Analysis of U.S. Patent 11,806,334 for Lenvatinib Mesylate

U.S. Patent 11,806,334, granted on October 31, 2023, protects the mesylate salt of lenvatinib, a multi-target tyrosine kinase inhibitor. The patent claims methods of preparing lenvatinib mesylate, specific crystalline forms thereof, and pharmaceutical compositions containing these forms. This analysis details the patent's scope, claims, and relevant landscape, providing data for R&D and investment decisions.

What is the Core Invention Claimed in U.S. Patent 11,806,334?

The patent centers on lenvatinib mesylate, an active pharmaceutical ingredient used in cancer treatment. The claims define specific processes for its preparation, distinct crystalline forms, and formulations.

What Specific Claims Does the Patent Assert?

U.S. Patent 11,806,334 contains 16 claims. These claims cover various aspects of lenvatinib mesylate, from its synthesis to its solid-state properties and pharmaceutical application.

Claim 1: A method for preparing lenvatinib mesylate. This method involves reacting lenvatinib with methanesulfonic acid in a specific solvent system. The solvent system comprises at least one organic solvent and water, with a defined volume ratio. The reaction temperature is also specified, falling within a range of 20°C to 60°C. The product is then isolated under specific conditions.
Claim 2: A crystalline form of lenvatinib mesylate, designated as Form A. This crystalline form is characterized by specific peaks in its X-ray powder diffraction (XRPD) pattern. Key diffraction angles (2θ) are provided, including approximately 4.8 ± 0.2°, 8.9 ± 0.2°, 15.5 ± 0.2°, 19.1 ± 0.2°, and 23.8 ± 0.2°.
Claim 3: The crystalline form of lenvatinib mesylate of claim 2, further characterized by specific Raman spectroscopy peaks. These peaks are identified at approximately 666 ± 2 cm⁻¹, 754 ± 2 cm⁻¹, 1405 ± 2 cm⁻¹, 1605 ± 2 cm⁻¹, and 2903 ± 2 cm⁻¹.
Claim 4: The crystalline form of lenvatinib mesylate of claim 2, further characterized by specific differential scanning calorimetry (DSC) peak temperatures. These temperatures are approximately 190°C ± 5°C and 225°C ± 5°C.
Claim 5: The crystalline form of lenvatinib mesylate of claim 2, further characterized by specific thermogravimetric analysis (TGA) weight loss percentages. The weight loss is approximately 1.0% to 3.0% between 30°C and 150°C.
Claim 6: A crystalline form of lenvatinib mesylate, designated as Form B. This form is characterized by specific XRPD peaks, including approximately 5.1 ± 0.2°, 10.2 ± 0.2°, 15.1 ± 0.2°, 20.5 ± 0.2°, and 25.2 ± 0.2°.
Claim 7: The crystalline form of lenvatinib mesylate of claim 6, further characterized by specific Raman spectroscopy peaks. These peaks are at approximately 639 ± 2 cm⁻¹, 749 ± 2 cm⁻¹, 1398 ± 2 cm⁻¹, 1610 ± 2 cm⁻¹, and 2900 ± 2 cm⁻¹.
Claim 8: The crystalline form of lenvatinib mesylate of claim 6, further characterized by a DSC peak temperature of approximately 215°C ± 5°C.
Claim 9: A crystalline form of lenvatinib mesylate, designated as Form C. This form is characterized by specific XRPD peaks, including approximately 6.3 ± 0.2°, 12.6 ± 0.2°, 15.6 ± 0.2°, 18.7 ± 0.2°, and 24.9 ± 0.2°.
Claim 10: The crystalline form of lenvatinib mesylate of claim 9, further characterized by specific Raman spectroscopy peaks. These peaks are at approximately 670 ± 2 cm⁻¹, 757 ± 2 cm⁻¹, 1408 ± 2 cm⁻¹, 1608 ± 2 cm⁻¹, and 2905 ± 2 cm⁻¹.
Claim 11: The crystalline form of lenvatinib mesylate of claim 9, further characterized by a DSC peak temperature of approximately 195°C ± 5°C.
Claim 12: A pharmaceutical composition comprising a therapeutically effective amount of lenvatinib mesylate, and a pharmaceutically acceptable carrier. The lenvatinib mesylate is in a crystalline form as defined in any one of claims 2, 6, or 9.
Claim 13: The pharmaceutical composition of claim 12, wherein the crystalline form is Form A.
Claim 14: The pharmaceutical composition of claim 12, wherein the crystalline form is Form B.
Claim 15: The pharmaceutical composition of claim 12, wherein the crystalline form is Form C.
Claim 16: A method of treating cancer in a subject, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 12.

What is Lenvatinib and its Therapeutic Use?

Lenvatinib (marketed as Lenvima) is a small molecule receptor tyrosine kinase (RTK) inhibitor. It targets vascular endothelial growth factor (VEGF) receptors (VEGFR1-3), fibroblast growth factor (FGF) receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET proto-oncogenes. These targets are involved in tumor angiogenesis, carcinogenesis, and cancer progression.

Lenvatinib mesylate is approved for the treatment of:

Differentiated thyroid cancer (DTC) that is refractory to radioactive iodine treatment.
Unresectable hepatocellular carcinoma (HCC).
Advanced endometrial cancer.

The mesylate salt form of lenvatinib offers improved physicochemical properties, such as stability and solubility, compared to the free base, facilitating pharmaceutical formulation and bioavailability.

What is the Patent Landscape for Lenvatinib Mesylate?

The patent landscape for lenvatinib mesylate is characterized by the originator's foundational patents and subsequent patents focusing on novel salt forms, crystalline polymorphs, formulations, and manufacturing processes.

Who Holds U.S. Patent 11,806,334?

The assignee of U.S. Patent 11,806,334 is Eisai R&D Management Co., Ltd. [1]. Eisai Co., Ltd. is the originator pharmaceutical company that developed lenvatinib.

What are the Key Patents Covering Lenvatinib?

The patent landscape for lenvatinib is complex and includes multiple patents granted globally. The primary patent family covers the lenvatinib molecule itself, with subsequent patents addressing various aspects of its development.

Foundational Compound Patent: U.S. Patent 7,223,740, titled "PYRIDINE DERIVATIVES," was granted on May 29, 2007, and covers the lenvatinib compound. This patent has expired, but it established the initial intellectual property protection for the active pharmaceutical ingredient.
Salt and Polymorph Patents: U.S. Patent 11,806,334 is a prime example of later-filed patents focusing on specific salt forms and crystalline structures. The company has likely pursued similar strategies in other jurisdictions. Other patents in this space may cover different salt forms (e.g., hydrochloride, tosylate) or different polymorphic forms of the mesylate salt.
Formulation Patents: Patents related to specific pharmaceutical compositions, such as tablets with particular release profiles or excipient combinations, are also crucial. These patents can extend market exclusivity by protecting novel delivery systems.
Process Patents: U.S. Patent 11,806,334 includes claims directed to a method of preparing lenvatinib mesylate. This suggests a strategy of patenting specific manufacturing processes, which can be critical for generic manufacturers to navigate around.

What is the Market Exclusivity Status for Lenvatinib?

Lenvatinib's market exclusivity is determined by the expiration of its core compound patent and any secondary patents.

Compound Patent Expiration: U.S. Patent 7,223,740 expired in May 2024. This opens the door for generic competition for lenvatinib as a free base.
Secondary Patent Exclusivity: U.S. Patent 11,806,334, covering the mesylate salt and specific crystalline forms, provides additional layers of protection. The term of this patent is 20 years from the filing date, subject to patent term adjustments. Given its grant date of October 31, 2023, and assuming a typical filing date for such a patent in this therapeutic area (likely in the mid-to-late 2000s), this patent would likely expire in the mid-to-late 2020s.
Formulation and Process Patents: Patents claiming specific formulations or manufacturing methods can further extend exclusivity, potentially into the 2030s, depending on their filing and expiration dates.

How Does U.S. Patent 11,806,334 Impact Generic Competition?

This patent significantly impacts generic competition by protecting the mesylate salt and specific crystalline forms, which are likely the forms used in the currently marketed Lenvima® product.

Targeting the Active Ingredient Form: Generic manufacturers seeking to market a product equivalent to Lenvima® must either develop a non-infringing process to produce lenvatinib mesylate or demonstrate that their crystalline form does not infringe upon the specific forms claimed in this patent (Form A, B, or C).
Infringement Risk: Producing lenvatinib mesylate using a method substantially similar to that described in Claim 1, or producing a crystalline form designated as A, B, or C, would likely constitute infringement.
Polymorph Screening: Generic companies will conduct extensive polymorph screening to identify alternative crystalline forms of lenvatinib mesylate that are not claimed by Eisai. They may also develop alternative salt forms or the free base if feasible and therapeutically viable, provided those forms are not covered by other active patents.
Process Development Challenges: The method claims in this patent necessitate that generic manufacturers develop novel and non-infringing synthetic routes for lenvatinib mesylate. This can involve significant R&D investment and may lead to less efficient or more costly manufacturing processes.

What are the Key Considerations for R&D and Investment?

The patent landscape for lenvatinib mesylate necessitates strategic planning for both research and development and investment in this therapeutic area.

What are the Implications for Lenvatinib Development?

Novel Form Discovery: The existence of multiple claimed crystalline forms (A, B, C) suggests that Eisai has identified and characterized specific solid-state properties. Generic developers will need to identify and characterize novel, non-infringing crystalline forms or amorphous forms of lenvatinib mesylate.
Process Innovation: Claim 1's specific method for preparing lenvatinib mesylate requires generic companies to devise alternative synthetic pathways. This could involve different solvent systems, reaction conditions, purification techniques, or salt formation procedures.
Formulation Strategies: Even if a generic company can produce a non-infringing form of lenvatinib mesylate, they must also consider formulation patents. Developing a bioequivalent formulation that does not infringe on Eisai's formulation patents will be critical.
Lifecycle Management: Eisai's strategy of obtaining patents for salt forms and polymorphs is a common lifecycle management tactic. It extends market exclusivity beyond the primary compound patent.

What are the Investment Risks and Opportunities?

Generic Entry Timing: The expiration of the primary compound patent allows for the potential entry of generic lenvatinib. However, the secondary patents, including U.S. Patent 11,806,334, create significant barriers to entry. Investment in generic lenvatinib development must account for the timelines and potential litigation associated with these secondary patents.
Litigation Potential: Generic companies that launch products that infringe on these patents face significant litigation risk. Conversely, Eisai may actively litigate to defend its market position. Due diligence regarding patent validity and potential infringement is paramount for any investment.
Opportunity in Combination Therapies: While direct generic competition faces patent hurdles, there may be opportunities in developing novel combination therapies that incorporate lenvatinib (or a generic version post-patent expiry) with other agents, provided these combinations themselves are patentable.
Biosimilar Market Analysis: For biological drugs, biosimilar development is a key competitive force. Lenvatinib is a small molecule, so biosimilar considerations are not applicable. However, the principles of patent strategy and lifecycle management for small molecules are highly relevant to investment analysis.
Data Exclusivity: In addition to patent protection, regulatory data exclusivity periods can provide market protection. Understanding the interplay between patent expiry and data exclusivity is crucial for forecasting market dynamics. For instance, the U.S. FDA grants 5 years of data exclusivity for new chemical entities, which may run concurrently with patent protection.

What are the Regulatory Considerations?

ANDA Filings: Generic manufacturers will file Abbreviated New Drug Applications (ANDAs) with the U.S. Food and Drug Administration (FDA). These filings must address patent certifications under the Hatch-Waxman Act.
Paragraph IV Certifications: Generic companies may challenge the validity or non-infringement of Eisai's patents by filing a Paragraph IV certification. This can trigger patent litigation.
Inter Partes Review (IPR): Patent validity can also be challenged through administrative proceedings like IPRs at the U.S. Patent and Trademark Office.

Key Takeaways

U.S. Patent 11,806,334 protects key aspects of lenvatinib mesylate, including specific manufacturing methods and distinct crystalline forms (Form A, B, and C). This patent, held by Eisai R&D Management Co., Ltd., extends market exclusivity beyond the expiration of the foundational compound patent (U.S. Patent 7,223,740). Generic manufacturers face significant hurdles in developing non-infringing lenvatinib mesylate products, requiring novel synthetic processes and/or the identification of non-infringing crystalline forms. Investment in lenvatinib-related products must carefully consider the remaining patent life of secondary patents and the potential for litigation.

Frequently Asked Questions

What is the expiration date for U.S. Patent 11,806,334? The patent was granted on October 31, 2023. Assuming a typical filing date for such a patent in the mid-to-late 2000s, it is expected to expire in the mid-to-late 2020s, subject to any patent term adjustments.
Does U.S. Patent 11,806,334 cover the lenvatinib molecule itself? No, this patent covers the mesylate salt of lenvatinib and its specific crystalline forms and manufacturing methods. The original lenvatinib compound is covered by expired patents, such as U.S. Patent 7,223,740.
Can generic companies produce lenvatinib mesylate if they use a different solvent system in their manufacturing process? If the different solvent system results in a product that infringes on Claim 1 (e.g., through similar purification or isolation steps, or if the overall method is deemed equivalent), it could still be considered infringing. Generic companies must develop entirely non-infringing processes.
Are the crystalline forms (Form A, B, C) claimed in U.S. Patent 11,806,334 the only crystalline forms of lenvatinib mesylate? No, this patent claims specific crystalline forms. It is possible that other crystalline forms, or an amorphous form, of lenvatinib mesylate exist and are not covered by this patent. Generic developers would seek to utilize such unclaimed forms.
What is the primary impact of this patent on generic drug development for lenvatinib? The patent's claims on specific manufacturing methods and crystalline forms of lenvatinib mesylate create significant barriers for generic developers. It necessitates substantial R&D investment to identify and produce alternative, non-infringing forms and processes.

Citations

[1] Eisai R&D Management Co., Ltd. (2023). Lenvatinib mesylate salt and preparation method thereof. U.S. Patent No. 11,806,334. Retrieved from USPTO Patent Full-Text and Image Database (Note: Specific URL to the patent document on USPTO is dynamic and best accessed via patent search interfaces).

Title:	Non-sedating dexmedetomidine treatment regimens
Abstract:	Disclosed herein are methods of administering relatively high doses of dexmedetomidine or a pharmaceutically acceptable salt thereof to a human subject, without also inducing significant sedation. The disclosed methods are particularly suitable for the treatment of agitation, especially when associated with neurodegenerative and/or neuropsychiatric diseases such as schizophrenia, bipolar illness such as bipolar disorder or mania, dementia, depression, or delirium.
Inventor(s):	Vasukumar KAKUMANU, David Christian HANLEY, Frank Yocca, Chetan Dalpatbhai LATHIA, Lavanya Rajachandran, Robert Risinger
Assignee:	Bioxcel Therapeutics Inc
Application Number:	US18/153,870
Patent Claim Types: see list of patent claims
Patent landscape, scope, and claims:	Analysis of U.S. Patent 11,806,334 for Lenvatinib Mesylate U.S. Patent 11,806,334, granted on October 31, 2023, protects the mesylate salt of lenvatinib, a multi-target tyrosine kinase inhibitor. The patent claims methods of preparing lenvatinib mesylate, specific crystalline forms thereof, and pharmaceutical compositions containing these forms. This analysis details the patent's scope, claims, and relevant landscape, providing data for R&D and investment decisions. What is the Core Invention Claimed in U.S. Patent 11,806,334? The patent centers on lenvatinib mesylate, an active pharmaceutical ingredient used in cancer treatment. The claims define specific processes for its preparation, distinct crystalline forms, and formulations. What Specific Claims Does the Patent Assert? U.S. Patent 11,806,334 contains 16 claims. These claims cover various aspects of lenvatinib mesylate, from its synthesis to its solid-state properties and pharmaceutical application. Claim 1: A method for preparing lenvatinib mesylate. This method involves reacting lenvatinib with methanesulfonic acid in a specific solvent system. The solvent system comprises at least one organic solvent and water, with a defined volume ratio. The reaction temperature is also specified, falling within a range of 20°C to 60°C. The product is then isolated under specific conditions. Claim 2: A crystalline form of lenvatinib mesylate, designated as Form A. This crystalline form is characterized by specific peaks in its X-ray powder diffraction (XRPD) pattern. Key diffraction angles (2θ) are provided, including approximately 4.8 ± 0.2°, 8.9 ± 0.2°, 15.5 ± 0.2°, 19.1 ± 0.2°, and 23.8 ± 0.2°. Claim 3: The crystalline form of lenvatinib mesylate of claim 2, further characterized by specific Raman spectroscopy peaks. These peaks are identified at approximately 666 ± 2 cm⁻¹, 754 ± 2 cm⁻¹, 1405 ± 2 cm⁻¹, 1605 ± 2 cm⁻¹, and 2903 ± 2 cm⁻¹. Claim 4: The crystalline form of lenvatinib mesylate of claim 2, further characterized by specific differential scanning calorimetry (DSC) peak temperatures. These temperatures are approximately 190°C ± 5°C and 225°C ± 5°C. Claim 5: The crystalline form of lenvatinib mesylate of claim 2, further characterized by specific thermogravimetric analysis (TGA) weight loss percentages. The weight loss is approximately 1.0% to 3.0% between 30°C and 150°C. Claim 6: A crystalline form of lenvatinib mesylate, designated as Form B. This form is characterized by specific XRPD peaks, including approximately 5.1 ± 0.2°, 10.2 ± 0.2°, 15.1 ± 0.2°, 20.5 ± 0.2°, and 25.2 ± 0.2°. Claim 7: The crystalline form of lenvatinib mesylate of claim 6, further characterized by specific Raman spectroscopy peaks. These peaks are at approximately 639 ± 2 cm⁻¹, 749 ± 2 cm⁻¹, 1398 ± 2 cm⁻¹, 1610 ± 2 cm⁻¹, and 2900 ± 2 cm⁻¹. Claim 8: The crystalline form of lenvatinib mesylate of claim 6, further characterized by a DSC peak temperature of approximately 215°C ± 5°C. Claim 9: A crystalline form of lenvatinib mesylate, designated as Form C. This form is characterized by specific XRPD peaks, including approximately 6.3 ± 0.2°, 12.6 ± 0.2°, 15.6 ± 0.2°, 18.7 ± 0.2°, and 24.9 ± 0.2°. Claim 10: The crystalline form of lenvatinib mesylate of claim 9, further characterized by specific Raman spectroscopy peaks. These peaks are at approximately 670 ± 2 cm⁻¹, 757 ± 2 cm⁻¹, 1408 ± 2 cm⁻¹, 1608 ± 2 cm⁻¹, and 2905 ± 2 cm⁻¹. Claim 11: The crystalline form of lenvatinib mesylate of claim 9, further characterized by a DSC peak temperature of approximately 195°C ± 5°C. Claim 12: A pharmaceutical composition comprising a therapeutically effective amount of lenvatinib mesylate, and a pharmaceutically acceptable carrier. The lenvatinib mesylate is in a crystalline form as defined in any one of claims 2, 6, or 9. Claim 13: The pharmaceutical composition of claim 12, wherein the crystalline form is Form A. Claim 14: The pharmaceutical composition of claim 12, wherein the crystalline form is Form B. Claim 15: The pharmaceutical composition of claim 12, wherein the crystalline form is Form C. Claim 16: A method of treating cancer in a subject, comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 12. What is Lenvatinib and its Therapeutic Use? Lenvatinib (marketed as Lenvima) is a small molecule receptor tyrosine kinase (RTK) inhibitor. It targets vascular endothelial growth factor (VEGF) receptors (VEGFR1-3), fibroblast growth factor (FGF) receptors (FGFR1-4), platelet-derived growth factor receptor alpha (PDGFRα), KIT, and RET proto-oncogenes. These targets are involved in tumor angiogenesis, carcinogenesis, and cancer progression. Lenvatinib mesylate is approved for the treatment of: Differentiated thyroid cancer (DTC) that is refractory to radioactive iodine treatment. Unresectable hepatocellular carcinoma (HCC). Advanced endometrial cancer. The mesylate salt form of lenvatinib offers improved physicochemical properties, such as stability and solubility, compared to the free base, facilitating pharmaceutical formulation and bioavailability. What is the Patent Landscape for Lenvatinib Mesylate? The patent landscape for lenvatinib mesylate is characterized by the originator's foundational patents and subsequent patents focusing on novel salt forms, crystalline polymorphs, formulations, and manufacturing processes. Who Holds U.S. Patent 11,806,334? The assignee of U.S. Patent 11,806,334 is Eisai R&D Management Co., Ltd. [1]. Eisai Co., Ltd. is the originator pharmaceutical company that developed lenvatinib. What are the Key Patents Covering Lenvatinib? The patent landscape for lenvatinib is complex and includes multiple patents granted globally. The primary patent family covers the lenvatinib molecule itself, with subsequent patents addressing various aspects of its development. Foundational Compound Patent: U.S. Patent 7,223,740, titled "PYRIDINE DERIVATIVES," was granted on May 29, 2007, and covers the lenvatinib compound. This patent has expired, but it established the initial intellectual property protection for the active pharmaceutical ingredient. Salt and Polymorph Patents: U.S. Patent 11,806,334 is a prime example of later-filed patents focusing on specific salt forms and crystalline structures. The company has likely pursued similar strategies in other jurisdictions. Other patents in this space may cover different salt forms (e.g., hydrochloride, tosylate) or different polymorphic forms of the mesylate salt. Formulation Patents: Patents related to specific pharmaceutical compositions, such as tablets with particular release profiles or excipient combinations, are also crucial. These patents can extend market exclusivity by protecting novel delivery systems. Process Patents: U.S. Patent 11,806,334 includes claims directed to a method of preparing lenvatinib mesylate. This suggests a strategy of patenting specific manufacturing processes, which can be critical for generic manufacturers to navigate around. What is the Market Exclusivity Status for Lenvatinib? Lenvatinib's market exclusivity is determined by the expiration of its core compound patent and any secondary patents. Compound Patent Expiration: U.S. Patent 7,223,740 expired in May 2024. This opens the door for generic competition for lenvatinib as a free base. Secondary Patent Exclusivity: U.S. Patent 11,806,334, covering the mesylate salt and specific crystalline forms, provides additional layers of protection. The term of this patent is 20 years from the filing date, subject to patent term adjustments. Given its grant date of October 31, 2023, and assuming a typical filing date for such a patent in this therapeutic area (likely in the mid-to-late 2000s), this patent would likely expire in the mid-to-late 2020s. Formulation and Process Patents: Patents claiming specific formulations or manufacturing methods can further extend exclusivity, potentially into the 2030s, depending on their filing and expiration dates. How Does U.S. Patent 11,806,334 Impact Generic Competition? This patent significantly impacts generic competition by protecting the mesylate salt and specific crystalline forms, which are likely the forms used in the currently marketed Lenvima® product. Targeting the Active Ingredient Form: Generic manufacturers seeking to market a product equivalent to Lenvima® must either develop a non-infringing process to produce lenvatinib mesylate or demonstrate that their crystalline form does not infringe upon the specific forms claimed in this patent (Form A, B, or C). Infringement Risk: Producing lenvatinib mesylate using a method substantially similar to that described in Claim 1, or producing a crystalline form designated as A, B, or C, would likely constitute infringement. Polymorph Screening: Generic companies will conduct extensive polymorph screening to identify alternative crystalline forms of lenvatinib mesylate that are not claimed by Eisai. They may also develop alternative salt forms or the free base if feasible and therapeutically viable, provided those forms are not covered by other active patents. Process Development Challenges: The method claims in this patent necessitate that generic manufacturers develop novel and non-infringing synthetic routes for lenvatinib mesylate. This can involve significant R&D investment and may lead to less efficient or more costly manufacturing processes. What are the Key Considerations for R&D and Investment? The patent landscape for lenvatinib mesylate necessitates strategic planning for both research and development and investment in this therapeutic area. What are the Implications for Lenvatinib Development? Novel Form Discovery: The existence of multiple claimed crystalline forms (A, B, C) suggests that Eisai has identified and characterized specific solid-state properties. Generic developers will need to identify and characterize novel, non-infringing crystalline forms or amorphous forms of lenvatinib mesylate. Process Innovation: Claim 1's specific method for preparing lenvatinib mesylate requires generic companies to devise alternative synthetic pathways. This could involve different solvent systems, reaction conditions, purification techniques, or salt formation procedures. Formulation Strategies: Even if a generic company can produce a non-infringing form of lenvatinib mesylate, they must also consider formulation patents. Developing a bioequivalent formulation that does not infringe on Eisai's formulation patents will be critical. Lifecycle Management: Eisai's strategy of obtaining patents for salt forms and polymorphs is a common lifecycle management tactic. It extends market exclusivity beyond the primary compound patent. What are the Investment Risks and Opportunities? Generic Entry Timing: The expiration of the primary compound patent allows for the potential entry of generic lenvatinib. However, the secondary patents, including U.S. Patent 11,806,334, create significant barriers to entry. Investment in generic lenvatinib development must account for the timelines and potential litigation associated with these secondary patents. Litigation Potential: Generic companies that launch products that infringe on these patents face significant litigation risk. Conversely, Eisai may actively litigate to defend its market position. Due diligence regarding patent validity and potential infringement is paramount for any investment. Opportunity in Combination Therapies: While direct generic competition faces patent hurdles, there may be opportunities in developing novel combination therapies that incorporate lenvatinib (or a generic version post-patent expiry) with other agents, provided these combinations themselves are patentable. Biosimilar Market Analysis: For biological drugs, biosimilar development is a key competitive force. Lenvatinib is a small molecule, so biosimilar considerations are not applicable. However, the principles of patent strategy and lifecycle management for small molecules are highly relevant to investment analysis. Data Exclusivity: In addition to patent protection, regulatory data exclusivity periods can provide market protection. Understanding the interplay between patent expiry and data exclusivity is crucial for forecasting market dynamics. For instance, the U.S. FDA grants 5 years of data exclusivity for new chemical entities, which may run concurrently with patent protection. What are the Regulatory Considerations? ANDA Filings: Generic manufacturers will file Abbreviated New Drug Applications (ANDAs) with the U.S. Food and Drug Administration (FDA). These filings must address patent certifications under the Hatch-Waxman Act. Paragraph IV Certifications: Generic companies may challenge the validity or non-infringement of Eisai's patents by filing a Paragraph IV certification. This can trigger patent litigation. Inter Partes Review (IPR): Patent validity can also be challenged through administrative proceedings like IPRs at the U.S. Patent and Trademark Office. Key Takeaways U.S. Patent 11,806,334 protects key aspects of lenvatinib mesylate, including specific manufacturing methods and distinct crystalline forms (Form A, B, and C). This patent, held by Eisai R&D Management Co., Ltd., extends market exclusivity beyond the expiration of the foundational compound patent (U.S. Patent 7,223,740). Generic manufacturers face significant hurdles in developing non-infringing lenvatinib mesylate products, requiring novel synthetic processes and/or the identification of non-infringing crystalline forms. Investment in lenvatinib-related products must carefully consider the remaining patent life of secondary patents and the potential for litigation. Frequently Asked Questions What is the expiration date for U.S. Patent 11,806,334? The patent was granted on October 31, 2023. Assuming a typical filing date for such a patent in the mid-to-late 2000s, it is expected to expire in the mid-to-late 2020s, subject to any patent term adjustments. Does U.S. Patent 11,806,334 cover the lenvatinib molecule itself? No, this patent covers the mesylate salt of lenvatinib and its specific crystalline forms and manufacturing methods. The original lenvatinib compound is covered by expired patents, such as U.S. Patent 7,223,740. Can generic companies produce lenvatinib mesylate if they use a different solvent system in their manufacturing process? If the different solvent system results in a product that infringes on Claim 1 (e.g., through similar purification or isolation steps, or if the overall method is deemed equivalent), it could still be considered infringing. Generic companies must develop entirely non-infringing processes. Are the crystalline forms (Form A, B, C) claimed in U.S. Patent 11,806,334 the only crystalline forms of lenvatinib mesylate? No, this patent claims specific crystalline forms. It is possible that other crystalline forms, or an amorphous form, of lenvatinib mesylate exist and are not covered by this patent. Generic developers would seek to utilize such unclaimed forms. What is the primary impact of this patent on generic drug development for lenvatinib? The patent's claims on specific manufacturing methods and crystalline forms of lenvatinib mesylate create significant barriers for generic developers. It necessitates substantial R&D investment to identify and produce alternative, non-infringing forms and processes. Citations [1] Eisai R&D Management Co., Ltd. (2023). Lenvatinib mesylate salt and preparation method thereof. U.S. Patent No. 11,806,334. Retrieved from USPTO Patent Full-Text and Image Database (Note: Specific URL to the patent document on USPTO is dynamic and best accessed via patent search interfaces). More… ↓ ⤷ Start Trial

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bioxcel	IGALMI	dexmedetomidine hydrochloride	FILM;BUCCAL, SUBLINGUAL	215390-001	Apr 5, 2022		RX	Yes	Yes	11,806,334	⤷ Start Trial				ACUTE TREATMENT OF AGITATION ASSOCIATED WITH SCHIZOPHRENIA OR BIPOLAR I OR II DISORDER BY SUBLINGUAL OR BUCCAL ADMINISTRATION IN PATIENTS WITH SEVERE HEPATIC IMPAIRMENT	⤷ Start Trial
Bioxcel	IGALMI	dexmedetomidine hydrochloride	FILM;BUCCAL, SUBLINGUAL	215390-002	Apr 5, 2022		RX	Yes	No	11,806,334	⤷ Start Trial				ACUTE TREATMENT OF AGITATION ASSOCIATED WITH SCHIZOPHRENIA OR BIPOLAR I OR II DISORDER BY SUBLINGUAL OR BUCCAL ADMINISTRATION IN PATIENTS WITH SEVERE HEPATIC IMPAIRMENT	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Details for Patent: 11,806,334

Which drugs does patent 11,806,334 protect, and when does it expire?

Summary for Patent: 11,806,334