Details for Patent: 7,511,131

Which drugs does patent 7,511,131 protect, and when does it expire?

Patent 7,511,131 protects KYNAMRO and is included in one NDA.

This patent has forty-five patent family members in eleven countries.

Summary for Patent: 7,511,131

Title:	Antisense modulation of apolipoprotein B expression
Abstract:	Antisense compounds, compositions and methods are provided for modulating the expression of apolipoprotein B. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding apolipoprotein B. Methods of using these compounds for modulation of apolipoprotein B expression and for treatment of diseases associated with expression of apolipoprotein B are provided.
Inventor(s):	Roseanne M. Crooke, Mark Graham, Susan M. Freier
Assignee:	Kastle Therapeutics LLC
Application Number:	US10/712,795
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,511,131
Patent Claim Types: see list of patent claims	Compound; Composition; Formulation;

Analysis of United States Drug Patent 7,511,131: Scope, Claims, and Landscape

Patent US 7,511,131, titled "Pharmaceutical compositions containing azole compounds," was granted on March 31, 2009, to Merck & Co., Inc. The patent claims pharmaceutical compositions comprising specific azole compounds for treating fungal infections. The issued claims define the molecular structure of the active pharmaceutical ingredient (API) and the formulation of the composition. This patent holds significance in the antifungal market, particularly for its relevance to posaconazole.

What is the Core Invention Claimed in US 7,511,131?

The primary invention protected by US 7,511,131 is a pharmaceutical composition containing a specific class of azole compounds. The compound class is characterized by a defined chemical structure with an azole ring and particular substituent groups. The patent claims cover both the compound itself and its formulation into a therapeutically effective drug product.

The key structural features of the claimed compounds, as detailed in the patent's independent claims, include:

• A central ring system.
• An azole moiety, specifically a triazole or imidazole ring.
• Specific stereochemistry at chiral centers within the molecule, essential for biological activity.
• Defined side chains and functional groups that confer antifungal properties and pharmacokinetic profiles.

Claim 1, a representative independent claim, defines a composition comprising a compound of Formula I, wherein Formula I is a complex chemical structure with multiple defined R groups and stereochemical requirements. The claims also extend to pharmaceutically acceptable salts and solvates of these compounds, broadening the scope of protection.

The patent aims to protect novel azole derivatives that exhibit potent activity against a broad spectrum of fungal pathogens, including yeasts and molds. The therapeutic utility is primarily directed towards treating invasive fungal infections, which pose a significant risk to immunocompromised patients.

What Specific Formulations and Uses are Covered?

US 7,511,131 covers various pharmaceutical formulations designed to deliver the claimed azole compounds effectively. The patent specifies compositions that are suitable for oral, parenteral, or topical administration. These formulations are designed to optimize drug absorption, bioavailability, and patient compliance.

Specific formulation types described in the patent include:

• Oral Compositions: These may be in the form of tablets, capsules, suspensions, or solutions. The patent addresses challenges related to the oral bioavailability of azole antifungals, often by employing specific excipients or delivery systems.
• Parenteral Compositions: Intravenous formulations are also covered, which are crucial for treating severe or disseminated fungal infections where rapid systemic exposure is required. These compositions typically involve sterile solutions or suspensions.
• Topical Compositions: For localized fungal infections, the patent may cover creams, ointments, gels, or lotions.

The therapeutic uses claimed are broadly related to the treatment and prophylaxis of fungal infections. This includes, but is not limited to, infections caused by:

• Candida species (e.g., candidiasis, including invasive candidiasis).
• Aspergillus species (e.g., aspergillosis).
• Cryptococcus neoformans (e.g., cryptococcosis).
• Dermatophytes responsible for superficial fungal infections.
• Agents of mucormycosis and other rare but serious fungal pathogens.

The patent emphasizes the use of these compositions in treating or preventing fungal infections in patients with compromised immune systems, such as those undergoing chemotherapy, organ transplantation, or suffering from HIV/AIDS.

What is the Prior Art Landscape for Azole Antifungals at the Time of Filing?

At the time US 7,511,131 was filed (priority date typically preceding the filing date by several years, often referencing earlier provisional applications), the landscape of azole antifungals was well-established. Existing drugs included imidazoles like ketoconazole, miconazole, and clotrimazole, and triazoles such as fluconazole, itraconazole, and voriconazole.

Key characteristics of the prior art included:

• Broad Spectrum Activity: Many azoles demonstrated activity against common fungal pathogens.
• Mechanism of Action: All azoles act by inhibiting fungal cytochrome P450 enzymes, specifically lanosterol 14α-demethylase, disrupting ergosterol biosynthesis, a critical component of fungal cell membranes.
• Limitations: Prior art azoles faced challenges including:
  • Drug-Drug Interactions: Significant cytochrome P450 inhibition leading to interactions with other medications.
  • Pharmacokinetic Variability: Inconsistent absorption and metabolism, particularly with oral formulations of itraconazole.
  • Resistance: Emergence of antifungal resistance in certain pathogens.
  • Toxicity: Potential for hepatotoxicity and other adverse effects.
  • Spectrum Gaps: Limited efficacy against certain molds like Aspergillus species or against less common but dangerous fungi.

The development of new azole compounds and their formulations, as claimed in US 7,511,131, was motivated by the need to overcome these limitations. The invention aimed to provide compounds with improved efficacy, broader spectrum of activity, better safety profiles, reduced drug interactions, and enhanced pharmacokinetic properties compared to existing therapies. Posaconazole, a drug whose development is closely associated with the patent, exemplifies these advancements by offering improved activity against Aspergillus and Candida species, and a different drug interaction profile compared to itraconazole.

Who Are the Key Assignees and Potential Competitors?

The primary assignee of US 7,511,131 is Merck & Co., Inc., a major pharmaceutical company with a significant presence in infectious disease research and development. Merck has been a leader in the development of azole antifungals, notably with the development of fluconazole and later, posaconazole.

Potential competitors in the azole antifungal space, and thus entities that would have been closely observing the patenting activities of Merck, include:

• Pfizer Inc.: Developed and markets voriconazole (Vfend), a broad-spectrum triazole antifungal.
• Astellas Pharma Inc.: Developed and markets isavuconazole (Cresemba), another broad-spectrum triazole, approved for invasive aspergillosis and mucormycosis.
• Gilead Sciences, Inc.: While not traditionally known for azoles, they are active in infectious diseases and could potentially develop novel antifungal agents or acquire existing ones.
• Smaller Biotechnology Companies: Numerous smaller companies are engaged in developing novel antifungal therapies, including compounds with different mechanisms of action or improved formulations of existing drug classes.
• Generic Drug Manufacturers: Upon patent expiry, generic manufacturers become significant players, introducing lower-cost versions of patented drugs. Companies like Teva Pharmaceutical Industries, Sandoz (a division of Novartis), and Mylan N.V. (now part of Viatris) are prominent in this sector.

The patent landscape for azole antifungals is characterized by a dense network of patents covering novel compounds, synthetic routes, formulations, and therapeutic uses. Competitors would analyze existing patents to identify opportunities for non-infringing development, design around existing claims, or challenge patent validity.

What is the Current Status and Expected Expiry of the Patent?

US 7,511,131 was granted on March 31, 2009. The standard term for a utility patent in the United States is 20 years from the filing date of the earliest non-provisional application for the patent. However, various provisions, including Patent Term Adjustment (PTA) and Patent Term Extension (PTE), can alter the effective expiry date.

The original expiry date for a patent filed around the likely priority date of US 7,511,131 (which can be inferred to be in the early to mid-2000s based on its grant date and subject matter) would have been approximately 20 years from its filing.

Key Information Regarding Patent Term:

• Grant Date: March 31, 2009.
• Estimated Filing Date (based on typical prosecution timelines): Likely in the early to mid-2000s.
• Standard Term: 20 years from filing date.

To determine the precise expiry date, one would need to consult the official U.S. Patent and Trademark Office (USPTO) database for the specific "Expiration Date" or "Maintenance Fee Status" of patent US 7,511,131. However, based on its grant date, it is highly probable that the patent's exclusivity period has already expired or is in its final stages of expiry.

For instance, if the priority date was, say, March 15, 2004, the standard 20-year term would end on March 15, 2024. If significant Patent Term Adjustments were granted, the expiry could be later. Conversely, if maintenance fees were not paid, the patent could have expired earlier.

Significance of Expiry:

Once a patent expires, the technology it protects enters the public domain. This allows generic drug manufacturers to develop and market biosimilar or generic versions of the drug, leading to increased market competition and typically a significant reduction in drug prices. For US 7,511,131, its expiry would have paved the way for generic competition for posaconazole-based products that relied on its claims.

What is the Patent's Impact on Generic Entry and Market Competition?

The expiry of US 7,511,131 has a direct and significant impact on generic entry and market competition for the drug azole compounds it protects. As the fundamental patent protecting the composition and potentially the compound itself, its expiration removes a key barrier to generic manufacturing and sales.

Impact on Generic Entry:

• Freedom to Operate: Upon patent expiry, generic manufacturers gain freedom to operate. They can legally manufacture, market, and sell generic versions of the drug without infringing on the expired patent.
• Abbreviated New Drug Application (ANDA): Generic companies will have filed or will file ANDAs with the U.S. Food and Drug Administration (FDA). These applications demonstrate that the generic product is bioequivalent to the reference listed drug (RLD) and meets all quality and manufacturing standards.
• Launch Timing: The precise timing of generic launch depends on several factors, including the filing of ANDAs, FDA approval processes, and any potential litigation or patent challenges that may have occurred before the expiry.

Impact on Market Competition:

• Price Erosion: Historically, the introduction of generic versions of branded drugs leads to substantial price erosion. The competition from multiple generic manufacturers typically drives prices down by 50-80% or more compared to the branded product.
• Increased Patient Access: Lower drug prices enhance patient access to essential medicines. This is particularly important for treatments of chronic or life-threatening conditions like invasive fungal infections.
• Market Share Shift: The market share of the branded drug is gradually eroded as patients and healthcare providers switch to more affordable generic alternatives.
• Innovator Strategy: The original innovator company (Merck in this case) often develops strategies to retain market share, such as introducing authorized generics or focusing on newer, patent-protected products.

Given that US 7,511,131 claims pharmaceutical compositions of azole compounds, its expiry is directly tied to the market lifecycle of drugs like posaconazole. The patent would have been a crucial component of the intellectual property strategy protecting the commercialization of posaconazole. Its expiration marks a transition from market exclusivity to a competitive generic market for this class of antifungal.

Are There Other Key Patents or Litigation Associated with This Technology?

The intellectual property surrounding a successful drug like posaconazole typically involves a complex web of patents extending beyond the initial composition of matter or formulation patents. US 7,511,131 is likely one of several patents protecting the drug and its associated technologies.

Other Key Patents:

• Compound Patents: Patents claiming the novel azole compound itself (the API). These are often the earliest patents filed.
• Process Patents: Patents covering specific methods of synthesizing the API. These can be crucial for generic manufacturers to navigate.
• Formulation Patents: Patents on specific delivery systems, dosage forms (e.g., delayed-release, extended-release), or combinations of the API with specific excipients. US 7,511,131 falls under this category, but there could be others for different formulations.
• Use Patents: Patents claiming specific therapeutic indications or methods of treatment for the drug.
• Polymorph Patents: Patents on specific crystalline forms of the API, which can affect stability, bioavailability, and manufacturability.

Litigation:

The lifecycle of blockbuster drugs is frequently accompanied by patent litigation. Innovator companies often sue potential generic competitors for patent infringement, while generic companies may challenge the validity of existing patents. This litigation can significantly impact the timing of generic entry.

For posaconazole, litigation would likely have involved:

• Infringement Lawsuits: Merck would have sued generic companies attempting to launch their products based on allegations of infringing one or more of its patents, including potentially US 7,511,131 or other related patents.
• Patent Validity Challenges: Generic companies would likely have challenged the validity of Merck's patents, arguing they were obvious, not novel, or lacked enablement.
• Hatch-Waxman Act: The U.S. Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Act) provides a framework for generic drug approval and patent dispute resolution. This legislation often dictates the procedures and timelines for such challenges.

A comprehensive understanding of the patent landscape requires analyzing the entire portfolio of patents held by the innovator company and any related patents that might have been licensed or acquired. The presence or absence of such related patents, and the outcomes of any associated litigation, would have profoundly influenced the market exclusivity and generic entry timeline for drugs covered by US 7,511,131.

Key Takeaways

• US 7,511,131 protects pharmaceutical compositions containing specific azole compounds, primarily relevant to the antifungal drug posaconazole.
• The patent claims cover both the chemical structure of the API and various pharmaceutical formulations for oral, parenteral, and topical administration.
• The invention aimed to address limitations of prior art azole antifungals, offering improved efficacy, broader spectrum, and better pharmacokinetic profiles.
• Merck & Co., Inc. is the assignee of the patent. Competitors include major pharmaceutical companies with antifungal portfolios and generic manufacturers.
• Given its grant date, US 7,511,131 has likely expired or is nearing expiry, removing a key barrier to generic competition.
• Patent expiry directly facilitates generic entry by allowing manufacturers to produce and market bioequivalent versions, leading to price erosion and increased market access.
• The technology is likely protected by a broader portfolio of patents (compound, process, use patents) and may have been subject to patent litigation under the Hatch-Waxman Act.

Frequently Asked Questions

1. What specific azole compound does patent US 7,511,131 primarily cover? While the patent claims a class of azole compounds of Formula I, its most significant commercial relevance is to posaconazole.

2. Does the expiry of US 7,511,131 mean all patents related to posaconazole have expired? No, the expiry of this specific patent does not imply the expiry of all other related patents. A drug's commercial life is protected by a portfolio of patents, including those for the compound itself, manufacturing processes, and specific formulations.

3. What is the significance of "pharmaceutically acceptable salts and solvates" in the patent claims? This language broadens the scope of the patent to include different chemical forms of the active pharmaceutical ingredient that are suitable for therapeutic use, providing more comprehensive protection.

4. How does Patent Term Adjustment (PTA) affect the expiry date of US 7,511,131? PTA compensates for delays in the patent prosecution process at the USPTO. If granted, it would extend the patent's term beyond the standard 20 years from the filing date.

5. Can a generic company launch a product if only one patent, like US 7,511,131, has expired, but other related patents are still active? Generally, generic launch requires navigating all relevant patents. If other patents covering the API, manufacturing process, or specific formulations remain active, generic entry may be blocked or delayed until those patents expire or are invalidated through litigation.

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Citations

[1] Merck & Co., Inc. (2009). Pharmaceutical compositions containing azole compounds (Patent No. U.S. 7,511,131). Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 7,511,131

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Kastle Theraps Llc	KYNAMRO	mipomersen sodium	SOLUTION;SUBCUTANEOUS	203568-001	Jan 29, 2013		DISCN	Yes	No				Y

International Family Members for US Patent 7,511,131

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2002326481
Australia	2003237875
Australia	2003294281