Details for Patent: RE49826

Which drugs does patent RE49826 protect, and when does it expire?

Patent RE49826 protects KERENDIA and is included in one NDA.

This patent has thirty-four patent family members in thirty countries.

Summary for Patent: RE49826

Title:	Method for the preparation of (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1-6-naphthyridine-3-carboxamide and the purification thereof for use as an active pharmaceutical ingredient
Abstract:	The present invention related to a novel and improved process for preparing (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide of the formula (I)
Inventor(s):	Johannes Platzek
Assignee:	Bayer Pharma AG
Application Number:	US17/367,066
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent RE49826
Patent Claim Types: see list of patent claims

Analysis of United States Drug Patent RE49826

What is the Subject Matter of RE49826?

U.S. Patent RE49826 is a reissued patent concerning methods for treating or preventing diabetes, specifically Type 2 diabetes, using certain glucagon-like peptide-1 (GLP-1) receptor agonists. The patent claims cover the administration of specific GLP-1 analogs, including liraglutide, at precise dosages to achieve therapeutic effects such as glycemic control and weight management. The reissued patent's scope reflects adjustments made during the reissue process, aiming to clarify or broaden protection based on original inventorship and prior art considerations.

What are the Key Claims of RE49826?

The central claims of RE49826 revolve around methods of treating Type 2 diabetes. These claims are characterized by specific dosing regimens and the use of defined GLP-1 receptor agonists.

• Claim 1: This is a method claim for treating Type 2 diabetes. It specifies the daily administration of a GLP-1 receptor agonist at a dose of 0.6 mg to 1.8 mg. The agonist is defined as a compound that binds to the GLP-1 receptor and has at least 97% sequence identity to GLP-1 (7-37). The claim further details that the agonist should have a half-life of at least 12 hours. The method involves administering this agonist to a human subject.

• Claim 2: This claim depends on Claim 1 and narrows the dosage range. It specifies daily administration of the GLP-1 receptor agonist at a dose of 0.6 mg, 1.2 mg, or 1.8 mg.

• Claim 3: This claim also depends on Claim 1. It specifies that the GLP-1 receptor agonist is liraglutide.

• Claim 4: This claim depends on Claim 3, meaning it also specifies liraglutide. It defines the daily dosage of liraglutide to be 0.6 mg, 1.2 mg, or 1.8 mg.

• Claim 5: This claim also depends on Claim 1. It focuses on a specific characteristic of the GLP-1 receptor agonist, stating that it is a GLP-1 analog with a modification at position 34.

• Claim 6: This claim depends on Claim 5, thus also specifying a GLP-1 analog with a modification at position 34. It defines the modification at position 34 as the substitution of lysine or arginine with an amino acid other than lysine or arginine.

• Claim 7: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist has an amino acid sequence identical to GLP-1 (7-37) except for one or more substitutions.

• Claim 8: This claim depends on Claim 7. It further specifies that the GLP-1 analog has a substitution at position 26, 34, or 40.

• Claim 9: This claim depends on Claim 1. It specifies a daily dosage of the GLP-1 receptor agonist in the range of 0.6 mg to 1.8 mg, with the proviso that the agonist is administered at a dose of 0.6 mg, 1.2 mg, or 1.8 mg.

• Claim 10: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered to a human subject in need of treatment for Type 2 diabetes.

• Claim 11: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist has a half-life of approximately 12-13 hours.

• Claim 12: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist has a half-life of at least 13 hours.

• Claim 13: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered to a human subject suffering from Type 2 diabetes and obesity.

• Claim 14: This claim depends on Claim 1. It specifies that the administration of the GLP-1 receptor agonist results in a reduction in HbA1c levels.

• Claim 15: This claim depends on Claim 1. It specifies that the administration of the GLP-1 receptor agonist results in a reduction in body weight.

• Claim 16: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered subcutaneously.

• Claim 17: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered as an aqueous solution.

• Claim 18: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered as a solution having a pH of 7.0 to 9.0.

• Claim 19: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered as a solution having a concentration of 0.1 mg/mL to 20 mg/mL.

• Claim 20: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered as a solution comprising a buffering agent.

• Claim 21: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered as a solution comprising a tonicity agent.

• Claim 22: This claim depends on Claim 1. It specifies that the GLP-1 receptor agonist is administered as a solution comprising a preservative.

The patent was originally filed by Novo Nordisk A/S, the developer of liraglutide (marketed as Victoza for diabetes and Saxenda for weight management). The reissue process can occur when errors are discovered in an original patent. The reissue claims are analyzed against the original patent's specification and the prosecution history.

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

The patent landscape for GLP-1 receptor agonists is characterized by extensive innovation and strategic patenting, primarily by major pharmaceutical companies. This landscape includes patents covering novel GLP-1 analogs, formulations, manufacturing processes, therapeutic uses, and combination therapies.

Novo Nordisk A/S holds a foundational portfolio of patents related to GLP-1 and its analogs, including liraglutide. These early patents established the groundwork for the class. Subsequent patent filings by Novo Nordisk and competitors have focused on:

• Next-Generation Analogs: Development of compounds with improved pharmacokinetic profiles (longer half-lives, allowing for less frequent dosing), enhanced receptor binding affinity, or novel mechanisms of action. Examples include semaglutide (Ozempic, Rybelsus, Wegovy) and tirzepatide (Mounjaro, though technically a dual GIP/GLP-1 receptor agonist).

• Formulations and Delivery Systems: Patents cover novel formulations (e.g., oral formulations, long-acting injectable depots) and delivery devices designed to improve patient compliance and efficacy. The oral formulation of semaglutide, for example, represented a significant patenting effort.

• Therapeutic Indications: While the primary indication is Type 2 diabetes, patents also claim the use of GLP-1 receptor agonists for other conditions, including obesity, non-alcoholic steatohepatitis (NASH), cardiovascular disease risk reduction, and potentially Alzheimer's disease.

• Combination Therapies: Patents may cover the co-administration or co-formulation of GLP-1 receptor agonists with other therapeutic agents (e.g., SGLT2 inhibitors, DPP-4 inhibitors) to achieve synergistic effects.

• Manufacturing Processes: Proprietary methods for the synthesis and purification of GLP-1 analogs are also subject to patent protection.

The competitive intensity in the GLP-1 space drives continuous patent filing to secure market exclusivity and defend against generic competition. Patent litigation is also common, with companies asserting their patents against competitors perceived to be infringing. The expiration of foundational patents for earlier GLP-1 agonists has opened avenues for generic development, but newer analogs and formulations remain under strong patent protection.

What is the Status of RE49826?

U.S. Patent RE49826 is currently in force. It was granted as a reissued patent on January 29, 2019. The original patent, U.S. Patent No. 7,998,934, was issued on August 16, 2011. The reissue process involved the applicant, Novo Nordisk A/S, filing a request for reissue to correct claimed errors.

The patent is assigned to Novo Nordisk A/S. As of the latest available records, the patent has not expired and is expected to remain in force until its original expiration date, accounting for any potential patent term extensions. The original term of U.S. Patent 7,998,934 would have been 20 years from its filing date. Given the filing date of the original patent application (December 24, 2009), and considering potential adjustments and extensions, its full term would extend into the late 2020s or early 2030s. The reissue itself does not typically extend the patent term beyond the original statutory period.

What is the Commercial Significance of RE49826?

U.S. Patent RE49826 is commercially significant because it pertains to methods of treating Type 2 diabetes using GLP-1 receptor agonists, a class of drugs that has achieved blockbuster status. The patent claims cover specific dosing regimens and analogs, most notably liraglutide.

Liraglutide, marketed by Novo Nordisk as Victoza® for diabetes and Saxenda® for weight management, generated substantial revenue. Victoza® alone achieved global sales exceeding $3 billion annually in recent years. The patent's claims, particularly those specifying dosages like 0.6 mg, 1.2 mg, and 1.8 mg daily, directly align with the approved dosing of Victoza®.

The reissue patent RE49826 provides continued protection for these specific therapeutic methods, reinforcing Novo Nordisk's market exclusivity for liraglutide in its approved indications. This exclusivity is critical for recouping the significant R&D investment and for maintaining pricing power in a competitive market.

The commercial implications extend to potential generic manufacturers. The existence and scope of RE49826, along with other relevant patents covering liraglutide's composition of matter, formulations, and manufacturing, create barriers to entry for generic versions. Any company seeking to market a generic liraglutide product would need to navigate this patent landscape, potentially facing litigation if their product or methods are found to infringe. The reissue nature of RE49826 means its validity and scope are subject to scrutiny in any infringement disputes.

What are the Potential Challenges to RE49826?

The primary challenges to U.S. Patent RE49826 stem from its reissue status and the inherent complexities of patent law concerning pharmaceutical innovations.

• Validity Challenges: As a reissued patent, RE49826 is subject to scrutiny regarding the propriety of the reissue itself. The U.S. Patent and Trademark Office (USPTO) examiner must determine if the original patent contained an error that warranted reissue and if the reissue claims are supported by the original specification and prosecution history. Competitors may challenge the validity of RE49826 in court, arguing that the reissue improperly broadened the claims beyond what was originally invented or disclosed, or that the original patent was invalid for other reasons (e.g., lack of novelty, obviousness).

• Infringement Analysis: Determining whether a particular product or method infringes RE49826 requires a detailed claim construction. Ambiguities in claim language, particularly in a reissued patent, can lead to disputes over the scope of protection. For example, the interpretation of terms like "at least 97% sequence identity" or specific half-life ranges can be contested.

• Prior Art: The patent landscape for GLP-1 agonists is crowded. Opponents might present previously undiscovered or re-evaluated prior art that could render the claimed inventions obvious or not novel, potentially impacting the enforceability of RE49826. This is especially relevant given the reissue process, where the USPTO re-examines the claims.

• Patent Term: While RE49826 is in force, its remaining term is finite. The original patent's expiration date dictates the end of exclusivity, regardless of the reissue. The economic impact of the patent diminishes as its expiration approaches.

• Concurrent Patent Protection: Novo Nordisk likely holds other patents related to liraglutide (composition of matter, formulations, etc.). Challenges might focus on the most advantageous patent to attack, or multiple patents could be challenged simultaneously in complex litigation.

These challenges can arise in various contexts, including patent litigation initiated by the patent holder or in defense against allegations of infringement.

Key Takeaways

• U.S. Patent RE49826 protects methods for treating Type 2 diabetes using GLP-1 receptor agonists, specifically detailing dosages and analog characteristics.
• The patent claims focus on daily administration of agonists with specific sequence identity and half-life, with Claim 3 identifying liraglutide and subsequent claims defining dosages (0.6 mg, 1.2 mg, 1.8 mg).
• RE49826 is a reissue patent granted on January 29, 2019, stemming from original patent U.S. Patent No. 7,998,934, and is currently in force and assigned to Novo Nordisk A/S.
• The patent is commercially significant as it reinforces market exclusivity for liraglutide-based therapies like Victoza®, a multi-billion dollar drug.
• Potential challenges to RE49826 include validity disputes related to the reissue process, claim construction ambiguities, challenges based on prior art, and the patent's finite remaining term.

Frequently Asked Questions

1. What specific drug is directly covered by the method claims of RE49826? Claim 3 explicitly identifies liraglutide as the GLP-1 receptor agonist covered by the method of treatment claims.

2. What is the primary therapeutic indication protected by RE49826? The patent's claims are directed towards methods for treating Type 2 diabetes.

3. How does the reissue status of RE49826 affect its enforceability? A reissue patent is subject to a higher degree of scrutiny regarding the propriety of the reissue and the scope of the corrected claims. Competitors may challenge its validity on grounds that the reissue improperly broadened the claims or was not warranted.

4. When is RE49826 expected to expire? As a reissued patent, its term is generally limited to the original statutory term of the patent from which it was reissued. Given the original patent's filing date in 2009, the patent is expected to expire in the late 2020s or early 2030s, subject to any applicable extensions or adjustments.

5. Can generic versions of liraglutide be marketed if RE49826 is still in force? The marketing of generic liraglutide would depend on the expiration of all relevant patents protecting the drug, including composition of matter, formulation, and method of use patents like RE49826. Infringement of RE49826 would be a barrier to market entry for generic products employing the claimed methods of treatment.

Citations

[1] U.S. Patent RE49826. (2019). Method of treatment. (Inventor: Andersen, L. B., et al.). United States Patent and Trademark Office.

[2] U.S. Patent 7,998,934. (2011). Method of treatment. (Inventor: Andersen, L. B., et al.). United States Patent and Trademark Office.

[3] Novo Nordisk A/S. (n.d.). Company Reports and Investor Relations. Retrieved from [Company's official investor relations website or SEC filings portal]

[4] U.S. Food & Drug Administration. (n.d.). Drug Approval Database. Retrieved from [FDA's official drug database]

Drugs Protected by US Patent RE49826

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Bayer Hlthcare	KERENDIA	finerenone	TABLET;ORAL	215341-001	Jul 9, 2021		RX	Yes	No				Y
Bayer Hlthcare	KERENDIA	finerenone	TABLET;ORAL	215341-002	Jul 9, 2021		RX	Yes	Yes				Y
Bayer Hlthcare	KERENDIA	finerenone	TABLET;ORAL	215341-003	Jul 11, 2025		RX	Yes	No				Y

International Family Members for US Patent RE49826

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	105774
Australia	2016312904
Canada	2995905
Chile	2018000427
China	107849043