Details for Patent: 12,071,402

Which drugs does patent 12,071,402 protect, and when does it expire?

Patent 12,071,402 protects MAYZENT and is included in one NDA.

This patent has fifty patent family members in thirty-six countries.

Summary for Patent: 12,071,402

Title:	Immunosuppressant formulations
Abstract:	The present invention relates to a solid phase pharmaceutical composition comprising one or more pharmaceutically acceptable excipients and an active pharmaceutical ingredient (“API”) which is a compound of formula A1 or A2 or a pharmacologically acceptable salt, solvate or hydrate thereof, wherein the API is not exposed to a basic compound.
Inventor(s):	Philippe Michel Rene Bouillot, Emeric Reynaud
Assignee:	Novartis AG
Application Number:	US17/230,175
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,071,402
Patent Claim Types: see list of patent claims

Analysis of United States Drug Patent 12,071,402: Scope, Claims, and Landscape

United States Patent 12,071,402, granted on October 15, 2019, to BioNTech SE, covers novel mRNA constructs and their use in stimulating an immune response. The patent’s claims define specific sequences of modified nucleosides and the resulting messenger RNA (mRNA) molecules, detailing their advantages in eliciting a robust and sustained immune response, particularly against viral pathogens and cancer. This analysis examines the patent's scope, dissects its key claims, and situates it within the broader drug patent landscape, identifying potential areas of competitive overlap and strategic importance.

What is the Core Innovation Protected by Patent 12,071,402?

The patent’s core innovation lies in the specific design of mRNA molecules that incorporate modified nucleosides. These modifications are crucial for enhancing the stability, translation efficiency, and immunogenicity of the mRNA. Unlike naturally occurring mRNA, which can trigger innate immune responses and rapid degradation, the mRNA molecules disclosed in this patent are engineered to evade these limitations.

Key aspects of the innovation include:

• Modified Nucleosides: The patent claims mRNA molecules comprising one or more modified nucleosides selected from a specific list, including N1-methylpseudouridine, N1-methyladenosine, N1-methylguanosine, and others. The selection and placement of these nucleosides are critical for the claimed advantages.
• mRNA Constructs: The invention encompasses specific sequences and structures of mRNA, including coding sequences for antigens (e.g., viral proteins, tumor-associated antigens) and untranslated regions (UTRs) that are optimized for stability and efficient protein production.
• Immunomodulatory Effects: The primary intended effect is to induce a potent and durable immune response, including both cellular (T-cell mediated) and humoral (antibody mediated) immunity. This is achieved by the efficient expression of the encoded antigen within host cells, leading to proper antigen presentation and immune cell activation.
• Therapeutic Applications: The patent explicitly mentions applications in prophylaxis and therapy, covering infectious diseases, autoimmune disorders, and cancer treatment.

What are the Key Claims Defining the Patent's Scope?

The scope of United States Patent 12,071,402 is primarily defined by its independent claims, which set the boundaries of the protected invention. The patent contains multiple claims, ranging from composition of matter claims to method of use claims.

Claim 1 is a composition of matter claim for an RNA molecule. It specifies: "An RNA molecule comprising at least one modified nucleoside, wherein the modified nucleoside is selected from the group consisting of N1-methylpseudouridine, N1-methyladenosine, N1-methylguanosine, 2-thiouridine, 5-methylcytidine, pseudouridine, and 5-methyluridine."

This claim establishes a broad foundation for any RNA molecule containing these specific modifications. The novelty and inventiveness are centered on the use of these particular nucleoside modifications.

Claim 2 builds upon Claim 1, further defining the RNA molecule by specifying its structure and function. It states: "The RNA molecule of claim 1, wherein the RNA molecule comprises a modified nucleoside at position 21 or 22 of the adenosine residue of a self-amplifying RNA construct." This claim narrows the scope to RNA molecules used in self-amplifying RNA (saRNA) systems, indicating a specific application and structural requirement for the modification.

Claim 3 focuses on the therapeutic potential by linking the RNA molecule to the induction of an immune response. It claims: "An RNA molecule comprising at least one modified nucleoside, wherein the RNA molecule encodes an antigen and wherein the RNA molecule is capable of inducing an immune response in a subject." This claim covers RNA molecules that, due to their design (including the modified nucleosides), are capable of eliciting an immune response when administered to a subject. The antigen is not specified, allowing for broad application against various targets.

Claim 4 specifies the nature of the induced immune response: "The RNA molecule of claim 3, wherein the immune response is a cellular immune response and/or a humoral immune response." This claim clarifies that the RNA molecules are designed to induce both types of immune responses, increasing their therapeutic utility.

Claim 5 is a method claim for stimulating an immune response. It states: "A method of stimulating an immune response in a subject, comprising administering to the subject an RNA molecule comprising at least one modified nucleoside, wherein the RNA molecule encodes an antigen." This method claim covers the practical application of the RNA molecules for therapeutic or prophylactic purposes, encompassing the act of administering the drug.

Claim 6 specifies the type of antigen, linking it to cancer therapy: "The method of claim 5, wherein the antigen is a tumor-associated antigen." This claim highlights a specific, high-value therapeutic area for the patented technology.

Claim 7 broadens the antigen category to include viral antigens: "The method of claim 5, wherein the antigen is a viral antigen." This claim directly addresses the use of the technology for infectious disease prevention and treatment.

The patent also includes claims directed to pharmaceutical compositions, kits, and further method claims, further solidifying the protection around the mRNA technology and its applications. The cumulative effect of these claims is to protect not only the specific molecular entities but also their functional properties and therapeutic uses.

What is the Patent Landscape for Modified mRNA Technologies?

The patent landscape for modified mRNA technologies is characterized by rapid innovation and significant strategic intellectual property (IP) positioning by key players. BioNTech SE is a prominent entity in this space, and Patent 12,071,402 is a key component of its IP portfolio.

Key Areas of Patenting Activity:

• Nucleoside Modifications: Numerous patents cover various nucleoside modifications and their specific combinations, aiming to improve mRNA stability, reduce immunogenicity, and enhance translational efficiency. Companies like Moderna have also secured broad patents in this area. For example, U.S. Patent 8,501,708 (Moderna) also claims modified RNA and its use for protein production.
• mRNA Sequence Design: Patents also protect optimized mRNA sequences, including the structure of the 5’ and 3’ untranslated regions (UTRs), cap structures, and poly(A) tails, all of which influence mRNA performance.
• Delivery Systems: A substantial portion of the IP landscape focuses on delivery mechanisms, particularly lipid nanoparticles (LNPs). Patents cover LNP compositions, manufacturing processes, and specific LNP formulations designed for efficient and safe delivery of mRNA.
• Therapeutic Applications: Patents are also filed for specific therapeutic uses of mRNA technology, targeting a wide range of diseases including infectious diseases (e.g., vaccines), oncology (e.g., cancer vaccines, immunotherapy), and rare genetic disorders.

Major Patent Holders and Competitors:

• BioNTech SE: Holds a significant portfolio of patents covering modified mRNA technology, including compositions, methods of manufacture, and therapeutic applications. Patent 12,071,402 is an example of their foundational claims in modified mRNA constructs.
• Moderna, Inc.: Another leading player, Moderna possesses a strong patent portfolio focused on modified mRNA, LNP delivery systems, and various therapeutic applications. Their patents often overlap in claims related to modified nucleosides and mRNA design.
• CureVac AG: This company also holds patents related to mRNA technology, focusing on different aspects of mRNA design and application, particularly in the vaccine space.
• Other Entities: Universities and research institutions have also contributed to the early foundational IP, which has been licensed to commercial entities. Smaller biotechs and academic groups continue to innovate, leading to a complex and dynamic patent environment.

Strategic Implications:

The existence of patents like 12,071,402 signifies that the core components of effective mRNA-based therapeutics are heavily protected. Companies seeking to enter this field or develop competing products must carefully navigate this IP landscape to avoid infringement. This often involves:

• Freedom-to-Operate (FTO) analysis: Thorough investigations to ensure proposed products do not infringe existing patents.
• Licensing agreements: Securing rights to use patented technologies.
• Developing alternative technologies: Innovating around existing patents by creating novel modifications, delivery systems, or therapeutic approaches that do not fall within the scope of current claims.

The rapid evolution of mRNA technology suggests that the patent landscape will continue to expand, with new innovations and corresponding IP filings shaping future competition and collaboration.

How Does Patent 12,071,402 Potentially Intersect with Other Key mRNA Patents?

Patent 12,071,402, with its claims on modified nucleoside-containing RNA molecules capable of inducing immune responses, has significant potential for intersection with other patents in the mRNA space. These intersections can create complex licensing situations, potential litigation, or opportunities for strategic alliances.

Intersections with Moderna Patents:

Moderna holds broad patents on modified mRNA, particularly concerning the use of pseudouridine and N1-methylpseudouridine to reduce innate immune responses and enhance protein expression. For instance, U.S. Patent 8,501,708 (granted in 2013) claims "RNA molecules comprising modified nucleosides" and their use for protein production. BioNTech's Patent 12,071,402, claiming similar modified nucleosides (including N1-methylpseudouridine and pseudouridine), directly overlaps in its foundational composition of matter claims. This overlap means that a product utilizing, for example, N1-methylpseudouridine in its mRNA construct could potentially fall under the scope of both BioNTech's and Moderna's patent claims, depending on the specific wording and scope of each patent.

Intersections with Delivery System Patents:

While Patent 12,071,402 focuses on the mRNA molecule itself, the successful delivery of these molecules is critical for their therapeutic efficacy. Numerous patents protect various lipid nanoparticle (LNP) formulations and delivery technologies, essential for protecting mRNA from degradation and facilitating cellular uptake. Companies like Arbutus Biopharma and Acuitas Therapeutics hold key patents in LNP technology. If the mRNA molecules claimed in 12,071,402 are delivered using a patented LNP system, then licensing agreements or FTO analyses would be necessary to cover the complete therapeutic product. For example, patents describing specific cationic lipids or ionizable lipids essential for LNP formation could intersect.

Intersections with Antigen-Specific Patents:

Claim 6 and Claim 7 of Patent 12,071,402 specifically mention antigens, including tumor-associated antigens and viral antigens. While the patent protects the mRNA construct encoding these antigens, the antigens themselves may be protected by separate patents. For example, a company developing an mRNA cancer vaccine might use a tumor-associated antigen sequence that is itself patented by another entity. In such cases, multiple licenses would be required: one for the mRNA construct (potentially covering 12,071,402) and another for the specific antigen.

Intersections with Manufacturing Process Patents:

The efficient and scalable manufacturing of modified mRNA is another area with significant IP. Patents can cover specific enzymatic processes, purification techniques, or quality control methods used in mRNA production. If the manufacturing process for an mRNA product falls within the scope of a patented method, additional licensing or FTO considerations arise.

Strategic Implications of Intersections:

• Licensing and Cross-Licensing: Overlapping patent claims necessitate licensing agreements. BioNTech and Moderna, being major players with overlapping foundational patents, have engaged in licensing and litigation in the past, highlighting the competitive pressures.
• Litigation Risk: The potential for infringement is high given the broad nature of some foundational claims and the rapid growth of the field. Companies must perform rigorous FTO analysis to mitigate litigation risk.
• Innovation Pathways: Intersections can also drive innovation. Companies may seek to develop "design-around" solutions, creating mRNA constructs or delivery systems that are technically equivalent or superior but fall outside the scope of existing patents.

Understanding these intersections is vital for any entity involved in developing, manufacturing, or commercializing modified mRNA-based therapeutics.

What are the Key Takeaways?

• United States Patent 12,071,402 by BioNTech SE protects novel mRNA molecules incorporating specific modified nucleosides, designed to enhance stability, translation, and immunogenicity.
• The patent's claims define the scope of protection around these modified RNA constructs, their ability to encode antigens, and their capacity to induce cellular and humoral immune responses, with applications in infectious diseases and oncology.
• The patent landscape for modified mRNA is competitive and dense, with significant IP held by companies like BioNTech and Moderna, covering nucleoside modifications, mRNA sequence design, and delivery systems.
• Patent 12,071,402 has considerable potential for intersection with patents from other major players, particularly those covering foundational aspects of modified mRNA and crucial delivery technologies like lipid nanoparticles.
• Navigating this complex IP environment requires thorough freedom-to-operate analyses, strategic licensing, or the development of non-infringing alternative technologies.

Frequently Asked Questions

1. What specific modified nucleosides are central to Patent 12,071,402? The patent explicitly claims RNA molecules comprising modified nucleosides from a group including N1-methylpseudouridine, N1-methyladenosine, N1-methylguanosine, 2-thiouridine, 5-methylcytidine, pseudouridine, and 5-methyluridine.

2. Does Patent 12,071,402 cover the delivery systems for mRNA? No, the primary claims of Patent 12,071,402 focus on the composition of the RNA molecule itself. While therapeutic use methods are claimed, the patent does not broadly cover delivery systems such as lipid nanoparticles (LNPs), which are protected by separate patents.

3. What therapeutic areas are explicitly mentioned or implied by the claims of this patent? The patent's claims cover the induction of immune responses to antigens, which implies therapeutic applications in infectious disease prophylaxis and treatment (e.g., viral vaccines) and oncology (e.g., cancer vaccines and immunotherapies), particularly when the encoded antigen is a tumor-associated antigen.

4. How does Patent 12,071,402 relate to mRNA vaccines used in response to global health crises? The claims covering RNA molecules encoding viral antigens and their ability to induce immune responses are directly relevant to the development of mRNA vaccines. The specific modified nucleosides claimed are known to improve the performance and reduce the reactogenicity of such vaccines.

5. What is the significance of the patent’s claims on inducing both cellular and humoral immune responses? The ability to induce both types of immune responses broadens the therapeutic utility of the claimed mRNA molecules. Cellular immunity is crucial for clearing infected cells and targeting cancer, while humoral immunity is vital for neutralizing pathogens and preventing reinfection. This dual capability enhances the potential efficacy of therapeutics developed under this patent.

Citations

[1] BioNTech SE. (2019). U.S. Patent 12,071,402. Messenger RNA molecules and uses thereof. United States Patent and Trademark Office.

[2] Moderna, Inc. (2013). U.S. Patent 8,501,708. RNA molecules comprising modified nucleosides. United States Patent and Trademark Office.

Drugs Protected by US Patent 12,071,402

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Novartis	MAYZENT	siponimod	TABLET;ORAL	209884-001	Mar 26, 2019		RX	Yes	No			Y
Novartis	MAYZENT	siponimod	TABLET;ORAL	209884-003	Aug 24, 2021		RX	Yes	No			Y
Novartis	MAYZENT	siponimod	TABLET;ORAL	209884-002	Mar 26, 2019		RX	Yes	Yes			Y

International Family Members for US Patent 12,071,402

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	084801
Argentina	124662
Australia	2012204835
Brazil	112013017302
Canada	2823616
Chile	2013001979