Last updated: February 19, 2026
This report analyzes Australian patent AU2014247092, detailing its scope, key claims, and the surrounding patent landscape. The patent, filed on October 29, 2014, by Bristol-Myers Squibb Company, concerns novel pharmaceutical compositions for treating immune-mediated diseases. The invention describes specific formulations of anti-PD-1 antibodies, primarily nivolumab, designed to enhance stability and shelf-life, thereby improving therapeutic utility and ease of administration.
What is the Core Invention Described in AU2014247092?
The core invention of AU2014247092 is a pharmaceutical composition comprising an anti-PD-1 antibody and specific excipients. The primary objective is to create a stable liquid formulation of the anti-PD-1 antibody that can be stored for extended periods without significant degradation. This is particularly relevant for antibodies, which are complex protein molecules susceptible to aggregation and denaturation.
The patent focuses on formulations that include:
- An anti-PD-1 antibody, such as nivolumab.
- A buffer system, typically citrate or histidine.
- A surfactant, such as polysorbate 80.
- A stabilizer, often a sugar like sucrose or trehalose.
The specific concentrations and combinations of these components are claimed to prevent aggregation, maintain antibody activity, and ensure acceptable physical and chemical stability for at least 18 months at refrigerated temperatures.
What are the Key Claims of AU2014247092?
AU2014247092 contains several independent and dependent claims that define the scope of the protected invention. The independent claims typically cover the pharmaceutical composition itself, while dependent claims specify particular embodiments and variations.
Independent Claims generally cover:
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A pharmaceutical composition comprising:
- An anti-PD-1 antibody.
- A citrate buffer.
- A surfactant.
- A stabilizer.
The claims specify ranges for the concentrations of these components and the pH of the formulation. For example, claims may define the antibody concentration (e.g., 10 mg/mL to 100 mg/mL), buffer concentration (e.g., 10 mM to 50 mM), surfactant concentration (e.g., 0.01% to 0.1%), and stabilizer concentration (e.g., 1% to 10%). The pH is typically defined within a narrow range, for instance, between pH 5.5 and pH 6.5, to optimize antibody stability.
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A method of preparing a stable liquid pharmaceutical formulation of an anti-PD-1 antibody, comprising combining the antibody with the specified excipients under conditions that maintain the antibody's integrity.
Dependent Claims often refine the scope by specifying:
- The specific anti-PD-1 antibody, such as nivolumab.
- The precise type of buffer (e.g., sodium citrate).
- The specific type of surfactant (e.g., polysorbate 80).
- The specific type of stabilizer (e.g., sucrose).
- The storage conditions under which the formulation is stable (e.g., 2-8°C).
- The duration of stability (e.g., at least 18 months).
These claims are critical for defining what constitutes infringement and for establishing the novelty and inventive step of the claimed formulations over prior art. The patent aims to protect formulations that offer superior stability compared to existing antibody formulations, thereby facilitating broader clinical use and market availability.
How Does AU2014247092 Define "Stable"?
The patent defines "stable" in terms of specific measurable parameters related to the physical and chemical integrity of the anti-PD-1 antibody in the liquid formulation. Stability is assessed through various analytical techniques, and the patent typically requires that these parameters remain within acceptable limits for a defined storage period.
Key indicators of stability defined or implied by the patent include:
- Aggregation: Measured by techniques like Size Exclusion Chromatography (SEC-HPLC) or Dynamic Light Scattering (DLS). The patent aims to limit the formation of high molecular weight species (e.g., dimers, trimers, and larger aggregates) and low molecular weight species (e.g., fragments).
- Purity: Assessed by methods such as Reversed-Phase HPLC (RP-HPLC) or SDS-PAGE, to ensure the antibody's primary structure remains intact and that degradation products are minimized.
- Potency/Activity: Determined through bioassays that measure the antibody's ability to bind to its target (PD-1) or to elicit a biological response. The patent requires that the antibody retains a significant percentage of its initial activity after storage.
- Appearance: Visual inspection to detect visible particles or changes in color, which can indicate instability.
- pH: Monitoring the pH of the formulation over time to ensure it remains within the specified range, as pH shifts can impact protein stability.
- Extractables and Leachables: While not always explicitly detailed in claims, formulation stability is also linked to the compatibility of the antibody with packaging materials, minimizing the leaching of substances from containers that could degrade the antibody.
The patent aims to demonstrate that the specific combination of excipients and the controlled manufacturing process result in a formulation that maintains the antibody in a state where these degradation pathways are significantly inhibited for at least 18 months at standard refrigerated conditions (2-8°C).
What is the Geographic Scope of AU2014247092?
The geographic scope of AU2014247092 is Australia. This patent grants exclusive rights to the patent holder within the territory of Australia. This means that no third party can make, use, import, sell, or offer for sale the patented invention within Australia without the permission of the patent holder, Bristol-Myers Squibb Company.
The patent was filed as an international application under the Patent Cooperation Treaty (PCT), with the international publication number WO2015061258A1. The Australian application is a national phase entry of this international application. While the PCT process allows for a unified filing, national phase entries are required to seek patent protection in individual countries or regions. Therefore, AU2014247092 specifically pertains to the protection of the invention within Australia.
What is the Current Status of AU2014247092?
The current status of AU2014247092 is granted patent. The patent was formally granted by the Australian Patent Office.
Key milestones include:
- Filing Date: October 29, 2014
- Publication Date: May 7, 2015 (as WO2015061258A1, the international publication)
- Grant Date: The specific grant date would be available on the Australian Patent Office's register. However, as a granted patent, it is currently in force.
- Expiry Date: Patents in Australia are typically granted for a term of 20 years from the filing date, subject to the payment of renewal fees. For AU2014247092, the expiry date would be October 29, 2034.
As a granted patent, Bristol-Myers Squibb Company holds exclusive rights in Australia for the claimed invention until its expiry date.
Who is the Assignee/Owner of AU2014247092?
The assignee and owner of Australian patent AU2014247092 is Bristol-Myers Squibb Company. This pharmaceutical company is a global biopharmaceutical leader focused on discovering, developing, manufacturing, and marketing innovative medicines that help patients prevail over serious diseases. Bristol-Myers Squibb is a key player in the development and commercialization of immuno-oncology therapies, including nivolumab.
What is the Prior Art Landscape for AU2014247092?
The prior art landscape for AU2014247092 is characterized by existing patents and scientific literature related to:
- Anti-PD-1 Antibodies: Numerous patents cover the discovery, development, and therapeutic use of anti-PD-1 antibodies, including nivolumab, pembrolizumab, and others. These patents typically claim the antibodies themselves, methods of treatment using them, and specific indications.
- Protein Formulations: A vast body of prior art exists concerning the stabilization of therapeutic proteins, including antibodies. This includes various buffer systems, surfactants, cryoprotectants, lyoprotectants, and antioxidants used to prevent aggregation, oxidation, and other degradation pathways.
- Liquid Formulations of Antibodies: Prior art includes patents and publications describing stable liquid formulations of therapeutic antibodies, often focusing on specific buffer compositions, pH ranges, and excipient combinations to achieve long shelf lives.
When AU2014247092 was filed, the novelty and inventive step would have been assessed against this existing knowledge. The patent's claims are directed towards a specific combination of excipients and a specific pH range that achieves a demonstrable improvement in the stability of anti-PD-1 antibodies, particularly in liquid formulations. Prior art may have disclosed some of the components used in the claimed formulation, but the patent asserts that the particular synergistic combination and resulting stability profile were not obvious to a person skilled in the art.
For example, prior art might have disclosed the use of citrate buffers for protein stabilization or polysorbate 80 as a surfactant. However, AU2014247092 would likely distinguish itself by demonstrating superior stability or achieving stability under more challenging conditions through its unique formulation. The patentable aspect lies in the unexpected stability achieved by the specific inventive formulation of anti-PD-1 antibodies.
How Does AU2014247092 Relate to Marketed Products?
AU2014247092 is directly related to the formulation of Opdivo® (nivolumab), a blockbuster immuno-oncology drug marketed by Bristol-Myers Squibb. Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby restoring T-cell anti-tumor immune activity.
The patent protects the stable liquid formulation of nivolumab, which is crucial for its commercialization and therapeutic use. A stable liquid formulation simplifies manufacturing, distribution, and administration compared to lyophilized (freeze-dried) formulations, which require reconstitution before use. This improved formulation can reduce preparation time for healthcare professionals and potentially improve patient convenience and treatment adherence.
The claims of AU2014247092 define the specific composition that enables Opdivo® to be supplied as a ready-to-use liquid infusion, ensuring its efficacy and safety throughout its shelf life. Therefore, this patent plays a significant role in securing the market position and intellectual property protection for this critical therapeutic product in Australia.
What is the Competitive Landscape for Anti-PD-1 Formulations in Australia?
The competitive landscape for anti-PD-1 formulations in Australia is dynamic and characterized by:
- Innovator Products: Bristol-Myers Squibb's Opdivo® (nivolumab) and Merck & Co.'s Keytruda® (pembrolizumab) are the primary innovator products. Both companies hold extensive patent portfolios covering the antibodies themselves, methods of use, and specific formulations.
- Patent Expiries and Biosimilicipated Entry: As key patents for these first-generation PD-1 inhibitors approach expiry, the landscape will evolve with the potential entry of biosimilars. However, formulation patents like AU2014247092 can extend market exclusivity for the innovator by protecting specific stable formulations.
- Second-Generation Therapies: Research and development are ongoing for next-generation immuno-oncology drugs, including dual checkpoint inhibitors, combination therapies, and antibodies targeting different immune checkpoints.
- Formulation Innovation: Companies are continuously seeking to improve existing drug formulations to enhance stability, delivery, and patient convenience. This includes developing pre-filled syringes, alternative concentration formulations, and novel delivery systems.
- Regulatory Approvals: Therapeutic Goods Administration (TGA) approval in Australia is a critical hurdle for any new drug or formulation entering the market.
For AU2014247092, the competitive implications are:
- Exclusivity for BMS: The patent grants Bristol-Myers Squibb exclusive rights to its specific stable liquid formulation of nivolumab in Australia until October 2034. This prevents competitors from marketing a directly equivalent formulation of nivolumab in Australia.
- Biosimilar Differentiation: If and when biosimilars of nivolumab become available in Australia, they will need to be formulated differently to avoid infringing on AU2014247092 and other formulation patents. This could lead to biosimilars being offered in lyophilized forms or with alternative excipient compositions.
- Strategic Value: Formulation patents are strategically important as they can provide a secondary layer of protection beyond the primary antibody patent, particularly as blockbuster drugs approach the expiry of their core patents.
Key Takeaways
- Australian patent AU2014247092 protects a stable liquid pharmaceutical composition of anti-PD-1 antibodies, primarily nivolumab.
- The patent defines specific combinations of buffers (citrate), surfactants (polysorbate 80), and stabilizers (sugars) to achieve extended shelf life at refrigerated temperatures.
- The core claims focus on formulations that prevent antibody aggregation and degradation, ensuring therapeutic efficacy and ease of administration.
- The patent is owned by Bristol-Myers Squibb Company and grants exclusive rights in Australia until October 29, 2034.
- This patent is crucial for the commercial viability of Opdivo® (nivolumab) in Australia, protecting its stable liquid formulation from direct infringement by competitors.
- The competitive landscape involves innovator products, the potential for biosimilars, and ongoing formulation innovation. AU2014247092 acts as a barrier to direct formulation replication for nivolumab biosimilars.
Frequently Asked Questions
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What is the primary therapeutic target of the anti-PD-1 antibody mentioned in AU2014247092?
The primary therapeutic target of the anti-PD-1 antibody is the Programmed Cell Death Protein 1 (PD-1) receptor, a key regulator of the immune system's response.
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Can other anti-PD-1 antibodies be formulated according to AU2014247092?
The patent claims an anti-PD-1 antibody, implying that while nivolumab is a primary example, other anti-PD-1 antibodies could potentially be formulated using the claimed composition, provided they are compatible with the specified excipients and buffer system.
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What is the practical implication of a "stable liquid formulation" for patients and healthcare providers?
A stable liquid formulation eliminates the need for reconstitution before administration, simplifying preparation for healthcare providers, reducing potential for dosing errors, and allowing for ready-to-use administration, potentially leading to more efficient patient treatment workflows.
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Does AU2014247092 prevent the use of other excipients in anti-PD-1 antibody formulations in Australia?
The patent specifically claims compositions containing particular excipients and ranges. It does not broadly prevent the use of all other excipients for anti-PD-1 antibody formulations; rather, it protects the specific stable formulation defined in its claims. Competitors can develop formulations using different excipients or combinations that do not infringe on this patent.
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What is the significance of the citrate buffer and polysorbate 80 in the claimed formulation?
The citrate buffer maintains the formulation at an optimal pH for antibody stability, while polysorbate 80, a non-ionic surfactant, is used to prevent surface-induced aggregation and adsorption of the antibody to container surfaces. The specific combination and concentration contribute to the overall enhanced stability of the anti-PD-1 antibody.
Citations
[1] Bristol-Myers Squibb Company. (2014). Novel pharmaceutical compositions for treating immune-mediated diseases. Australian Patent AU2014247092.
[2] World Intellectual Property Organization. (2015). Novel pharmaceutical compositions for treating immune-mediated diseases. International Patent Application WO2015061258A1.
[3] Australian Patent Office. (n.d.). Patent Register Search. Retrieved from the official Australian Patent Office database.
[4] Bristol-Myers Squibb Company. (n.d.). Opdivo® (nivolumab) product information. Retrieved from official Bristol-Myers Squibb Australia website or TGA database.
