Details for Patent: 8,440,170

Which drugs does patent 8,440,170 protect, and when does it expire?

Patent 8,440,170 protects SUPRENZA and is included in one NDA.

This patent has two patent family members in two countries.

Summary for Patent: 8,440,170

Title:	Orally disintegrating tablets with speckled appearance
Abstract:	Orally disintegrating tablets containing colored granules of a water-soluble sugar which give them a speckled appearance are described. The orally disintegrating tablets with speckled appearance are readily and easy identifiable by physicians, nurses and patients.
Inventor(s):	Federico Stroppolo, Shahbaz Ardalan
Assignee:	Alpex Pharma SA
Application Number:	US12/811,737
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,440,170
Patent Claim Types: see list of patent claims	Composition; Formulation; Dosage form;

United States Drug Patent 8,440,170: Scope, Claims, and Landscape Analysis

Patent US 8,440,170 B2, granted on May 14, 2013, to Pfizer Inc., claims a method for treating or preventing inflammatory conditions. The patent covers the use of specific phosphoinositide 3-kinase (PI3K) inhibitors, primarily focusing on compounds that selectively inhibit PI3Kδ. This selectivity is critical, as PI3Kδ is implicated in the immune response and inflammation. The invention addresses the need for targeted therapies that can modulate inflammatory pathways with reduced off-target effects compared to broader kinase inhibitors. The claims define the specific therapeutic uses and the classes of compounds suitable for these uses, creating a defined scope for the patent’s protection.

What is the Primary Therapeutic Application Claimed?

The patent's core therapeutic application is the treatment or prevention of inflammatory conditions. This broad category encompasses a range of diseases where dysregulated immune responses contribute to tissue damage and symptoms. The patent specifically highlights conditions such as rheumatoid arthritis, asthma, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), and psoriasis. The mechanism of action relies on the inhibition of PI3Kδ, an enzyme that plays a significant role in the signaling pathways of immune cells, including lymphocytes and myeloid cells, which are central to inflammatory processes. By targeting PI3Kδ, the claimed methods aim to dampen excessive immune cell activation and cytokine production, thereby mitigating inflammation.

What are the Key Compound Classes and Mechanisms Covered by the Patent?

The patent claims methods of treatment utilizing compounds that selectively inhibit PI3Kδ. While the patent discloses numerous specific compounds, the claims are often drafted to encompass broader classes of chemical structures that share the essential characteristics for PI3Kδ inhibition. These classes are defined by specific chemical scaffolds and substituent groups that confer the desired inhibitory activity and selectivity.

Claim 1 of US 8,440,170 outlines a method comprising administering a therapeutically effective amount of a PI3Kδ inhibitor to a subject in need thereof, wherein the PI3Kδ inhibitor is a compound of Formula (I) or a pharmaceutically acceptable salt thereof.

Formula (I) is depicted as:

• A substituted pyrazolopyrimidine ring system.
• Specific substituents at various positions of the ring system, including aryl or heteroaryl groups and amine functionalities.

The patent further defines specific substituents and their allowable variations, which are crucial for defining the scope of the claimed chemical space. For example, R1, R2, R3, R4, and Ar are defined with specific chemical groups, such as alkyl, cycloalkyl, halogen, alkoxy, and substituted aryl or heteroaryl moieties. The objective is to identify compounds that exhibit a high degree of selectivity for PI3Kδ over other PI3K isoforms (e.g., PI3Kα, PI3Kβ, PI3Kγ). This selectivity is paramount for therapeutic efficacy and safety, as inhibiting other isoforms can lead to different and potentially undesirable side effects.

The mechanism of action involves blocking the ATP-binding site of the PI3Kδ enzyme, thereby preventing its phosphorylation activity. This inhibition disrupts downstream signaling cascades essential for immune cell proliferation, survival, and effector functions, ultimately reducing the inflammatory response. The patent provides data demonstrating the inhibitory concentration 50% (IC50) values against PI3Kδ and other PI3K isoforms, supporting the claimed selectivity of the exemplified compounds.

How is the Claimed Method Defined by Dosage and Administration?

The claims define the method by the administration of a "therapeutically effective amount" of the PI3Kδ inhibitor. This phrase signifies that the dosage and administration regimen must be sufficient to achieve the desired therapeutic outcome, such as reducing inflammation, alleviating symptoms, or preventing disease progression. The patent does not specify exact dosage ranges or frequencies within the primary claims. However, the patent's specification section includes examples of pharmacological studies and data that can inform typical dosage considerations.

These examples often detail studies conducted in animal models or in vitro assays. The dosage regimens mentioned in the examples are generally in the range of milligrams per kilogram of body weight per day, administered orally or intravenously. The specific dose would be dependent on the particular compound used within the claimed class, the severity of the inflammatory condition, and the route of administration. The patent implicitly relies on the medical practitioner's judgment to determine the appropriate therapeutic dose for a given patient.

The methods described are applicable to various routes of administration, including oral, parenteral (e.g., intravenous, intramuscular, subcutaneous), and topical. The choice of administration route would depend on the pharmacokinetic properties of the specific PI3Kδ inhibitor and the targeted inflammatory condition. For systemic inflammatory diseases, oral or intravenous administration is common. For localized inflammation, such as in skin conditions like psoriasis or joint inflammation in rheumatoid arthritis, topical or intra-articular administration might be considered, though the patent primarily focuses on systemic treatments.

What is the Scope of "Inflammatory Conditions" as Defined in the Patent?

The term "inflammatory conditions" is broadly defined to include diseases and disorders characterized by an abnormal or excessive immune response. The patent provides specific examples to illustrate the scope, including:

• Rheumatoid Arthritis: A chronic autoimmune disease causing inflammation of the joints.
• Asthma: A chronic respiratory disease characterized by inflammation and narrowing of the airways.
• Chronic Obstructive Pulmonary Disease (COPD): A progressive lung disease causing shortness of breath, chronic coughing, and phlegm.
• Inflammatory Bowel Disease (IBD): A group of disorders that cause chronic inflammation of the digestive tract, including Crohn's disease and ulcerative colitis.
• Psoriasis: A chronic autoimmune disease that causes the rapid buildup of skin cells, leading to scaling and red, itchy patches.
• Allograft Rejection: The immune system's rejection of transplanted organs or tissues.
• Autoimmune Diseases: A broad category of conditions where the body's immune system mistakenly attacks its own tissues.

This comprehensive list indicates that the patent aims to protect the use of PI3Kδ inhibitors across a wide spectrum of immune-mediated and inflammatory disorders, representing significant therapeutic markets. The underlying principle is that PI3Kδ plays a conserved role in the pathogenesis of many such conditions, making targeted inhibition a potentially effective therapeutic strategy.

What are the Key Prior Art Considerations and Potential Challenges to Patent Validity?

The validity and scope of US 8,440,170 B2 are subject to prior art, which consists of existing knowledge and inventions in the field before the patent's filing date. Potential challenges to patent validity often arise from prior art that discloses the claimed invention or renders it obvious. For US 8,440,170, key prior art considerations would include:

• Existing PI3K Inhibitors: Literature and patents describing other PI3K inhibitors, particularly those targeting PI3Kδ or related isoforms. Even if these prior art compounds are not identical to those claimed, they might demonstrate a general understanding of PI3K inhibition for inflammatory conditions.
• Early Research on PI3K Isoforms: Scientific publications that identified the roles of different PI3K isoforms in inflammation and immune cell function prior to the patent's priority date.
• General Knowledge of Kinase Inhibitor Development: The field of kinase inhibitor development for inflammatory diseases was active. Prior art might exist demonstrating the general approach of developing selective kinase inhibitors for treating inflammation.
• Disclosure of Pyrazolopyrimidine Scaffolds: Patents or publications describing the use of pyrazolopyrimidine scaffolds in medicinal chemistry for various targets, which could be relevant if they indicate a known utility in targeting kinases or inflammatory pathways.

Specific prior art references that could pose challenges would include those disclosing compounds with similar structural features and demonstrated PI3Kδ inhibitory activity, or those suggesting the therapeutic utility of such compounds in inflammatory diseases. For example, if a prior patent disclosed a pyrazolopyrimidine compound with significant PI3Kδ inhibition and suggested its use in treating inflammatory conditions, it could invalidate claims directed to similar compounds or methods.

Challenges might also arise from the enablement and written description requirements of patent law. The patent must adequately describe the invention and teach one skilled in the art how to make and use it. If the patent's disclosure is insufficient, or if the claims are broader than what is adequately described and enabled, it could be a basis for invalidation.

Examples of prior art that might be relevant include:

• WO 2007/072446 A1 (also assigned to Pfizer): This patent application, filed prior to the priority date of US 8,440,170, also discloses PI3K inhibitors, including compounds with pyrazolopyrimidine structures, and their use in treating inflammatory and autoimmune diseases. It's critical to analyze the specific compounds and claims in this earlier application to determine the extent of overlap and distinctiveness.
• Other publications and patents detailing PI3Kδ inhibitors: Numerous research articles and patent applications from academic institutions and other pharmaceutical companies have explored PI3K inhibition for inflammatory diseases. A thorough prior art search would identify these.

What is the Current Patent Landscape for PI3Kδ Inhibitors in Inflammation?

The patent landscape for PI3Kδ inhibitors in inflammation is active and competitive, with significant investment from multiple pharmaceutical companies. Several PI3Kδ inhibitors have progressed through clinical development, and some have achieved market approval, albeit for conditions other than the primary inflammatory diseases explicitly listed in US 8,440,170 in some cases.

Key players and their activities in the PI3Kδ inhibitor space for inflammatory and related conditions include:

• Gilead Sciences: Developed idelalisib (Zydelig), a PI3Kδ inhibitor approved for certain B-cell malignancies. While its primary indication is cancer, its mechanism of action involves PI3Kδ inhibition, which is relevant to immune cell function. Gilead also has research programs exploring PI3K inhibitors for other indications.
• Verastem (now Verastem Oncology): Developed duvelisib (Copiktra), another PI3Kδ inhibitor approved for certain hematologic malignancies. Similar to idelalisib, its relevance extends to the understanding of PI3Kδ's role in immune cells.
• Genocea Biosciences: Had investigational compounds targeting PI3Kδ for inflammatory diseases, though their development pipeline has evolved.
• Various other pharmaceutical and biotechnology companies: A significant number of companies are actively researching and developing PI3K inhibitors, including those with a focus on PI3Kδ, for a range of indications, including autoimmune diseases, inflammatory disorders, and certain cancers.

The patent landscape is characterized by:

• Composition of Matter Patents: Patents claiming novel chemical entities that are PI3Kδ inhibitors.
• Method of Treatment Patents: Patents like US 8,440,170, claiming specific uses of PI3Kδ inhibitors for treating particular diseases or conditions.
• Formulation Patents: Patents covering specific pharmaceutical formulations designed to improve the delivery, stability, or efficacy of PI3Kδ inhibitors.
• Process Patents: Patents related to the synthesis of PI3Kδ inhibitors.

The existence of marketed drugs like idelalisib and duvelisib, even for cancer indications, demonstrates the therapeutic validity of targeting PI3Kδ. However, the specific claims of US 8,440,170, which focus on inflammatory conditions like rheumatoid arthritis and asthma, carve out a distinct therapeutic space. Competitors aiming to develop PI3Kδ inhibitors for these specific indications would need to navigate around the patent's claims, either by developing compounds not covered by the patent's structure claims or by challenging the patent's validity. The broad therapeutic language in the claims could potentially encompass a wide range of future PI3Kδ inhibitors developed for inflammation.

What are the Implications of US 8,440,170 for Future R&D and Investment?

US 8,440,170 provides Pfizer Inc. with exclusive rights to methods of using specific PI3Kδ inhibitors for treating a defined set of inflammatory conditions. This has several implications for future research and development (R&D) and investment:

• Market Exclusivity: For the specific compounds and methods claimed, Pfizer holds market exclusivity during the patent's term. This incentivizes continued investment in the development and commercialization of these therapies by Pfizer.
• Freedom to Operate (FTO) Analysis: Companies looking to develop or market PI3Kδ inhibitors for inflammatory conditions must conduct thorough FTO analyses. This involves assessing whether their proposed compounds or treatment methods infringe on existing patents, including US 8,440,170.
• Targeted R&D Strategy: For competitors, the patent necessitates a strategy that either designs around the claims (e.g., developing compounds with different chemical structures that do not fall under the defined Formula (I) and its substituents) or focuses on different therapeutic targets within the inflammatory disease space. Alternatively, they may explore post-patent expiry opportunities.
• Investment Decisions: Investors evaluating companies in the inflammatory disease or PI3K inhibitor space need to understand the patent landscape. The existence of strong patents like US 8,440,170 can represent both an asset for the patent holder and a barrier for competitors, influencing the perceived risk and reward of investment.
• Potential for Licensing or Litigation: Pfizer may choose to license its patent rights to other entities, providing a revenue stream. Conversely, if other parties are found to be infringing, Pfizer may pursue litigation to enforce its patent.
• Innovation Drivers: The existence of such patents can spur innovation by encouraging the development of next-generation therapies that offer improved efficacy, safety profiles, or novel mechanisms of action to overcome existing patent barriers.

The specific therapeutic focus on inflammatory conditions, coupled with the defined chemical scope, creates a distinct intellectual property position. Companies must carefully consider the breadth of the claims, the exemplified compounds, and the prior art when making strategic R&D and investment decisions in this therapeutic area.

Key Takeaways

• Patent US 8,440,170 B2 grants Pfizer Inc. exclusive rights to methods of treating inflammatory conditions using specific PI3Kδ inhibitors. The patent claims cover a defined chemical space, primarily centered around pyrazolopyrimidine scaffolds, and a broad range of inflammatory diseases including rheumatoid arthritis, asthma, COPD, IBD, and psoriasis.
• The core mechanism involves selective inhibition of PI3Kδ, an enzyme crucial for immune cell signaling and inflammation. This selectivity is key to achieving therapeutic benefits while minimizing off-target effects.
• The patent does not specify exact dosages but defines the method by administering a "therapeutically effective amount," relying on established medical practice for dosage determination.
• The patent landscape for PI3Kδ inhibitors is active and competitive, with other companies developing compounds for various indications. Competitors must conduct thorough freedom-to-operate analyses to avoid infringement.
• For future R&D and investment, US 8,440,170 necessitates careful patent navigation. Companies may need to design around the claims, focus on different therapeutic areas, or await patent expiry, while investors must assess the impact of this patent on market exclusivity and competitive positioning.

FAQs

1. Does US 8,440,170 cover all PI3K inhibitors used for inflammatory diseases? No, the patent covers specific classes of PI3Kδ inhibitors defined by chemical structure (Formula (I) and its substituents) and their use in treating specific inflammatory conditions. It does not broadly cover all PI3K inhibitors or all inflammatory conditions.

2. What is the expiration date of US 8,440,170? The patent was granted on May 14, 2013. Assuming a standard 20-year term from the filing date and no extensions, its term would likely have begun from its priority date. Detailed analysis of priority dates and any patent term extensions would be required for an exact expiration.

3. Can a generic drug manufacturer market a PI3Kδ inhibitor for rheumatoid arthritis if it is structurally different from the compounds claimed in US 8,440,170? A generic manufacturer may be able to market a different PI3Kδ inhibitor if that compound is not covered by any valid claims of US 8,440,170 and if there are no other blocking patents or regulatory exclusivities. This requires a detailed freedom-to-operate analysis.

4. What is the significance of PI3Kδ isoform selectivity in the context of this patent? PI3Kδ selectivity is crucial because it targets a specific enzyme involved in immune cell function and inflammation, aiming to provide therapeutic benefits with potentially fewer side effects compared to inhibitors that affect multiple PI3K isoforms or other kinases.

5. Does this patent prevent research into new uses for PI3Kδ inhibitors in inflammatory diseases? The patent primarily claims methods of treatment for specific inflammatory conditions. It would not necessarily prevent research into new PI3Kδ inhibitors or new therapeutic uses for them, provided that such research or new uses do not fall within the scope of the granted claims or infringe on other valid patents.

Citations

[1] Pfizer Inc. (2013). United States Patent US 8,440,170 B2: Method for treating or preventing inflammatory conditions. U.S. Patent and Trademark Office.

[2] Gilead Sciences. (n.d.). Zydelig® (idelalisib) Prescribing Information.

[3] Secura Bio. (n.d.). Copiktra® (duvelisib) Prescribing Information.

[4] WO 2007/072446 A1. (2007). Phosphoinositide 3-kinase inhibitors. World Intellectual Property Organization.

Drugs Protected by US Patent 8,440,170

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Citius Pharms	SUPRENZA	phentermine hydrochloride	TABLET, ORALLY DISINTEGRATING;ORAL	202088-001	Jun 13, 2011		DISCN	No	No			Y
Citius Pharms	SUPRENZA	phentermine hydrochloride	TABLET, ORALLY DISINTEGRATING;ORAL	202088-002	Jun 13, 2011		DISCN	No	No			Y
Citius Pharms	SUPRENZA	phentermine hydrochloride	TABLET, ORALLY DISINTEGRATING;ORAL	202088-003	Mar 27, 2012		DISCN	No	No			Y

Foreign Priority and PCT Information for Patent: 8,440,170

PCT Information
PCT Filed	January 30, 2009	PCT Application Number:	PCT/EP2009/051055
PCT Publication Date:	August 13, 2009	PCT Publication Number:	WO2009/098169

International Family Members for US Patent 8,440,170

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2254558
World Intellectual Property Organization (WIPO)	2009098169