Posted: April 15th, 2013
Ajinomoto v. Global Bio-Chem Technology, Helm et all. District Court The Hague, The Netherlands, 20 March 2013, Case No. C/09.268116 / HA ZA 06-2131
Ajinomoto is the proprietor of EP 0 796 912 relating to a “novel lysine decarboxylase gene and process for producing L-lysine”. Both Ajinomoto and defendants Global et al. produce and sell L-lysine. Global et al. claim that the L-lysine produced by them is produces using fermentation methods with micro-organisms. On 20 March 2013, the District Court of The Hague ruled that EP ‘912 was valid, in spite of Gobal et al.’s arguments based on lack of novelty, obviousness, insufficient disclosure and added matter, and it ruled that Global et al. had infringed the patent.
Lysine is produced using bacteria, in particular the E. Coli bacteria. A problem with E. Coli is that it also breaks down a proportion of the lysine it produces. The cadA and ldc genes are genes that code for an enzyme, lysine decarboxylase, which facilitates the decomposition of L-lysine. EP ‘912 relates to a gene in the E-coli bacteria in which the cadA and ldc genes are significantly decreased or disappeared. Claim 1 relates to a gene that codes for the newly identified lysine decarboxylase enzyme with a specifically defined amino acid sequence, or with an amino acid sequence that deviates from the sequence by 3 amino acids or less. Claims 5, 6 and 7 relate to E.coli bacteria wherein the ldc and/or cadA genes are modified in such a way, that the activity of lysine decarboxylase coded by the genes is decreased or disappeared. Claim 9 relates to a method for the production of lysine by cultivating such E.coli micro-organism.
Global c.s. have argued that claim 5 of the patent lacks novelty, because E.coli bacteria having a decreased or disappeared ldc activity already existed in nature. This argument was denied by the Court, which found that the claim should be interpreted to read that the mutation in the ldc gene must be the result of human intervention. Therefore, the natural occurrence of the aforementioned bacteria does not affect the novelty of the claim.
With regard to obviousness/ inventive step, it was decided that a publication by Meng & Bennett was the closest prior art, because it describes the DNA sequence of the cadA gene as well as the homology between the cadA gene and the ldc gene of H.alvei. Meng & Bennett also mentions that the existence of a second gene coding for lysine decarboxylase (the ldc gene) had also been observed in E.coli. The objective technical problem was formulated as “to find the second lysine decarboxylase gene in E.coli, determine its base sequence and its activity to inhibit the production of L-lysine. The Court ruled that the patent is non-obvious, since at the priority date, the skilled person would not have been convinced that there indeed was a second lysine decarboxylase gene. The existence of such gene in E.coli had only been suggested very cautiously in some prior art documents (Goldemberg, Canellakis) and had even been questioned in other publications (Yamamoto, Lane). Furthermore, the skilled person would not have had a reasonable idea of the degree of homology (the degree of similarity in DNA sequence) between the cadA gene and the ldc gene van lysine carboxylase, as it was known that this can vary quite considerably. Knowing the degree of homology is important when choosing the appropriate method investigate the presence of the ldc gene (in particular so-called ‘Southern blotting’). Thirdly, the skilled person would not know which hybridisation conditions he would have to use when applying the Southern blotting method, which means he would have to revert to trail and error. And finally, it is mentioned in Meng & Bennett that preliminary Souther blot experiments had not lead to a positive result, which would cause the skilled person to believe that the degree of homology between cadA and ldc is not very high. He will therefore question whether the Southern blot technique will enable him to find the ldc gene at all, which means that, even though he would realise this route is a route he could use, it had not been established that he would use this route.
Global et al. had also argued that the patent lacked sufficient disclosure, inter alia because it was unclear what the wording “without any substantial deterioration of lysine decarboxylase activity” in claim 1 meant. Global et al. had not argued that the skilled person was not able to determine, without due burden, whether there is a substantial deterioration, but that it was unclear when a deterioration should be considered “substantial”. The Court found that this was not an insufficiency argument, but a lack of clarity argument, which, after grant of the patent, can not be brought as a nullity ground. In addition, Global et al. had argued that claim 1, describing the gene with normal lysine decarboxylase activity, mentions that the defined amino acid sequence may deviate by 3 amino acid residues, this contradicts claim 4, which describes a method for creating a micro-organism in which the ldc gene has been mutated so as to decrease or eliminate the lysine decarboxylase activity, and which allows that the gene is modified by changing only one or two amino acids. However, according to the court, the skilled person will understand that there is a significant difference between a change in amino acids outside the active center of the gene (which is what claim 1 means to refers to) and a change within this active center (claim 4) and therefore the claims are not contradictory.
Invalidity arguments based on alleged added matter were also dismissed.
In addition, Global et al. had contended that article 9 of the Biotech Directive 98/44/EC and its interpretation by the CJEU in Monsanto v Cefetra lead to the conclusion that the L-lysine produced by Global et al. was not infringing. According to Gobal et al., the Monsanto judgment required that the DNA found in the lysine must perform its function in order for the product to be infringing, and since this is not the case in the matter at hand, there can be no infringement of the claim. The Court ruled, however, that Global et al. fail to acknowledge that the Monsanto case related to the alleged infringement of a product claim for a gene sequence, whereas this case relates to the infringement of a method claim for the production of L-lysine, not a gene sequence but an amino acid, through fermentation. Article 9 does not apply to a method claim which is not directed at a product with genetic information. This may be different if the method claim had been directed at the creation of a gene sequence and the product directly obtained from that would be alleged to infringe the patent, but that is not the case here, according to the Court.
The District Court concluded that the EP 912 was valid and had been infringed by Global et al.
Read the judgment (in Dutch) here.
Head note: Jaap Bremer