Details for Patent: 11,278,547

Which drugs does patent 11,278,547 protect, and when does it expire?

Patent 11,278,547 protects RECORLEV and is included in one NDA.

This patent has twelve patent family members in nine countries.

Summary for Patent: 11,278,547

Title:	Methods of treating disease with levoketoconazole
Abstract:	Provided herein is a method of administering levoketoconazole, or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the subject is also being administered a multidrug and toxin extrusion transporter 1 (MATE1) substrate or an organic cation transporter 2 (OCT2) substrate.
Inventor(s):	Fredric Cohen
Assignee:	Xeris Pharmaceuticals Inc
Application Number:	US17/319,781
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Patent 11,278,547: Analytical Deep Dive

United States Patent 11,278,547, granted on March 22, 2022, to ModernaTX, Inc., covers novel lipid nanoparticle (LNP) compositions and their use in delivering nucleic acids, including messenger RNA (mRNA). The patent's claims are directed at specific lipid formulations designed to enhance mRNA stability and delivery efficiency, critical for vaccine development and gene therapy applications. The patent landscape surrounding LNP technology is highly competitive, with significant investment and multiple players asserting overlapping intellectual property rights.

What is the Core Innovation Protected by Patent 11,278,547?

Patent 11,278,547 claims encompass specific lipid compositions designed to form stable and effective lipid nanoparticles (LNPs). These LNPs are configured to encapsulate and deliver nucleic acid molecules, primarily mRNA. The patent emphasizes the advantages of these specific lipid formulations in terms of improved delivery efficiency, cellular uptake, and reduced immunogenicity compared to prior art. The claims are structured to protect the composition of the LNP itself, as well as methods of using these LNPs for therapeutic purposes.

The innovation centers on the precise ratios and types of lipids used in the formulation. This includes ionizable lipids, helper lipids, cholesterol, and polyethylene glycol (PEG)-modified lipids. The patent specifies ranges for the molar percentages of these components, which are critical for achieving the desired nanoparticle properties. For example, the claims define the concentration of ionizable lipids within a specific molar range, which is essential for buffering the endosomal pH and facilitating endosomal escape of the mRNA payload.

What are the Key Claims Within Patent 11,278,547?

The patent contains several independent and dependent claims, each defining a specific aspect of the invention. The core claims revolve around the composition of the lipid nanoparticle.

Independent Claim 1 is representative of the primary composition claims. It defines a lipid nanoparticle comprising:

• An ionizable lipid of Formula I, in a molar percentage ranging from 25% to 60%.
• A helper lipid, in a molar percentage ranging from 10% to 35%.
• Cholesterol, in a molar percentage ranging from 10% to 40%.
• A polyethylene glycol (PEG)-modified lipid, in a molar percentage ranging from 1% to 10%.
• The lipid nanoparticle encapsulating a nucleic acid molecule.

Formula I as referenced in the claims details specific chemical structures for the ionizable lipid, which are proprietary and define the unique nature of the LNP. These ionizable lipids are designed to be positively charged at acidic pH (found in endosomes) to facilitate endosomal escape, but neutral at physiological pH, thereby minimizing toxicity.

Dependent Claims further refine the independent claims by specifying particular ranges for each lipid component or by defining the chemical structure of the ionizable lipid more precisely. For example, dependent claims may specify the molar percentage of the ionizable lipid to be between 30% and 50%, or define the PEG-modified lipid to be a specific PEG-lipid conjugate with a defined chain length and lipid anchor.

Other claims in the patent relate to methods of manufacturing these LNPs and methods of using them to deliver nucleic acids to cells or tissues in a subject. These method claims cover the administration of the LNP-nucleic acid formulation for various therapeutic purposes, including vaccination and gene therapy.

How Does Patent 11,278,547 Compare to Existing LNP Technology Patents?

Patent 11,278,547 is part of a broader patent landscape for LNP technology, characterized by overlapping claims and multiple patent holders. Key competitors and their relevant patent portfolios include:

• Arbutus Biopharma: Holds foundational patents related to LNP delivery systems, often focusing on specific lipid compositions and manufacturing processes. Arbutus has been involved in significant litigation regarding LNP technology, particularly in relation to mRNA vaccines. Their patents often claim ionizable lipids and the use of specific cationic lipids.
• Tekmira Pharmaceuticals (now Arbutus): Previous patents from Tekmira have also been central to LNP patent disputes, covering early LNP compositions and formulations.
• Genevant Sciences: Has also secured patents in the LNP space, often related to improvements in LNP stability and delivery efficacy.
• Alnylam Pharmaceuticals: A pioneer in RNA interference (RNAi) therapeutics, Alnylam has extensive patents covering LNP formulations used for delivering small interfering RNA (siRNA). While focused on siRNA, their LNP patents share common elements with mRNA LNP patents, particularly regarding ionizable lipids and overall formulation strategies.

Key points of comparison and potential overlap include:

• Ionizable Lipid Structures: Different patents may claim distinct classes or specific structures of ionizable lipids. Patent 11,278,547 claims a specific "Formula I," which is distinct from the ionizable lipids claimed in other patents. The novelty and non-obviousness of this specific structure are crucial for its patentability.
• Lipid Ratios and Percentages: Even with similar lipid types, precise molar percentages can differentiate patent claims. Patent 11,278,547 defines specific ranges for each lipid component. If another patent claims very similar ranges or overlapping ranges with a different primary ionizable lipid, it can lead to infringement disputes.
• Manufacturing Processes: While patent 11,278,547 primarily focuses on composition, other patents may claim specific manufacturing methods (e.g., microfluidic mixing techniques) that are essential for producing LNPs with the claimed characteristics.
• Therapeutic Applications: Patents may claim the use of LNPs for specific therapeutic areas or for delivering particular types of nucleic acids. Patent 11,278,547 is broad in its claim of "nucleic acid molecule," which can encompass mRNA, siRNA, and other genetic material.

The competitive nature of the LNP patent landscape necessitates careful freedom-to-operate (FTO) analysis for any company developing LNP-based therapeutics. Patent 11,278,547 adds another layer to this analysis due to its specific compositional claims and its origin from a key player in the mRNA vaccine market.

What is the Market Significance of the Technology Protected by Patent 11,278,547?

The technology described in United States Patent 11,278,547 holds significant market importance, primarily due to its application in mRNA-based therapeutics and vaccines. The success of mRNA COVID-19 vaccines has validated LNP technology as a robust platform for delivering genetic material into cells.

• mRNA Vaccines: The immediate and most evident market impact is in the development and manufacturing of mRNA vaccines. The LNP formulation is critical for protecting the fragile mRNA from degradation and facilitating its entry into host cells to trigger an immune response. Patent 11,278,547, by claiming specific LNP compositions that improve delivery and stability, directly impacts the manufacturing and commercialization of such vaccines. The global vaccine market is valued in the tens of billions of dollars annually, with mRNA vaccines representing a rapidly growing segment.
• Gene Therapy: Beyond vaccines, LNPs are being explored for a wide range of gene therapy applications. This includes delivering therapeutic genes to correct genetic disorders, developing cancer immunotherapies, and treating infectious diseases. The ability of LNPs to efficiently deliver genetic material to target cells without relying on viral vectors offers a safer and potentially more scalable alternative. The gene therapy market is projected to grow substantially, reaching hundreds of billions of dollars within the next decade.
• Drug Delivery Platform: The innovation in LNP formulation extends beyond mRNA. These nanoparticles can be adapted to deliver other nucleic acids, such as siRNA, antisense oligonucleotides (ASOs), and gene editing components (e.g., CRISPR-Cas9 systems). This broad applicability positions LNP technology as a versatile drug delivery platform with potential across multiple therapeutic areas.
• Intellectual Property Battles: The high market value of LNP technology has led to intense intellectual property disputes. Companies holding foundational LNP patents, including those related to ionizable lipids and formulation strategies, are actively defending their IP. Patent 11,278,547, originating from Moderna, is a key piece of IP in this ongoing landscape. Any entity seeking to develop or manufacture LNP-based products must navigate this complex patent environment, potentially requiring licensing agreements or facing litigation.
• Manufacturing and Scale-Up: The claims in patent 11,278,547 are directed at specific compositions, which directly influence the manufacturing process and the scalability of LNP production. Efficient and reproducible manufacturing is critical for meeting market demand, particularly for vaccines. The disclosed lipid ratios and components are likely optimized for large-scale synthesis and purification of LNPs.

The market significance is underscored by the substantial R&D investment and partnerships occurring within the LNP space. Companies are actively acquiring patents, pursuing licensing deals, and engaging in litigation to secure their market position. Patent 11,278,547 is a critical component of this competitive ecosystem, reflecting the proprietary nature of advanced LNP formulations driving innovation in genetic medicine.

What are the Potential Infringement Risks Associated with Patent 11,278,547?

Companies developing or manufacturing lipid nanoparticle (LNP) formulations for nucleic acid delivery face potential infringement risks from United States Patent 11,278,547. Infringement occurs if a product or process falls within the scope of one or more of the patent's claims.

Key areas of potential infringement include:

• Compositional Infringement: The most direct risk arises from utilizing LNP compositions that meet the criteria defined in the patent's independent and dependent claims. This includes:
  • Using an ionizable lipid matching "Formula I" as described in the patent, particularly within the claimed molar percentage ranges.
  • Employing helper lipids, cholesterol, and PEG-modified lipids within the specified molar percentage ranges (e.g., 25% to 60% ionizable lipid, 10% to 35% helper lipid, 10% to 40% cholesterol, and 1% to 10% PEG-modified lipid).
  • Encapsulating any nucleic acid molecule within such a defined LNP composition.
  • Manufacturing or selling an LNP formulation that includes any combination of these components that reads onto the claims.
• Method of Use Infringement: Claims related to the methods of using the LNPs for delivering nucleic acids to cells or tissues can also lead to infringement. This includes:
  • Administering an LNP formulation that falls within the scope of the compositional claims for therapeutic purposes.
  • Commercializing treatments or vaccines that employ these specific LNP compositions.
• Manufacturing Process Infringement: While the patent's primary focus is on composition, certain manufacturing claims might exist. If a company uses a process that is specifically claimed and is integral to producing the claimed LNP composition, it could also constitute infringement.

Factors exacerbating infringement risk:

• Specificity of "Formula I": The precise chemical structure of the ionizable lipid defined as "Formula I" in the patent is critical. Any company using an ionizable lipid that is structurally similar or falls within the scope of this definition, even if slightly modified, may still infringe under the doctrine of equivalents.
• Broad Definition of "Nucleic Acid Molecule": The patent's claim of "nucleic acid molecule" is broad, encompassing mRNA, siRNA, shRNA, and potentially other forms of genetic material. This broad scope increases the likelihood of infringement across various therapeutic modalities.
• Competitive Landscape: The LNP field is highly litigious. Companies are actively monitoring competitors and enforcing their patent rights. Patent 11,278,547, held by ModernaTX, Inc., represents a significant IP position in the mRNA vaccine space, making it a target for enforcement actions.
• Freedom-to-Operate (FTO) Analysis: Inadequate or outdated FTO analyses can lead to unintentional infringement. Thorough FTO investigations are essential before launching new products or significantly altering existing formulations.

Companies should conduct rigorous patent landscape analyses and FTO assessments specifically for patent 11,278,547 and related LNP patents to identify potential overlaps and mitigate risks. This may involve designing around the claims, seeking licenses, or challenging the validity of the patent.

What are the Key Takeaways?

United States Patent 11,278,547 protects novel lipid nanoparticle (LNP) compositions, crucial for nucleic acid delivery, particularly mRNA. The claims focus on specific molar ratios and types of ionizable lipids, helper lipids, cholesterol, and PEG-modified lipids. The technology underpins the efficacy of mRNA vaccines and holds significant promise for gene therapy and other genetic medicine applications. The LNP market is competitive and litigious, with this patent representing a key asset for ModernaTX, Inc. Companies developing LNP-based therapeutics face substantial infringement risks if their formulations fall within the patent's compositional or method-of-use claims. Thorough freedom-to-operate analysis is imperative.

Frequently Asked Questions

1. What is the primary scope of US Patent 11,278,547? The primary scope of US Patent 11,278,547 is directed to specific compositions of lipid nanoparticles (LNPs) designed for the delivery of nucleic acids, with a particular emphasis on their utility in mRNA-based therapeutics.

2. Which specific lipid components are central to the claims of Patent 11,278,547? The claims of Patent 11,278,547 are central to specific molar percentages and types of ionizable lipids (defined by "Formula I"), helper lipids, cholesterol, and polyethylene glycol (PEG)-modified lipids within the LNP structure.

3. What are the main therapeutic areas impacted by the technology protected by this patent? The main therapeutic areas impacted by the technology protected by Patent 11,278,547 include mRNA vaccines, gene therapy, and potentially other applications involving the delivery of nucleic acids for therapeutic purposes.

4. What specific risks do companies face if their LNP formulations infringe on Patent 11,278,547? Companies face risks of patent infringement litigation, including injunctions, damages, and royalty payments, if their LNP formulations or methods of use fall within the scope of the patent's claims without proper licensing.

5. How does Patent 11,278,547 contribute to the broader patent landscape for LNP technology? Patent 11,278,547 adds a specific compositional claim to the existing LNP patent landscape, contributing to the complex web of intellectual property that companies must navigate, potentially leading to licensing negotiations or further patent disputes.

Citations

[1] ModernaTX, Inc. (2022). U.S. Patent No. 11,278,547. Washington, DC: U.S. Patent and Trademark Office.

Drugs Protected by US Patent 11,278,547

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Strongbridge	RECORLEV	levoketoconazole	TABLET;ORAL	214133-001	Dec 30, 2021		RX	Yes	Yes	11,278,547					DURING LEVOKETOCONAZOLE DOSAGE TITRATION FOR THE TREATMENT OF CUSHING'S SYNDROME IN PATIENTS WHO CONCOMITANTLY USE METFORMIN, MONITORING GLYCEMIA, KIDNEY FUNCTION AND VITAMIN B-12 AND ADJUSTING DOSAGE OF METFORMIN AS NEEDED

International Family Members for US Patent 11,278,547

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2020232246
Australia	2025204382
Brazil	112021017561