Skip to content

NL – Teva v. Synthon (Copaxone appeal)

17 Nov 2016

Teva Pharmaceutical Industries Ltd v. Synthon B.V., Court of Appeal The Hague, 25 October 2016, Case no. ECLI:NL:GHDHA:2016:3368

Teva is the proprietor of EP 2 361 924 for a “process for preparation of mixtures of trifluoroacetyl glatiramer acetate using purified hydrobromic acid”. This patent had been nullified by the District Court of The Hague in proceedings in first instance initiated by Synthon, for lack of inventive step.

Teva lodged an appeal against this decision, but based its appeal only on the patent claims as set out in its auxiliary requests 1e (which had been denied by the EPO Opposition Division) and, alternatively, 1f (which had been upheld by the OD). In essence, the appeal judgment focussed on the assessment of novelty and inventive step of the claimed process for obtaining glatiramer acetate (GA), which process involved the use of a solution of hydrobromic acid (HBr) in acetic acid which is essentially devoid of free bromine and which comprises less than 100 ppm of metal ion impurities.

Synthon argued that a product in accordance with EP 924 had been the subject of public prior use and EP 924 therefore lacked novelty. It referred to a declaration of Chemada, Teva’s supplier of the HBr/acetic acid solution, which stated that the solution was made and stored in non-metallic containers. The Court of Appeal rejects this argument, pointing out that the declaration does not prove that the solution would not have come into contact with metal during transportation, storage and addition to the reaction vessel. Therefore, Teva did not prove that the GA manufactured and supplied by Teva prior to EP ‘924 priority date could not have contained more than 100 ppm metal ion impurities. In addition, Teva has not convincingly established either that Teva made us of a solution that was devoid of free bromine. Therefore, the Court of Appeal found that EP ‘924 was novel.

The Court of Appeal goes on to assess the alleged obviousness, by stating that each of the two improvements over the prior art achieved by the invention, i.e. the minimalisation of metal ion impurities and of free bromine,  were not interconnected and did not have a synergistic effect. Therefore, the Court assessed both aspects individually.

As regards the metal ion impurity, it agreed with Teva that the insight provided by EP ‘924 that a discoloration of the GA was attributable to the presence of metal ions in the HBr/acetic acid solution and that such discoloration could be avoided by using a solution that is produced, transported and stored in a way which ensures it does not come into contact with metal, was non-obvious. However, the claims of EP ‘924 do not contain a limitation saying that the HBR/acetic acid solution may not contain more than 100 ppm to avoid discoloration of the GA, nor did they mention that any control measures should be applied to ensure the metal ion impurity level of the HBr/acetic acid solution was below 100 ppm. It was customary before the priority date to use a HBr/acetic acid solution that had been produced and transported in such a way that it did not come into contact with metal.

Therefore, in most cases the problem of discoloration did not occur which means that, in such cases, the patent did not provide any solution to a problem, i.e. no technical effect (advance) had been achieved. With reference to the AgrEvo decision of the Technical Boards of Appeal (T 939/92), the Court concluded that the insight that metal ions in the HBr/acetic acid solution could cause discoloration of GA did not render EP ‘924 inventive.

As regards the bromine impurities, Teva argued that the District Court had wrongly formulated the objective technical problem as “the prevention of bromine contamination in the peptide mixture”, because the invention laid down in EP ‘924 was a problem invention, as it was unknown at the priority date that bromine contamination was a problem in the first place.

The Court of Appeal disagreed with Teva and relied on an FDA report which refers to rat studies in which it was shown that bromine impurities in GA caused toxicity and which concluded that bromine levels should therefore be a low as possible. The report also teaches that contamination by brominated tyrosine (tyrosine is one of the amino acids contained in the polypeptide GA) can occur during the synthesis of GA. Insofar as it was not already common general knowledge that bromine contamination was caused by the presence of free bromine in the HBr/acetic acid solution and what he could do to reduce the contamination, he would consult a number of handbooks and other publications. These documents would teach him that tyrosine reacts easily with free bromine present in the HBr/acetic acid solution and that contamination by brominated tyrosine can be reduced by using a bromine scavenger such as phenol. Therefore, the insight that the presence of free bromine in the HBr/acetic acid solution should be reduced as much as possible to avoid bromination of tyrosine during the synthesis of GA, was obvious.

In light of the above, the Court of Appeal rejects the appeal and confirms the nullification of EP ‘924 for lack of inventive step.

A copy of the judgment can be found here.

Headnote: Jaap Bremer, BarentsKrans