On 31 July 2002, the UK Court of Appeal handed down its judgement in the case of Kirin Amgen -v- Transkaryotic Therapies finding that Amgen’s European patent for recombinant erythropoeitin (EPO) was valid but not infringed by TKT’s EPO product made by "gene activation" technology. The dispute is part of a world-wide series of litigation including an appeal pending before the U.S. Supreme Court.
Although the case itself will have important commercial implications (the EPO market is estimated to be worth over $1 billion annually), the reasoning behind the decision may affect the value of gene patents held by biotech and pharma companies and will have a far wider influence. Indeed, the decision raises the prospect of any biotech patent to therapeutically useful recombinant proteins being side-stepped by using gene activation technology.
"Traditional" genetic manipulation techniques developed during the 1980s depended on isolating pieces of DNA from cells before re-packaging them and inserting them into cells which then "express" the protein coded for by the relevant DNA. Transkaryotic Therapies (TKT) however, employ a technique whereby natural copies of genes present in living cells are "switched on" by inserting other promoter DNA sequences into the genome in proximity to the gene of interest. The site for insertion of the promoter is chosen by using the sequence information of the gene.
Patent claims for a newly identified DNA sequence must, by necessity, exclude a DNA sequence or partial sequence contained within the human body but can include such a DNA sequence when isolated from the human body. This fundamental principle is set out clearly in the European Biotech Directive (Article 5, 98/44/EC) and forms the basis of any claim to a gene sequence. The Court of Appeal decision confirms that claims to recombinant proteins are restricted to proteins produced from a gene sequence that has first been isolated.
Amgen alleged that TKT infringed a product-by-process claim to a protein made by expression of the DNA sequence of the EPO gene. The trial judge originally found that Amgen’s invention was to provide a DNA sequence to allow recombinant production of EPO. Since TKT’s process could only be carried out once that sequence had been identified, it represented an immaterial variant of the patent and so infringed.
The Court of Appeal disagreed on this point. In relation to the invention, it held that "there can be no doubt that at the heart of the invention was the discovery and sequencing of the gene that produced EPO. That work …enabled recombinant EPO to be produced…However, that gene sequence was not claimed as the invention we expect because a claim to the sequence per se would not be patentable….In effect the claim is to an exogenous DNA sequence suitable for expressing EPO when introduced to a host cell".
The Court of Appeal went on to find that TKT’s product is "very different. The DNA sequence is endogenous. It is not suitable for expressing EPO until after introduction of the [promoter]". Notwithstanding the fact that the DNA sequence disclosed by Amgen’s patent was "part of the essential knowledge that was required before the TKT process could be carried out", the Court of Appeal found that the TKT gene activation process worked in a materially different way and so did not infringe.
It is not known whether either party intends to seek permission to appeal further to the House of Lords.