Facts
Supreme Court decision
Comment
The Supreme Court in Civil Matters recently considered the validity of a patent concerning the use of adamantine derivatives for the prevention and treatment of cerebral ischemia and the respective supplementary protection certificate (SPC) for the active substance memantine.(1) The patent expired while the litigation was pending; the SPC was intended to last until 2014.
The plaintiffs claimed that the invention was not novel, in particular in view of a clinical trial that had been published before the patent application was filed.(2) In the publication, the results of a randomised, single-blind clinical trial were reported and discussed. During the trial, Alzheimer's disease patients received memantine infusions (in the control group, patients were given placebo infusions). Statistical evaluation showed no significant differences between the two groups. Therefore, the study provided no evidence of the superiority of memantine over a placebo. The authors concluded that it would be most unlikely that a treatment consisting of memantine alone would mitigate the therapeutic problems relating to severe dementia of the Alzheimer's type.
At first instance, the Federal Patent Court regarded the publication as novelty destroying, as it showed that memantine had been considered as treatment for Alzheimer's disease in the state of the art, regardless of the fact that it eventually proved unsuccessful.
While the Supreme Court concurred with this result (ie, that the subject matter of the patent and the respective SPC was not patentable, as it lacked the required novelty), it opposed the Federal Patent Court's view on the publication Progress in Neuro-Psycho-Pharmacology and Biological Psychiatry.
The Supreme Court explained that in examining whether the subject matter of a patent has been described in a prior art publication, it is necessary to look at the prior art document in its entirety from the perspective of a person skilled in the art. By doing so, it should not be considered how a person skilled in the art could modify a general idea expressed in the publication or implement a technical teaching contained in the publication by using his or her expertise. Rather, what the person skilled in the art can directly and clearly derive from the publication is the only relevant consideration.
The Supreme Court criticised the fact that the Federal Patent Court had focused on the authors' assumption at the beginning of the trial that memantine could be used for the treatment of Alzheimer's disease. However, a person skilled in the art would recognise that this assumption proved incorrect during the trial. Therefore, the court held that the publication did not disclose the use of memantine for the treatment of Alzheimer's disease. The court also clarified that the mere fact that the study had been published, despite its negative outcome, did not indicate that the authors still believed in the efficacy of memantine.
However, the court found that the subject matter was not novel compared to other state-of-the-art documents. It pointed out that at the priority date, persons skilled in the art were aware that patients with symptoms pertaining to an unspecified cerebro-organic psychosyndrome could be successfully treated with memantine. As the court-appointed expert explained, the term 'cerebro-organic psychosyndrome' was used to refer to symptoms such as memory loss and affective and association disorders associated with various causes. Due to the lack of research that had been carried out into the etiology of the disease at that time, Alzheimer's disease belonged to the group of diseases collectively referred to as 'cerebro-organic psychosyndromes'. At the time of priority, reaching a diagnosis of Alzheimer's disease was very complicated. Therefore, persons skilled in the art could not have known the percentage of the group of patients with cerebro-organic psychosyndrome that had Alzheimer's disease. However, it seems clear that Alzheimer's patients constituted a substantial part of the group.
A person skilled in the art would have known that memantine helped mitigating symptoms, in particular reduced vigilance, in patients suffering from cerebro-organic psychosyndrome. In fact, it had been observed that the drug Amantadin, when used for the treatment of Parkinson's disease, increased patients' vigilance. This led to the search for similar substances with an increased psychotropic effect. Memantine was identified as such a substance. In a study it had been shown that patients who were treated with memantine significantly improved with regard to vigilance and short-term memory.
Further, in a double-blind study, patients with cerebro-organic psychosyndrome had been treated with memantine or DH-ergotoxine. Both substances caused an improvement in the patients' psychopathology; memantine was considered to be non-inferior to DH-ergotoxine with regard to therapeutic efficacy.
Therefore, the court found that the patent was not novel compared to the state of the art. It provided no teaching on how a disease that had not previously been treated with memantine could be treated; nor did it disclose the suitability of memantine for the treatment of a patient group that had not previously been treated with the drug.
The court conceded that the patent provides a scientific explanation for the effect of memantine on Alzheimer's patients. The patent discloses the pharmacology of memantine, namely the blocking of NMDA-receptors, and thus the inhibition of prolonged influx of Ca2+ ions, which forms the basis of neuronal excitotoxicity.
Thus, the patent constituted scientific progress in explaining the effects of the use of memantine for the treatment of Alzheimer's disease that had begun years before. It allowed for a better understanding of the drug's biological effects. Also, it provided a clear indication of the use of memantine for Alzheimer's disease so that physicians can apply memantine with the aim of reaching a specific effect, rather than to treat unspecified symptoms.
However, this does not constitute a technical teaching. Rather, it constituted a biological discovery that excluded it from patent protection under Article 52(II)(a) of the European Patent Treaty. The technical teaching would be to treat Alzheimer's patients with memantine. The patent neither provides a different dosage nor otherwise provides additional specific information on how the substance should be applied. The court emphasised that while the scientific explanation of the effects of the drug was a commendable achievement and constituted progress from a medical and pharmacological point of view, this could not be considered in examining patentability.
Comment
This decision is interesting with regard to the interpretation of the clinical trial in which the effect of memantine on Alzheimer's patients had been analysed, but found ineffective. It shows that the mere idea that memantine could be used to treat Alzheimer's patients was not considered novelty destroying, since it proved wrong in the clinical trial. Of course, the court's findings would have differed if the outcome of the clinical trial had been positive.
The wording of the decision seems to suggest that the Supreme Court regretted its decision in view of the effort that the applicants had made in identifying the biological mechanism of memantine. However, given the prior art and the fact that the patent did not provide further technical teaching, the court had little choice but to invalidate the patent.
For further information on this topic please contact Nora Keßler at Klinkert Zindel Partner by telephone (+49 69 972 65 600), fax (+49 69 972 65 6099) or email ([email protected]).
Endnotes
(1) Case X ZR 68/08, June 9 2011.
(2) Fleischhacker et al, Progress in Neuro-Psycho-Pharmacology and Biological Psychiatry, 1986, 10, pages 87 to 93.