Here in the UK, pharmaceutical patents will be revoked by the courts for lack of an inventive step if a motivated routine experimenter would inevitably have reached the invention from the prior art. This creates particular difficulties for “second therapeutic application” inventions, particularly those concerning successful drugs where the invention is based on a modification of the drug or its administration rather than a new disease to be treated.
Dosage inventions are particularly vulnerable to being considered non-inventive, once it is obvious to put a drug into a program that evaluates dose-response. For example, in last year’s “dosage regime” case (Actavis v ICOS), the UK Supreme Court held that once it was obvious to take tadalafil forward into a routine program that would find its therapeutic dosage plateau, the skilled team would have tested lower doses in order to establish the lowest effective dose. It would thus have arrived obviously at the invention, which was to use a low (5mg/day) dose of tadalafil which provided efficacy coupled with a substantial reduction in side effects. In this respect the Supreme Court agreed with the Court of Appeal but differed from the trial judge.
As the Supreme Court acknowledged, care is necessary to avoid such inventions being considered obvious when in reality the advantages could not have been predicted in advance.
The presence of a sound technical reason why even a routine experimenter trying to optimise in drug development would not have modified the prior art in the way of the invention provides a good foundation for establishing an inventive step. The European Patent Office (EPO) reinforces this by requiring that any modification of the prior art being examined for inventiveness must first have a reasonable expectation of solving a defined objective problem. No expectation of solving the problem means no reason to modify the prior art, so no obviousness.
This is nicely illustrated in a decision of EPO Board of Appeal 3.3.02 (Müller, Lenzen, Blasi) published this week (T709/17).
In T709/17, concerning European Patent No. 2470529, the invention was a new micronized form of the known antifungal voriconazole, having a specific surface area of 0.5 to 2 m2 per gram. The closest prior art taught that the drug was micronized to a specific surface area of 3 to 5 m2 per gram. The reduced specific surface area was proved in the patent to provide better flowability while maintaining comparable solubility.
The opponent argued that it was routine for a skilled team to optimise specific surface area when investigating voriconazole, so that the adjustment in the specific surface area was obvious.
The Board disagreed. It held that the skilled person investigating known micronized voriconazole had no reasonable expectation that the modification would improve flowability while maintaining comparable solubility. Reducing the specific surface area implies increasing the particle size compared with the prior art. This would have been expected to reduce the solubility and not maintain it. The claimed invention was therefore not obvious.