No compulsory licence for Sanofi's Praluent in Germany

On 4 June 2019, the German Federal Supreme Court refused Sanofi's request for a preliminary compulsory licence regarding Amgen's patent EP 2 215 214 (docket number X ZB 2/19).

Facts of the case

Sanofi distributes the medicinal product Praluent, containing the active ingredient Alirocumab, in Germany. Alirocumab is a monoclonal antibody directed against the proprotein convertase subtilisin/kexin type 9 (PCSK9).

PCSK9 impairs the reduction of too-high levels of low density lipoproteins (LDL cholesterol levels). Alirocumab inhibits the PCSK9 protein, and by doing so, achieves a reduction in blood's LDL cholesterol level.

The defendent, Amgen, owns EP 2 215 214 relating to antigen binding proteins against PCSK9 (the Patent). The Patent has been upheld in opposition proceedings in amended version. The appeals against this decision have not yet been decided.

Amgen also distributes the medicinal product Repatha that contains the antibody Evolocumab, which is directed against PCSK9 as well.

Amgen sued Sanofi for infringement of its patent at the District Court Düsseldorf, asking (among other things) for injunctive relief.

Sanofi filed a complaint for the grant of a compulsory licence at the Federal Patent Court in July 2018 (based on Sec. 24 German Patent Act), and requested in parallel the grant of a preliminary compulsory licence according to Sec. 85 German Patent Act.

Sanofi (among others) argued that Praluent had superior therapeutic properties – in particular, a reduction of the associated mortality risk – compared to Repatha.

The first instance decision of the Federal Patent Court

In its decision handed down on 6 September 2018(docket number 3 LiQ 1/18 (EP)), The Federal Patent Court refused to grant a preliminary compulsory licence, because:

• Firstly, claimants had not sufficiently attempted to be granted a contractual licence for their product, Praluent.
• Secondly, they had also not made a plausible argument that there is a public interest in the availability of Praluent – ie that Praluent does indeed have higher therapeutic properties than Amgen's Repatha.

Federal Supreme Court affirms the first instance decision

Upon Sanofi's appeal, the Federal Supreme Court finally settled the matter, refusing the preliminary grant of a compulsory licence by affirming the reasoning of the Federal Patent Court.

The Federal Supreme Court also saw no sufficient efforts on Sanofi's side to achieve the grant of a contractual licence. Not only had the claimants expressed their interest in being granted a licence relatively late in the game, they only offered a very low royalty fee and had not replied to Amgen's letter until the end of the first instance proceedings.

Furthermore, the Federal Supreme Court ruled that subsequent letters sent by Sanofi during the appeal proceedings did not constitute a serious effort on their behalf.

Regarding the argument of public interest, the Federal Supreme Court again follows the Federal Patent Court: a plausible case could not be made that Praluent had relevant therapeutic advantages over Repatha.

Both products are based on the same mechanism of action. Although this pharmacological effect is important, it is achieved by both antibodies. Therefore, the Federal Supreme Court found that the mechanism of action itself does not qualify as a sufficient reason for the grant of a compulsory licence.

Moreover, although one clinical study has shown Praluent's mortality risk to be less than that of Repatha, the Federal Supreme Court ruled this statistically insignificant. What's more, the absolute number of deaths involved is likewise insignificant, because the product is not distinguished based on this characteristic.

As such, the lower number of deaths in the Praluent trial group could be due to coincidence only, rather than any intrinsic property of the product itself.

Commentary

It should be noted that relying on Sec. 24 German Patent Act to determine how sufficient a party's efforts were when seeking a compulsory licence is very much dependant on the individual case in question.

Nevertheless, at least from the public available information about the licence seeking efforts, the holding of the Federal Supreme Court seems to be somewhat in contradiction to its decision in the preceding compulsory licence case on Raltegravir (decision of July 11, 2017, docket number X ZB 2/17), where there has been a similar low effort from the party seeking the compulsory licence that the same Senate had however considered sufficient at that time.

Regarding the question of public interest, this decision underlines a key difficulty facing manufacturers of biosimilar products or products that are generally based on the same mechanism of action: It is extremely difficult to explain (and prove) that a competing product has a substantial additional therapeutic benefit over the innovator product.

This is especially the case for so along as the innovator product is on the market and sufficient supply for the patients is secured.