When the EU passed the Biotech Patent Directive in 1998 the hope was that it would put an end to the legal wrangling over the patenting of gene sequences. While it clarified many issues there are still cases going through the court and patents being challenged.
The story starts in the early 1990s when companies started to sequence the human genome and produce automated sequences. They produced vast amounts of raw sequences and tried to obtain patents for them. "This was just raw data and they were presenting this to the patent office," says Philip Webber, a partner with Dehns and a legal expert in biotechnology patents. "The patent offices did not know what to do so they called a moratorium in order to have further discussions."
This led to the Biotech Patent Directive, which basically said that gene sequences could be patented as long as they were isolated from the body and included some indication of the function; it said that finding a gene sequence was just a discovery.
"You basically had to find a use for the bit of DNA," Webber says. "The patent system is there to protect useful inventions. You had to do a bit more work to convert the discovery of raw sequences into a patentable invention."
The findings of the directive were then passed into law in the different EU countries, although not all in the same way. In France, for example, the patent can only be enforced against a use specified in the patent. In the US, a similar route to the EU was taken. They said that those applying for a patent had to disclose a specific, substantial and credible function of the protein encoded by the gene.
Many patents have now been granted on this basis, but the arguments today concentrate on how much information needs to be given in the patent application to show that it has a function that can be translated into a commercial value.
HGS problem definition
One of the most recent cases in the UK concerns a company called Human Genome Sciences (HGS) that filed a patent related to a polypeptide. This brought to light difficulties in one of the methods used to define the function in a gene sequence. There are two ways of doing this. One method, as used by HGS, is to use computer-based predictions and compare these with other known genes and thus from there assert that it is likely to have similar functionality. The other method is to use laboratory methods and testing to see exactly what it does - these are preferred by the courts, although patents have been accepted based on computer sequencing.
The HGS application used no experimental data to support its assertions and the validity of the patent that was initially granted was challenged by pharmaceutical manufacturer Eli Lilly. This ended up at the Court of Appeal, which ruled the HGS patent was invalid. At the time of writing, HGS still has the option of taking this further to the Supreme Court.
"The message the HGS case sends to biotech companies is that you have to do a lot more research to show there is some practical value before you file the patent application," said Webber. "This might mean delaying filing the patent application. You cannot do this later as a judge will say it is too late once it comes to court. It has to be in the patent application when you file it. And you cannot reapply. One of the conditions of getting a patent is that it must not be in the public domain. Information on the HGS patent is now in the public domain so they couldn't reapply."
If HGS was to find a new use for the sequence, it could apply for a new patent purely on that use (say for the treatment of diseases not mentioned in the original patent).
Myriad's patenting problems
The major case in the US over this issue concerns a company called Myriad Genetics. It has two patents known as BRCA1 and BRCA2, which can be used for testing women for breast cancer.
"They have been charging high prices for anyone who wants the cancer checked using this," Webber says. "This has given them bad publicity. The patent was challenged in Europe and had its scope restricted. In the US, in March 2010, a court threw out the patent."
The problem with the US decision was that this was thrown out by a lower court on the grounds that patenting genes is not allowed, although this is not the case legally, which is why Myriad will appeal the decision at a higher court where they can call on patent specialists. "The higher court will not do what the lower court did on the same grounds," said Webber, "but there might be political pressure put on the court to find other reasons to throw it out."
Monsanto's biotech woe
Another case that has potential implications for biotech companies concerns Monsanto, which produces transgenic plants and weed killer. This case is important for deciding whether a patent is valid in its own right or just for the functions specified in the patent.
Monsanto found a gene that made a plant resistant to its own herbicide, which would enable a farmer to spray a field and kill all plants apart from the ones from Monsanto. The plant in question produces soya beans that can be turned into oil. The crushed bean can then be turned into animal food.
A company in Argentina, where Monsanto's patent was not valid, was producing such animal food and then started exporting it to Europe where Monsanto does have a patent. Monsanto has taken the company to the European Court of Justice, which has still to make a decision but has produced a preliminary opinion.
"The preliminary opinion is that the patent only covers a gene if it is performing its function," Webber says. "In this case it is not. This has implications because when you sell a gene, it is not performing a function. It is just a gene in a test tube. So this again might limit the scope of gene patents in Europe to when it is just performing its function."
Despite the examples above, Webber believes the gene patenting rules are working. "There are few examples of bad gene patents," he said. "Generally people filing these patents are doing so for the public good. Yes, they will make money on them but they are producing drugs and tests and they need the patents to protect their investment. It takes a lot of money to take a discovery from the bench through all the trials and testing to get it into the market. Without the patent protection, there is no reason to make that investment."
He also points out that dodgy patents can be challenged and that this is relatively cheap to do. However, the issue of gene patents is still going through a learning curve and companies involved in this area will be watching closely the cases mentioned here as they all have potential ramifications for future gene patents.