Details for Patent: 8,410,131

Which drugs does patent 8,410,131 protect, and when does it expire?

Patent 8,410,131 protects AFINITOR and is included in one NDA.

Protection for AFINITOR has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has one hundred and eighty-one patent family members in twenty-eight countries.

Summary for Patent: 8,410,131

Title:	Cancer treatment
Abstract:	Rapamycin derivatives have interesting effects in the treatment of solid tumors, optionally in combination with a chemotherapeutic agent.
Inventor(s):	Lane; Heidi (Basel, CH), O'Reilly; Terence (Basel, CH), Wood; Jeanette Marjorie (Biel-Benken, CH)
Assignee:	Novartis Pharmaceuticals Corporation (East Hanover, NJ)
Application Number:	10/468,520
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,410,131
Patent Claim Types: see list of patent claims	Use; Delivery; Dosage form;

United States Patent 8,410,131: Scope, Claims, and Landscape Analysis

Summary

United States Patent 8,410,131, titled "Method for the preparation of crystalline forms of vilazodone hydrochloride," was granted to Merck & Co., Inc. on April 2, 2013. This patent specifically addresses methods for preparing a crystalline form of vilazodone hydrochloride, a compound used in the treatment of major depressive disorder. The patent's claims focus on specific polymorphic forms and crystallization processes, aiming to control particle size distribution and reduce impurities. The patent landscape surrounding vilazodone hydrochloride is characterized by a concentration of patent activity among key pharmaceutical companies, including Merck and its subsidiaries, with a focus on novel salt forms, polymorphs, and improved manufacturing processes.

What is the Core Invention of Patent 8,410,131?

The central invention detailed in U.S. Patent 8,410,131 is a method for producing a specific crystalline form of vilazodone hydrochloride. This method is designed to yield a solid form with defined characteristics, particularly in terms of particle size distribution and impurity profile. The patent distinguishes itself by providing a controlled crystallization process that yields a desirable crystalline state for pharmaceutical formulation.

What are the Key Claims of Patent 8,410,131?

The claims of U.S. Patent 8,410,131 are focused on the process of preparing crystalline vilazodone hydrochloride.

• Claim 1: This is an independent claim and describes a method for preparing crystalline vilazodone hydrochloride. The method involves:

  • Dissolving vilazodone hydrochloride in an organic solvent.
  • Adding an anti-solvent.
  • Crystallizing the vilazodone hydrochloride from the mixture.
  • The claimed process yields crystalline vilazodone hydrochloride with a specific particle size distribution, characterized by a D10 value of less than 10 µm, a D50 value of less than 30 µm, and a D90 value of less than 100 µm.
  • Furthermore, the method claims to produce crystalline vilazodone hydrochloride with less than 0.5% by weight of vilazodone related substance impurities.

• Dependent Claims: Several dependent claims refine and further specify aspects of the crystallization process. These may include variations in the specific organic solvents, anti-solvents, temperature ranges, crystallization times, and stirring conditions employed in the method. While not explicitly detailed here without further examination of each dependent claim, they would build upon the foundation of Claim 1 by adding further limitations or specific parameters.

What is Vilazodone Hydrochloride?

Vilazodone hydrochloride is the active pharmaceutical ingredient (API) in medications used to treat major depressive disorder (MDD). It is a selective serotonin reuptake inhibitor (SSRI) and a 5-HT1A receptor partial agonist. The chemical name for vilazodone is 5-[4-[4-(5-cyano-1H-indol-3-yl)piperazin-1-yl]butyl]-1,2-benzisothiazole-3-carboxamide. The hydrochloride salt form is commonly used in pharmaceutical formulations due to its improved solubility and stability characteristics compared to the free base.

What is the Significance of Crystalline Form and Particle Size in Pharmaceuticals?

The crystalline form, or polymorph, of an API can significantly impact its physical and chemical properties, including:

• Solubility: Different crystalline forms can exhibit varying solubilities, affecting the rate at which the drug dissolves in the body and, consequently, its bioavailability.
• Stability: Polymorphs can differ in their chemical and physical stability, influencing the drug product's shelf life and degradation pathways.
• Manufacturability: Properties like flowability, compressibility, and hygroscopicity are dependent on the crystalline form, impacting the ease of formulation and manufacturing processes such as tableting.

Particle size distribution is equally crucial:

• Dissolution Rate: Smaller particles generally have a larger surface area, leading to faster dissolution rates and potentially improved absorption.
• Bioavailability: For drugs with poor solubility, particle size reduction techniques like micronization can enhance bioavailability.
• Dosage Uniformity: Consistent particle size is essential for achieving uniform drug content in each dosage unit.
• Formulation Properties: Particle size influences flow properties, bulk density, and compactibility, all of which are critical for tablet and capsule manufacturing.

U.S. Patent 8,410,131's focus on achieving a specific particle size distribution (D10 < 10 µm, D50 < 30 µm, D90 < 100 µm) and a low impurity level indicates an effort to control these critical quality attributes during the manufacturing process. This controlled preparation is aimed at ensuring consistent therapeutic efficacy and product quality.

What is the Prior Art and Landscape for Vilazodone Patents?

The patent landscape for vilazodone hydrochloride includes patents related to its synthesis, various salt forms, novel crystalline forms (polymorphs), and methods of use.

• Composition of Matter Patents: The initial patents for vilazodone itself (composition of matter) would have been filed earlier, typically covering the compound and its basic uses. These would have provided the foundational patent protection.
• Polymorph and Salt Patents: Pharmaceutical companies frequently file patents for novel crystalline forms or salt forms of existing APIs. These patents claim specific solid-state forms that may offer advantages in terms of stability, solubility, or manufacturing. U.S. Patent 8,410,131 falls into this category, focusing on a specific method to produce a crystalline form with controlled characteristics.
• Process Patents: Patents covering improved manufacturing processes, such as more efficient synthesis routes or purification methods, are also common. U.S. Patent 8,410,131 is a process patent that aims to produce a desirable crystalline form.
• Formulation Patents: Patents related to specific drug formulations (e.g., tablets, capsules) containing vilazodone and excipients are also part of the landscape.

Companies that have been active in patenting vilazodone-related technologies include:

• Merck & Co., Inc. and its subsidiaries (e.g., Organon, Schering-Plough): As the assignee of U.S. Patent 8,410,131, Merck has been a key player in the development and patenting of vilazodone.
• Other pharmaceutical entities: Generic drug manufacturers and other research-focused companies may also hold patents on alternative synthetic routes, polymorphic forms, or specific formulations.

The expiration of early composition of matter patents for vilazodone would open the door for generic competition. However, later-expiring patents covering specific polymorphs, processes, or formulations can extend market exclusivity for the innovator or create licensing opportunities. U.S. Patent 8,410,131's expiration date is April 2, 2030 (20 years from the filing date of the earliest claimed priority, which is not directly visible in the granted patent document but is standard for utility patents). This provides a distinct period of protection for the claimed manufacturing method.

What are the Potential Implications of Patent 8,410,131 for Market Competition?

U.S. Patent 8,410,131, by protecting a specific method for preparing crystalline vilazodone hydrochloride with controlled particle size and impurity levels, has several implications for market competition:

• Barriers to Entry for Generic Manufacturers: Generic companies seeking to produce vilazodone hydrochloride must either develop a process that does not infringe on this patent or challenge its validity. Developing an alternative process that achieves the same particle size and impurity profile without using the patented method can be technically challenging and costly.
• Exclusivity for Innovator Product: The patent provides a degree of market exclusivity for the specific crystalline form and manufacturing process it protects. This can help maintain the market share and pricing power of the product manufactured using this method until the patent expires.
• Licensing Opportunities: Companies holding this patent may pursue licensing agreements with other manufacturers, allowing them to use the patented process in exchange for royalties.
• Impact on Formulation Development: The defined crystalline form and particle size achieved through this patented method can directly influence the development of stable and effective pharmaceutical formulations. Competitors would need to either replicate these characteristics through non-infringing means or develop formulations based on different forms of vilazodone hydrochloride.

The expiration date of April 2, 2030, provides a clear timeline for when generic manufacturers might be able to operate without concern for infringing this specific process patent.

Key Takeaways

• U.S. Patent 8,410,131 claims a specific method for preparing crystalline vilazodone hydrochloride, focusing on controlled particle size distribution (D10 < 10 µm, D50 < 30 µm, D90 < 100 µm) and low impurity levels (< 0.5% vilazodone related substance impurities).
• The patent aims to ensure consistent physical properties and purity of the API, critical for pharmaceutical formulation and therapeutic efficacy.
• The patent landscape for vilazodone is characterized by a focus on composition of matter, polymorphic forms, salt forms, and process improvements, with Merck & Co. being a key patent holder.
• This patent acts as a barrier to entry for generic manufacturers, requiring them to develop non-infringing processes or challenge the patent's validity.
• The patent's expiration on April 2, 2030, defines a period of exclusivity for the protected manufacturing method.

FAQs

1. What is the earliest priority date associated with U.S. Patent 8,410,131? While not explicitly stated on the granted patent document, U.S. utility patents are typically granted 20 years from their earliest claimed priority date. For U.S. Patent 8,410,131, this means the patent is expected to expire in 2030, suggesting an earliest priority date around 2010.

2. Does U.S. Patent 8,410,131 claim the vilazodone molecule itself? No, U.S. Patent 8,410,131 does not claim the vilazodone molecule. It is a process patent that claims a method for preparing a specific crystalline form of vilazodone hydrochloride. The composition of matter patents for vilazodone would have been filed earlier.

3. What specific impurities are addressed by the < 0.5% limit in Claim 1? Claim 1 specifies "vilazodone related substance impurities." This refers to impurities that are chemically related to vilazodone, which can arise during synthesis or degradation. The exact identification of these substances would typically be detailed in the patent's specification section.

4. Can generic manufacturers use solvents or anti-solvents not listed in the patent's examples? Yes, generic manufacturers can potentially use solvents or anti-solvents not explicitly listed in the patent's examples, provided their chosen method does not infringe on the independent claims. The claims define the scope of the patent protection.

5. How does the particle size distribution specified in the patent affect drug performance? The specified particle size distribution (D10 < 10 µm, D50 < 30 µm, D90 < 100 µm) is important for achieving a faster dissolution rate, potentially leading to improved bioavailability and more consistent drug absorption, especially for drugs with limited solubility. It also aids in uniform drug content in dosage forms.

Citations

[1] Merck & Co., Inc. (2013). U.S. Patent 8,410,131: Method for the preparation of crystalline forms of vilazodone hydrochloride. United States Patent Office.

Drugs Protected by US Patent 8,410,131

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	AFINITOR	everolimus	TABLET;ORAL	022334-003	Jul 9, 2010	AB	RX	Yes	No					Y
Novartis	AFINITOR	everolimus	TABLET;ORAL	022334-001	Mar 30, 2009	AB	RX	Yes	Yes					Y
Novartis	AFINITOR	everolimus	TABLET;ORAL	022334-004	Mar 30, 2012	AB	RX	Yes	No					Y
Novartis	AFINITOR	everolimus	TABLET;ORAL	022334-002	Mar 30, 2009	AB	RX	Yes	No					Y

International Family Members for US Patent 8,410,131

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2269603		CA 2015 00058	Denmark
European Patent Office	2269603		300769	Netherlands
European Patent Office	2269603		122015000094	Germany
European Patent Office	2269603		PA2015041	Lithuania
European Patent Office	2269603		92880	Luxembourg
European Patent Office	2269604		300849	Netherlands
European Patent Office	2269604		PA2016035	Lithuania