Patenting genes
Authors: Gert Matthijs
Journal: BMJ (2004)

Patents on genes have been granted for many years. Until January 2001, when the first patent for the first breast cancer gene (BRCA1) was granted by the European Patent Office to Myriad Genetics, a US company, most geneticists in Europe had never worried that genes and genetic tests could become exclusive property of a laboratory or a company. A patent allows a company to develop commercial laboratory testing services based on the gene sequences and charge other laboratories wanting to run genetic tests. Myriad Genetics holds several patents on the breast cancer genes BRCA1 and BRCA2 and offers a specific test called BRACAnalysis to detect abnormalities in these genes. The company opted to exert its monopoly right strictly on the genes, by requesting that all diagnostic testing be done at its laboratory in the United States. The Belgian, Dutch, French, and other European genetic centres and cancer institutes have filed oppositions against these patents.1 Recently, the European Patent Office has revoked the first BRCA1 patent granted to Myriad Genetics.2



Patenting the familial breast cancer genes

The familial breast cancer genes, BRCA1 and BRCA2, have been located on chromosome 17 and 13 respectively as a result of a large, international collaborative effort in the early nineties. The BRCA1 gene was eventually cloned by Myriad Genetics in 1994. The BRCA2 gene was sequenced in 1995, first at the Sanger Institute, and almost at the same time by Myriad Genetics.

Several patents on BRCA1 and BRCA2 have been granted by the United States Patent and Trademark Office between 1997 and 2000. In Europe, a total of five patents have been granted by the European Patent Office, between 2001 and 2004. In the meantime, many European laboratories had already set up BRCA1 and BRCA2 testing.



But earlier this year, the European Patent Office also granted a patent on the second breast cancer gene, BRCA2, to Cancer Research UK, the charity trust which has funded breast cancer research at the Sanger Institute in the United Kingdom.3 However, Cancer Research UK has immediately announced that it will allow public laboratories throughout Europe to use the patent for free.3 Even if the latter sounds like good news, it further illustrates the arbitrariness of patenting and licensing in the field of gene based diagnostics.

Patents are meant to reward the inventors but also to promote progress through the generation of useful new products. In this way, patents are thought to be beneficial to the public. Gene patents typically cover the clinical applications of mutation analysis, as well as the use of the gene sequences for the development of treatment. Under current patent law both in Europe and in the United States, genes can be patented “if their isolation from their natural environment involves a technical step.”4 This is obviously controversial. The Nuffield Council on Bioethics has already concluded that the description of an association between a gene and a disease amounts to little more than a discovery.5 Similarly, the American College of Medical Genetics has taken the position that genes and their mutations are naturally occurring substances that should not be patented.6

For the time being, most European laboratories that established mutation analysis for BRCA1 and BRCA2 in the few years since the genes were discovered, continue to perform their own testing. If, nevertheless, a few samples are sent to the Myriad Genetics laboratories, it is because Myriad beats the European laboratories by offering speed for the analysis. However, together with the result comes an invoice of some $2500 (£1400; €2100, if purchased directly from Myriad Genetics, or €3980 when purchased via Bioscientia, the European licensee for the BRACAnalysis). In general the European laboratories use more cost effective tests.7 The difference for the patients is huge, however, because the local tests are free or largely reimbursed and the overseas invoices are not.

There is other evidence that the costs for the genetic tests will increase as a result of patenting. A survey about the effect of the patent on the hereditary haemochromatosis gene has revealed that Bio-Rad Laboratories, the current owner of the patent, requests up front payments of the order of $25 000 per laboratory plus a per test fee of about $20.8 This is a lot for a simple diagnostic test. Many laboratories in the United States have already refrained from offering this test.8 In the end patents will thus slow down biomedical innovation and delay the availability of cheaper tests.

One reason why the market system does not always operate properly in the case of patents on genes is because genes and genetic sequences are different from classical chemical compounds. Genes and genetic sequences have an informational content. One cannot “invent around” the sequence if it is patented, because each gene and each gene sequence is unique in its kind. Hence, through patenting, a “double” monopoly arises.1

At first glance, this problem could practically be circumvented by the free licences, like the one offered to the European public laboratories by Cancer Research UK on BRCA2. However, this will be criticised by patent owners and supporters of the patenting system because it seemingly disregards the efforts and funds that the grantees have invested. In general, patent specialists and patents offices claim that the problem is in licensing, not patenting. I agree that Europe lacks a system that ensures guidance and surveillance of licensing of genetic inventions. Still, I believe that a claim to exclude gene based diagnostics from patenting is legitimate from the standpoint that the patenting system should not interfere with the availability of a genetic test for the patient. The basis for such an exemption has been laid years ago. Article 52(4) of the European Patent Convention of 1973 excludes “diagnostic methods, practised on the human body” from patenting.9 This definition dates back to the days when people did not want surgical methods and other medical practices to be patented. This could be updated to include genetic testing.

This is a way to avoid monopolies on the use of a genetic sequence for diagnostic purposes in humans, without interfering with patent protection of other genetic applications, including the development of therapeutics. The latter requires huge investments, but the first does not: once the relation between a gene and a disease is established, diagnostic tests can be developed at relatively low cost.1

Several initiatives have recently been taken to deal with aspects of patenting and licensing of genes by international organisations like the Organisation for Economic Co-operation and Development (OECD), the Human Genome Organisation (HUGO), and the European Society for Human Genetics (ESHG), and by a few national governments. I wish to call on the medical community and the national and international medical associations also to take part in this important discussion.