Who holds the patent for Dimethyl Fumarate?

Overview of Dimethyl Fumarate

Chemical Properties and Uses 
Dimethyl Fumarate (DMF) is a small molecule with a molecular weight of 144.13 g/mol and is a methyl ester of fumaric acid. It is characterized by its white to off‐white appearance and high solubility in water, making it amenable to a variety of formulation strategies. Chemically, DMF is an α,β-unsaturated carboxylic ester that is produced either through esterification (Fisher esterification) of fumaric acid with methanol or via isomerization reactions. Its structure promotes rapid metabolism upon oral administration, where it is quickly hydrolyzed by gastrointestinal esterases into its primary active metabolite, monomethyl fumarate (MMF). This rapid conversion ensures that DMF exerts its pharmacological effects primarily through the action of MMF systemically, despite DMF’s vital role as the dosing compound in various commercial formulations.

Medical Applications 
DMF has been in clinical use for several decades, largely due to its immunomodulatory and anti-inflammatory properties. Originally employed in the treatment of psoriasis, one of its most well-known applications is in the management of relapsing forms of multiple sclerosis (MS). Over the years, additional research has expanded its potential into neuroprotection, as DMF influences several molecular pathways including the activation of the Nrf2 transcription factor, which leads to the upregulation of antioxidant response elements. Apart from its indication in MS and psoriasis, studies suggest possible roles in addressing diabetic nephropathy and even in novel technological applications such as modulating gene editing (for instance, in CRISPR/Cas9 systems). Its pleiotropic benefits have underscored the importance of DMF in several therapeutic domains, thereby driving ongoing pharmaceutical research and patenting activities.

Patent Landscape for Dimethyl Fumarate

Key Patent Holders 
The intellectual property surrounding DMF is diverse, reflecting its multifaceted clinical applications and the various composition strategies that have been developed over time. Several prominent companies and institutions hold patents or patent applications related to DMF:

- BIOGEN MA INC. 
BIOGEN MA INC. is one of the key players in this arena. They hold patents that cover not only the active pharmaceutical ingredient formulations but also specific delayed-release compositions and bead formulations for treating multiple sclerosis. Multiple patent records list BIOGEN as the current assignee, highlighting a strong emphasis on formulations that improve pharmacokinetic profiles and therapeutic efficacy.

- ALMIRALL, S.A. 
ALMIRALL, S.A. is another significant patent holder in the field of pharmaceutical compositions containing DMF. They have secured patents that typically cover formulations comprising DMF with various diluents, microcrystalline cellulose, and other excipients. Their patents often focus on compositions that omit a gastro-resistant coating yet are effective for inflammatory autoimmune diseases.

- ZIM LABORATORIES LIMITED 
ZIM LABORATORIES LIMITED is prominently represented in the context of DMF formulations designed for delayed release applications. Patents illustrate their work in developing DMF formulations manufactured by techniques such as extrusion-spheronization or layering methods. Their patents specifically highlight control over particle size (for example, ensuring the D90 is less than 50 µm) to meet the required release profiles.

- The Air Force Medical University of the Chinese People’s Liberation Army 
A unique patent application involving DMF comes from this institution, wherein DMF is used in combination with pargyline hydrochloride and metadoxine to impede the DNA cleavage activity of SpCas9 within CRISPR-Cas9 gene editing systems. This demonstrates a novel avenue of application, extending DMF’s therapeutic potential beyond immunomodulation into gene editing regulation.

- CURACLE CO., LTD. 
CURACLE CO., LTD. holds a patent that focuses on a specific application of DMF in diabetic nephropathy. This patent outlines the use of DMF or its pharmaceutically acceptable salts in achieving defined pharmacokinetic parameters, thereby providing therapeutic benefits in the prevention or treatment of diabetic nephropathy.

- Other Patent Holders 
Beyond these major companies, other researchers and smaller entities have contributed to the DMF intellectual property space. For instance, a patent from a group including HARSHA B. SAKHARKAR and colleagues reveals innovations in the development of DMF cocrystals intended to enhance the physicochemical properties and potentially the clinical performance of DMF. Additionally, patent filings that emphasize sustained- or extended-release formulations in tablet or capsule form are evident and contribute to the landscape by diversifying the delivery modalities of DMF.

Patent Details and Claims 
A closer examination of the patent documents and their claims demonstrates that the patents differ depending on the intended use, formulation technology, and manufacturing processes. The patents held by BIOGEN MA INC. frequently claim innovative formulations such as:
- Delayed Release Formulations: 
These formulations are designed to optimize the release profile of DMF, often by controlling the particle size or through specialized coating or matrix systems.
- Bead and Multiphasic Compositions: 
Some patents describe pharmaceutical bead formulations where an immediate-release bead composition is combined with a controlled-release bead composition, allowing fine-tuning of the drug’s plasma concentration profile over time.
- Pharmacokinetic Parameter Optimization: 
Patents ensure that the formulations exhibit specific pharmacokinetic profiles, which is critical for both efficacy and safety in patients, particularly in complex diseases like multiple sclerosis and diabetic nephropathy.

ALMIRALL's patents focus on non-coated formulations that rely on particular combinations of diluents and excipients to maximize absorption in the gastrointestinal tract. Similarly, ZIM LABORATORIES LIMITED’s patents emphasize controlled particle size and the use of systems like extrusion-spheronization to achieve sustained release in the treatment of chronic conditions like MS.

Each patent distinguishes itself by addressing specific formulation challenges such as the stability of DMF, its rapid hydrolysis in the GI tract, and the necessity to mitigate gastrointestinal side effects by adjusting the release properties of the drug. In doing so, these patents encompass a range of technical details from manufacturing methods to the specific ratios of DMF to its excipients, illustrating the comprehensive nature of the patent landscape.

Implications of Patent Ownership

Market Impact 
The distribution of patents among several key players indicates a highly competitive market landscape. With BIOGEN MA INC. and ALMIRALL, S.A. holding a large share of patents geared towards therapeutic applications in multiple sclerosis and autoimmune diseases, these companies have secured strong market positions. Their patents allow these players to offer innovative formulations with improved patient compliance and less frequent dosing, which can lead to enhanced market penetration and patient outcomes.

Moreover, the patents held by ZIM LABORATORIES LIMITED on delayed-release compositions assure that innovative delivery mechanisms are protected, making it challenging for competitors to replicate these specific formulations without infringing on proprietary technologies. The market impact is therefore significant because the companies controlling these formulations can leverage both clinical and regulatory advantages, impacting pricing strategies, market exclusivity periods, and ultimately, patient access to these therapies.

The additional patents held by institutions such as CURACLE CO., LTD. and the Chinese Air Force Medical University represent moves to capture niche applications of DMF that expand its therapeutic spectrum beyond traditional autoimmune indications. These patents not only protect novel uses but also lay the groundwork for further market expansion into areas like diabetic nephropathy and gene editing applications, thus broadening the commercial potential of DMF.

Competitive Landscape 
The existence of multiple patent holders creates a competitive landscape where each entity focuses on different aspects of DMF technology. Companies such as BIOGEN MA INC. and ALMIRALL, S.A. compete based on clinical efficacy and the robustness of their formulations, whereas ZIM LABORATORIES LIMITED concentrates on optimizing release profiles and manufacturing processes to minimize side effects while maintaining efficacy. This multifaceted patent environment leads to a scenario where collaboration, licensing agreements, or even patent litigation might occur as companies navigate overlapping claims and unpredictable global markets.

Furthermore, the competitive landscape is not static. Innovations in formulation science, manufacturing technology, and even repurposing DMF for other indications drive continuous new patent filings. The involvement of academic and military research institutions introduces additional layers of complexity and potential collaboration, further stimulating scientific and commercial advances. The competitive environment benefits patients in the long run by fostering innovation, while also encouraging companies to invest in robust clinical studies and post-market surveillance, thereby reinforcing the overall quality and safety of DMF-based therapies.

Future Prospects

Patent Expiry and Generic Entry 
A critical consideration in the DMF patent landscape involves the expiry dates of current patents and the potential for generic entry. Patents such as those from BIOGEN MA INC. have clear expiry dates, which suggests that once the patent protection lapses, generic manufacturers may have the opportunity to enter the market. Such generic entries could lead to increased competition, lower drug prices, and broadened patient access, particularly for a drug as essential as DMF in chronic conditions like multiple sclerosis.

However, the staggered filing dates and overlapping claims in different jurisdictions (for instance, US, EU, Australia, and India) could delay the timeline for generic entry until all key patents expire. In addition, if new patents are secured for alternative formulations, further extended-release mechanisms, or novel delivery systems, these innovations may provide extended market protection even after the original patents expire. This continued innovation could lead to incremental improvements in the clinical performance of DMF formulations, thus preserving a degree of exclusivity despite eventual generic competition.

Innovations and New Developments 
Innovation in the field of DMF is ongoing and multifaceted. While traditional applications in multiple sclerosis and psoriasis remain dominant, emerging research into DMF’s broader pharmacological effects—including its anti-oxidative stress properties and its role in enhancing cellular defense systems via Nrf2 activation—opens the door to additional therapeutic uses. Patents such as that from CURACLE CO., LTD. that focus on diabetic nephropathy illustrate the trend towards repurposing DMF for metabolic and vascular conditions. 

Moreover, the application of DMF in non-traditional fields such as gene editing modulation by the Chinese Air Force Medical University highlights how innovative uses of DMF can create entirely new patent families and therapeutic modalities. Not only does this expand the potential market for DMF formulations, but it also encourages interdisciplinary research that spans both pharma and biotechnology sectors.

Investment in new drug delivery systems, as evidenced by the patents focusing on delayed or sustained release, continues to be a vibrant area of development. These innovations are primarily driven by the need to maintain therapeutic levels of DMF while reducing side effects—a balance that is critical to maximizing clinical benefits, especially in diseases requiring long-term management. 

Advances in formulation technology, coupled with robust clinical data, promise to further enhance DMF’s competitive edge. While improvements in manufacturing methods and formulation strategies represent incremental innovations, the potential for breakthrough technologies—such as cocrystallization to improve solubility and bioavailability—could lead to a renaissance in DMF-based therapies. As patents expire, these innovations will again become critical in maintaining competitive differentiation in a landscape that is increasingly crowded with generics and alternative therapies.

Conclusion 
In summary, the patent ownership for Dimethyl Fumarate is distributed among several key players and institutions. BIOGEN MA INC. has a dominant portfolio covering a variety of formulations and delivery systems for DMF, particularly in the treatment of multiple sclerosis. ALMIRALL, S.A. holds important patents for non-coated formulations designed for treating autoimmune diseases. ZIM LABORATORIES LIMITED has secured patents focusing on advanced delayed-release and controlled-release formulations, while CURACLE CO., LTD. has innovated in the area of diabetic nephropathy. Additionally, the Chinese institution The Air Force Medical University of the Chinese People’s Liberation Army has contributed to expanding DMF’s applications into the realm of gene editing. There are also patents by academic and private groups, such as the work involving DMF cocrystals by researchers led by HARSHA B. SAKHARKAR.

This diverse portfolio of patents reflects not only the multifaceted medicinal potential of DMF but also the varied strategies that companies and institutions employ to optimize its efficacy, safety, and marketability. The competitive landscape is thereby enriched by overlapping and complementary intellectual property rights, which drive innovation but simultaneously set the stage for eventual patent expiry and the entry of generics. As patents expire, the market could see increased competition and improved affordability, yet ongoing innovations in drug delivery, formulation technologies, and expanded therapeutic indications are likely to continue to extend the commercial life cycle of DMF.

Thus, from a general perspective, while multiple organizations hold patents related to Dimethyl Fumarate across different aspects of its application and formulation, BIOGEN MA INC. frequently emerges as a leading entity in terms of both the number and the strategic value of their patents. Concurrently, the contributions of ALMIRALL, S.A., ZIM LABORATORIES LIMITED, CURACLE CO., LTD., and other institutions ensure that DMF remains a dynamic field of pharmaceutical innovation with far-reaching implications for the medical and competitive landscapes.

In conclusion, the patent landscape for Dimethyl Fumarate is complex and multifaceted, emphasizing the widespread interest in optimizing its clinical use and ensuring robust market protection. The range of patent holders—from global pharmaceutical giants to specialized research institutions—illustrates how DMF continues to evolve as a critical therapeutic agent. As these patents guide clinical use and competitive dynamics, they also provide a framework for future innovations, ensuring that the legacy of DMF remains influential in both current treatments and emerging medical applications.

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