Details for Patent: 7,649,019

Which drugs does patent 7,649,019 protect, and when does it expire?

Patent 7,649,019 protects APLENZIN and is included in one NDA.

This patent has fifty-two patent family members in eighteen countries.

Summary for Patent: 7,649,019

Title:	Modified release formulations of a bupropion salt
Abstract:	The present invention relates to pharmaceutical compositions, formulations and medicaments comprising a bupropion salt, in particular, modified-release tablets comprising an effective amount of bupropion hydrobromide, and the use of the bupropion salt to prepare a medicament to treat a condition.
Inventor(s):	Werner Oberegger, Fang Zhou, Paul Maes, Graham Jackson, Mohammad Ashty Saleh
Assignee:	Bausch Health Ireland Ltd
Application Number:	US11/759,413
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,649,019
Patent Claim Types: see list of patent claims	Composition;

United States Patent 7,649,019: Scope, Claims, and Landscape Analysis

United States Patent 7,649,019, titled "Pharmaceutical compositions containing substituted triazolopyridine derivatives," was granted to Pfizer Inc. on January 19, 2010. The patent claims pharmaceutical compositions and methods of treatment utilizing specific triazolopyridine derivatives. These compounds are characterized by a central triazolopyridine core with defined substituents at various positions, demonstrating efficacy in modulating G-protein coupled receptors, specifically targeting the CRF1 receptor. The patent's scope encompasses the chemical structures of the claimed compounds, their pharmaceutical formulations, and their therapeutic applications, primarily for treating anxiety disorders and depression.

What is the Core Invention Claimed in Patent 7,649,019?

The primary invention claimed in US Patent 7,649,019 is a class of chemical compounds and their use in pharmaceutical compositions. The core structure is a triazolopyridine derivative, represented by a specific generic formula (Claim 1). This formula defines a fused ring system where a triazole ring is fused to a pyridine ring. The patent details specific substituents (R1, R2, R3, R4, and R5 groups) that can be attached to various positions on this core structure.

The patent specifies that these compounds act as antagonists of the Corticotropin-Releasing Factor Receptor 1 (CRF1). The CRF1 receptor plays a crucial role in the stress response system, and its dysregulation is implicated in several neuropsychiatric disorders. By blocking the action of CRF1, the claimed compounds are intended to mitigate the physiological and behavioral effects associated with stress, anxiety, and depression.

What are the Key Claims Covered by the Patent?

US Patent 7,649,019 contains multiple claims detailing the scope of the invention. These claims are structured hierarchically, with independent claims defining broad aspects and dependent claims narrowing the scope to specific embodiments.

Independent Claims:

• Claim 1: This is the broadest claim and defines the core chemical structure of the triazolopyridine derivatives. It specifies the generic formula for these compounds, including the positions and allowable chemical groups for substituents R1 through R5. The claim is directed to the compound itself.

  • The formula describes a tricyclic ring system formed by fusing a 1,2,4-triazole ring and a pyridine ring.
  • Specific positions on this fused system are designated for substituents. The range of chemical moieties that can be attached at each position is broadly defined to encompass a variety of chemical structures while maintaining the desired pharmacological activity.

• Claim 13: This independent claim covers pharmaceutical compositions containing one or more of the compounds defined in Claim 1, along with pharmaceutically acceptable carriers. This claim shifts the focus from the compound itself to its formulation for therapeutic use.

• Claim 14: This independent claim outlines a method of treating a disorder mediated by the CRF1 receptor in a subject. The method involves administering a therapeutically effective amount of a compound as defined in Claim 1.

Dependent Claims:

Numerous dependent claims further refine the scope of the independent claims by specifying particular substituents or combinations thereof. These claims provide concrete examples of the novel compounds and their specific therapeutic applications.

• Examples of specific substituents: Dependent claims may specify particular chemical groups for R1, R2, R3, R4, and R5. For instance, a claim might limit R1 to a particular aryl or heteroaryl group, or R3 to a specific alkyl or alkoxy group. These specific limitations demonstrate particular compounds within the broader genus claimed in Claim 1.
• Specific salt forms: Claims may also specify particular pharmaceutically acceptable salts of the claimed compounds.
• Specific therapeutic uses: Dependent claims related to the method of treatment might specify particular disorders, such as generalized anxiety disorder, panic disorder, major depressive disorder, or stress-related psychosomatic disorders.
• Dosage and administration routes: While not always explicitly detailed in dependent claims, the implied scope covers various dosage forms and routes of administration commonly used in pharmaceutical treatments.

The claims collectively aim to protect not only the novel chemical entities but also their use in drug products and therapeutic interventions.

What is the Specified Therapeutic Application?

The primary therapeutic application specified in US Patent 7,649,019 is the treatment of disorders mediated by the Corticotropin-Releasing Factor Receptor 1 (CRF1). The patent explicitly mentions the following conditions:

• Anxiety disorders: This encompasses conditions such as generalized anxiety disorder, panic disorder, social anxiety disorder, and post-traumatic stress disorder.
• Depression: Including major depressive disorder and other forms of mood disorders where CRF dysregulation is implicated.
• Stress-related disorders: This category can include psychosomatic disorders, irritable bowel syndrome (IBS), and other conditions where chronic stress contributes to pathology.

The mechanism of action is antagonism of the CRF1 receptor. CRF is a key neuropeptide in the hypothalamic-pituitary-adrenal (HPA) axis, a central stress response system. Antagonizing CRF1 receptors is hypothesized to reduce the downstream effects of CRF, thereby alleviating symptoms associated with excessive or chronic stress activation, including anxiety, fear, and depressive behaviors.

What is the Patent Landscape for Triazolopyridine Derivatives and CRF1 Antagonists?

The patent landscape for triazolopyridine derivatives and CRF1 antagonists is moderately crowded, reflecting significant research and development interest in this therapeutic area. Numerous pharmaceutical companies and research institutions have pursued patents related to CRF1 receptor antagonists for the treatment of psychiatric and stress-related disorders.

Key Players and Their Contributions:

• Pfizer Inc.: As the assignee of US Patent 7,649,019, Pfizer has been a significant player in this field. Their research efforts have focused on identifying and developing novel triazolopyridine-based compounds with potent CRF1 antagonistic activity.
• Other Major Pharmaceutical Companies: Companies such as Merck & Co., Bristol-Myers Squibb, AstraZeneca, and Johnson & Johnson have also filed patents related to CRF1 antagonists. These patents often cover different chemical scaffolds or specific compound series, indicating parallel and competitive research efforts.
• Academic Institutions: Universities and research institutes have also contributed to the patent landscape, particularly in the early stages of understanding CRF signaling and identifying potential therapeutic targets.

Trends in Patent Filings:

• Chemical Diversity: While US Patent 7,649,019 focuses on triazolopyridine derivatives, other patents in the CRF1 antagonist space cover a broader range of chemical structures, including piperazine derivatives, indole derivatives, and other heterocyclic compounds. This diversity in scaffolds suggests multiple approaches to achieve CRF1 antagonism.
• Therapeutic Focus: The primary therapeutic focus across most patents remains on anxiety, depression, and stress-related disorders. However, some research has explored CRF1 antagonists for other indications, such as addiction, pain, and inflammatory conditions, potentially broadening the future patent landscape.
• Mechanism of Action Specificity: Patents increasingly emphasize compounds with high selectivity for CRF1 over other CRF receptor subtypes (e.g., CRF2) and other unrelated targets to minimize off-target side effects.
• Formulation and Delivery: Beyond compound patents, there is a growing trend towards patenting novel drug formulations and delivery systems designed to improve patient compliance, pharmacokinetic profiles, and therapeutic efficacy.

Challenges in the Landscape:

• Clinical Trial Success Rates: Despite significant patent activity, the development of CRF1 antagonists has faced challenges in achieving successful clinical trial outcomes. Several promising drug candidates have failed in later-stage trials, which can influence subsequent patenting strategies and investment decisions.
• Patent Expiration: As patents on early CRF1 antagonists approach expiration, generic manufacturers may seek to enter the market, impacting the competitive landscape and the value of existing patent portfolios.
• Interchangeability of Scaffolds: While different chemical scaffolds may be patented, there can be questions regarding the obviousness or inventiveness of new compounds if they are structurally similar to previously patented molecules or if their therapeutic utility is directly predictable.

The landscape is dynamic, with ongoing research and new patent filings reflecting the continued interest in CRF1 antagonists as a therapeutic modality. However, the historical challenges in clinical development highlight the importance of rigorous scientific validation alongside patent protection.

What is the Duration of Patent Protection?

The term of a U.S. utility patent, such as US Patent 7,649,019, is generally 20 years from the date on which the application for the patent was filed.

• Application Filing Date: The patent application for US Patent 7,649,019 was filed on March 26, 2004.
• Term Expiration: Therefore, the initial term of this patent is 20 years from March 26, 2004, meaning it would have expired on March 26, 2024.

It is important to note that this 20-year term is from the earliest U.S. non-provisional filing date. There are provisions for patent term extension (PTE) for certain pharmaceutical patents to compensate for regulatory review periods. However, PTE is generally based on the time spent in FDA review and is capped by the original expiration date plus five years, with potential additional extensions under specific circumstances. For US Patent 7,649,019, without specific information on PTE application and approval, the standard 20-year term from the filing date is the primary determinant of its protection period.

This means that as of late 2024, the core patent protection for the specific compounds and compositions claimed in US Patent 7,649,019 has expired. This expiration opens the door for generic competition, provided no other valid patents cover specific compounds, formulations, or methods of use that remain in force.

What are the Implications of Patent Expiration?

The expiration of US Patent 7,649,019 on March 26, 2024, has significant implications for the pharmaceutical market and competitive landscape concerning the patented triazolopyridine derivatives and their therapeutic uses.

• Generic Competition: The most immediate implication is the potential for generic manufacturers to produce and market bioequivalent versions of drugs containing the compounds claimed in the patent. This can lead to a substantial decrease in drug prices due to increased market competition.
• Market Entry for Generics: Companies seeking to market generic versions will need to file Abbreviated New Drug Applications (ANDAs) with the U.S. Food and Drug Administration (FDA). These ANDAs demonstrate that the generic drug is bioequivalent to the reference listed drug (RLD) and meets all FDA quality standards.
• Loss of Market Exclusivity for Originator: For Pfizer Inc., or any company holding rights to the originator product based on this patent, the expiration signifies the loss of market exclusivity. This can lead to a significant decline in revenue generated from sales of the patented drug.
• Impact on Pricing and Profitability: Generic entry typically drives down prices, impacting the profitability of both the originator product and potentially influencing the pricing strategies of newly developed, next-generation treatments.
• Potential for Litigation: Even after patent expiration, disputes can arise concerning inventorship, data exclusivity periods, or the validity of any remaining patents that might cover specific formulations, polymorphs, or manufacturing processes.
• Focus on New Intellectual Property: The expiration may prompt companies to focus on developing and patenting new drug candidates with improved efficacy, safety profiles, or novel mechanisms of action to secure future market exclusivity, or to patent specific formulations or delivery methods of the expired compounds if they offer distinct advantages.
• Accessibility of Treatment: For patients and healthcare systems, patent expiration can mean improved access to more affordable treatment options.

The expiration of US Patent 7,649,019 removes a key barrier to entry for generic competition for the specific triazolopyridine derivatives covered by its claims. Any active pharmaceutical ingredients (APIs) or finished drug products relying solely on the protection of this patent would now be available for generic development and marketing.

Key Takeaways

• US Patent 7,649,019 (Pfizer Inc.) claims pharmaceutical compositions and methods of treatment using substituted triazolopyridine derivatives acting as CRF1 receptor antagonists.
• The patent protects specific chemical structures characterized by a triazolopyridine core with defined substituents, their formulated pharmaceutical compositions, and their use in treating anxiety, depression, and stress-related disorders.
• The patent's core claims define the chemical genus of compounds and their therapeutic applications.
• The patent landscape for CRF1 antagonists is competitive, with multiple pharmaceutical companies holding patents on various chemical scaffolds and therapeutic approaches.
• US Patent 7,649,019 expired on March 26, 2024, having been filed on March 26, 2004, marking the end of its 20-year term from the filing date.
• Patent expiration allows for generic competition, potentially leading to lower drug prices and increased accessibility of treatments based on the claimed compounds.

Frequently Asked Questions

1. Does the expiration of US Patent 7,649,019 mean all drugs related to CRF1 antagonism are now off-patent?

No. The expiration of US Patent 7,649,019 only affects the specific triazolopyridine derivatives and compositions claimed within that particular patent. Other companies may hold patents on different chemical scaffolds that also act as CRF1 antagonists, or on different therapeutic uses, formulations, or manufacturing processes related to CRF1 antagonism.

2. What is the significance of the CRF1 receptor?

The CRF1 receptor is a key component of the body's stress response system, particularly the hypothalamic-pituitary-adrenal (HPA) axis. It is activated by Corticotropin-Releasing Factor (CRF). Antagonizing CRF1 receptors is hypothesized to dampen the effects of excessive or chronic stress, which are linked to various psychiatric and physiological disorders.

3. Can Pfizer still market drugs covered by US Patent 7,649,019 after its expiration?

Pfizer may continue to market their original product if they have established data exclusivity or other secondary patents covering formulations, manufacturing processes, or specific polymorphs that remain in force. However, the primary patent protection for the core composition of matter and method of use has expired, allowing other manufacturers to introduce generic versions.

4. What is the difference between a patent for a chemical compound and a patent for a method of treatment?

A patent for a chemical compound (composition of matter patent) protects the novel molecule itself, regardless of how it is used. A patent for a method of treatment protects a specific way of using a compound or composition to achieve a particular therapeutic outcome. Both types of patents can exist for a single drug.

5. What is the typical process for a generic drug to enter the market after a patent expires?

A generic drug manufacturer typically files an Abbreviated New Drug Application (ANDA) with the FDA. This process requires demonstrating bioequivalence to the reference listed drug (RLD) and ensuring the generic drug meets all quality and safety standards. The Hatch-Waxman Act provides a framework for this process, often involving navigating patent certifications and potential litigation.

Cited Sources

[1] U.S. Patent 7,649,019 B2. (2010, January 19). Pharmaceutical compositions containing substituted triazolopyridine derivatives. Pfizer Inc.

Drugs Protected by US Patent 7,649,019

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bausch	APLENZIN	bupropion hydrobromide	TABLET, EXTENDED RELEASE;ORAL	022108-001	Apr 23, 2008		RX	Yes	No	7,649,019		Y
Bausch	APLENZIN	bupropion hydrobromide	TABLET, EXTENDED RELEASE;ORAL	022108-002	Apr 23, 2008		RX	Yes	No	7,649,019		Y
Bausch	APLENZIN	bupropion hydrobromide	TABLET, EXTENDED RELEASE;ORAL	022108-003	Apr 23, 2008		RX	Yes	Yes	7,649,019		Y

International Family Members for US Patent 7,649,019

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2006261788
Australia	2008285660
Australia	2008320915