API and IP Newsletter 1.) NCE approval- Atrasentan 2.) Semaglutide case: With the revocation of the composition patent, a generic launch in Europe could be possible earlier.

Content

NCE approval- Atrasentan

General information

The FDA (Food and Drug Administration) Drug Approval Process Training Course: Procedures for Submission of INDs, NDAs, ANDAs and 505(b)(2) (ONLINE EVENT: June 11-12, 2025) - ResearchAndMarkets.com

No damages for Glenmark in battle over Mundipharma’s Targin

Intellectual Property

Semaglutide case: With the revocation of the composition patent, a generic launch in Europe could be possible earlier.

NCE approval- Atrasentan

 

We monitor NCE approvals for small molecules. One approval from the FDA in April 2025 is for the small-molecule atrasentan.

 

Atrasentan, sold under the brand name Vanrafia, is a medication used to reduce proteinuria.

Proteinuria, also known as albuminuria, refers to the presence of excessive protein, mainly albumin, in the urine. This condition typically indicates that the kidneys' filtering mechanisms (glomeruli) are not functioning correctly, allowing more protein to leak into the urine.

Jefferies analysts expect that Vanrafia, Novartis's second IgA nephropathy therapy (the first was iptacopan), could achieve $1.5 billion in peak sales.

 

Atrasentan, initially sponsored by AbbVie, transitioned to Novartis through the acquisition of Chinook Therapeutics, the company that developed and later owned the worldwide rights to the drug. AbbVie's involvement started with sponsoring the drug before Chinook bought the rights. Novartis then acquired Chinook in a deal valued at $3.2 billion in 2023, thus taking ownership of atrasentan. 

 

Abbott Laboratories and AbbVie share a history stemming from Abbott's spin-off of its research-based pharmaceuticals business into AbbVie in 2012. Atrasentan is an old compound; therefore, few patent families are assigned to Abbott, few are assigned to AbbVie, and few are assigned to Novartis.

 

Several polymorphs have been reported.

The compound atrasentan was first reported in US 5,767,144.

Subsequently, several published international applications reported atrasentan monohydrochloride salts.

WO2006/034085 reports amorphous atrasentan monohydrochloride.

WO2006/034094 reports crystalline Form I of atrasentan monohydrochloride.

WO2006/034084 reports crystalline Form II of atrasentan monohydrochloride.

WO2006/034234 reports crystalline Form III of atrasentan monohydrochloride.

 

There are various methods for use patents, resulting in a complex patent landscape. Since this molecule is old and since US 5,767,144 has expired long ago, there could be many generic companies that would challenge the OB listed patents on the NCE-1 date in April 2029.

 

Example 9 of WO 2006/034085 describes the condensation of 5-((E)-2-nitroethenyl)-1,3-benzodioxole and ethyl 3-(4-methoxyphenyl)-3-oxopropanoate to synthesise amorphous atrasentan. Piramal and several contract research organisations (CROs) are importing at least one of these intermediates and may be developing a generic version of atrasentan.

General information

The FDA (Food and Drug Administration) Drug Approval Process Training Course: Procedures for Submission of INDs, NDAs, ANDAs and 505(b)(2) (ONLINE EVENT: June 11-12, 2025) - ResearchAndMarkets.com

This programme will be especially beneficial to those responsible for preparing US registration documents (INDs,NDAs, Biologics License Applications, etc), regulatory affairs personnel, lawyers and others responsible for advising companies on strategies for developing new drugs for the US market.

News here 

No damages for Glenmark in battle over Mundipharma’s Targin

Mundipharma does not have to pay Glenmark damages for the cancelled launch of a generic painkiller. Düsseldorf Higher Regional Court has upheld last year's first-instance decision, rejecting Glenmark's claim in the dispute over Targin.

News here

Intellectual Property 

Semaglutide case: With the revocation of the composition patent, a generic launch in Europe could be possible earlier. 

Case Overview-Semaglutide

The document is a datasheet and decision from the Boards of Appeal of the European Patent Office (EPO) concerning appeal case T 1701/22, with a decision date of January 16, 2025. The appeal was filed by Novo Nordisk A/S ("the Appellant"), the patent proprietor, against a decision by the Opposition Division to revoke European patent No. 2866825. The patent pertains to the use of long-acting GLP-1 peptides, specifically semaglutide, for the treatment of obesity.

Several opponents ("Respondents") challenged the patent:

• Teva Pharmaceutical Industries Ltd

• Generics (UK) Limited

• Galenicum Health S.L.U.

The core issue revolves around whether the claimed use of semaglutide for obesity treatment involves an inventive step over the prior art, particularly in light of document D10. The Opposition Division had previously found the patent lacking in inventive step under Article 56 EPC (European Patent Convention).

Key Patent Claim & Arguments

The primary assertion at the heart of the dispute is:

"A composition comprising the GLP-1 agonist semaglutide and one or more pharmaceutically acceptable excipients for use in the prevention or treatment of obesity, wherein said use comprises administration of said GLP-1 agonist in an amount of at least 0.7 mg per week; and said composition is in the form of an aqueous formulation with pH between 3 and 10."

The appellant argued that the invention, specifically the use of semaglutide at a dosage of at least 0.7 mg/week in an aqueous formulation, was not obvious in view of prior art document D10 or other prior art.

Prior art documents cited

Summary of Appellant's (Novo) Arguments

Novo Nordisk, the patent holder, argued that its patent was inventive and should be upheld. Here are the key points made by Novo:

1. Closest Prior Art: Novo contended that document D10, a key piece of prior art, contained multiple teachings that needed to be individually assessed to determine the most relevant starting point for evaluating inventive step. They specifically argued that the exenatide example in D10, demonstrating effective weight reduction in an animal model, should be considered the most promising starting point. They claimed that focusing on other passages in D10, particularly those related to other GLP-1 receptor agonists, would be speculative and based on hindsight.
2. Inventive Step: The appellant claimed that the key difference between their invention and D10 was the use of semaglutide at a specific dosage (at least 0.7 mg/week) in a specific formulation. They argued that D10 taught away from using GLP-1 receptor agonists alone due to potential side effects, and that the prior art did not suggest that semaglutide, at the claimed dosage, would provide a safe and effective treatment for obesity.
3. Objective Technical Problem: They defined the objective technical problem as providing an improved, highly effective, and safe therapy for treating or preventing obesity. They asserted that their invention, using semaglutide as a single agent, solves this problem.
4. Obviousness: Novo Nordisk argued that it was not obvious to arrive at their invention from D10. They claimed that the prior art did not highlight semaglutide as particularly advantageous over other GLP-1 receptor agonists like exenatide or liraglutide for obesity treatment. They also argued that the skilled person would not have expected that the claimed dosage of semaglutide (0.7 mg/week) would provide improved therapy, and that the prior art did not suggest the use of an aqueous formulation with a specific pH range. They highlighted post-published data describing semaglutide as a "game changer" in obesity treatment, further supporting their claim of inventive step.

Summary of Respondents' Arguments

The opponents of the patent (Respondents) argued that the claimed invention lacked an inventive step and was obvious in light of the prior art. Here are the key points of their arguments:

1. Closest Prior Art: The respondents argued that document D10 represented the closest prior art and that claim 8 of D10 (related to a combination of a GLP-1 receptor agonist and a DPP-4 inhibitor) provided a feasible starting point for assessing inventive step.
2. Inventive Step: The respondents claimed that the distinguishing feature of the patent was the formulation of the composition as an aqueous formulation with a pH between 3 and 10, but that this feature had no apparent technical effect.
3. Obviousness: They argued that selecting any GLP-1 receptor agonist from claim 2 of document D10 would have been an obvious choice to solve the objective technical problem. They claimed that D10 had already established that semaglutide was suitable for treating obesity and recommended the highest dose of 1.6 mg per week. Furthermore, they argued that the weight-reducing effects of different GLP-1 receptor agonists, including semaglutide, were already described in common general knowledge. They also argued that the prior art disclosed suitable parenteral formulations and their pH, making the claimed formulation obvious.

EPO Board of Appeal's Reasoning & Decision

The Board of Appeal sided with the opponents and dismissed the appeal. Their reasoning can be summarised as follows:

1. Closest Prior Art: The Board agreed that document D10 was a suitable starting point for assessing inventive step. While the appellant argued for the exenatide example as the starting point, the Board considered claim 8 of D10 a more appropriate starting point as it directly related to the treatment of obesity.
2. Obviousness: The Board found that the skilled person, based on the knowledge in D10 and common general knowledge, would have had a reasonable expectation of success in using semaglutide for treating obesity. They noted that D10 already suggested semaglutide as a potential treatment and provided dosage ranges.
3. The Board addressed each aspect of the main claim. First, by establishing that Semaglutide was not surprisingly effective. Second, by concluding that the claimed dosage regimen was consistent with ranges described in the prior art. Third, by stating that "no surprising effect is apparent for the claimed formulation in an aqueous solution with pH between 3 and 10."
4. Motivation to Select Semaglutide: The Board rejected the appellant's argument that the skilled person would not have been motivated to select semaglutide. They noted that semaglutide had been successfully tested in clinical trials and that the prior art supported its potential for weight reduction.
5. Aqueous Formulation: The Board stated that it would have been obvious to formulate semaglutide as an aqueous solution with a pH between 3 and 10.
6. Auxiliary Request: Regarding the auxiliary request, the Board found that the change in claim wording ("consisting of" instead of "comprising") did not overcome the lack of inventive step. Since the limitation to a composition consisting of only semaglutide pertained to its formulation and did not affect the administration of further formulations (such as a DPP-4 inhibitor), the inventive-step assessment starting from claim 8 of document D10 did not change.

In Conclusion

1. The ruling indicates that the Board believed that the potential benefits of Semaglutide as a therapeutic option could have been derived from existing information and routine practices without the need to exercise innovative skills.
2. The EPO Board of Appeal concluded that the patent's claimed subject matter lacked an inventive step and was obvious in light of the prior art. Consequently, the Board dismissed Novo Nordisk's appeal, upholding the decision to revoke European Patent No. 2866825. This patent would have otherwise expired in June 2033, and generics would have had to wait until then for their launches. 
3. However, Novo had applied SPC for EP1863839; it would be valid until 2031, making the likelihood of generic launches of semaglutide before 2031 appear challenging. 

Decision here