mercredi, mai 11, 2011

Spain: Appeal court lifts preliminary injunction against sale of escitalopram generics

In a March 8 2011 decision the Barcelona Court of Appeal confirmed a decision of Barcelona Commercial Court No 4 (April 12 2010) lifting the preliminary injunctions requested by Lundbeck, previously granted ex parte by the court, against various companies to prohibit them from selling escitalopram generic medicaments for which they had obtained marketing approval (for further details please see "Lundbeck not Reddy for patent injunction reversal on copycat drug").

Lundbeck holds the patent EP347.066 - ES2.986.891, as well as SPC 200200019 derived from it, which claims a certain manufacturing process for the active ingredient escitalopram. Escitalopram is an anti-depressant commercialised by Lundbeck under the trademark CIPRALEX.

Lundbeck requested the adoption of preliminary injunctions against various companies based on the infringement of its patent since, according to Lundbeck, the defendants' products contained escitalopram manufactured following Lundbeck's patented process and not by the process declared by them (a process by Indian company Dr Reddy's, which falls outside the scope of Lundbeck's patent). To support this argument, Lundbeck argued that:

  • the open part of the drug master file filed by the defendants was insufficient to prove that the process used to manufacture the escitalopram in their medicaments was actually the one declared by Dr Reddy's, and that only a certificate issued by the health authorities could prove that fact;
  • the presence of diol traces in the defendants' product (less than one part per million (ppm)) could not be explained if Dr Reddy's process had been used to manufacture the escitalopram, but would appear only if Lundbeck's patented process was being used;
  • the optical purity of the defendants' escitalopram (99.3%) could not be achieved using Dr Reddy's process; and,
  • the presence of significant impurities of didesmethyl-escitalopram and desmethyl-escitalopram ('markers' of the use of Dr Reddy's process) was irrelevant because Dr Reddy's could add them afterwards to cover up the infringement, or could be admixing escitalopram obtained by the two processes.

However, the court rejected Lundbeck's objections and lifted the preliminary injunctions, based on the consideration that the active ingredient of the defendants' escitalopram medicaments was manufactured and supplied by Dr Reddy's, as had been accredited by the defendants through the open part of the drug master file and two expert reports.

Lundbeck appealed the court decision based on the same arguments used at first instance, insisting that the process used by the defendants was the one protected by its patent. Lundbeck also argued that during the first instance proceedings it would have challenged the conclusiveness of the drug master file submitted by the defendants. According to the plaintiff, it would have depended on the defendants to prove that the drug master file deposited before the health authorities was the same as the one filed in the proceedings, and that it was actually used by them, without attributing to the plaintiff an impossible proof.

In response, the appeal court made clear that while a certificate issued by the health authorities is an optimum means to demonstrate the process used in the preparation of the active ingredient of a medicament, it is not the only means, and this fact can be justified in other ways. The court considered that the evidence submitted by the defendants (the drug master file and two independent expert opinions) was sufficient to prove that the process used to manufacture the escitalopram contained in their products was actually Dr Reddy's process.

With regard to the objections raised by Lundbeck, the court concluded that the diol traces contained in the defendants' escitalopram were irrelevant, and did not consider it to be proven or very credible that their presence was due to Dr Reddy's using Lundbeck's process to hide this fact later by reducing the contents of diol with successive recrystallisations in ethanol. This was considered less plausible, especially since the defendants had demonstrated that Dr Reddy's did not use ethanol, but rather ethyl acetate as recrystallising solvent, which, according to Lundbeck itself, would not enable the amounts of diol to be reduced.

As for the optical purity, the court stated that there was no evidence in the proceedings to prove the degree of optical purity obtained using the patented process, thus impeding the court from comparing the results from either process. Thus, it concluded that this allegation was irrelevant with regard to the alleged infringement.

Finally, the court established that the presence of didesmethyl-escitalopram and desmethyl-escitalopram in the defendants' products (more than 100ppm each), which were 'markers' of the use of Dr Reddy's process, merely confirmed that the process effectively used was Dr Reddy's process.

Hence, the appeal court upheld the decision issued by Barcelona Commercial Court No 4 and lifted the preliminary injunctions, as it considered that the requirement of appearance of right had not been met. According to the appeal court, the defendants fulfilled sufficiently the burden of proving their active ingredient manufacturing process, whereas Lundbeck did not manage to rebut their evidence in this regard.

The main trial in the first instance main proceedings is due to take place in July 2011.

For further information on this topic please contact Sara Pelaz at Grau & Angulo by telephone (+34 91 353 36 77), fax (+34 91 350 26 64) or email (s.pelaz@gba-ip.com).