Genomic data analys is and patenting life

The unravelling of the genetic code is being carried out alongside a debate on the ethics of patenting the data the genome project has generated, as Catriona Kelly reports

The availability of genomic data as a result of advances in research has led to a turbulent public debate over patenting of the human genome. As many organisations, both public and private, endeavour to detail the human genome and analyse the resultant data in order to increase understanding of disease, the question of patent protection for the technology applied and the information itself has led to unexplored territory.

The problems with the situation are many and complex, not least because of the ethical arguments involved. Laying aside the question of ownership of human DNA, the scientific complexities over defining ownership are intricate and subtle.

In 1998, Human Genome Sciences patented a set of DNAs citing their likely biological functions as projected from sequence analyses. Proposed use of each DNA in the patents was based on these analyses, detailing uses including wound healing, coagulation, to treat solid tumours, luekemia, parasitic infections and psoriasis.

However, it was discovered by another company that one of these genes plays a part in HIV infection. Because of the patent applied for by HGS, it would have rights to the use of the genes.

According to Dr Janis Fraser of Fish and Richardson in Boston, MA, US, speaking at the recent ACS meeting in Washington, DC, the discovery provoked 'outrage that a company that did little more than find the gene could be awarded a patent giving that company the right to control who could use it'. But, she said, HGS played by the rules by describing in the patent application for the gene a use that is 'arguably specific, substantial and plausible'. She added, 'There is no requirement under US law that a patent be withheld just because other, more valuable uses come to light after the application is filed. Those who find those later uses may well be entitled to their own method claims covering those uses, but that is a different matter.'

So the politics of practice are intricate, but rules are absolute — the application for a patent demands that certain criteria are met.

In the US, Europe and Japan, there are three such criteria for a patent application. The first concerns the part of the gene sequence that is submitted in the application.

The US patent office can refuse to allow claims for partial DNA sequence to cover whole DNA. In the past, according to Fraser, the Patent Office in the US has chosen to allow or refuse patents in such circumstances. In Europe and Japan, the Patent offices consider a partial sequence to be sufficient if it is clear that a full sequence could be determined 'without undue burden'.

In addition to the issue of how much of the gene sequence is available, there is an additional criterion regarding obviousness. In the US, patent law says that an obvious method of obtaining a nucleic acid does not automatically make the acid itself an obvious compound.

As long as the claim is crafted in a way that does not inadvertently include naturally occuring or prior art compounds, this criterion is easily met, Fraser said. In Europe and Japan, she said, the law tends toward the viewpoint that any part of a sequence is obvious as it does not require inventive input to uncover a sequence or part of a sequence. The European patent office says that, generally, a gene will be deemed non-obvious as long as neither the purified protein nor any homologous gene is in the prior art.

The third criterion for patenting a gene is usefulness. The US regime requires a utility that is specific, substantial and plausible. A substantial and specific use must be one that would apply in the real world, says Fraser, and this use is 'something that someone might actually do, and not just research in order to find out what the thing might be good for,' she said. 'We need to know enough about the gene, or its protein, to propose a non-generic use that is custom-fit to the particular gene.'

Furthermore, she said, the US Patent Office may take a critical view of a patent application for which the utility of the claimed gene is based on prior art gene of known function. Neither will it be satified with a claim that says the gene or protein could be used in therapy. Without evidence of the genetic therapy in vivo, says Fraser, the applicant has little chance of satisfying the US patent office. However, it may be possible to apply for patent based on non-therapeutic uses, in in vitro assays, including screening assays for new drugs. 'As long as a single specific use is described, or can be inferred from the specification, the utility requirenment of US law is met.

In Europe and the US 'standards are similar', she said. 'Where a potential use is implicitly or explicitly disclosed in the specification, and that use is specific to the claimed gene, the gene should satisfy European and Japanese utility criteria.'

However, she adds, neither the EPO or the JPO is biased against therapeutic uses as is shown in US practice.

Christine Debrouck, a vice president and director at GlaxoSmithKline, outlined the European situation during the eyeforpharma conference held recently in Basel, Switzerland. 'Patents can be thought of as negative rights — they prevent others from exploiting that which is patented, in granting a monopoly in exchange for the scientific advance. That which is patented must be new.'

Critics of biotech gene sequencing say that it cannot possibly be new — but the patent concerns the process for isolating the pharma product, and it must include an inventive step, not obvious to some one in the field. The patent must be capable of industrial application. Inventions that are not patentable include the discovery as such, and inventions that are contrary to morality, such as the cloning of humans.

In the US, the first patent for an expressed sequence tag was granted in 1998. Since then, there have been 6,000 patents issed regarding full length sequences, and 20,000 applications submitted in all.

Much of the debate in the US, is centred around utility and there is concern over the adequacy of the description guidelines, such that patent applications may become more demanding in future.

Europe is covered by the European Biotechnology directive, which was adopted by Brussels in 1998.

In the directive, it says that the human body in its natural state is not patentable, but adds that an element isolated from its natural state or produced by a technical process, for example gene sequencing, may constitute a patentable item provided it has an industrial application. In addition, research such as that performed in academia is not patent infringement, which can lead to some interesting issues.

Patents put information in the public domain while protecting the rights of the inventor. Many companies hold patents for genes. Among them are Millennium Pharmaceuticals, Incyte Pharmaceuticals, and Celera Genomics. In the US, many non-profit organisations also hold patents, including the US Government, academic institutions and hospitals.

Genomic data for its own sake is not patentable, but where genes are shown to have a realistic use that is not obvious, they may be patented.

Responsible laws are in place to prevent irresponsible use of the information available, and in time the wealth of benefits available from genetic data research may be sufficient to silence its critics.