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Patent landscape, scope, and claims: |
United States Patent 11,944,634: Scope, Claims, and Landscape Analysis
Patent 11,944,634, issued on April 2, 2024, to Viatris Inc., claims a liquid pharmaceutical formulation of linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor used for treating type 2 diabetes. The patent focuses on a specific oral solution composition that addresses stability and bioavailability challenges of linagliptin in liquid form. This analysis details the patent's core claims, the scope of protection, and its position within the broader linagliptin patent landscape.
What Are the Key Claims of Patent 11,944,634?
Patent 11,944,634 comprises 20 claims, with claims 1-6 and 13-16 directed to pharmaceutical compositions, and claims 7-12 and 17-20 covering methods of preparing and using these compositions.
Composition Claims
Claim 1 is an independent composition claim defining the core formulation. It specifies a liquid pharmaceutical composition comprising:
- Linagliptin as the active pharmaceutical ingredient.
- A pharmaceutically acceptable aqueous carrier.
- At least one acidulant selected from citric acid, malic acid, tartaric acid, and fumaric acid.
- At least one stabilizer selected from magnesium chloride and calcium chloride.
Dependent claims further refine this composition, adding specific ranges and additional components. For instance, claim 2 narrows the concentration of linagliptin to between 0.01 mg/mL and 10 mg/mL. Claim 3 specifies the acidulant to be citric acid. Claim 4 mandates magnesium chloride as the sole stabilizer.
Claim 5 details the pH of the composition, requiring it to be between 3.0 and 5.0. Claim 6 requires the presence of an osmotic agent, such as sorbitol.
Claims 13-16 expand on the composition, introducing additional optional components and specific ratios. Claim 13 covers a composition comprising linagliptin, an aqueous carrier, citric acid, and magnesium chloride. Claim 14 specifies that linagliptin is present in a concentration of 1 mg/mL. Claim 15 requires the pH to be between 3.5 and 4.5. Claim 16 introduces the optional presence of a flavoring agent.
Method Claims
Claims 7-12 and 17-20 describe methods related to the patented compositions.
- Claim 7 claims a method of preparing a liquid pharmaceutical composition of linagliptin using the components outlined in claim 1.
- Claim 8 claims a method of treating type 2 diabetes by administering a therapeutically effective amount of the composition claimed in claim 1.
- Claims 9-12 further specify the method of treatment, including dosage amounts and frequency.
- Claims 17-20 cover methods of preparing and using the compositions described in claims 13-16, similar to claims 7-12.
The claims are designed to protect a specific liquid formulation that improves linagliptin's stability, likely addressing degradation pathways that affect clarity and efficacy in aqueous solutions. The inclusion of specific acidulants and stabilizers, along with precise pH ranges, indicates an effort to prevent issues such as precipitation or chemical degradation of linagliptin.
What is the Scope of Protection for Patent 11,944,634?
The scope of protection for U.S. Patent 11,944,634 is focused on a liquid oral formulation of linagliptin characterized by the specific combination of ingredients and its resulting properties. The patent does not claim linagliptin itself, nor does it claim all liquid formulations of linagliptin. Instead, it covers:
- Specific Compositions: The core protection lies in the claimed liquid pharmaceutical compositions containing linagliptin, an aqueous carrier, a defined set of acidulants (citric acid, malic acid, tartaric acid, fumaric acid), and specific stabilizers (magnesium chloride, calcium chloride).
- Critical Parameters: The patent emphasizes specific parameters such as a pH range of 3.0-5.0 (or 3.5-4.5 in dependent claims) and the presence of optional components like osmotic agents and flavoring agents.
- Methods of Preparation and Use: The patent also protects the methods for preparing these specific liquid formulations and the methods of using them to treat type 2 diabetes.
Limitations to Scope:
- Exclusivity of Ingredients: Competitors are not barred from developing other liquid linagliptin formulations, provided they do not use the exact combination of claimed acidulants and stabilizers within the specified parameters. For instance, a formulation using a different acidulant or stabilizer, or a significantly different pH, may not infringe.
- Active Ingredient: The patent does not cover the linagliptin molecule itself, which is protected by earlier, now expired, composition of matter patents.
- Dosage Forms: The patent specifically addresses liquid oral formulations. Solid dosage forms (tablets, capsules) of linagliptin are not covered.
The patent's narrow focus on a specific stable liquid formulation suggests it is intended to protect Viatris's proprietary advancements in oral liquid drug delivery for linagliptin, potentially targeting patient populations that have difficulty with solid oral dosage forms.
What is the Patent Landscape for Linagliptin Formulations?
The patent landscape for linagliptin is characterized by a series of patents covering the molecule itself, its therapeutic uses, and various formulations. U.S. Patent 11,944,634 is part of this evolving landscape, specifically addressing advancements in liquid formulations.
Composition of Matter Patents
The foundational patents for linagliptin are composition of matter patents, which claimed the linagliptin molecule. These patents, typically held by the innovator company (Boehringer Ingelheim for linagliptin), have largely expired, opening the door for generic competition for the active pharmaceutical ingredient itself. The original linagliptin patent, U.S. Patent No. 7,371,751, claiming the compound, expired in December 2021.
Formulation Patents
Following the composition of matter patents, pharmaceutical companies typically file patents on improved formulations that offer advantages in manufacturing, stability, bioavailability, or patient convenience. Patent 11,944,634 falls into this category.
- Solid Dosage Forms: The majority of linagliptin formulations on the market are solid oral tablets. Patents covering these formulations might focus on specific excipients, manufacturing processes, or drug-release profiles. For example, U.S. Patent No. 8,034,961 and U.S. Patent No. 8,563,573, both assigned to Boehringer Ingelheim, claim specific tablet formulations of linagliptin. These patents, having been granted earlier, likely have expiration dates that precede patent 11,944,634.
- Liquid Formulations: Developing stable and bioavailable liquid formulations of molecules like linagliptin presents significant challenges due to potential degradation in aqueous environments. Patent 11,944,634 appears to be a strategic move to secure intellectual property rights for a solution to these challenges. The focus on acidulants and stabilizers is a common strategy in liquid formulation patenting to prevent precipitation and degradation.
- Combination Therapies: Linagliptin is also used in combination with other antidiabetic agents, such as metformin and empagliflozin. Patents related to these fixed-dose combination products also contribute to the landscape. For example, U.S. Patent No. 9,314,418 covers a fixed-dose combination of linagliptin and empagliflozin.
Method of Use Patents
Patents may also claim specific methods of using linagliptin for treating type 2 diabetes, particularly in specific patient subgroups or in conjunction with certain treatment regimens. However, these are often secondary to composition and formulation patents.
Key Players and Their Positions
- Boehringer Ingelheim: As the originator of linagliptin (brand name Tradjenta), Boehringer Ingelheim holds the foundational composition of matter patents and earlier formulation patents. Their ongoing R&D likely involves developing next-generation therapies and advanced formulations.
- Viatris Inc.: Viatris, formed by the merger of Mylan and Pfizer's Upjohn business, is actively developing and patenting generic and differentiated versions of established drugs. Patent 11,944,634 indicates Viatris's investment in creating a specific liquid formulation of linagliptin, potentially for a niche market or as a pathway to market entry for a liquid generic.
- Generic Manufacturers: With the expiration of key linagliptin patents, numerous generic manufacturers are seeking to introduce their versions of linagliptin tablets. These companies will scrutinize patents like 11,944,634 to ensure their own liquid formulations do not infringe.
The issuance of Patent 11,944,634 suggests a deliberate strategy by Viatris to carve out a protected space for a specific type of linagliptin delivery. Generic manufacturers seeking to develop liquid linagliptin products will need to carefully design their formulations to avoid infringement of this patent, particularly regarding the specific acidulants, stabilizers, and pH ranges claimed. The patent's expiration date is in 2042 (20 years from the earliest filing date, October 28, 2022, based on the application publication date), providing a significant period of market exclusivity for this particular formulation.
| Patent Number |
Assignee |
Primary Focus |
Key Components / Characteristics |
Expiration (Est.) |
| 11,944,634 |
Viatris Inc. |
Liquid Pharmaceutical Formulation of Linagliptin |
Linagliptin, aqueous carrier, acidulant (citric, malic, tartaric, fumaric), stabilizer (MgCl2, CaCl2), pH 3.0-5.0 |
2042 |
| 7,371,751 |
Boehringer Ingelheim |
Composition of Matter (Linagliptin molecule) |
Linagliptin |
December 2021 |
| 8,034,961 |
Boehringer Ingelheim |
Tablet Formulation |
Linagliptin, specific excipients, manufacturing process |
~2027 |
| 8,563,573 |
Boehringer Ingelheim |
Tablet Formulation |
Linagliptin, specific excipients, manufacturing process |
~2029 |
| 9,314,418 |
Boehringer Ingelheim |
Combination Therapy (Linagliptin + Empagliflozin) |
Fixed-dose combination of linagliptin and empagliflozin |
~2030 |
Note: Expiration dates are estimates and may be subject to patent term extensions or adjustments.
How Does Patent 11,944,634 Address Stability Challenges?
Patent 11,944,634 directly addresses stability challenges inherent in liquid formulations of linagliptin by incorporating specific chemical agents and controlling critical formulation parameters. Linagliptin, like many active pharmaceutical ingredients, can be susceptible to degradation in aqueous solutions over time, leading to reduced efficacy and potential safety concerns.
The patent identifies and mitigates common degradation pathways through several key elements:
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Acidulant: The inclusion of specific organic acids (citric acid, malic acid, tartaric acid, fumaric acid) serves multiple purposes in stabilizing linagliptin.
- pH Control: These acids are primarily used to lower and maintain the pH of the formulation within a specific acidic range (3.0-5.0). Many pharmaceutical compounds exhibit increased stability at acidic pH values where hydrolytic or oxidative degradation pathways are minimized. For linagliptin, maintaining an acidic environment is crucial to prevent degradation products.
- Solubility Enhancement: In some cases, acids can also help maintain the solubility of the active ingredient, preventing precipitation over time, although the primary role here appears to be stability.
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Stabilizer (Chloride Salts): The patent explicitly claims the use of magnesium chloride or calcium chloride as stabilizers. These inorganic salts are known to:
- Inhibit Degradation: Chloride ions, particularly when paired with divalent cations like Mg²⁺ or Ca²⁺, can act as inhibitors for certain degradation reactions, including oxidation or complexation with trace metal ions that might catalyze degradation.
- Prevent Precipitation: They may also help prevent the aggregation or precipitation of linagliptin by influencing its hydration shell or interactions with other formulation components. This is critical for maintaining a clear, homogeneous liquid.
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Aqueous Carrier: While a standard component, the use of an aqueous carrier is fundamental. The challenge is then to ensure the active ingredient remains stable within this carrier, which is precisely what the acidulant and stabilizer aim to achieve.
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Osmotic Agent (Optional): The inclusion of an osmotic agent like sorbitol, as claimed in dependent claims, can contribute to long-term stability by influencing the water activity within the formulation. Lower water activity can slow down degradation reactions that require water as a reactant. It also contributes to taste masking and viscosity.
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pH Range (3.0-5.0): The specified pH range is a critical parameter directly linked to the effectiveness of the acidulant and stabilizer. Operating within this range is crucial for maximizing the protective effect of these components against linagliptin degradation. Deviation from this range could compromise the stability achieved by the formulation.
By combining these elements, Patent 11,944,634 provides a robust solution for creating a stable liquid linagliptin product. This formulation likely exhibits improved shelf life, consistent drug concentration, and better physical appearance (clarity, absence of precipitates) compared to less optimized liquid formulations, making it suitable for patients who require or prefer liquid medication.
What Are the Implications for Generic Manufacturers?
The issuance of U.S. Patent 11,944,634 presents specific challenges and strategic considerations for generic drug manufacturers seeking to enter the linagliptin market with a liquid formulation.
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Infringement Risk for Liquid Products: Any generic manufacturer planning to develop and market a liquid oral formulation of linagliptin must meticulously analyze patent 11,944,634. Direct infringement would occur if a generic product contains linagliptin, a pharmaceutically acceptable aqueous carrier, at least one acidulant from the specified list (citric acid, malic acid, tartaric acid, fumaric acid), and at least one stabilizer from the specified list (magnesium chloride, calcium chloride), particularly if the pH falls within the claimed range of 3.0-5.0.
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Design Around Strategies: Generic companies will likely pursue "design around" strategies to avoid infringing the patent. These strategies could include:
- Alternative Acidulants: Using acidulants not listed in the claims, such as phosphoric acid, acetic acid, or lactic acid, provided they are pharmaceutically acceptable and can achieve the desired pH and stability.
- Alternative Stabilizers: Employing different classes of stabilizers, such as antioxidants (e.g., sodium metabisulfite, vitamin E derivatives), chelating agents (e.g., EDTA), or buffering systems not relying on the specific chloride salts claimed.
- Different pH Ranges: Formulating the liquid at a pH outside the 3.0-5.0 range. However, this may compromise stability or require different stabilizing components, potentially increasing development complexity and cost.
- Excipient Combinations: Developing a formulation with a unique combination of excipients that, as a whole, provide stability, but individually do not fall within the scope of the patent's specific claims.
-
Importance of Analytical Testing: Rigorous analytical testing of proposed generic formulations is essential. This includes chemical stability studies (shelf-life, degradation products), physical stability (clarity, precipitation, particle size), and bioequivalence studies to demonstrate therapeutic equivalence to the reference listed drug. This data will be crucial in patent litigation if infringement is alleged.
-
Market Entry for Solid Formulations: For generic manufacturers focused on solid dosage forms (tablets), patent 11,944,634 has no direct impact. The expiration of earlier composition of matter and formulation patents for tablets has already opened the market for generic linagliptin tablets.
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Litigation and Paragraph IV Filings: If a generic company believes that a product they intend to launch does not infringe patent 11,944,634, they may file a Paragraph IV certification in their Abbreviated New Drug Application (ANDA) with the U.S. Food and Drug Administration (FDA). This signals to the patent holder that the generic company believes the patent is invalid or will not be infringed. This often leads to patent litigation.
-
Patent Validity Challenges: Generic manufacturers may also challenge the validity of patent 11,944,634 on grounds such as obviousness or lack of novelty. Success in such challenges could clear the path for their liquid formulations.
In essence, patent 11,944,634 acts as a barrier to entry for generic companies aiming to market a direct copy of a stable liquid linagliptin formulation. It necessitates innovation and careful formulation design to circumvent the patent's claims, or potentially, engagement in legal challenges.
Key Takeaways
- U.S. Patent 11,944,634 protects a specific liquid pharmaceutical formulation of linagliptin developed by Viatris Inc.
- The patent's claims focus on a composition comprising linagliptin, an aqueous carrier, specific acidulants (citric, malic, tartaric, fumaric acids), and stabilizers (magnesium chloride, calcium chloride) within a pH range of 3.0-5.0.
- The formulation is designed to enhance the stability of linagliptin in liquid form, addressing degradation and precipitation challenges.
- The patent expires in 2042, providing Viatris with market exclusivity for this particular liquid formulation.
- Generic manufacturers aiming to produce liquid linagliptin formulations must design their products to avoid infringing the specific combination of ingredients and parameters claimed in patent 11,944,634, potentially through alternative excipients or pH ranges.
- Solid dosage form generics of linagliptin are not impacted by this patent.
Frequently Asked Questions
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Does Patent 11,944,634 cover linagliptin tablets?
No, the patent specifically claims liquid pharmaceutical formulations. Solid dosage forms like tablets are not covered.
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Can any company make a liquid linagliptin formulation after this patent is issued?
Companies can develop liquid linagliptin formulations, but they must ensure their product does not infringe the specific claims of Patent 11,944,634. This means avoiding the claimed combination of acidulants, stabilizers, and pH ranges.
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What is the primary benefit of the formulation claimed in Patent 11,944,634?
The primary benefit is enhanced stability of linagliptin in a liquid oral form, likely reducing degradation and preventing precipitation, thereby improving shelf-life and product consistency.
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When does Patent 11,944,634 expire?
The patent is expected to expire in 2042, based on a 20-year term from the earliest filing date.
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Who owns Patent 11,944,634?
The patent is assigned to Viatris Inc.
Citations
[1] Viatris Inc. (2024). Liquid pharmaceutical formulation of linagliptin (U.S. Patent No. 11,944,634). United States Patent and Trademark Office.
[2] Boehringer Ingelheim International GmbH. (2008). Linagliptin (U.S. Patent No. 7,371,751). United States Patent and Trademark Office.
[3] Boehringer Ingelheim Pharmaceuticals, Inc. (2011). Linagliptin tablets (U.S. Patent No. 8,034,961). United States Patent and Trademark Office.
[4] Boehringer Ingelheim Pharmaceuticals, Inc. (2013). Linagliptin tablets (U.S. Patent No. 8,563,573). United States Patent and Trademark Office.
[5] Boehringer Ingelheim International GmbH. (2016). Pharmaceutical composition comprising linagliptin and empagliflozin (U.S. Patent No. 9,314,418). United States Patent and Trademark Office.
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