BioWorld Today Correspondent

LONDON – The prospects for commercializing any treatments based on human embryonic stem cell research carried out in Europe are looking dim after a final court ruling that any invention involving the removal of a stem cell from an embryo cannot be patented.

The ruling, made on ethical grounds by the European Court of Justice, takes a very wide definition of a human embryo, including not only those generated by in vitro fertilization, but also a human ovum into which the cell nucleus of a mature human cell has been transplanted and an unfertilized human ovum, which has been stimulated to divide by parthogenesis.

The judgment covers patents for industrial or commercial purposes or for the purposes of scientific research. That means it covers any products or applications of the 100 or so established embryonic stem cell lines held in cell banks. Specifically, the European Court of Justice said in its ruling, "An invention is excluded from patentability where the implementation of the process requires either the prior destruction of human embryos or their prior use as base material." That applies whether or not the patent application refers to the use of human embryos.

Europe's top embryonic stem cell researchers, including Oliver Brüstle, whose work on converting human embryonic stem cells to neural cells prompted the legal case, and Ian Wilmut, the scientist who pioneered the development of cell nuclear replacement, reacted strongly against the ruling.

Wilmut, whose work led to the birth of the first cloned mammal – Dolly the sheep – said he regretted the court's ruling. "It will unfortunately make it less likely that companies in Europe will invest in research to develop treatments to use embryonic stem cells for treatment of human diseases."

Wilmut is now leading one of the UK's major research groups in the field as head of the Medical Research Council's Center for Regenerative Medicine in Edinburgh, Scotland, and he contended research carried out in Europe is more likely to be commercialized in other parts of the world, following the ruling.

Brüstle, professor of reconstructive neurobiology at the University of Bonn Medical Center in Germany, agreed, saying that as a result of "this unfortunate decision" the fruits of years of translational research by European scientists will be wiped away. "European researchers may conduct basic research, which is then implemented elsewhere [and] eventually re-imported to Europe," he said.

However, Alexander Denoon, a specialist in life sciences at the London law firm Lawford Davies Denoon, said that while unwelcome, the decision is not catastrophic because lawyers and patent attorneys will find ways around it. "[They] have known about this concern for some time and have been drafting to try and take account of this issue."

But even if routes can be found around the ruling for products in development, there will be a disincentive to invest in clinical development of cell therapies if they cannot get European patent protection.

Peter Coffey, of the Institute of Ophthalmology at University College London, who is collaborating with Pfizer Inc. in the development of retinal pigment epithelium cells derived from embryonic stem cell lines for use in the treatment of wet and dry macular regeneration, said, "I can give a therapy, I can show how it works in a small group of patients, but we need companies to commercialize this research." Coffey is offended that his work to cure blindness has in effect been judged immoral. The Court of Justice's "devastating" decision will stop embryonic stem cell-based therapies from being used to treat disabling and life-threatening diseases in Europe, he said.

As a consequence, research conducted in Europe will be commercialized in the U.S. or Asia, said another leading researcher, Austin Smith, of the Wellcome Trust Centre for Stem Cell Research at Cambridge University. "We are funded to do research for the public good, yet prevented from taking our discoveries to the market place."

The decision will hamper inward investment by industry, noted Tony Peatfield, director of corporate affairs at the UK Medical Research Council (MRC), which has plans to invest £130 million (US$203 million) on stem cell and regenerative medicine research over the next four years. The full impact of the ruling will need to be considered, but Peatfield pledged to "provide as supportive an environment as possible within this new patent area."

The case was started by the environmental group Greenpeace, which successfully appealed against the grant of a patent in 1997 covering Brüstle's process for obtaining neural precursor cells from human blastocysts. The cells are intended to treat Parkinson's and other neurodegenerative diseases. The case was subsequently appealed by Brüstle at Germany's Court of Justice, which asked the European Court to rule on the definition of an embryo, as specified in the 1998 European Directive covering biotechnology inventions. The question was if the exclusion from patentability on ethical grounds laid down in the 1998 Directive covers all stages from fertilization, or if an embryo has to have reached a certain stage of development.

In its ruling, the European Court of Justice takes the widest possible definition, saying any human ovum must be considered a human embryo as soon as it is fertilized. The European Court deals with questions on the interpretation of EU law, it does not rule on disputes themselves.

The case will now be referred back to Germany's Court of Justice for a final judgment. However, the European Court of Justice ruling in this case is valid in the national courts of other EU countries hearing similar cases, meaning it will have wide repercussions.