Patent Pain for Stem Cell Research

Confused how Greenpeace managed to call out Europe’s highest court to break-up the stem-cell party? 

These beautiful dancing fronds are a bundle of human neurons. These cells have not been taken from a brain; instead they have been grown from human embryonic stem-cells. With the capability to turn into any type of cell, human embryonic stem-cells (hESC) have the potential to cure the incurable, from the degenerative diseases of old age, to broken spinal chords. But research into hESC has provoked ethical debate, with religious groups, and organisations such as Greenpeace, being longstanding opponents of their use. Image: Nissim Benvenisty

Way back in 1997, the German Patent Office received an application for a patent from a Dr. Oliver Brüstle. The application was for neural precursor cells that could be used in the treatment of neural defects, and a method for making these cells from pluripotent stem-cells. Dr (now Professor) Brüstle was granted his patent, and he duly put his invention to work developing a new treatment for Parkinson’s Disease.  But now, 14 years after he originally filed his application, the subject matter of Professor Brüstle’s patent is being scrutinized by Europe’s highest court, with implications for the whole stem-cell research field in Europe.

As reported last week in the Guardian, the European Court of Justice (ECJ) will soon rule on whether inventions that use human embryonic stem cells (hESC) in any capacity can be patented under European Law. The Advocate General (a sort of Yoda-of-the-court figure, who provides a legal assessment of the problem before the court makes its judgement) has already given his opinion, and to the dismay of the stem-cell research community, has come out against allowing inventions such as Prof. Brüstle’s, to be patented. But why has this issue arisen now? And if the court does follow it’s Advocate General, will it really lead to the devastation of stem-cell therapies, as supporters of the technology claim?

Following the grant of Brüstle’s original patent, Greenpeace (as it frequently does when it unearths a patent that is not to it’s tastes) took proceedings to the German patents court, alleging that under both German and European Law the patent was invalid. The significant piece of European legislation can be found in the 1998 Biotechnology Directive: 

Article 6

(1)Inventions shall be considered unpatentable where their commercial exploitation would be contrary to ordre public or morality; …

(2) On the basis of paragraph 1, the following, in particular, shall be considered unpatentable:

 …

(c) uses of human embryos for industrial or commercial purposes

Greenpeace argued that because Brüstle relied on pluripotent stem-cells (a type of hESC) to make his neural precursor cells, the invention involved the commercial use of embryos, and was therefore unpatentable according to the Biotechnology Directive. Brüstle obviously disagreed, and the case worked its way up to a higher court, the Bundesgerichtshof. On examining the facts, the Bundesgerichtshof felt a legal brick wall had been reached, and so referred three questions pursuant to hESC and European Law to the ECJ for clarification.

The most pertinent of these questions, currently under deliberation at the ECJ, is the third one. If an invention, which doesn’t actually involve the destruction of embryos per se, but none-the-less specifies ingredients (e.g. pluripotent stem-cells) that can only be obtained through the destruction of embryos, does the invention fall within the scope of Art 6(2)(c) of the Biotechnology Directive? The Advocate General, Judge Yves Bot, was of the opinion that such inventions do use “human embryos for industrial or commercial purposes”, and thus, being contrary to ordre public and morality, cannot be patented.

Despite the dramatic language, a declaration of being “contrary to morality” does not mean such technology is rendered illegal.  A patent does not give you permission to use a particular invention; instead it gives you the right to exclude others from using it. So, if this judgement introduces no legal barrier to using stem-cell technology (in fact, it does quite the opposite, as patents are exclusionary in nature), what is all the fuss about?

Predictably, it is about money. The thirteen stem-cell academics, who wrote to Nature to protest at the Advocate General’s opinion, put the problem as such.  Without the promise of patent protection for stem-cell inventions, who will invest in the development of stem-cell therapies? Universities do not possess the resources to take treatments from the lab to the market, and so rely on assigning or licensing their inventions to big pharmaceutical companies. In the absence of legally guaranteed monopolies, what motivation will these companies have for sponsoring university research or funding expensive clinical trials to allow European stem-cell therapies to reach the marketplace? Instead Pharma companies will take their investments and research grants overseas – the US, for example, following the departure of George W., is as a much more stem-cell research friendly place. In contrast to what the Guardian reports, this is not so much a problem of stem-cell treatments being threatened, but a problem of stem-cell research moving elsewhere.

In their letter, the academics argue that an in vitro fertilised egg is not an embryo, a position which was neatly contradicted by Judge Yves Bot, at least from a legal perspective. But the academics also make a rather more compelling point; in actual fact, sourcing pluripotent hESC no longer requires the routine destruction of embryos. Cell lines (cells that are propagated in a Petri dish ad infinitum) are well established, and as a result, pluripotent stem-cells are available through international cell banks. They can be ordered online. This facet of the stem-cell conundrum does not appear to have been touched upon by the Advocate General. In fact, in paragraph 114 of his judgement (case C-34/10), Bot states the opposite, reasoning that for every additional number of cases of disease treated with stem-cell therapies, a proportional number of embryos would have to be created and destroyed. This, it appears, is simply not the case.

It is unusual for the ECJ not to follow the advice of its Advocate General, but not impossible. It will be interesting to see whether the outrage of the scientific community, and the concerns that have been raised regarding European research interests, have any impact. It will be particularly interesting to see whether the matter of established cell-lines, which seems to have been overlooked in the Advocate General’s statement, will be addressed at all. Can the ECJ come to a judgement that is more lenient on stem-cell inventions than that advised by Judge Yves Bot? 

Watch this vacuole.

(A postscript. Greenpeace has been fighting Mr Brüstle’s patent for many years now, and this case will now return to German courts. Lawyers are expensive. If you love the planet and want to donate to an organisation that fights Earth’s corner, please, please reconsider before donating to Greenpeace. There are many other groups that do a marvellous job of caring for the planet, campaigning against climate change and preserving endangered species, without wasting your hard-earned cash on lengthy lawsuits.)