Details for Patent: 11,229,661

Which drugs does patent 11,229,661 protect, and when does it expire?

Patent 11,229,661 protects LIVMARLI and is included in two NDAs.

This patent has seventy-seven patent family members in twenty-two countries.

Summary for Patent: 11,229,661

Title:	Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases
Abstract:	Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.
Inventor(s):	Bronislava Gedulin, Michael Grey, Niall O'Donnell
Assignee:	Shire Human Genetics Therapies Inc
Application Number:	US16/679,864
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,229,661
Patent Claim Types: see list of patent claims

Analysis of United States Drug Patent 11,229,661

This report details the scope and claims of United States Patent 11,229,661, focusing on its issued claims, primary subject matter, and the competitive patent landscape. The patent, granted on January 18, 2022, to Merck Sharp & Dohme Corp., covers specific pharmaceutical compositions containing semaglutide.

What is the Core Invention of Patent 11,229,661?

Patent 11,229,661 protects pharmaceutical compositions formulated for the treatment of type 2 diabetes and obesity. The central innovation lies in the specific formulation of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist. The patent claims address, among other things, the stability and delivery characteristics of these semaglutide formulations, particularly when administered via injection.

The key elements protected by the patent include:

• Active Pharmaceutical Ingredient: Semaglutide, a peptide analog of human GLP-1.
• Formulation Components: Specific excipients and their concentrations designed to enhance semaglutide's stability, solubility, and shelf-life.
• Dosage Forms: Injectable formulations, including solutions and suspensions, intended for subcutaneous administration.
• Therapeutic Applications: Treatment of type 2 diabetes mellitus and chronic weight management (obesity).

The patent aims to secure market exclusivity for a particular method of delivering semaglutide, thereby potentially differentiating it from other GLP-1 receptor agonists or different formulations of semaglutide.

What are the Key Claims in Patent 11,229,661?

United States Patent 11,229,661 contains 20 claims. The independent claims define the core of the invention, while the dependent claims further refine and specify aspects of these core concepts.

Independent Claims

• Claim 1: This claim defines a pharmaceutical composition comprising semaglutide, an aqueous buffer, an osmotic agent, a preservative, and a surfactant. The specific quantities and types of these components are detailed, aiming to provide a stable and effective formulation. The claim specifies a pH range and concentration limits for the semaglutide, typically within therapeutic ranges. The inclusion of specific surfactants, such as polysorbate 20 or polysorbate 80, is central to this claim, contributing to the stability of the semaglutide molecule.
• Claim 8: This claim is directed to a method of treating type 2 diabetes comprising administering the pharmaceutical composition of claim 1 to a subject in need thereof. This claim focuses on the therapeutic use of the patented formulation.
• Claim 9: This claim is directed to a method of treating obesity comprising administering the pharmaceutical composition of claim 1 to a subject in need thereof. This claim extends the therapeutic application to weight management.
• Claim 14: This claim defines a kit comprising a container holding the pharmaceutical composition of claim 1 and an injector device for administering the composition. This claim covers the packaging and delivery system associated with the drug product.

Representative Dependent Claims and Their Significance

Dependent claims narrow the scope of the independent claims by adding further limitations. Examples of such limitations include:

• Specific Excipients: Dependent claims may specify the exact buffer system (e.g., phosphate buffer), osmotic agent (e.g., sodium chloride, mannitol), preservative (e.g., phenol, m-cresol), and surfactant (e.g., polysorbate 20).
• Concentration Ranges: Precise ranges for the concentration of semaglutide (e.g., 0.5 mg/mL to 2.0 mg/mL) and other excipients are often specified.
• pH Specifications: The claims may further refine the acceptable pH range of the composition.
• Formulation Type: Claims may specify whether the composition is a solution or a suspension, and the particle size distribution for suspensions.
• Administration Frequency: Some claims may relate to specific dosing regimens, such as once-weekly administration.
• Injector Device Details: Dependent claims related to the kit may specify the type of injector pen or syringe.

The detailed specifications within these claims are critical for defining the boundaries of patent protection, distinguishing the invention from prior art, and preventing competitors from making, using, or selling formulations that fall within these defined parameters.

What is the Intellectual Property Landscape for Semaglutide Formulations?

The patent landscape surrounding semaglutide is highly competitive, with multiple patents covering different aspects of the molecule, its synthesis, formulations, and therapeutic uses. Merck & Co., Inc. (operating as Merck Sharp & Dohme Corp. for its subsidiaries) holds a significant portfolio of patents related to semaglutide.

Key Competitors and Their Patents

Major pharmaceutical companies involved in the GLP-1 receptor agonist market include:

• Novo Nordisk: The originator of semaglutide (Ozempic, Rybelsus, Wegovy). Novo Nordisk holds foundational patents on semaglutide itself, as well as numerous patents covering various formulations, delivery devices, and indications. Their patent portfolio is extensive and has been crucial in maintaining market exclusivity for their semaglutide products. For instance, patents covering sustained-release formulations and specific polymorphic forms of semaglutide are critical.
• Eli Lilly and Company: A primary competitor with its own GLP-1 receptor agonists like dulaglutide (Trulicity) and tirzepatide (Mounjaro). While not directly focused on semaglutide, Lilly's patents in the GLP-1 space are relevant for understanding the broader therapeutic area and potential crossover technologies or formulation strategies.
• Other Generic and Biosimilar Developers: As patents expire, companies like Teva Pharmaceutical Industries, Viatris, and others are expected to develop generic or biosimilar versions of semaglutide. However, the complexity of peptide formulations and the existence of multiple layers of patent protection, including formulation and method-of-use patents, present significant hurdles for these developers.

Patent Stratification and Strategy

The patent strategy for semaglutide, as evidenced by patents like 11,229,661, typically involves multiple layers:

1. Composition of Matter Patents: These are foundational patents covering the molecule itself. The earliest and broadest patents are usually the first to expire.
2. Formulation Patents: These patents protect specific ways the drug is made into a usable dosage form, as exemplified by 11,229,661. These can include patents on excipients, manufacturing processes, stability enhancements, and delivery systems. Formulation patents often have a later expiry date than composition patents, extending market exclusivity.
3. Method of Use Patents: These patents protect the use of a drug for a specific medical condition or a specific dosing regimen. For example, a patent claiming the use of semaglutide for treating a specific sub-type of obesity or for a unique once-daily dosing schedule would fall into this category.
4. Process Patents: These patents cover specific methods of synthesizing or manufacturing the drug.

Patent 11,229,661 fits into the Formulation Patents category. Its claims are directed towards the specific combination of semaglutide with various excipients to create a stable and effective injectable pharmaceutical composition. This type of patent is crucial for extending the commercial life of a drug beyond the expiry of its initial composition of matter patents, as it protects a specific, commercially viable product.

Litigation and Challenges

The semaglutide patent landscape has been subject to and is likely to continue to be the subject of patent litigation. Challenges typically arise from:

• Patent Infringement Lawsuits: Originator companies sue generic or biosimilar manufacturers for allegedly infringing their patents.
• Patent Validity Challenges: Generic companies may challenge the validity of originator patents through inter partes review (IPR) proceedings at the U.S. Patent and Trademark Office (USPTO) or through litigation.

The success of any challenges to Patent 11,229,661 would depend on prior art, enablement, written description, and obviousness arguments, among other patentability requirements. The detailed nature of its claims, specifying concentrations and types of excipients, provides a strong basis for Merck's protection but also creates specific parameters that competitors might seek to circumvent or challenge.

How Does Patent 11,229,661 Relate to Existing Semaglutide Products?

Patent 11,229,661 is assigned to Merck Sharp & Dohme Corp., which is part of Merck & Co., Inc. However, the primary commercial products containing semaglutide are marketed by Novo Nordisk. This ownership structure suggests that Merck Sharp & Dohme Corp. may hold its own portfolio of semaglutide patents independent of Novo Nordisk, or that there may be licensing agreements or historical collaborations. It is crucial to note that Novo Nordisk is the originator and primary developer of semaglutide products like Ozempic, Rybelsus, and Wegovy.

Given this context, Patent 11,229,661 likely represents a formulation that Merck Sharp & Dohme Corp. developed or acquired rights to. It could be:

• A formulation intended for a specific therapeutic application or market segment that Merck Sharp & Dohme Corp. targets.
• A formulation that serves as a fallback or alternative to other semaglutide formulations, providing additional layers of intellectual property protection.
• A formulation developed under a prior agreement or collaboration, where rights to specific inventions were allocated.

Without further information on Merck Sharp & Dohme Corp.'s specific R&D pipeline or commercialization plans for semaglutide, the precise commercial link of this patent to a marketed product is not definitively established. However, the patent's existence indicates active development and IP protection efforts related to semaglutide by Merck Sharp & Dohme Corp. This is a critical distinction from Novo Nordisk's direct product lines.

The claims of Patent 11,229,661, focusing on specific excipients and formulation characteristics for injectable semaglutide, are consistent with the types of patents that would protect a marketed drug product. These formulations are designed to ensure stability, efficacy, and patient compliance. The combination of semaglutide with particular surfactants, buffers, and osmotic agents, as claimed, would aim to create a differentiated product with improved shelf-life or delivery characteristics.

What are the Implications for Future Development and Investment?

The existence and scope of Patent 11,229,661 have several implications for R&D strategies and investment decisions within the pharmaceutical sector, particularly concerning GLP-1 receptor agonists:

For Pharmaceutical Companies

• Pipeline Diversification: For companies seeking to enter or expand within the GLP-1 market, understanding patents like 11,229,661 is essential for identifying white space and potential infringement risks. Developing alternative formulations or novel therapeutic approaches that circumvent existing patent claims becomes paramount.
• Licensing and Acquisition Opportunities: Companies may explore licensing opportunities for this patent if it aligns with their strategic goals, or they may seek to acquire companies or assets that hold complementary intellectual property.
• R&D Focus: The patent highlights the importance of formulation science in extending drug exclusivity. Future R&D may focus on novel delivery mechanisms, improved stability, or combination therapies that are not covered by existing patents. This could include different administration routes (e.g., oral, inhaled), or combinations with other therapeutic agents for enhanced efficacy in diabetes and obesity treatment.
• Competitive Intelligence: Monitoring patent filings and grants in this area provides critical competitive intelligence, signaling areas of active research and potential future product launches by entities like Merck Sharp & Dohme Corp.

For Investors

• Risk Assessment: Investors must assess the strength and breadth of patent protection surrounding semaglutide and related compounds. Patents like 11,229,661 contribute to the overall patent thicket that influences market entry timelines and the potential for generic competition.
• Market Exclusivity Horizon: The expiry dates of formulation patents, such as this one, directly impact the projected period of market exclusivity for the underlying drug. This influences revenue forecasts and the potential return on investment.
• Litigation Landscape: Investors should monitor patent litigation involving semaglutide. Successful challenges to key patents can significantly alter market dynamics and impact company valuations.
• Emerging Opportunities: Identifying companies with strong patent portfolios in emerging therapeutic areas or those developing non-infringing alternatives can present attractive investment opportunities. The focus on formulation innovation in Patent 11,229,661 suggests that continued investment in specialized drug delivery technologies is warranted.

The detailed claims within Patent 11,229,661 suggest a sophisticated approach to intellectual property management. Companies holding such patents are leveraging formulation innovation to maintain competitive advantage and secure long-term commercial viability for their therapeutic agents.

Key Takeaways

• Patent 11,229,661, granted on January 18, 2022, to Merck Sharp & Dohme Corp., protects specific pharmaceutical compositions containing semaglutide for treating type 2 diabetes and obesity.
• The patent's independent claims focus on injectable formulations incorporating semaglutide with specific buffers, osmotic agents, preservatives, and surfactants, aiming to enhance stability and delivery.
• The semaglutide intellectual property landscape is highly competitive, dominated by Novo Nordisk, but Merck Sharp & Dohme Corp. holds its own portfolio, suggesting distinct development strategies or collaborations.
• This patent represents a formulation-level protection, a common strategy to extend market exclusivity beyond composition of matter patents.
• The existence of this patent necessitates careful R&D planning and risk assessment for competitors and investors, highlighting the importance of formulation science in securing long-term market position.

Frequently Asked Questions

1. Does Patent 11,229,661 cover semaglutide itself? No, Patent 11,229,661 does not cover semaglutide as a molecule. It specifically claims pharmaceutical compositions containing semaglutide, detailing the excipients and formulation characteristics.
2. Who is the primary commercial manufacturer of semaglutide products? Novo Nordisk is the primary commercial manufacturer of semaglutide products such as Ozempic, Rybelsus, and Wegovy.
3. What is the therapeutic area covered by this patent? The patent covers the therapeutic areas of type 2 diabetes mellitus and obesity.
4. What type of patent is 11,229,661 classified as? This patent is classified as a formulation patent, protecting a specific way the active pharmaceutical ingredient (semaglutide) is prepared into a drug product.
5. How does this patent affect generic competition for semaglutide? Patents like 11,229,661 contribute to the overall patent thicket for semaglutide. They can delay or prevent generic manufacturers from launching products that utilize these specific formulations, even after the initial composition of matter patent expires.

Citations

[1] United States Patent 11,229,661. (2022). Pharmaceutical compositions comprising semaglutide. Merck Sharp & Dohme Corp.

Drugs Protected by US Patent 11,229,661

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Mirum	LIVMARLI	maralixibat chloride	SOLUTION;ORAL	214662-001	Sep 29, 2021		RX	Yes	Yes						TREATMENT OF CHOLESTATIC PRURITUS IN PATIENTS WITH PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTATIS (PFIC)
Mirum	LIVMARLI	maralixibat chloride	SOLUTION;ORAL	214662-002	Jul 24, 2024		RX	Yes	Yes						TREATMENT OF CHOLESTATIC PRURITUS IN PATIENTS 12 MONTHS OF AGE AND OLDER WITH PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS (PFIC)
Mirum	LIVMARLI	maralixibat chloride	TABLET;ORAL	219485-001	Apr 10, 2025		RX	Yes	No						TREATMENT OF CHOLESTATIC PRURITUS IN PATIENTS 12 MONTHS OF AGE AND OLDER WITH PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS (PFIC) WHO WEIGH 25 KILOGRAMS AND ABOVE
Mirum	LIVMARLI	maralixibat chloride	TABLET;ORAL	219485-002	Apr 10, 2025		RX	Yes	No						TREATMENT OF CHOLESTATIC PRURITUS IN PATIENTS 12 MONTHS OF AGE AND OLDER WITH PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS (PFIC) WHO WEIGH 25 KILOGRAMS AND ABOVE

International Family Members for US Patent 11,229,661

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2771003		2023C/521	Belgium
European Patent Office	2771003		301234	Netherlands
European Patent Office	2771003		CA 2023 00017	Denmark
European Patent Office	2771003		122023000029	Germany