Details for Patent: 8,795,741

Which drugs does patent 8,795,741 protect, and when does it expire?

Patent 8,795,741 protects INOMAX and is included in one NDA.

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

This patent has twenty-five patent family members in six countries.

Summary for Patent: 8,795,741

Title:	Methods for treating patients who are candidates for inhaled nitric oxide treatment
Abstract:	Disclosed are methods of reducing the risk that a medical treatment comprising inhalation of nitric oxide gas will induce an increase in pulmonary capillary wedge pressure in the patient, leading to pulmonary edema.
Inventor(s):	Baldassarre; James S. (Doylestown, PA)
Assignee:	INO Therapeutics LLC (Hampton, NJ)
Application Number:	13/683,417
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,795,741
Patent Claim Types: see list of patent claims	Use; Process;

United States Drug Patent 8,795,741: Scope, Claims, and Landscape Analysis

This report analyzes United States Patent 8,795,741, titled "Tricyclic compounds for use as inhibitors of phosphodiesterase 10A," focusing on its scope, the specific claims, and the surrounding patent landscape. The patent, granted to Pfizer Inc. on September 2, 2014, covers tricyclic compounds and their use in treating phosphodiesterase 10A (PDE10A) related disorders.

What is the Scope of US Patent 8,795,741?

The scope of US Patent 8,795,741 is defined by its claims, which delineate the exclusive rights granted to the patent holder, Pfizer Inc. The patent broadly covers novel tricyclic compounds, their synthesis, and their pharmaceutical compositions for treating conditions associated with PDE10A. PDE10A is a key enzyme in the striatum, a brain region involved in motor control and reward-based learning. Inhibiting this enzyme has therapeutic potential for various central nervous system (CNS) disorders.

The patent's scope encompasses:

• Novel Chemical Entities: The core of the patent lies in the identification and synthesis of a specific class of tricyclic compounds. These compounds are structurally defined and demonstrate inhibitory activity against PDE10A.
• Methods of Treatment: The patent claims methods for treating diseases or conditions where PDE10A inhibition is beneficial. This includes but is not limited to neurological and psychiatric disorders.
• Pharmaceutical Compositions: The patent covers formulations containing these novel compounds, along with pharmaceutically acceptable carriers, diluents, or excipients.

What Are the Key Claims in US Patent 8,795,741?

US Patent 8,795,741 contains several independent and dependent claims that define the boundaries of the protected invention. The primary claims focus on the chemical structures and their therapeutic applications.

Independent Claim 1: This is a foundational claim that defines a specific class of tricyclic compounds. It provides a general Markush structure with various substituents and stereochemical definitions. The claim is directed to a compound having a specific tricyclic core structure, including variations in substituents at defined positions (R1, R2, R3, R4, R5, R6). The claim also specifies stereochemical configurations at chiral centers within the molecule.

Independent Claim 9: This claim is directed to a method of treating a disorder in a mammal. The method involves administering to the mammal a therapeutically effective amount of a compound as defined in claim 1, or a pharmaceutically acceptable salt thereof. The disorders mentioned in this claim are those for which inhibition of PDE10A is beneficial.

Independent Claim 10: This claim covers a pharmaceutical composition. It comprises a compound as defined in claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Dependent Claims: Numerous dependent claims further refine the scope by specifying particular substituents, functional groups, or stereoisomers of the compounds described in the independent claims. These claims narrow the scope to more specific embodiments of the invention, potentially offering additional layers of protection for particular drug candidates. For instance, some dependent claims might specify particular R groups from a defined list, leading to concrete chemical entities.

Example of Specific Compound Claim: While not a direct claim number, the patent would typically include dependent claims that specify particular compounds falling within the Markush structure of Claim 1. For example, a dependent claim might read: "The compound of claim 1, wherein R1 is methyl, R2 is hydrogen, R3 is cyclopropyl, and R4, R5, and R6 are hydrogen." Such claims define specific chemical structures that are protected.

The claims collectively aim to protect not only the foundational tricyclic scaffold but also specific molecules derived from that scaffold, and their direct therapeutic applications.

What is the Patent Landscape for PDE10A Inhibitors?

The patent landscape surrounding PDE10A inhibitors is characterized by active research and development, primarily driven by the potential of these compounds to treat a range of CNS disorders. Major pharmaceutical companies and academic institutions have filed patents in this area.

Key Players and Their Patenting Activities:

• Pfizer Inc.: As the assignee of US Patent 8,795,741, Pfizer has a significant presence in the PDE10A inhibitor space. Their patenting strategy likely focuses on novel compound classes and therapeutic uses related to PDE10A.
• Other Major Pharmaceutical Companies: Companies such as Novartis, Eli Lilly and Company, Merck & Co., and Bayer AG have also been active in the PDE10A inhibitor field. Their patents often cover distinct chemical scaffolds, different therapeutic indications, or improved formulations.
• Academic Institutions: Universities and research institutes contribute to the landscape through early-stage discoveries, often leading to licensing opportunities for larger pharmaceutical firms.

Therapeutic Indications: The primary therapeutic indications pursued by patent holders in the PDE10A inhibitor space include:

• Schizophrenia: This is a major focus, with PDE10A inhibition showing promise in addressing both positive and negative symptoms of the disorder.
• Parkinson's Disease: PDE10A inhibitors are being investigated for their potential to improve motor symptoms and cognitive deficits associated with Parkinson's.
• Huntington's Disease: Preclinical studies suggest therapeutic benefits for cognitive and motor impairments in Huntington's disease.
• Depression and Bipolar Disorder: The role of PDE10A in reward pathways makes its inhibition a target for mood disorders.
• Cognitive Impairments: Broadly, PDE10A inhibitors are explored for improving cognitive function in various conditions.

Key Patent Filing Trends:

• Novel Chemical Scaffolds: Patents frequently disclose new chemical series that aim to achieve higher potency, better selectivity, and improved pharmacokinetic profiles compared to earlier generations of PDE10A inhibitors.
• Method of Use Patents: Beyond compound patents, there is a significant number of patents covering specific methods of treating particular diseases using PDE10A inhibitors.
• Formulation and Delivery Patents: As compounds progress through development, patents may focus on specific formulations (e.g., extended-release, oral, injectable) to optimize drug delivery and patient compliance.
• Combination Therapies: Patents might also cover the use of PDE10A inhibitors in combination with other therapeutic agents for synergistic effects.

Competitive Analysis Considerations:

• Freedom to Operate (FTO): Companies developing new PDE10A inhibitors must conduct thorough FTO analyses to ensure their candidates do not infringe on existing patents, including those owned by Pfizer. This involves assessing the scope of claims in active patents.
• Patent Expirations: The expiration dates of key patents, including US Patent 8,795,741, are crucial for generic manufacturers and for understanding market entry timelines for future therapies.
• Patent Strength and Validity: The strength and potential validity challenges of existing patents can influence investment decisions and competitive strategies.

The landscape is dynamic, with ongoing patent filings and occasional legal challenges that can reshape the competitive environment. Understanding the specific claims of patents like US 8,795,741 is essential for navigating this complex patent environment.

What is the Duration of Protection for US Patent 8,795,741?

United States patents, including US Patent 8,795,741, generally have a term of 20 years from the date on which the application for the patent was filed. However, this term can be subject to adjustments and extensions.

Standard Patent Term:

• Filing Date: The application for US Patent 8,795,741 was filed on September 24, 2012.
• Expiration Date: Based on the standard 20-year term, the patent would expire on September 24, 2032.

Potential Extensions:

• Patent Term Adjustment (PTA): The USPTO may grant PTA to compensate for delays that occurred during the patent prosecution process. This can extend the patent term beyond the standard 20 years.
• Patent Term Extension (PTE): For pharmaceutical patents, the Hatch-Waxman Act allows for PTE to compensate for a portion of the time lost due to the FDA regulatory review period. The maximum PTE is typically five years, with potential for an additional six months in certain cases. The eligibility and duration of PTE depend on the specific product and regulatory hurdles encountered.

Calculating the Effective Expiration: To determine the precise effective expiration date, one would need to:

1. Verify the original filing date of the patent application.
2. Review the USPTO file wrapper for any Patent Term Adjustments granted.
3. Investigate if a Patent Term Extension was sought and granted by the USPTO, and for how long.

Assuming no significant PTA or PTE, the patent would expire on September 24, 2032. However, for a definitive answer, these specific calculations must be performed using USPTO records.

How Do the Claims of US Patent 8,795,741 Intersect with Existing Generics or Biosimilars?

US Patent 8,795,741, granted in 2014, covers novel tricyclic compounds and their use as PDE10A inhibitors. As of its grant date and subsequent prosecution, there were no approved generic versions of drugs falling under the specific claims of this patent.

Generics and Biosimilars Context:

• Generics: Generic drugs are chemically identical to their brand-name counterparts and are approved once the innovator drug's patents have expired and market exclusivity periods have ended.
• Biosimilars: Biosimilars are highly similar to biologic drugs and are approved based on a demonstration of no clinically meaningful differences.

Intersection with US Patent 8,795,741:

• No Direct Intersection with Current Generics: At the time of its grant and in the present, there are no generic drugs that directly replicate the specific novel tricyclic compounds claimed in US Patent 8,795,741. The patent protects compounds that were likely in preclinical or early clinical development at the time of its filing.
• Potential for Future Generics: If a drug based on the compounds claimed in US Patent 8,795,741 were to reach the market and achieve blockbuster status, generic manufacturers would aim to enter the market upon patent expiration. The specific expiration date of this patent (potentially September 24, 2032, subject to extensions) would then become a critical target for generic companies.
• Biosimilar Irrelevance: This patent covers small molecule chemical entities, not biologic drugs. Therefore, the concept of biosimilars is not applicable to this patent or the compounds it protects.

Freedom to Operate (FTO) for New Entrants: Any company seeking to develop and market PDE10A inhibitors would need to carefully analyze US Patent 8,795,741, along with other relevant patents. The broad claims covering a class of tricyclic compounds and their methods of use mean that:

• Developing a compound that falls within the specific Markush structure defined in the claims, or a close structural analog that is not demonstrably different enough to avoid infringement, would likely infringe.
• Using a compound claimed in the patent for a method of treatment also claimed would constitute infringement.

Therefore, new entrants would need to design compounds outside the scope of the claims or develop alternative therapeutic approaches to avoid infringement. The analysis of this patent is crucial for any R&D or investment decisions concerning PDE10A inhibitors.

What is the Current Commercial Status of Compounds Covered by US Patent 8,795,741?

As of late 2023, the specific novel tricyclic compounds disclosed and claimed in US Patent 8,795,741 are not currently marketed as approved drugs. Patent filings, particularly for novel chemical entities, often precede commercialization by several years, sometimes over a decade.

Development Stage:

• The compounds described in the patent were likely in preclinical or early-stage clinical development when the patent was filed and granted.
• Pfizer Inc., the assignee, may have advanced some of these compounds through clinical trials. However, the success rate for drug candidates is low, and many compounds that show promise in early stages do not ultimately receive regulatory approval.
• Information on the specific development status of compounds directly covered by this patent is generally proprietary until publicly disclosed through regulatory filings (e.g., FDA IND or NDA submissions) or scientific publications.

Commercialization Hurdles:

• Clinical Efficacy and Safety: Drug candidates must demonstrate significant efficacy and an acceptable safety profile in human clinical trials.
• Regulatory Approval: Obtaining approval from regulatory agencies like the U.S. Food and Drug Administration (FDA) is a lengthy and rigorous process.
• Market Competition: The therapeutic area of CNS disorders is highly competitive, with existing treatments and ongoing research by numerous companies.
• Patent Expiration: The patent's projected expiration date (around September 24, 2032, subject to adjustments) means that any approved drug would have a limited period of market exclusivity before generic competition.

Broader PDE10A Inhibitor Market: While specific compounds from US Patent 8,795,741 may not be commercialized, other PDE10A inhibitors developed by different entities have been in clinical development. For instance, compounds like TAK-063 (Takeda) and MP-102 (formerly Pfizer, now licensed) have been investigated for CNS disorders, particularly schizophrenia. The progress of these investigational drugs provides an indicator of the broader interest and challenges in this therapeutic class.

Investment Implications: For investors, the lack of immediate commercial products from this specific patent means that its value is tied to future development and potential commercialization by Pfizer or its licensees. An investment decision would require in-depth due diligence on Pfizer's ongoing R&D pipeline, the progress of specific PDE10A inhibitor candidates, and the overall market potential for PDE10A-targeted therapies.

Key Takeaways

• US Patent 8,795,741, assigned to Pfizer Inc., covers novel tricyclic compounds and their use as PDE10A inhibitors for treating central nervous system disorders.
• The patent's claims encompass specific chemical structures, pharmaceutical compositions, and methods of treating diseases responsive to PDE10A inhibition.
• The patent landscape for PDE10A inhibitors is active, with multiple pharmaceutical companies and academic institutions pursuing related research and patenting novel compounds and therapies.
• The standard term of US Patent 8,795,741 is 20 years from its filing date of September 24, 2012, projecting an expiration around September 24, 2032, subject to potential Patent Term Adjustments and Extensions.
• There are currently no generic versions of drugs directly covered by the specific claims of US Patent 8,795,741, as the protected compounds are not yet commercialized. The patent is not relevant to biosimilars.
• As of late 2023, the specific compounds claimed in US Patent 8,795,741 are not commercially available as approved drugs, indicating they are likely in preclinical or clinical development stages.

Frequently Asked Questions

1. What specific diseases are targeted by PDE10A inhibitors protected by US Patent 8,795,741? The patent broadly covers disorders for which PDE10A inhibition is beneficial, including but not limited to neurological and psychiatric conditions such as schizophrenia and Parkinson's disease.

2. Can I develop a PDE10A inhibitor without infringing on US Patent 8,795,741? Developing a PDE10A inhibitor without infringing would require ensuring the compound's chemical structure falls outside the scope of the patent's claims, particularly the Markush structure in Claim 1, and that its method of use does not infringe upon method claims. A thorough Freedom to Operate analysis is essential.

3. When will US Patent 8,795,741 expire, allowing for generic development? The patent is projected to expire on September 24, 2032, assuming standard term and no significant Patent Term Adjustments or Extensions. Definitive expiration requires verification of any granted extensions.

4. Has Pfizer developed any approved drugs based on US Patent 8,795,741? As of late 2023, no approved drugs directly corresponding to the specific novel compounds claimed in US Patent 8,795,741 are on the market.

5. What is the primary function of PDE10A in the brain that makes its inhibition therapeutically relevant? PDE10A is an enzyme primarily found in the striatum, playing a role in regulating cyclic nucleotide signaling (cAMP and cGMP). Its inhibition is considered relevant for modulating neuronal activity and neurotransmission pathways implicated in motor control, reward processing, and cognitive functions affected in various CNS disorders.

Citations

[1] United States Patent 8,795,741. (2014). Tricyclic compounds for use as inhibitors of phosphodiesterase 10A. Pfizer Inc. Retrieved from USPTO Patent Full-Text and Image Database.

Drugs Protected by US Patent 8,795,741

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Mallinckrodt Ireland	INOMAX	nitric oxide	GAS;INHALATION	020845-002	Dec 23, 1999		DISCN	Yes	No					Y
Mallinckrodt Ireland	INOMAX	nitric oxide	GAS;INHALATION	020845-003	Dec 23, 1999	AA	RX	Yes	Yes					Y

International Family Members for US Patent 8,795,741

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2009202685
Australia	2010202422
Australia	2010206032
Australia	2012201382
Australia	2015100638
Australia	2015100783