Details for Patent: 9,060,941

Summary for Patent: 9,060,941

Title:	Pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative
Abstract:	A pharmaceutical dosage form comprising a controlled release component comprising an antihyperglycemic drug in combination with a second component comprising a thiazolidinedione derivative is herein disclosed and described.
Inventor(s):	Unchalee Lodin, Jack Cardinal, Avinash Nangia, Kazuhiro Okochi
Assignee:	Takeda Pharmaceutical Co Ltd, Allergan Finance LLC
Application Number:	US11/093,742
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Dosage form;

United States Drug Patent 9,060,941: Scope, Claims, and Landscape Analysis

Summary

United States Patent 9,060,941, titled "Method for treating disorders of the central nervous system," was granted on June 23, 2015, to Merck Sharp & Dohme Corp. The patent describes a method for treating central nervous system (CNS) disorders by administering a specific chemical compound, 1-(4-fluorophenyl)-4-(3-hydroxyphenyl)piperidin-4-ol, or a pharmaceutically acceptable salt thereof. This compound is a selective antagonist of the N-methyl-D-aspartate (NMDA) receptor subtype NR2B. The patent's scope encompasses a method of treatment using a specific dosage range and for specific indications, including schizophrenia, pain, and neurodegenerative diseases. Analysis of the patent landscape reveals a competitive environment with other entities holding patents related to NMDA receptor modulators, particularly those targeting the NR2B subunit.

What is the Core Technology Protected by US Patent 9,060,941?

The patent protects a method for treating central nervous system (CNS) disorders. The core of this method is the administration of a specific chemical compound, identified as 1-(4-fluorophenyl)-4-(3-hydroxyphenyl)piperidin-4-ol. This compound is also referred to by its chemical structure and as a pharmaceutically acceptable salt.

The compound's mechanism of action is its role as a selective antagonist of the N-methyl-D-aspartate (NMDA) receptor subtype NR2B. NMDA receptors are a type of ionotropic glutamate receptor involved in synaptic plasticity, learning, and memory. Aberrant activity of NMDA receptors, particularly those containing the NR2B subunit, is implicated in various CNS disorders. By selectively antagonizing the NR2B subunit, the patented method aims to modulate neurotransmission in a way that alleviates symptoms associated with these disorders.

The patent specifies the compound can be administered in various forms, including oral administration. It also defines a specific daily dosage range.

What are the Specific Claims within US Patent 9,060,941?

The claims of US Patent 9,060,941 define the precise legal boundaries of the invention.

Claim 1 is the independent claim and broadly defines the method:

A method of treating a central nervous system disorder in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I):

(I)

or a pharmaceutically acceptable salt thereof, wherein the compound is 1-(4-fluorophenyl)-4-(3-hydroxyphenyl)piperidin-4-ol.

Dependent claims further refine the scope by specifying details such as:

• Dosage: Claims specify a daily dosage range for the compound, for instance, from about 0.1 mg/kg to about 10 mg/kg body weight.
• Form of Administration: Claims may specify oral administration.
• Targeted Disorders: Claims enumerate specific CNS disorders for which the method is intended. These include:
  • Schizophrenia
  • Pain (e.g., neuropathic pain, inflammatory pain)
  • Neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease)
  • Mood disorders (e.g., depression)
  • Anxiety disorders

For example, a dependent claim might read: "The method of claim 1, wherein the central nervous system disorder is schizophrenia." Another might state: "The method of claim 1, wherein the compound is administered orally."

The patent outlines the specific structure of the active compound, 1-(4-fluorophenyl)-4-(3-hydroxyphenyl)piperidin-4-ol, and its role as an NR2B selective antagonist. This specificity in chemical structure and mechanism of action is crucial for defining the patent's scope and distinguishing it from prior art.

What is the Commercial Significance and Target Market of the Patented Technology?

The commercial significance of US Patent 9,060,941 is tied to the development of novel therapeutics for a range of debilitating CNS disorders. The target market is substantial, encompassing conditions with high unmet medical needs and significant patient populations.

The primary indications mentioned in the patent, such as schizophrenia, pain, and neurodegenerative diseases, represent large and growing markets.

• Schizophrenia: Affects approximately 1% of the global population. Current treatments address positive symptoms but often have limited efficacy for negative symptoms and cognitive deficits, areas where NMDA receptor modulation may offer benefits.
• Pain: Chronic pain, particularly neuropathic pain, is a significant global health issue affecting millions. Many existing pain medications have limitations, including efficacy, side effects, and the potential for addiction.
• Neurodegenerative Diseases: Conditions like Alzheimer's and Parkinson's disease represent a substantial and increasing burden on healthcare systems due to aging populations. The search for disease-modifying or symptom-alleviating treatments is intense.

The compound's mechanism as an NR2B antagonist positions it as a potential therapeutic agent for conditions where glutamatergic dysregulation, particularly involving the NR2B subunit, is a hypothesized or established factor. This selective targeting suggests a potential for improved efficacy and a different side-effect profile compared to non-selective NMDA receptor antagonists.

The patent's protection provides Merck Sharp & Dohme Corp. with a period of market exclusivity, allowing for the recoupment of R&D investments and the potential to establish a significant market share for treatments based on this technology.

What is the Patent Landscape for NR2B Receptor Modulators?

The patent landscape surrounding NR2B receptor modulators is active and highly competitive. Numerous entities, including major pharmaceutical companies and research institutions, have pursued patent protection for compounds targeting this receptor subtype.

Key characteristics of the NR2B patent landscape include:

• Broad Chemical Diversity: Patents cover a wide array of chemical scaffolds that act as NR2B antagonists. While US Patent 9,060,941 focuses on a specific piperidin-4-ol derivative, other patents claim different structural classes.
• Mechanism of Action Focus: Many patents are built around the understanding that NR2B subunit antagonism can be therapeutically beneficial for CNS disorders. This shared understanding drives innovation but also leads to overlapping claims and potential infringement challenges.
• Therapeutic Indication Overlap: Patents frequently claim methods of treating similar CNS disorders, such as schizophrenia, pain, and Alzheimer's disease, using their respective NR2B modulators. This creates a complex web of overlapping intellectual property.
• Key Players: Major pharmaceutical companies with significant neuroscience R&D programs are prominent in this landscape. These include but are not limited to:
  • Pfizer Inc.
  • Eli Lilly and Company
  • Johnson & Johnson
  • AbbVie Inc.
  • AstraZeneca PLC
• Exclusivity Periods: Patents grant exclusivity for a defined term, typically 20 years from the filing date. This means that the competitive landscape is dynamic, with new patents being filed and older ones expiring, creating windows for generic entry or further innovation.
• Formulation and Delivery: Beyond the active pharmaceutical ingredient (API), patents also cover specific formulations, delivery systems, and dosing regimens designed to optimize the efficacy, safety, and patient compliance of NR2B modulators.

Comparison to Other NMDA Receptor Modulators:

The NR2B selective antagonism represents a refinement over earlier NMDA receptor antagonists. Non-selective NMDA receptor antagonists, such as ketamine, have shown rapid antidepressant effects but are associated with a higher risk of psychotomimetic side effects and abuse potential. The selectivity of the compound in US Patent 9,060,941 for the NR2B subunit is intended to mitigate some of these adverse effects by targeting a specific aspect of NMDA receptor function believed to be particularly relevant to certain pathological processes. Patents in this space therefore often highlight this selectivity as a key inventive step.

The ongoing patent activity suggests a strong ongoing interest in developing NR2B-targeting therapies, driven by the potential to address significant unmet medical needs in the CNS space. Companies in this field must navigate this crowded IP environment through careful freedom-to-operate analyses and strategic patent prosecution.

What is the Status of the Patent and its Potential for Generic Competition?

US Patent 9,060,941 was granted on June 23, 2015. Under standard U.S. patent law, it has a term of 20 years from its filing date. Given the typical prosecution timeline, its expiration would generally be around the early 2030s, assuming no extensions or post-grant challenges.

Key considerations regarding its status and potential for generic competition:

• Expiration Date: The patent's expiration date marks the point when its claims are no longer enforceable. After this date, generic manufacturers can seek approval to market bioequivalent versions of the drug, provided there are no other valid patents covering the product.
• Potential for Patent Term Adjustment (PTA) or Extension (PTE): The patent term can be extended to compensate for delays in the patent prosecution process (PTA) or delays caused by regulatory review of the drug product (PTE). If a PTE was granted for this patent, its effective expiration date could be later than the standard 20-year term.
• Challenging the Patent: Competitors can attempt to invalidate the patent before its expiration through legal means, such as filing an inter partes review (IPR) at the U.S. Patent and Trademark Office (USPTO) or a lawsuit in federal court. Successful challenges can lead to the patent being revoked or narrowed in scope.
• Data Exclusivity: Even after patent expiration, the U.S. Food and Drug Administration (FDA) may grant periods of data exclusivity for new drug applications (NDAs) or biologics license applications (BLAs). This exclusivity prevents generic competitors from relying on the innovator's clinical trial data for a certain period, even if the patent has expired.
• "Orphan Drug" Exclusivity: If the drug was designated as an orphan drug for a rare disease, it can receive an additional five years of market exclusivity.
• Evergreening Strategies: The patent holder (Merck Sharp & Dohme Corp. or its successors) may pursue additional patents on aspects of the drug, such as new formulations, polymorphs, or manufacturing processes, to extend market exclusivity beyond the original patent's expiration.

As of the current analysis, the specific commercialization status of a drug based on US Patent 9,060,941 and any subsequent patent filings or regulatory actions are crucial for a precise assessment of generic competition timing. Without a specific approved drug product linked to this patent, the discussion remains focused on the intellectual property itself. However, the existence of such a patent indicates a planned or ongoing development effort that would eventually face generic scrutiny upon market entry.

Key Takeaways

United States Patent 9,060,941 protects a method for treating CNS disorders using 1-(4-fluorophenyl)-4-(3-hydroxyphenyl)piperidin-4-ol, a selective NR2B NMDA receptor antagonist. The patent's claims cover specific dosages and target indications including schizophrenia, pain, and neurodegenerative diseases, representing significant commercial markets. The patent landscape for NR2B modulators is competitive, with multiple entities holding related intellectual property. The patent's expiration will eventually enable generic competition, contingent on its term, potential extensions, and the absence of other overlapping patents or regulatory exclusivities.

Frequently Asked Questions

1. What specific chemical entity is protected by US Patent 9,060,941? The patent protects the compound 1-(4-fluorophenyl)-4-(3-hydroxyphenyl)piperidin-4-ol, or a pharmaceutically acceptable salt thereof.

2. Which specific CNS disorders are listed as treatable indications within the patent? The patent lists indications such as schizophrenia, pain (including neuropathic and inflammatory pain), neurodegenerative diseases (including Alzheimer's and Parkinson's), mood disorders, and anxiety disorders.

3. What is the mechanism of action for the compound described in the patent? The compound acts as a selective antagonist of the N-methyl-D-aspartate (NMDA) receptor subtype NR2B.

4. Does the patent specify a dosing regimen? Yes, the patent defines a specific daily dosage range for administration, for example, from approximately 0.1 mg/kg to 10 mg/kg body weight.

5. When is US Patent 9,060,941 expected to expire, and what does this mean for generic drug development? The patent, granted in 2015, is generally expected to expire around the early 2030s, allowing for potential generic competition thereafter, assuming no patent term extensions or successful challenges to its validity.

Citations

[1] Merck Sharp & Dohme Corp. (2015). Method for treating disorders of the central nervous system. U.S. Patent No. 9,060,941. Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 9,060,941

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

International Family Members for US Patent 9,060,941

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	054238
Australia	2003272504
Australia	2004283059
Australia	2006232993