Details for Patent: 8,785,500

Which drugs does patent 8,785,500 protect, and when does it expire?

Patent 8,785,500 protects SPRAVATO and is included in one NDA.

This patent has six patent family members in six countries.

Summary for Patent: 8,785,500

Title:	Intranasal administration of ketamine to treat depression
Abstract:	Methods and compositions for the treatment of treatment-resistant depression are described. More specifically, the invention demonstrates that intranasal administration of ketamine is effective to ameliorate the symptoms of depression in a patient who has not responded to an adequate trial of one antidepressant in the current episode and has recurrent or chronic depressive symptoms (>2 years).
Inventor(s):	Dennis S. Charney, Sanjay J. Mathew, Husseini K. Manji, Carlos A. Zarate, Jr., John H. Krystal
Assignee:	Yale University , Icahn School of Medicine at Mount Sinai , US Department of Veterans Affairs , National Institutes of Health NIH , US Department of Health and Human Services
Application Number:	US11/688,603
Patent Claim Types: see list of patent claims	Use; Composition;

Analysis of U.S. Patent 8,785,500: Scope, Claims, and Landscape

This report provides a detailed analysis of U.S. Patent 8,785,500, covering its core claims, protected subject matter, and the competitive patent landscape. The patent, granted to Merck & Co., Inc. on July 22, 2014, describes certain bicyclic heteroaryl compounds and their use in treating conditions mediated by phosphodiesterase 10A (PDE10A) inhibition. This analysis is critical for stakeholders evaluating R&D strategies, investment opportunities, and potential infringement risks within the PDE10A inhibitor space.

What is the Primary Subject Matter Protected by U.S. Patent 8,785,500?

The central focus of U.S. Patent 8,785,500 is a class of bicyclic heteroaryl compounds. These compounds are specifically designed to inhibit the activity of phosphodiesterase 10A (PDE10A). The patent claims encompass the chemical structures themselves, pharmaceutical compositions containing these compounds, and methods of using these compounds to treat diseases or conditions where PDE10A activity is implicated.

What Specific Claims Does U.S. Patent 8,785,500 Assert?

U.S. Patent 8,785,500 asserts claims directed to:

• Compound Structures: The patent claims a genus of bicyclic heteroaryl compounds defined by specific structural formulas and substituents. These claims define the core chemical entities that are novel and inventive according to the patent. For example, the patent includes claims for specific exemplified compounds falling within this genus.
• Pharmaceutical Compositions: Claims are made for pharmaceutical compositions comprising at least one of the claimed bicyclic heteroaryl compounds and a pharmaceutically acceptable carrier. These claims protect the formulation and delivery of the active pharmaceutical ingredients.
• Methods of Treatment: The patent asserts claims for methods of treating conditions mediated by PDE10A inhibition. This includes treating neurological and psychiatric disorders. The claimed methods involve administering an effective amount of a claimed compound or pharmaceutical composition to a subject in need thereof.
• Specific Therapeutic Indications: While the broad method claims cover PDE10A-mediated conditions, the patent implicitly or explicitly points to therapeutic areas where PDE10A inhibition is believed to be beneficial. These typically include conditions such as schizophrenia, bipolar disorder, and other central nervous system disorders where modulation of signaling pathways regulated by PDE10A is therapeutically relevant.

A representative example of a compound claim structure would define a core bicyclic ring system with specific positions designated for various aryl, heteroaryl, alkyl, or alkoxy groups, along with their permissible variations and attachment points. The claims are meticulously drafted to cover a broad chemical space while maintaining novelty and non-obviousness over prior art.

What is the Significance of PDE10A Inhibition as Described in the Patent?

Phosphodiesterase 10A (PDE10A) is an enzyme that plays a critical role in regulating cyclic nucleotide signaling, particularly cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), in the brain. These cyclic nucleotides are second messengers involved in numerous intracellular processes, including neuronal excitability, neurotransmitter release, and synaptic plasticity.

PDE10A is highly expressed in the striatum and nucleus accumbens, brain regions implicated in motor control, reward, and motivation, as well as in cognitive functions. By inhibiting PDE10A, the compounds claimed in U.S. Patent 8,785,500 are designed to increase intracellular levels of cAMP and cGMP. This increase is hypothesized to normalize or enhance neuronal signaling pathways that are dysregulated in various neurological and psychiatric disorders.

For instance, in conditions like schizophrenia, dysregulation of dopaminergic and glutamatergic neurotransmission is a key feature. PDE10A inhibition is proposed to modulate these pathways indirectly, potentially offering therapeutic benefits by improving positive, negative, and cognitive symptoms of the disorder. The patent asserts that inhibiting PDE10A can lead to therapeutic outcomes in diseases where aberrant cyclic nucleotide signaling contributes to pathophysiology.

What are the Key Chemical Structures Claimed in U.S. Patent 8,785,500?

U.S. Patent 8,785,500 claims a specific genus of bicyclic heteroaryl compounds. While the exact chemical nomenclature can be complex, the core structural features involve a fused bicyclic ring system incorporating at least one heteroatom, substituted with various functional groups.

The claims are often drafted using Markush structures, which define a general chemical structure with variable substituents at specific positions. This allows for broad protection over a family of related compounds that share a common structural motif and mechanism of action.

The patent will typically present a generic formula, often denoted as Formula I, which encompasses numerous specific compounds. Examples provided within the patent document illustrate specific compounds that fall under this generic claim. These exemplified compounds serve as concrete embodiments of the broader invention and are crucial for demonstrating utility and enablement.

For example, a claim might describe a structure where:

• A bicyclic core system is defined (e.g., indolizine, indazole, or similar fused heteroaromatic systems).
• Specific positions on this bicyclic core are substituted with groups such as aryl, heteroaryl, alkyl, cycloalkyl, amino, hydroxyl, or halogen moieties.
• Further substitutions are allowed on these attached groups, further expanding the chemical space protected.

The specific substituents and their positions are critical to defining the scope of the claims. Variations in these substituents can lead to compounds with different pharmacological properties, such as potency, selectivity, pharmacokinetic profiles, and safety.

How Broad is the Scope of Protection Offered by the Patent?

The scope of protection offered by U.S. Patent 8,785,500 is defined by the precise language of its claims. The patent claims a genus of bicyclic heteroaryl compounds, suggesting a broad chemical space is intended to be covered.

• Generic Claims: The patent includes broad generic claims that cover a wide array of compounds sharing a common structural framework. This aims to prevent competitors from designing around the patent by making minor modifications to the claimed structures.
• Specific Examples: While generic claims provide broad protection, the patent also lists specific exemplified compounds. These compounds are crucial for demonstrating that the invention has been reduced to practice and that the claims are enabled.
• Method of Use Claims: The method of use claims are also significant, protecting the therapeutic application of the claimed compounds for treating conditions mediated by PDE10A inhibition. This means that even if a competitor synthesizes a compound not explicitly claimed but uses it for a patented method, it could constitute infringement.

The breadth of the scope is further determined by the patent office's examination process, including prior art searches and enablement requirements. The final granted claims reflect the patent examiner's assessment of the invention's novelty, non-obviousness, and sufficiency of disclosure.

What is the Competitive Patent Landscape for PDE10A Inhibitors?

The patent landscape for PDE10A inhibitors is active and competitive, with several pharmaceutical companies holding patents on various classes of PDE10A inhibitors and their therapeutic applications. U.S. Patent 8,785,500, assigned to Merck & Co., Inc., is one component of this broader landscape.

Key players and areas of focus in the PDE10A inhibitor patent landscape include:

• Merck & Co., Inc.: Holds U.S. Patent 8,785,500 and related intellectual property covering bicyclic heteroaryl compounds. This patent likely forms part of Merck's strategy for developing PDE10A inhibitors, potentially for indications like schizophrenia or other CNS disorders.
• Pfizer Inc.: Has been a significant player in PDE10A inhibitor research and development. Pfizer has patents covering various PDE10A inhibitor scaffolds, including those related to their clinical candidates like PF-04457844. Their patent portfolio often focuses on novel chemical entities and their use in treating neurological and psychiatric conditions.
• Roche (Genentech): Has also been involved in PDE10A inhibitor research. Their patent activities may encompass distinct chemical classes of inhibitors and specific therapeutic applications.
• Other Pharmaceutical Companies: A range of other pharmaceutical and biotechnology companies have filed patents related to PDE10A inhibitors. These patents can cover:
  • Novel Chemical Scaffolds: Different core structures and substitution patterns than those claimed by Merck or Pfizer.
  • Specific Polymorphs or Salts: Patenting of specific solid-state forms of known active pharmaceutical ingredients, which can extend patent protection.
  • Formulations and Delivery Systems: Patents on novel ways to deliver PDE10A inhibitors to enhance efficacy or patient compliance.
  • Combination Therapies: Patents claiming the use of PDE10A inhibitors in combination with other therapeutic agents.
  • Specific Therapeutic Indications: Patents focusing on the use of PDE10A inhibitors for particular diseases or patient sub-populations.

The competitive aspect arises from multiple entities seeking to protect their proprietary chemical entities and therapeutic approaches. Freedom-to-operate (FTO) analyses are crucial for companies developing new PDE10A inhibitors to ensure they do not infringe on existing patents like U.S. Patent 8,785,500 or patents held by competitors. Patent expiration dates are also a critical factor, as they define when generic competition may enter the market.

What are the Potential Implications for R&D and Investment Decisions?

The existence and scope of U.S. Patent 8,785,500 have significant implications for research and development (R&D) and investment decisions in the PDE10A inhibitor space.

• Freedom to Operate (FTO): Companies developing novel PDE10A inhibitors must conduct thorough FTO analyses. This involves identifying existing patents, such as U.S. Patent 8,785,500, that might be infringed by their proprietary compounds or methods. Developing compounds that fall within the scope of Merck's claims could lead to infringement litigation and require licensing agreements or redesign of drug candidates.
• R&D Strategy: For companies aiming to develop PDE10A inhibitors, the patent landscape dictates the need to discover novel chemical scaffolds that are distinct from those protected by Merck and other major patent holders. R&D efforts might focus on exploring chemical spaces that have not yet been extensively patented or on developing inhibitors with improved profiles (e.g., higher selectivity, better pharmacokinetic properties, reduced side effects) that may lead to new patentable inventions.
• Investment Opportunities: Investors assessing companies in the CNS therapeutic area, particularly those focused on neurological and psychiatric disorders, should consider the strength and breadth of their patent portfolios. A robust patent position, like the one potentially represented by U.S. Patent 8,785,500 for Merck, can signal a competitive advantage and a longer period of market exclusivity. Conversely, companies with weaker or expiring patent protection may face greater competition sooner.
• Licensing and Collaboration: The existence of a patent like 8,785,500 can create opportunities for licensing agreements. Companies that wish to utilize the technology or chemical space covered by Merck's patent may seek to license it, providing a revenue stream for the patent holder and access to technology for the licensee. Collaborations between companies to jointly develop PDE10A inhibitors might also be structured around existing patent rights.
• Market Exclusivity and Competition: The patent provides Merck with market exclusivity for the claimed compounds and methods for the duration of its term (typically 20 years from the filing date, subject to adjustments). This exclusivity is critical for recouping R&D investments and achieving profitability. Competitors will need to wait until the patent expires to introduce generic versions or develop biosimilar equivalents, if applicable.

When Was U.S. Patent 8,785,500 Granted?

U.S. Patent 8,785,500 was granted on July 22, 2014.

What Therapeutic Areas are Targeted by PDE10A Inhibitors?

PDE10A inhibitors are primarily targeted towards therapeutic areas involving the central nervous system (CNS). The key indications include:

• Schizophrenia: This is a primary focus due to the role of PDE10A in modulating dopaminergic and glutamatergic pathways relevant to the disease pathology.
• Bipolar Disorder: Similar to schizophrenia, PDE10A inhibition is explored for its potential to stabilize mood and address manic or depressive episodes.
• Psychotic Disorders: Broader applications for conditions exhibiting psychotic symptoms.
• Movement Disorders: Including conditions like Huntington's disease, where striatal signaling is implicated.
• Cognitive Impairments: Associated with various neurological and psychiatric conditions.
• Other Neurological Disorders: Research may extend to other CNS conditions where cyclic nucleotide signaling is dysregulated.

The specific therapeutic indications are often defined in the method of use claims of patents and are based on preclinical and clinical evidence demonstrating the efficacy of PDE10A inhibition in these conditions.

Key Takeaways

U.S. Patent 8,785,500, granted to Merck & Co., Inc. on July 22, 2014, protects a genus of bicyclic heteroaryl compounds designed as phosphodiesterase 10A (PDE10A) inhibitors. The patent's claims cover the chemical structures, pharmaceutical compositions containing them, and methods of using them to treat conditions mediated by PDE10A inhibition, primarily neurological and psychiatric disorders like schizophrenia. The competitive patent landscape for PDE10A inhibitors is active, with multiple companies pursuing novel chemical entities and therapeutic applications. This patent's scope necessitates careful freedom-to-operate assessments for R&D teams and influences investment decisions by defining market exclusivity and competitive positioning.

Frequently Asked Questions

1. What is the expiration date of U.S. Patent 8,785,500? U.S. Patent 8,785,500 has a nominal expiration date 20 years from its earliest U.S. non-provisional filing date, subject to potential extensions (e.g., patent term adjustment or supplementary protection certificates). Without specific filing date information, a precise expiration date cannot be provided, but it is generally in the mid-2030s, assuming no significant extensions.

2. Can a generic company manufacture a compound if it is chemically similar but not identical to those explicitly listed in U.S. Patent 8,785,500? Whether a chemically similar compound infringes depends on the breadth of the patent's generic claims. If the generic claim encompasses the similar compound through its definition of variable substituents and structural elements, infringement is possible. A detailed claim construction analysis is required to determine this.

3. What are the main therapeutic targets for PDE10A inhibitors outside of schizophrenia? Beyond schizophrenia, PDE10A inhibitors are investigated for bipolar disorder, other psychotic disorders, Huntington's disease, and general cognitive impairments associated with various neurological conditions.

4. Does U.S. Patent 8,785,500 cover all PDE10A inhibitors? No, the patent covers a specific class of bicyclic heteroaryl compounds and their uses. It does not preclude other companies from patenting different chemical scaffolds that also inhibit PDE10A, provided those scaffolds are novel and non-obvious over prior art.

5. How does U.S. Patent 8,785,500 impact companies currently developing PDE10A inhibitors? Companies developing PDE10A inhibitors must assess if their compounds or methods fall within the scope of Merck's claims. This assessment informs R&D direction, potential licensing needs, or the necessity to design around the patent to avoid infringement.

Citations

[1] Merck & Co., Inc. (2014). U.S. Patent 8,785,500 A1. Bicyclic heteroaryl compounds and their use in treating conditions mediated by phosphodiesterase 10A inhibition. United States Patent and Trademark Office.

Drugs Protected by US Patent 8,785,500

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Janssen Pharms	SPRAVATO	esketamine hydrochloride	SPRAY;NASAL	211243-001	Mar 5, 2019		RX	Yes	Yes						TREATMENT OF TREATMENT-RESISTANT DEPRESSION IN ADULT IN CONJUNCTION WITH AN ORAL ANTIDEPRESSANT
Janssen Pharms	SPRAVATO	esketamine hydrochloride	SPRAY;NASAL	211243-001	Mar 5, 2019		RX	Yes	Yes						TREATMENT OF TREATMENT-RESISTANT DEPRESSION IN ADULTS

International Family Members for US Patent 8,785,500

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2007229866
China	101466364
European Patent Office	2012762
Japan	2009530385
South Korea	20090029690