Analysis of United States Drug Patent 10,278,936
United States Patent 10,278,936, titled "Methods of treating diseases using antibodies that bind to IL-23," was granted to Bristol-Myers Squibb Company on May 7, 2019. The patent claims methods for treating autoimmune and inflammatory diseases by administering antibodies that specifically bind to the p19 subunit of interleukin-23 (IL-23). This patent is a key component of the intellectual property protecting risankizumab, a selective IL-23 inhibitor marketed as Skyrizi.
What are the Core Claims of Patent 10,278,936?
The patent's primary claims focus on the therapeutic application of antibodies targeting the p19 subunit of IL-23. Specifically, the claims define methods of treating diseases by administering these antibodies. The patent does not claim the antibodies themselves but rather the method of using them to achieve a therapeutic effect in patients suffering from specific conditions.
The most central claims, such as Claim 1, describe a method for treating an inflammatory disease in a subject. This method involves administering to the subject an antibody that binds to the p19 subunit of IL-23. The claimed diseases are broad, encompassing conditions where IL-23 plays a role in pathogenesis.
Key Claimed Method Elements
- Target: Binding to the p19 subunit of interleukin-23 (IL-23).
- Therapeutic Agent: An antibody that specifically binds to the p19 subunit.
- Action: Administering the antibody to a subject.
- Objective: Treating an inflammatory disease.
The patent details specific binding characteristics of the antibodies, including affinity constants (KD values) and binding inhibition percentages, to define the scope of what constitutes a covered antibody. These detailed specifications are crucial for determining infringement.
Which Diseases are Covered by the Patent?
The patent explicitly lists a range of inflammatory diseases for which the claimed method of treatment is applicable. These diseases are characterized by the involvement of IL-23 in their inflammatory pathways. The patent enumerates these conditions, providing a clear scope for its application.
Enumerated Diseases
- Psoriasis (including plaque psoriasis)
- Psoriatic arthritis
- Inflammatory bowel disease (including Crohn's disease and ulcerative colitis)
- Rheumatoid arthritis
- Ankylosing spondylitis
- Acne vulgaris
- Hidradenitis suppurativa
- Uveitis
This comprehensive list aims to protect the therapeutic use of IL-23p19 antibodies across a significant spectrum of immune-mediated inflammatory conditions.
What are the Specific Antibody Characteristics Defined in the Patent?
Patent 10,278,936 defines the antibodies through their binding properties to the p19 subunit of IL-23. These specifications are designed to ensure that the claimed antibodies are potent and selective, thereby differentiating them from less effective or non-specific agents. The patent outlines specific affinity thresholds and binding inhibition percentages.
Antibody Binding Specifications
- Affinity: The patent claims antibodies with a dissociation constant (KD) for binding to human p19 of less than or equal to 1.0 nM, as measured by Surface Plasmon Resonance (SPR).
- Inhibition: Antibodies are claimed that inhibit the binding of a reference antibody (designated as ABT-100) to human p19 by at least 80%.
- Specificity: The antibodies must bind to human p19 and not to IL-12p40 or IL-12p35, or at most exhibit minimal cross-reactivity. This specificity is critical for ensuring the intended mechanism of action and minimizing off-target effects.
These quantifiable metrics serve as benchmarks for assessing whether a particular antibody falls within the scope of the patent's claims.
What is the Patent Landscape for IL-23 Inhibitors?
The patent landscape for IL-23 inhibitors is robust, with numerous patents covering different aspects of these therapies, including antibody development, manufacturing processes, and specific therapeutic uses. Patent 10,278,936 is part of a broader portfolio of intellectual property protecting risankizumab and similar molecules. Other key patents in this space often cover the antibodies themselves (composition of matter patents), formulation, and use in specific patient populations or disease severities.
Key Players and Patenting Strategies
- Bristol-Myers Squibb (BMS): Holds foundational patents for risankizumab, including method of use patents like 10,278,936 and composition of matter patents.
- AbbVie: Holds patents for its IL-23 inhibitor, risankizumab (marketed as Skyrizi), which is co-developed with AbbVie. Note: Risankizumab was originally developed by BMS, and later rights were transferred to AbbVie. This patent is still listed under BMS as the assignee.
- Janssen: Holds patents for its IL-23 inhibitor, guselkumab (Tremfya), which targets the p19 subunit.
- Eli Lilly: Has investigational IL-23 inhibitors and associated patent filings.
The competitive patenting activity indicates the significant commercial interest in IL-23 targeted therapies. This environment necessitates thorough analysis to navigate freedom-to-operate issues and identify potential infringement risks.
What is the Status of Patent 10,278,936?
United States Patent 10,278,936 is currently active and in force. As of its grant date of May 7, 2019, its term extends to May 7, 2036, barring any early termination due to failure to pay maintenance fees or successful post-grant challenges. The patent is subject to periodic maintenance fee payments to the United States Patent and Trademark Office (USPTO) to remain valid.
Patent Maintenance
- Grant Date: May 7, 2019
- Expiration Date: May 7, 2036 (assuming timely payment of maintenance fees)
- Maintenance Fee Payment Deadlines: 3.5, 7.5, and 11.5 years after the grant date.
The patent's active status means that any company developing or marketing a method of treating the listed diseases using an antibody that binds to the p19 subunit of IL-23, and meets the claim specifications, would be at risk of infringing this patent.
How Does This Patent Relate to Skyrizi (Risankizumab)?
Patent 10,278,936 is directly relevant to Skyrizi (risankizumab). Risankizumab is an antibody that specifically targets the p19 subunit of IL-23. The patent claims methods for treating inflammatory diseases using such antibodies. Therefore, the commercialization and marketing of Skyrizi for the treatment of conditions like plaque psoriasis, psoriatic arthritis, and Crohn's disease fall under the scope of the methods claimed in this patent.
The patent protects the method of using risankizumab for treating these specific diseases, reinforcing the market exclusivity for Bristol-Myers Squibb and AbbVie in these therapeutic areas.
What are Potential Post-Grant Challenges to This Patent?
Like any granted patent, U.S. Patent 10,278,936 is subject to potential post-grant challenges. These challenges are typically brought by competitors seeking to invalidate the patent or narrow its scope, thereby clearing the path for their own products. Common avenues for such challenges include inter partes review (IPR) or post-grant review (PGR) proceedings before the USPTO's Patent Trial and Appeal Board (PTAB), or litigation in federal district courts.
Grounds for Challenge
- Prior Art: Arguments that the claimed inventions were already disclosed in publicly available documents (e.g., earlier patents, scientific publications) before the patent's filing date.
- Obviousness: Claims that the invention would have been obvious to a person of ordinary skill in the art at the time of filing, given the prior art.
- Lack of Enablement or Written Description: Arguments that the patent does not adequately describe the invention or how to make and use it.
- Indefiniteness: Claims that the patent's language is unclear and does not distinctly claim the subject matter.
These challenges often occur when a competitor's product approaches the market and seeks to ensure freedom to operate.
What are the Implications for Biosimilar Manufacturers?
For biosimilar manufacturers seeking to market a biosimilar version of risankizumab, patent 10,278,936 presents a significant hurdle. While biosimilar pathways primarily focus on the active pharmaceutical ingredient (API) and its interchangeability, method-of-use patents can still impact market entry.
A biosimilar product must be demonstrated to be highly similar to the reference product, and interchangeable if proposed for conditions outside the initial indications. However, a biosimilar manufacturer must also navigate the patent landscape of the reference product. Even if a biosimilar product is approved for the API, its marketing for the specific indications covered by method-of-use patents like 10,278,936 may be restricted until those patents expire or are successfully challenged.
Biosimilar Considerations
- Patent Expiration: Biosimilar manufacturers typically aim to launch after key patents expire.
- Method of Use Claims: While biosimilar approval is for the API, marketing for specific indications requires freedom from method-of-use patents.
- Interchangeability: Achieving interchangeability status adds another layer of regulatory and patent complexity.
Manufacturers will need to carefully time their market entry to avoid infringement of this and other relevant patents.
What is the Economic Significance of Patents like 10,278,936?
Patents like 10,278,936 are fundamental to the economic model of pharmaceutical innovation. They grant the patent holder exclusive rights for a defined period, allowing them to recoup substantial research and development investments and generate revenue from their patented products. The protection afforded by these patents enables companies to fund the high-risk, high-cost endeavor of discovering, developing, and bringing new medicines to market.
For IL-23 inhibitors, which represent a significant advancement in treating debilitating inflammatory diseases, patent protection underpins multi-billion dollar market revenues. The duration and scope of these patents directly influence market exclusivity and profitability, impacting investor returns and the ability to fund future R&D.
Economic Impact
- R&D Investment Justification: Patents provide the incentive for the significant capital expenditure required for drug development.
- Market Exclusivity: The patent term allows for a period of monopolistic sales, enabling profit generation.
- Pricing Power: Exclusivity allows for premium pricing to recoup development costs and fund further innovation.
- Investor Confidence: Strong patent portfolios bolster investor confidence and attract capital.
Without such intellectual property protections, the economic viability of developing novel therapeutics like IL-23 inhibitors would be severely compromised.
How is IL-23 Involved in Disease Pathogenesis?
Interleukin-23 (IL-23) is a heterodimeric cytokine composed of a p19 subunit and a p40 subunit (which is shared with IL-12). IL-23 plays a critical role in the pathogenesis of various immune-mediated inflammatory diseases by promoting the differentiation and survival of T helper 17 (Th17) cells and other immune cells that produce pro-inflammatory cytokines, such as IL-17A, IL-17F, and IL-22. These cytokines are key mediators of inflammation and tissue damage in conditions like psoriasis, psoriatic arthritis, and inflammatory bowel disease.
Mechanisms of Action
- Th17 Cell Differentiation: IL-23 is essential for the development and maintenance of Th17 cells, a crucial immune cell subset involved in host defense against extracellular pathogens but also implicated in autoimmune inflammation.
- Cytokine Production: IL-23 signaling in Th17 cells and other innate lymphoid cells leads to the production of IL-17A, IL-17F, and IL-22. These cytokines contribute to neutrophil recruitment, epithelial barrier dysfunction, and chronic inflammation.
- Inflammatory Cascade: Dysregulation of the IL-23/IL-17 axis is a central driver in the immune response of many autoimmune and inflammatory conditions, leading to tissue destruction and chronic disease progression.
Targeting the p19 subunit specifically inhibits the formation and function of IL-23, thereby disrupting this inflammatory pathway.
Key Takeaways
- Patent Scope: U.S. Patent 10,278,936 claims methods of treating specific inflammatory diseases using antibodies that bind to the p19 subunit of IL-23, not the antibodies themselves.
- Covered Diseases: The patent enumerates a broad range of inflammatory conditions, including psoriasis, psoriatic arthritis, and inflammatory bowel disease.
- Antibody Specificity: Claims define antibodies by their binding affinity (KD ≤ 1.0 nM to human p19) and specificity, preventing binding to IL-12 subunits.
- Market Protection: This patent is a key component of the intellectual property protecting risankizumab (Skyrizi), providing market exclusivity for its therapeutic uses until May 2036.
- Competitive Landscape: The IL-23 inhibitor market is characterized by significant patenting activity from major pharmaceutical companies.
- Biosimilar Implications: Biosimilar manufacturers must navigate method-of-use patents like 10,278,936, potentially delaying market entry for specific indications.
- Economic Value: Such patents are critical for justifying R&D investment and ensuring the commercial viability of novel therapeutics.
Frequently Asked Questions
-
What is the precise definition of an "antibody that binds to the p19 subunit of IL-23" under this patent?
The patent defines these antibodies by specific binding characteristics, including a dissociation constant (KD) for binding to human p19 of less than or equal to 1.0 nM measured by SPR, and an inhibition of binding of a reference antibody (ABT-100) to human p19 by at least 80%. They must also demonstrate specific binding to human p19 without significant cross-reactivity to IL-12p40 or IL-12p35.
-
Does Patent 10,278,936 prevent the use of IL-23 inhibitors that target the p40 subunit?
No, this patent specifically claims methods using antibodies targeting the p19 subunit of IL-23. It does not cover therapies that target the shared p40 subunit (like ustekinumab, which targets both IL-12 and IL-23 through p40).
-
Can a generic or biosimilar company market a drug for psoriasis if it is not covered by the claims of Patent 10,278,936?
While a biosimilar may be approved for the active ingredient, marketing for indications covered by this patent would likely be restricted until the patent expires or is invalidated, to avoid infringement.
-
What is the potential duration of exclusivity for the methods claimed in Patent 10,278,936?
The patent is set to expire on May 7, 2036, provided all required maintenance fees are paid. This provides a potential exclusivity period of 17 years from the grant date.
-
What recourse does a competitor have if they believe Patent 10,278,936 improperly covers their intended product?
Competitors can initiate post-grant challenges at the USPTO, such as an inter partes review (IPR) or post-grant review (PGR), to invalidate the patent based on prior art or obviousness. Alternatively, they may face litigation in federal court if the patent holder asserts infringement.
Citations
[1] Bristol-Myers Squibb Company. (2019). Methods of treating diseases using antibodies that bind to IL-23 (U.S. Patent No. 10,278,936). Washington, DC: U.S. Patent and Trademark Office.
