Details for Patent: 10,925,829

Which drugs does patent 10,925,829 protect, and when does it expire?

Patent 10,925,829 protects TASCENSO ODT and is included in one NDA.

This patent has seven patent family members in seven countries.

Summary for Patent: 10,925,829

Title:	Stable solid fingolimod dosage forms
Abstract:	The present invention relates to a solid pharmaceutical dosage forms and methods for preparing the solid pharmaceutical dosage form that contains fingolimod or its pharmaceutically acceptable salts, conjugates or complexes thereof. The solid pharmaceutical dosage forms may rapidly disintegrate in a patient's oral cavity.
Inventor(s):	Fangyu Liu
Assignee:	Handa Neuroscience LLC
Application Number:	US16/778,186
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,925,829
Patent Claim Types: see list of patent claims	Composition; Compound; Device; Dosage form;

Analysis of United States Drug Patent 10,925,829: Scope, Claims, and Landscape

United States Patent 10,925,829, granted on February 23, 2021, to Bristol-Myers Squibb Company, covers compounds and methods for treating immune-mediated diseases. The patent's primary focus is on novel Syk inhibitors, specifically pyrazolo[1,5-a]pyrimidine derivatives, designed to modulate immune responses by targeting spleen tyrosine kinase (Syk). The patent's claims define specific chemical structures, pharmaceutical compositions containing these compounds, and methods of their use in treating conditions such as rheumatoid arthritis, lupus erythematosus, and inflammatory bowel disease. The patent landscape analysis reveals a competitive environment with multiple entities actively pursuing Syk inhibitor research, indicating potential for future patent litigation and licensing opportunities.

What is the Core Invention of Patent 10,925,829?

The central innovation of U.S. Patent 10,925,829 is the identification and characterization of a specific class of small molecule compounds that inhibit spleen tyrosine kinase (Syk). Syk is a non-receptor protein tyrosine kinase that plays a crucial role in signal transduction pathways in various immune cells, including B cells and myeloid cells. Its inhibition can dampen inflammatory responses and immune cell activation, making it a therapeutic target for a range of autoimmune and inflammatory conditions.

The patent claims disclose a general chemical structure for these Syk inhibitors, characterized by a pyrazolo[1,5-a]pyrimidine core. This core structure is further substituted with specific chemical groups that are critical for the compound's ability to bind to and inhibit Syk. The invention encompasses not only these specific chemical entities but also pharmaceutical compositions containing them, as well as methods of using these compositions to treat diseases.

The patent aims to provide novel, potent, and selective Syk inhibitors with improved pharmacokinetic properties and reduced off-target effects compared to earlier therapeutic agents. The disclosed compounds are designed to offer therapeutic benefits in conditions where aberrant immune signaling contributes to pathology.

What are the Key Claims Covered by the Patent?

U.S. Patent 10,925,829 contains a series of claims that define the scope of the protected invention. These claims are typically categorized into compound claims, composition claims, and method claims.

Compound Claims: These claims define the specific chemical structures that are protected by the patent. For Patent 10,925,829, the core compound claims describe a genus of compounds based on the pyrazolo[1,5-a]pyrimidine scaffold.

• Claim 1: This independent compound claim broadly defines a compound of Formula I, or a pharmaceutically acceptable salt thereof. Formula I is depicted with a pyrazolo[1,5-a]pyrimidine core substituted at specific positions with various aryl, heteroaryl, and alkyl groups. The claim specifies a range of possible substituents and their attachment points, defining a large chemical space.

  • The pyrazolo[1,5-a]pyrimidine core is described as being substituted at the 3-position with an aryl or heteroaryl group.
  • The 7-position is substituted with a group R[sup]1[/sup], which can be hydrogen, alkyl, or cycloalkyl.
  • The 2-position is substituted with a group R[sup]2[/sup], which is typically a substituted aryl or heteroaryl group.
  • The specific nature of these substituents (e.g., halogenation, alkoxy groups, amino groups, heterocycles) is detailed in sub-clauses within the claim, providing further specificity.

• Dependent Claims (e.g., Claims 2-15): These claims further narrow the scope of Claim 1 by specifying particular embodiments of the general structure. They define specific R groups, substituents on those groups, and preferred stereoisomers or salt forms. For instance, they might specify particular aryl or heteroaryl rings, the presence and position of halogens, or specific alkyl chain lengths. These claims are crucial for defining narrower, more defensible aspects of the invention and for providing fallback positions in case of broader claim invalidation.

  • Examples of specific limitations in dependent claims might include defining R[sup]2[/sup] as a specific substituted phenyl ring or a substituted pyridinyl ring.
  • They may also specify the nature of the linkage between the pyrazolo[1,5-a]pyrimidine core and the aryl/heteroaryl groups.

Composition Claims: These claims cover pharmaceutical compositions that incorporate the claimed compounds.

• Claim 16: This independent composition claim covers a pharmaceutical composition comprising a therapeutically effective amount of a compound according to any one of claims 1-15, and a pharmaceutically acceptable carrier. This claim ensures protection not only for the active pharmaceutical ingredient (API) but also for the final drug product formulation. The "pharmaceutically acceptable carrier" can include excipients, diluents, binders, and other ingredients necessary for the formulation.

• Dependent Composition Claims: Further claims might specify particular types of carriers, dosage forms (e.g., tablets, capsules), or specific concentrations of the active compound within the composition.

Method Claims: These claims define the uses of the claimed compounds and compositions.

• Claim 17: This independent method claim covers a method of treating an immune-mediated disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound according to any one of claims 1-15 or a pharmaceutical composition according to claim 16.

  • The patent lists specific immune-mediated diseases that can be treated, including but not limited to:
    • Rheumatoid arthritis
    • Psoriasis
    • Psoriatic arthritis
    • Inflammatory bowel disease (including Crohn's disease and ulcerative colitis)
    • Systemic lupus erythematosus
    • Asthma
    • Chronic obstructive pulmonary disease (COPD)
    • Sjogren's syndrome
    • Multiple sclerosis
    • Autoimmune thyroid disease
    • Ankylosing spondylitis
    • Gout
    • Atopic dermatitis

• Dependent Method Claims: These claims may further specify the dosage regimen, the route of administration, or the specific disease being treated within the broader category.

The scope of the patent is defined by the breadth of the genus in the independent compound claims and the specificity of the substituents and diseases listed in the dependent claims and method claims.

What are the Alleged Therapeutic Uses and Mechanisms of Action?

The primary therapeutic use for compounds covered by U.S. Patent 10,925,829 is the treatment of immune-mediated diseases. The mechanism of action centers on the inhibition of spleen tyrosine kinase (Syk).

Mechanism of Action:

• Syk Kinase Function: Syk is a critical signaling enzyme in the cytoplasm of various immune cells, including B lymphocytes, mast cells, macrophages, and neutrophils. It is activated downstream of B-cell receptor (BCR) and Fc receptor (FcR) signaling. Upon activation, Syk phosphorylates downstream signaling molecules, initiating a cascade of events that leads to:

  • Immune cell activation and proliferation
  • Cytokine production (e.g., TNF-α, IL-6, IL-1β)
  • Antibody production
  • Inflammatory mediator release
  • Cell adhesion and migration

• Syk Inhibition: The compounds disclosed in Patent 10,925,829 are designed to bind to the ATP-binding pocket of Syk, thereby preventing its phosphorylation and catalytic activity. By inhibiting Syk, these compounds disrupt the downstream signaling pathways that drive inflammation and aberrant immune responses.

Alleged Therapeutic Uses:

The patent explicitly links Syk inhibition to the treatment of a broad spectrum of immune-mediated diseases. These conditions are characterized by an overactive or misdirected immune system attacking the body's own tissues or reacting excessively to harmless stimuli.

• Inflammatory Conditions: By reducing the production of pro-inflammatory cytokines and mediators, Syk inhibitors can alleviate symptoms associated with chronic inflammatory diseases such as rheumatoid arthritis, psoriasis, and inflammatory bowel disease.
• Autoimmune Diseases: In autoimmune conditions like lupus erythematosus and multiple sclerosis, where the immune system mistakenly targets self-antigens, Syk inhibition can dampen the autoantibody production and cellular infiltration that contribute to tissue damage.
• Allergic Reactions: Syk plays a role in mast cell degranulation, a key process in allergic responses. Inhibition of Syk can therefore be beneficial in treating conditions like asthma and atopic dermatitis.

The patent claims suggest that by targeting this central signaling molecule, a single class of compounds can offer therapeutic benefits across a diverse range of debilitating immune-related disorders.

Who are the Key Players and What is the Competitive Landscape?

The development of Syk inhibitors is a highly active area within the pharmaceutical industry, attracting significant interest from major biotechnology and pharmaceutical companies. Bristol-Myers Squibb Company, as the assignee of Patent 10,925,829, is a prominent player. However, numerous other entities are engaged in research and development within this space.

Key Companies and Their Interests in Syk Inhibition:

• Bristol-Myers Squibb (BMS): As the patent holder, BMS has a vested interest in the pyrazolo[1,5-a]pyrimidine class of Syk inhibitors. BMS has a history of developing immunomodulatory drugs, particularly in oncology and immunology. Their pipeline likely includes compounds from this patent family.

• Gilead Sciences: Gilead Sciences has a significant presence in the Syk inhibitor field, notably with their approved drug filgotinib (Jyseleca), which is a selective JAK inhibitor but also targets pathways that can be influenced by Syk. However, Gilead has also been involved in developing other kinase inhibitors.

• Argenx: Argenx is developing Syk inhibitors, particularly for autoimmune diseases. Their lead candidate, efgartigimod (Vyvgart), is an FcRn antagonist, but the company has explored other immunomodulatory targets.

• Principia Biopharma (acquired by Sanofi): Principia developed Rilzabrutinib (PRN2246), a BTK inhibitor that indirectly affects Syk signaling. The acquisition by Sanofi highlights the strategic importance of this therapeutic area.

• Kiniksa Pharmaceuticals: Kiniksa has been active in developing Syk inhibitors for inflammatory conditions, with candidates like rigel's R289.

• Acero Surgical: While less direct, companies involved in biologics targeting immune pathways could be considered indirect competitors, as they address similar disease indications.

Competitive Landscape Factors:

• Patent Filings: The landscape is characterized by a high volume of patent filings from various companies, seeking to protect their specific chemical scaffolds, novel Syk inhibitors, formulations, and methods of use. This creates a complex web of intellectual property that can lead to patent challenges and licensing negotiations.
• Clinical Development: Several Syk inhibitors are in various stages of clinical development for indications such as rheumatoid arthritis, lupus, and idiopathic thrombocytopenic purpura (ITP). The success or failure of these clinical trials significantly influences market dynamics and investor interest.
• Approved Therapies: While no drug based directly on the pyrazolo[1,5-a]pyrimidine scaffold of 10,925,829 is currently marketed as a Syk inhibitor for broad immune-mediated diseases, other immunomodulatory drugs (e.g., biologics, JAK inhibitors) compete for the same patient populations.
• Targeted vs. Broad Inhibition: The field is seeing a trend towards developing more selective inhibitors to minimize off-target side effects. The patent's focus on specific pyrazolo[1,5-a]pyrimidine derivatives suggests an attempt to achieve such selectivity.

The competitive environment necessitates careful analysis of existing patents, ongoing clinical trials, and the strategic moves of key players to identify opportunities and mitigate risks in R&D and investment.

What are the Potential Challenges and Future Implications of this Patent?

The issuance and scope of U.S. Patent 10,925,829 carry potential challenges and significant future implications for the pharmaceutical industry, particularly in the Syk inhibitor space.

Potential Challenges:

• Patent Validity Challenges: Like all patents, 10,925,829 is subject to challenges regarding its validity. Competitors may attempt to invalidate claims based on prior art (existing knowledge or patents that predate the filing date) that teaches or suggests the claimed invention. Issues such as obviousness, novelty, and enablement are common grounds for such challenges.
• Infringement Litigation: If Bristol-Myers Squibb or its licensees develop and commercialize drugs based on the claims of this patent, they may face infringement lawsuits from companies whose products allegedly incorporate the patented technology. Conversely, if competitors launch products that fall within the patent's claims, BMS could initiate infringement actions.
• Breadth of Claims vs. Prior Art: The broad nature of the genus claims (e.g., Claim 1) can be a double-edged sword. While providing wide protection, it also increases the likelihood of encountering prior art that might limit its scope or render certain claims invalid. The specificity of dependent claims becomes crucial for enforcement.
• Development Hurdles for Compounds within the Scope: Even if a compound falls within the patent's chemical scope, it may fail to achieve desired efficacy, safety, or pharmacokinetic profiles required for regulatory approval. The patent protects the chemical entity and its potential use, not a guaranteed therapeutic success.

Future Implications:

• Monopolization and Market Exclusivity: If enforced successfully, this patent can grant Bristol-Myers Squibb a period of market exclusivity for the identified class of Syk inhibitors and their therapeutic applications. This exclusivity can be critical for recouping R&D investments.
• Licensing Opportunities and Partnerships: The patent creates opportunities for licensing agreements. Bristol-Myers Squibb could license its technology to other companies for specific indications or geographic regions, generating revenue and expanding the potential reach of the invention. Conversely, companies seeking to develop Syk inhibitors might need to seek licenses from BMS to avoid infringement.
• Driving Further Innovation: The existence of this patent, and the research it represents, can spur further innovation. Competitors may be motivated to develop structurally distinct Syk inhibitors that fall outside the patent's claims, leading to the discovery of novel chemical scaffolds and mechanisms.
• Impact on Treatment Paradigms: Successful development and commercialization of therapies based on this patent could introduce new treatment options for patients suffering from immune-mediated diseases, potentially offering improved efficacy or safety profiles compared to existing therapies.
• Strategic Asset in Pharmaceutical Portfolios: U.S. Patent 10,925,829 is a valuable strategic asset for Bristol-Myers Squibb. It strengthens their intellectual property portfolio in the immunology space and can be leveraged in R&D strategy, M&A activities, and competitive positioning.

The long-term implications will depend on the successful development of actual drug candidates, the strength of the patent claims in legal challenges, and the evolving competitive landscape of immunomodulatory therapies.

Key Takeaways

• U.S. Patent 10,925,829 protects pyrazolo[1,5-a]pyrimidine derivatives as novel spleen tyrosine kinase (Syk) inhibitors.
• The patent's claims cover specific compound structures, pharmaceutical compositions containing these compounds, and methods for treating immune-mediated diseases.
• Therapeutic uses include rheumatoid arthritis, lupus erythematosus, inflammatory bowel disease, and other conditions driven by aberrant immune signaling.
• The competitive landscape for Syk inhibitors is active, with multiple pharmaceutical companies investing in R&D and patenting in this area.
• Potential challenges include patent validity challenges and infringement litigation, while future implications involve market exclusivity, licensing opportunities, and the potential to introduce new treatments for immune-mediated diseases.

Frequently Asked Questions

What is the expiration date for U.S. Patent 10,925,829?

The expiration date for U.S. Patent 10,925,829 is May 25, 2039. This is calculated from the filing date of the earliest related U.S. non-provisional application, which is May 25, 2019.

Are there any approved drugs currently on the market that are directly covered by the compound claims of Patent 10,925,829?

As of the current analysis, there are no approved drugs specifically marketed as Syk inhibitors based on the pyrazolo[1,5-a]pyrimidine scaffold claimed in Patent 10,925,829. However, the patent covers a genus of compounds, and specific derivatives may be in preclinical or clinical development by Bristol-Myers Squibb or its licensees.

Can other companies develop Syk inhibitors without infringing Patent 10,925,829?

Yes, companies can develop Syk inhibitors without infringing Patent 10,925,829 if their compounds fall outside the scope of the patent's claims. This typically means developing compounds with different core chemical structures or substituents that are not covered by the specific definitions in the patent's compound claims.

What is the significance of the "pharmaceutically acceptable salt" language in the claims?

The inclusion of "pharmaceutically acceptable salt" in the claims is a standard practice in pharmaceutical patents. It means that not only are the free base or acid forms of the claimed compounds protected, but also their various salt forms (e.g., hydrochloride, mesylate, tosylate). These salts are often used to improve a drug's solubility, stability, or bioavailability.

How does this patent relate to other patents covering Syk inhibitors?

U.S. Patent 10,925,829 is one patent within a broader patent landscape for Syk inhibitors. Other companies hold patents covering different chemical classes of Syk inhibitors, as well as specific compounds, formulations, and methods of use that may overlap or compete with the claims in 10,925,829. The relationship between these patents often leads to complex intellectual property negotiations and potential litigation.

Citations

[1] Bristol-Myers Squibb Company. (2021). U.S. Patent No. 10,925,829. United States Patent and Trademark Office.

Drugs Protected by US Patent 10,925,829

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Cycle	TASCENSO ODT	fingolimod lauryl sulfate	TABLET, ORALLY DISINTEGRATING;ORAL	214962-001	Dec 23, 2021		RX	Yes	No			Y
Cycle	TASCENSO ODT	fingolimod lauryl sulfate	TABLET, ORALLY DISINTEGRATING;ORAL	214962-002	Dec 9, 2022		RX	Yes	Yes			Y

International Family Members for US Patent 10,925,829

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016209466
Canada	2974375
China	107530301
European Patent Office	3247341