Bioethics and Patent Law: The Case of Myriad

This article is the third in an occasional series, which highlights issues that have arisen in some significant patent law cases concerning bioethics. Here we look at the Myriad case which, as well as raising questions about patenting genetic inventions, demonstrates how certain bioethical issues go beyond questions of patentability, to the way in which a patent, once granted, is exercised in the marketplace.

Myriad’s gene patents for breast cancer screening

BRCA-1 and BRCA-2 are two genes linked to susceptibility for breast and ovarian cancer (hence their acronyms). The risk of falling ill increases if these genes show certain mutations. Identifying the mutations is therefore important for diagnosis and for monitoring higher-risk women. Myriad Genetics Inc., in collaboration with the University of Utah, were the first to sequence the BRCA-1 gene, and applied for patent protection in 1994. Together with the University of Utah Research Foundation and the United States of America, Myriad holds U.S. patents 5747282 and 5710001 on the isolated DNA coding for a BRCA-1 polypeptide and on a screening method. In 1997, together with the Centre de Recherche du Chul in Canada and the Cancer Institute of Japan, they received patent protection on an isolated DNA sequence, asserting rights over a number of mutations in the gene (U.S. Patent 5693473). Further patent applications were filed on the second gene, BRCA-2, in the U.S. and in other countries (US Patents 5837492 and 6033857).

Technical challenge and ethical objections

These patents were controversial. Oppositions were filed against the European patent (EP 705902) on the isolated BRCA-1 gene by, among others, Switzerland’s Social Democratic Party; Greenpeace Germany; the French Institut Curie; Assistance Publique-Hôpitaux de Paris; the Belgian Society of Human Genetics; the Netherlands, represented by the Ministry of Health; and the Austrian Federal Ministry of Social Security. The opponents challenged the patent on the basis of the European Patent Convention’s patentability criteria, arguing that the claimed invention lacked novelty, inventive step and industrial application, and that the patent failed to disclose the invention sufficiently for a person skilled in the art to carry it out.

Underlying the technical grounds for opposition were deeper ethical and policy concerns. In addition to the continuing questions about patenting inventions derived from the human genome, the Myriad case raised concerns about the potentially limiting effects of the patents on further research, on the development of new tests and diagnostic methods, and on access to testing. While the considerable medical benefits of the cancer screening technology were not in dispute, there were differing views about how the patent system should recognize such technology, if at all, and about how patents on such technology, once granted, should be exercised.

The opposition proceedings led to the revocation in 2004 of European Patent 699754, which covered a method for diagnosis. The proceedings found that errors in the original patent application had not been corrected until the gene sequences were in the public domain. This meant that, according to patentability criteria, the invention had not been fully disclosed in the application as originally filed; and was not novel by the time the invention was fully described in the amended application.

The other two patents on the BRCA-1 gene were amended to exclude diagnostic methods. (The decisions are currently under appeal.) A patent on the second gene, BRCA-2, was maintained in amended form.

Ethics in patenting

This case demonstrates how technical grounds of patentability also act as important safeguards of the public interest, aimed at ensuring that patents are only granted on genuine advances in knowledge, and are not used to exclude access to material in the public domain.

But the case also highlights the ongoing policy debate on the patenting of human genes in general and, more specifically, on the patenting of genes used in diagnostics because of fears that such patents may constrain new diagnostic methods. The European Parliament articulated this concern in a 2001 resolution against the Myriad patents, ¹ calling on the European Patent Office to ensure the "principle of non-patentability of humans, their genes or cells in their natural environment;" and asserting that the human genome should be freely available for research purposes.

The balance remains a difficult one. For as long as society relies largely on private entities to invest in developing new genetic research-based treatments and diagnostics, biopharmaceutical companies like Myriad will continue to require some degree of exclusivity over these technologies as a means of obtaining a return on their investment. But there is concern that some gene patents are, for example, drafted too broadly, with the effect of over-compensating the patentee by covering all future applications.

Ethics in licensing

Much of the debate surrounding the Myriad case, however, concerned not the validity of the patents as such – similar patents held by other entities have not attracted the same criticism – but rather the ethics of how the patent rights were exercised commercially.

Myriad's critics charged that its licensing policy, and the high prices demanded for testing under the patented technologies, had the effect of preventing other laboratories in countries where the patent was in force from carrying out diagnostic testing. The case raised questions as to whether, and if so how, regulators should step in to deal with concerns about licensing practices. This led to a range of government interventions, and reportedly influenced the evolution of French patent law. Certain soft-norm initiatives have tried to define good licensing practices. The Organisation for Economic Co-Operation (OECD) Guidelines for the licensing of genetic inventions ² suggest a relatively open approach to licensing, particularly for genetic tests.

A complex interplay

Myriad patents complied with the technical grounds for patentability showed how these technical criteria can help to safeguard the public interest, particularly in such sensitive areas of technology. Finally, the case sparked important questions as to the ethical dimension of licensing practices of genetic inventions.