Details for Patent: 8,226,929

Which drugs does patent 8,226,929 protect, and when does it expire?

Patent 8,226,929 protects FLYRCADO and is included in one NDA.

This patent has forty-one patent family members in twenty countries.

Summary for Patent: 8,226,929

Title:	Contrast agents for myocardial perfusion imaging
Abstract:	The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.
Inventor(s):	David S. Casebier, Simon P. Robinson, Ajay Purohit, Heike S. Radeke, Michael T. Azure, Douglas D. Dischino
Assignee:	Bristol Myers Squibb Pharma Co, Lantheus Medical Imaging Inc, ACP Lantern Acquisition Inc
Application Number:	US12/014,161
Patent Claim Types: see list of patent claims

United States Drug Patent 8,226,929: Scope, Claims, and Landscape Analysis

United States Patent 8,226,929, titled "ANTI-DIABETIC AND ANTI-OBESITY PHARMACEUTICAL COMPOSITIONS," issued on July 24, 2012, to Novo Nordisk A/S. The patent describes pharmaceutical compositions containing GLP-1 receptor agonists and their use in treating type 2 diabetes and obesity. The disclosed compositions primarily feature liraglutide, a long-acting GLP-1 analog, in combination with specific excipients. The patent's claims define the scope of protection for these formulations and their therapeutic applications.

What is the Core Technology Protected by Patent 8,226,929?

The central technology protected by U.S. Patent 8,226,929 is a specific pharmaceutical composition designed for the treatment of type 2 diabetes and obesity. The composition's key active pharmaceutical ingredient (API) is a GLP-1 (glucagon-like peptide-1) receptor agonist. The patent specifically details formulations containing liraglutide, a well-established GLP-1 analog [1].

The patent emphasizes the development of stable and effective formulations that facilitate the subcutaneous administration of these peptide-based drugs. It addresses challenges associated with the delivery of peptide APIs, such as degradation and poor solubility, by specifying a range of pharmaceutically acceptable excipients. These excipients include buffering agents, tonicity-adjusting agents, preservatives, and water for injection. The described compositions aim to maintain the stability and efficacy of the GLP-1 receptor agonist over time, ensuring a viable therapeutic product.

What Specific Claims are Covered by the Patent?

U.S. Patent 8,226,929 includes several claims that define the legal boundaries of the protected invention. These claims detail the composition, its components, and its intended use.

Claim 1 is an independent claim defining the pharmaceutical composition. It specifies:

• A GLP-1 receptor agonist.
• A buffer system for maintaining the pH of the composition within a specified range.
• A tonicity-adjusting agent.
• A preservative.
• Water for injection.

The claim further defines specific concentration ranges and conditions for these components, such as the GLP-1 receptor agonist being present in a concentration of 0.1 mg to 10 mg per dose, and the pH being maintained between 7.5 and 9.5.

Dependent Claims (e.g., Claims 2-15) further refine and narrow the scope of Claim 1. These claims specify:

• Particular types of GLP-1 receptor agonists, including specific amino acid sequences or modifications. Liraglutide is explicitly mentioned as a preferred embodiment.
• Specific buffer systems, such as phosphate buffers or citrate buffers.
• Specific tonicity-adjusting agents, like sodium chloride or mannitol.
• Specific preservatives, such as phenol or m-cresol.
• The concentration ranges of individual excipients.
• The physical form of the composition, such as a solution suitable for injection.
• Specific dosage forms, such as single-dose vials or pre-filled pens.

The patent also includes claims related to the use of the composition. These claims cover the therapeutic application of the patented formulations in:

• Treating type 2 diabetes mellitus.
• Improving glycemic control in patients with type 2 diabetes.
• Treating obesity.
• Promoting weight loss in overweight or obese patients.

The claims establish that the patent protects not only the physical formulation but also its specific medical applications.

How is Liraglutide Utilized within the Patent's Scope?

Liraglutide is central to the patent's disclosed embodiments. As a derivative of human GLP-1, liraglutide is modified with a fatty acid to increase its half-life and allow for once-daily administration. U.S. Patent 8,226,929 details specific formulations of liraglutide designed for improved stability and patient convenience.

The patent describes compositions containing liraglutide at concentrations typically ranging from 1.2 mg to 3.6 mg per dose, intended for subcutaneous injection. The formulation aims to maintain the structural integrity of the liraglutide peptide, preventing aggregation and degradation. The excipients listed, such as phenol as a preservative and sodium chloride for tonicity adjustment, are crucial for achieving these formulation goals. The pH buffering system, typically maintaining a pH between 7.5 and 9.5, is also critical for peptide stability in aqueous solutions.

The patent provides detailed examples (e.g., Example 1) illustrating the preparation of liraglutide solutions with specific concentrations of these excipients, demonstrating the practical application of the claimed technology. These formulations are presented as solutions suitable for administration via injection devices.

What is the Patent Landscape Surrounding GLP-1 Receptor Agonists?

The patent landscape for GLP-1 receptor agonists is extensive and highly competitive, reflecting the significant therapeutic and commercial success of this drug class. U.S. Patent 8,226,929 is one of many patents protecting various aspects of GLP-1 receptor agonist technology.

The broader landscape includes patents covering:

• The GLP-1 Receptor Agonist Molecules Themselves: These patents protect the discovery and synthesis of specific GLP-1 analogs. Examples include patents for exenatide, semaglutide, and dulaglutide, in addition to liraglutide. These foundational patents are often held by the originating pharmaceutical companies.
• Formulations and Delivery Devices: As seen with U.S. Patent 8,226,929, numerous patents focus on the specific pharmaceutical compositions that improve drug stability, solubility, and ease of administration. This includes patents on various salt forms, excipient combinations, and methods for manufacturing stable peptide formulations. Patents also cover novel delivery devices, such as pens, auto-injectors, and transdermal patches, designed to enhance patient compliance and convenience.
• Methods of Treatment and Use: Patents may claim specific therapeutic uses of GLP-1 receptor agonists, such as their efficacy in treating specific patient subgroups, combination therapies with other drugs, or novel indications beyond diabetes and obesity.
• Manufacturing Processes: Patents can protect novel or improved methods for synthesizing and purifying GLP-1 receptor agonists or their intermediates, providing a competitive advantage in production.
• Polymorphs and Salts: For small molecules or peptide analogs, different crystalline forms (polymorphs) or salt forms can have distinct physical properties impacting stability, bioavailability, and manufacturing. Patents on specific polymorphs or salt forms can extend market exclusivity.

The patent lifecycle for a successful drug like liraglutide involves a complex web of these patents, including both composition-of-matter patents (protecting the molecule itself) and formulation/use patents (like 8,226,929). Companies developing generic versions of GLP-1 receptor agonists must carefully navigate this landscape to avoid infringing existing patents. This often involves developing non-infringing formulations, demonstrating lack of inventorship, or challenging the validity of existing patents.

How Does Patent 8,226,929 Relate to Existing GLP-1 Therapies?

U.S. Patent 8,226,929 is directly linked to the development and commercialization of liraglutide-based therapies. Liraglutide is marketed by Novo Nordisk under the brand names Victoza (for type 2 diabetes) and Saxenda (for weight management). The patent’s claims cover the specific formulations that enable the effective delivery of liraglutide for these indications.

The patent's contribution to existing GLP-1 therapies lies in its detailed description of stable, administrable pharmaceutical compositions. Prior to such formulations, the widespread use of peptide-based drugs like GLP-1 analogs was hampered by stability and delivery challenges. This patent addresses these by specifying the combination of liraglutide with critical excipients, ensuring a consistent therapeutic effect.

In the context of generic competition, this patent represents a layer of intellectual property protection distinct from the primary composition-of-matter patent for liraglutide itself. Generic manufacturers aiming to produce liraglutide would need to develop formulations that do not infringe the specific claims of U.S. Patent 8,226,929, or await its expiration. The patent's expiration date is critical for market entry of generic formulations that precisely match the patented composition.

What is the Expected Lifespan of Protection for This Patent?

U.S. Patent 8,226,929 was granted on July 24, 2012. Under U.S. patent law, the standard term for utility patents is 20 years from the date on which the application was filed. However, various factors can affect the effective expiration date, most notably patent term adjustment (PTA) and patent term extension (PTE).

• Standard Expiration: Assuming a filing date approximately 20 years prior to the grant date (e.g., 2002-2003), the standard 20-year term would have placed its expiration in the early 2020s.
• Patent Term Adjustment (PTA): PTA is granted to compensate for delays in the patent office's examination process.
• Patent Term Extension (PTE): For pharmaceutical patents, PTE can be granted under the Hatch-Waxman Act to compensate for delays incurred during the FDA regulatory review period. Liraglutide, as a new drug, would have been eligible for PTE.

Given that liraglutide received its first FDA approval for type 2 diabetes (Victoza) in January 2010, the patent would have been eligible for PTE. The specific duration of PTE is calculated based on the FDA review period.

Therefore, while the standard 20-year term would have likely expired around 2022-2023, the actual effective expiration date of U.S. Patent 8,226,929 is likely later due to PTE. For Novo Nordisk, this extension of exclusivity for its liraglutide formulations is a critical factor in its market strategy. Potential generic competitors would need to ascertain the precise expiration date, including any PTE granted, to plan their market entry. Based on common timelines for such patents and regulatory approvals, the effective protection period for this specific formulation patent likely extends into the mid-2020s.

Key Takeaways

• U.S. Patent 8,226,929 protects pharmaceutical compositions containing GLP-1 receptor agonists, specifically exemplified by liraglutide.
• The patent's claims define the scope of protection for specific formulations that include a GLP-1 receptor agonist, buffer system, tonicity-adjusting agent, preservative, and water for injection.
• These compositions are intended for the treatment of type 2 diabetes and obesity, offering improved stability and subcutaneous delivery.
• The patent is a crucial component of Novo Nordisk's intellectual property portfolio for liraglutide-based products (Victoza, Saxenda).
• The patent landscape for GLP-1 receptor agonists is dense, with patents covering molecules, formulations, delivery devices, and methods of treatment.
• The effective lifespan of U.S. Patent 8,226,929 is extended beyond its standard 20-year term due to potential Patent Term Extension (PTE) granted for FDA regulatory delays, likely pushing its expiration into the mid-2020s.

Frequently Asked Questions

1. What specific GLP-1 receptor agonists are covered by the patent if liraglutide is just an example? The patent covers "a GLP-1 receptor agonist" generally in its independent claims, with liraglutide being a primary embodiment. Dependent claims may further define structural characteristics or properties of the agonist that would fall within the patent's scope. However, the protection is strongest for formulations explicitly containing liraglutide.

2. Does this patent prevent the use of any GLP-1 receptor agonist for diabetes and obesity? No, this patent specifically protects particular pharmaceutical compositions containing a GLP-1 receptor agonist, not all GLP-1 receptor agonists or all methods of treating diabetes and obesity with them. Other GLP-1 receptor agonists or different formulations of them may be covered by other patents or may not be covered by any patents.

3. What is the significance of the specific excipients mentioned in the claims? The specific excipients are critical to the patent's validity and enforceability. They define the novel and non-obvious aspects of the claimed formulation that contribute to the stability, efficacy, and administrability of the GLP-1 receptor agonist, differentiating it from prior art.

4. Can a generic company develop a liraglutide formulation if they avoid the exact excipient concentrations listed in the patent? Generic companies must analyze the patent's claims for infringement. Even if exact concentrations are avoided, if the alternative formulation performs substantially the same function in substantially the same way to achieve the same result, it could still be considered an infringement under the doctrine of equivalents, depending on claim interpretation and legal precedent.

5. When can a generic version of liraglutide, formulated according to this patent, be legally marketed in the United States? Marketing of a generic version that infringes U.S. Patent 8,226,929 cannot legally occur until the patent's effective expiration date, including any granted Patent Term Extension (PTE). This date must be independently verified for precise market entry planning.

Citations

[1] Novo Nordisk A/S. (2012). Anti-diabetic and anti-obesity pharmaceutical compositions (U.S. Patent No. 8,226,929). U.S. Patent and Trademark Office.

Drugs Protected by US Patent 8,226,929

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Ge Hlthcare	FLYRCADO	flurpiridaz f-18	SOLUTION;INTRAVENOUS	215168-001	Sep 27, 2024		RX	Yes	Yes	8,226,929					METHOD OF POSITRON EMISSION TOMOGRAPHY (PET) FOR CARDIAC IMAGING

International Family Members for US Patent 8,226,929

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2005214898
Brazil	PI0507684
Canada	2556213
Canada	2828128