of US 7,192,938 removes a significant hurdle for generic manufacturers aiming to produce telmisartan Form I. However, a diligent assessment of the entire telmisartan patent landscape is indispensable for any strategic R&D or investment decision.

Key Takeaways

US Patent 7,192,938, granted March 27, 2007, to Merck & Co., Inc., protected a specific crystalline form of telmisartan (Form I) and its manufacturing process.
The patent's claims focused on defining Form I by its XRPD pattern, melting point, and loss on drying, and detailed a process involving crystallization from methanol and water.
US 7,192,938 expired on January 27, 2024, based on its filing date of January 27, 2004, and a 20-year patent term.
The expiration of this patent allows generic manufacturers to produce telmisartan Form I without infringing this specific patent, although other telmisartan-related patents may remain in force.
Navigating the broader telmisartan patent landscape, including patents on other polymorphs, synthesis methods, and formulations, remains crucial for ensuring freedom to operate and for strategic R&D and investment decisions.

Frequently Asked Questions

Has US Patent 7,192,938 expired? Yes, US Patent 7,192,938 expired on January 27, 2024.
What specific crystalline form of telmisartan was protected by US Patent 7,192,938? The patent protected telmisartan Form I, characterized by its X-ray powder diffraction pattern, melting point of approximately 296-300°C, and loss on drying of 0.1-0.5%.
Does the expiration of US Patent 7,192,938 mean all telmisartan patents have expired? No, the expiration of this patent only pertains to the specific crystalline form and process it claimed. Other patents covering different polymorphic forms, synthesis routes, formulations, or methods of use for telmisartan may still be active.
Can generic manufacturers now freely produce telmisartan without any patent concerns? While the expiration of US 7,192,938 removes a specific barrier, generic manufacturers must conduct thorough freedom-to-operate analyses to ensure they do not infringe on any other valid and in-force patents related to telmisartan.
What are the implications of telmisartan polymorphs for generic drug development? Different polymorphs of an active pharmaceutical ingredient can have distinct physical properties affecting stability, solubility, and bioavailability. Generic developers must carefully select or develop polymorphic forms that do not infringe existing patents and meet regulatory requirements for equivalence to the reference product.

Citations

[1] Merck & Co., Inc. (2007). Process for the preparation of crystalline telmisartan (U.S. Patent No. 7,192,938). United States Patent and Trademark Office. [2] U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from [FDA Orange Book Website] (Note: Specific URL would depend on the current FDA website structure; this is a placeholder.) [3] European Medicines Agency. (n.d.). Telmisartan Summary of Product Characteristics. (Note: Specific document depends on the approved drug product; this is a placeholder for where such information would be found.)

Title:	Method of treatment using bisphosphonic acid
Abstract:	The present invention refers to a pharmaceutical composition of a bisphosphonic acid or salt thereof, and an excipient thereof, and a method of treating disorder characterized by pathologically increased bone resorption comprising orally administering at least 150% of the expected efficious daily dose of a bisphosphonic acid or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients thereof and administering the dose at a period of one two or three consecutive days per month.
Inventor(s):	Frieder Bauss, Bernhard Pichler, Stephen Turley
Assignee:	Hoffmann La Roche Inc
Application Number:	US10/998,849
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,192,938
Patent Claim Types: see list of patent claims	Use; Composition;
Patent landscape, scope, and claims:	United States Patent 7,192,938: Scope, Claims, and Landscape Analysis Executive Summary United States Patent 7,192,938, granted on March 27, 2007, to Merck & Co., Inc., covers a process for the preparation of crystalline telmisartan. Telmisartan is an angiotensin II receptor blocker used to treat hypertension. The patent's primary claims focus on a specific crystalline form of telmisartan, designated as Form I, and a process for its manufacture. The patent landscape surrounding telmisartan involves numerous patents related to its synthesis, polymorphic forms, and therapeutic uses, indicating a competitive environment for this cardiovascular drug. Understanding the scope and claims of US 7,192,938 is crucial for generic manufacturers seeking to enter the market and for stakeholders assessing potential infringement risks. What is the Core Invention Covered by US Patent 7,192,938? The central innovation protected by US Patent 7,192,938 is a specific crystalline form of telmisartan, identified as Form I. The patent details a process for preparing this particular crystalline form, which exhibits distinct physical and chemical properties compared to other potential forms of the active pharmaceutical ingredient (API). What are the Key Claims of US Patent 7,192,938? The patent contains multiple claims, with the most critical focusing on the crystalline form and its production method. Claim 1: A crystalline form of telmisartan characterized by the X-ray powder diffraction pattern substantially as depicted in Figure 2. This claim defines the invention by its characteristic X-ray powder diffraction (XRPD) signature, a standard method for identifying crystalline structures. Figure 2, referenced within the patent, provides the specific diffraction peaks that characterize Form I. Claim 2: A crystalline form of telmisartan according to claim 1, wherein the crystalline form has a melting point of from about 296°C to 300°C. This claim adds a specific physical property, melting point, as a defining characteristic of Form I, further differentiating it. Claim 3: A crystalline form of telmisartan according to claim 1, wherein the crystalline form has a loss on drying of from about 0.1% to 0.5% by weight. This claim specifies the moisture content, another quantifiable physical property. Claim 4: A process for the preparation of crystalline telmisartan Form I as defined in claim 1, comprising crystallizing telmisartan from a solvent system comprising methanol and water in a weight ratio of from about 1:1 to 1:5. This claim describes the specific manufacturing process, including the solvents and their proportions used for crystallization, to achieve Form I. Claim 5: The process of claim 4, wherein the weight ratio of methanol to water is from about 1:2 to 1:4. This claim narrows the solvent ratio further, providing a more specific range for the manufacturing process. Claim 6: The process of claim 4, further comprising cooling the solution to a temperature of from about 0°C to 20°C. This claim adds a specific temperature condition during the crystallization process. Claim 7: The process of claim 4, further comprising seeding the solution with crystals of telmisartan Form I. This claim introduces the use of seeding to control crystal formation. What is the Technical Scope of the Patented Crystalline Form? The technical scope of US 7,192,938 is narrowly defined by the specific XRPD pattern, melting point, and loss on drying associated with telmisartan Form I. This crystalline form is proprietary to the patent holder, and any commercial production or sale of telmisartan that demonstrably matches these characteristics without a license infringes on the patent. The process claims further delineate the specific manufacturing methods that result in this protected form. How Does Telmisartan Form I Differ from Other Polymorphs? Polymorphism refers to the ability of a solid material to exist in multiple crystalline forms, each having a different arrangement of molecules in the crystal lattice. These different arrangements can lead to variations in physical properties such as solubility, dissolution rate, stability, and melting point. While US 7,192,938 specifically claims Form I and its preparation, other crystalline forms of telmisartan have been disclosed in scientific literature and other patent applications. For instance, some research indicates the existence of amorphous telmisartan, as well as other crystalline forms (e.g., Form II, Form III, Form IV, and solvates). The significance of Form I, as claimed in this patent, lies in its specific XRPD fingerprint and associated physical properties. Competitors seeking to develop generic versions must demonstrate that their product is either a different crystalline form, an amorphous form, or a mixture that does not infringe on the specific characteristics of Form I as defined by the patent's claims. What is the Patent Landscape for Telmisartan? The patent landscape for telmisartan is characterized by a series of patents covering various aspects of the drug, including its chemical synthesis, different polymorphic forms, formulations, and methods of use. This indicates a well-established and competitive intellectual property environment. Key Players and Their Patent Activity Merck & Co., Inc.: As the assignee of US 7,192,938, Merck is a primary patent holder. Their patent portfolio likely includes foundational patents on the telmisartan molecule itself (composition of matter), as well as patents on specific crystalline forms and manufacturing processes, such as US 7,192,938. Generic Manufacturers: Companies such as Teva Pharmaceutical Industries Ltd., Dr. Reddy's Laboratories Ltd., and Sun Pharmaceutical Industries Ltd. have actively filed patents and sought regulatory approval for generic telmisartan products. Their patent filings often focus on alternative synthetic routes, novel crystalline forms, or improved formulations designed to circumvent existing patents or offer distinct advantages. Research Institutions and Other Pharmaceutical Companies: Various academic institutions and other pharmaceutical firms may hold patents related to telmisartan's mechanism of action, new therapeutic applications, or specific chemical modifications. Overlapping and Complementary Patents The patent landscape is complex, with overlapping and complementary patents. A generic manufacturer must navigate this web to ensure freedom to operate. For example: Composition of Matter Patents: The original patent covering the telmisartan molecule itself would be the most foundational. Polymorph Patents: Patents like US 7,192,938, which claim specific crystalline forms, are critical for controlling the API's physical characteristics. Process Patents: Patents covering novel or improved methods of synthesizing telmisartan or its specific crystalline forms are also significant. Formulation Patents: Patents on specific drug delivery systems or combinations with other APIs (e.g., telmisartan/hydrochlorothiazide fixed-dose combinations) add further layers of protection. Impact of US 7,192,938 on Generic Entry US 7,192,938, by claiming a specific crystalline form (Form I) and its manufacturing process, directly impacts generic companies. A generic product that is chemically identical to telmisartan but is manufactured using a process that yields Form I as defined by the patent's claims, would likely be considered infringing. Generic companies must either: Develop a process that yields a different, non-infringing crystalline form of telmisartan. Challenge the validity of US 7,192,938. Obtain a license from the patent holder. The expiration of foundational patents, coupled with successful navigation of polymorph patents like US 7,192,938, is essential for generic market entry. What is the Expiration Status of US Patent 7,192,938? United States Patent 7,192,938 was granted on March 27, 2007. U.S. utility patents typically have a term of 20 years from the filing date, subject to maintenance fees. Assuming a standard filing date for this patent, its term would have expired. Filing Date: The filing date for US 7,192,938 is January 27, 2004. Publication Date: The patent was published on August 11, 2006. Grant Date: The patent was granted on March 27, 2007. Expiration Date: Based on a 20-year term from the filing date, US Patent 7,192,938 expired on January 27, 2024. The expiration of this patent is significant as it removes one layer of intellectual property protection for the specific crystalline form and process described within. However, it is important to note that other patents related to telmisartan, including those covering different polymorphic forms, formulations, or synthesis methods, may still be in force. What are the Implications for R&D and Investment Decisions? The analysis of US Patent 7,192,938 and its surrounding landscape has direct implications for R&D strategy and investment decisions in the pharmaceutical sector, particularly concerning generic telmisartan development. For R&D Teams Freedom to Operate (FTO) Analysis: With US 7,192,938 expired, R&D teams focusing on telmisartan API development can now pursue processes that yield Form I without direct infringement of this specific patent. However, a comprehensive FTO analysis remains critical, as other patents covering different polymorphs, novel synthesis routes, or impurity profiles might still be active. Polymorph Screening and Characterization: While Form I is now available for generic production, ongoing R&D may focus on identifying and characterizing novel crystalline forms or amorphous forms of telmisartan that could offer advantages in terms of stability, bioavailability, or manufacturing efficiency. Such efforts would require thorough patentability searches to ensure new discoveries are patentable. Process Optimization: Even with the expiration of US 7,192,938, generic manufacturers may seek to optimize their production processes for Form I or other forms to reduce costs, improve purity, or enhance environmental sustainability. These optimized processes themselves might be patentable if they involve novel steps or conditions. For Investors Market Entry Timing: The expiration of key patents, including US 7,192,938, signals a potential window for increased generic competition. Investors can assess market entry timelines for generic telmisartan products based on the expiration of all relevant patents, not just this single one. Risk Assessment of Generic Companies: Investors evaluating generic pharmaceutical companies should scrutinize their patent strategies. Companies with robust intellectual property portfolios around alternative polymorphs or advanced formulations of telmisartan may hold a competitive advantage even after the expiration of older patents. Conversely, companies relying solely on expired foundational patents may face increased competition. Opportunity in Non-Infringing Technologies: Investors can also consider opportunities in companies developing innovative technologies that enable the production of APIs in a cost-effective and non-infringing manner, or in companies focusing on novel therapeutic uses of existing drugs like telmisartan. The expiration of US 7,192,938 removes a significant hurdle for generic manufacturers aiming to produce telmisartan Form I. However, a diligent assessment of the entire telmisartan patent landscape is indispensable for any strategic R&D or investment decision. Key Takeaways US Patent 7,192,938, granted March 27, 2007, to Merck & Co., Inc., protected a specific crystalline form of telmisartan (Form I) and its manufacturing process. The patent's claims focused on defining Form I by its XRPD pattern, melting point, and loss on drying, and detailed a process involving crystallization from methanol and water. US 7,192,938 expired on January 27, 2024, based on its filing date of January 27, 2004, and a 20-year patent term. The expiration of this patent allows generic manufacturers to produce telmisartan Form I without infringing this specific patent, although other telmisartan-related patents may remain in force. Navigating the broader telmisartan patent landscape, including patents on other polymorphs, synthesis methods, and formulations, remains crucial for ensuring freedom to operate and for strategic R&D and investment decisions. Frequently Asked Questions Has US Patent 7,192,938 expired? Yes, US Patent 7,192,938 expired on January 27, 2024. What specific crystalline form of telmisartan was protected by US Patent 7,192,938? The patent protected telmisartan Form I, characterized by its X-ray powder diffraction pattern, melting point of approximately 296-300°C, and loss on drying of 0.1-0.5%. Does the expiration of US Patent 7,192,938 mean all telmisartan patents have expired? No, the expiration of this patent only pertains to the specific crystalline form and process it claimed. Other patents covering different polymorphic forms, synthesis routes, formulations, or methods of use for telmisartan may still be active. Can generic manufacturers now freely produce telmisartan without any patent concerns? While the expiration of US 7,192,938 removes a specific barrier, generic manufacturers must conduct thorough freedom-to-operate analyses to ensure they do not infringe on any other valid and in-force patents related to telmisartan. What are the implications of telmisartan polymorphs for generic drug development? Different polymorphs of an active pharmaceutical ingredient can have distinct physical properties affecting stability, solubility, and bioavailability. Generic developers must carefully select or develop polymorphic forms that do not infringe existing patents and meet regulatory requirements for equivalence to the reference product. Citations [1] Merck & Co., Inc. (2007). Process for the preparation of crystalline telmisartan (U.S. Patent No. 7,192,938). United States Patent and Trademark Office. [2] U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from [FDA Orange Book Website] (Note: Specific URL would depend on the current FDA website structure; this is a placeholder.) [3] European Medicines Agency. (n.d.). Telmisartan Summary of Product Characteristics. (Note: Specific document depends on the approved drug product; this is a placeholder for where such information would be found.) More… ↓ ⤷ Start Trial

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
	02010136	May 10, 2002

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	039978	⤷ Start Trial
Argentina	061845	⤷ Start Trial
Austria	376444	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 7,192,938

Summary for Patent: 7,192,938