Brüstling with indignation, but definitely feeling totipotent

Totipotent eggs don't have it
all their own way ...

Today's the day the Kat has been waiting for since 2009, when he first discovered the battle between Brüstle and Greenpeace concerning the legality of human stem cell patents (click here for Mark Schweizer's piece on this very weblog on the decision of the German Bundesgerichtshof to refer these questions to a court higher, though less IP-savvy, than itself). To refresh the memories of readers who are too weary to press the hyperlink, the Court of Justice was asked  in Case C-34/10 to rule on the following questions:

"1. What is meant by the term 'human embryos' in Article 6(2)(c) of Directive 98/44/EC [on the Legal Protection of Biotechnological Inventions]?

(a) Does it include all stages of the development of human life, beginning with the fertilisation of the ovum, or must further requirements, such as the attainment of a certain stage of development, be satisfied?

(b) Are the following organisms also included:

1. unfertilised human ova into which a cell nucleus from a mature human cell has been transplanted;

2. unfertilised human ova whose division and further development have been stimulated by parthenogenesis?

(c) Are stem cells obtained from human embryos at the blastocyst stage also included?

2. What is meant by the expression 'uses of human embryos for industrial or commercial purposes'? Does it include any commercial exploitation within the meaning of Article 6(1) of the Directive, especially use for the purposes of scientific research?

3. Is technical teaching to be considered unpatentable pursuant to Article 6(2)(c) of the Directive even if the use of human embryos does not form part of the technical teaching claimed with the patent, but is a necessary precondition for the application of that teaching,

(a) because the patent concerns a product whose production necessitates the prior destruction of human embryos,

(b) or because the patent concerns a process for which such a product is needed as base material?".

Today Curia has published the Opinion of Advocate General Bot in ten official languages of the European Union, but regrettably not in English. According to Google Translate (French to English), the Opinion advises as follows:

"Article 6, paragraph 2 c) of Directive 98/44 ... should be interpreted as follows:

- The concept applies to human embryo at the stage of conception to initial totipotent cells and the whole process of development and body composition that results. This is so, including the blastocyst.

- The unfertilized eggs, which was established the nucleus of a mature human cell or were induced to divide and develop by parthenogenesis, also fall under the concept of human embryo in that the use of these techniques result in obtaining totipotent cells.

- Individually, pluripotent embryonic stem cells because they have not, by themselves, the ability to develop into a human being, do not fall within that concept.

- An invention must be excluded from patentability if the implementation of the technical process submitted to the patent requires, first, whether the destruction of human embryos or their use as starting material, even if the description of this process does no reference to the use of human embryos.

- The exception to the prohibition of patenting of uses of human embryos for industrial or commercial concerns only inventions for therapeutic or diagnostic target that apply to the human embryo and are useful".

The Latvia-to-English translation, however is differently nuanced:

""...- The term "human embryo" applies to the totipotent pirmšūnām conceived in the moment, as well as the entire human body and the development process, that it follows. This is especially true of the blastocyst.

- Unfertilized eggs are implanted into mature human cell nucleus or which are shared or develops partenoģenēzes way, also includes the concept of human embryos, the extent of these techniques result in the accrual of totipotent cells.

- Separately, pluripotent embryonic stem cells, since they alone can not develop as individuals, this shall not include.

- The invention is not patentable patentable if the technical implementation of the procedure initially is required for either the destruction of human embryos or their use of raw materials, even if this description of the process contains no reference to human embryos.

- Embryos for industrial or commercial use exception to the prohibition of patenting inventions for therapeutic or diagnostic only for purposes applicable to the human embryo and are useful ".

You have been warned.

The Curia has fortunately issued a press release in English -- but not Latvian -- in which it states as follows (this is a non-official explanation of a non-binding Opinion):

According to Advocate General M. Yves Bot, totipotent cells carrying within them the capacity to evolve into a complete human being must be legally classified as human embryos and must therefore be excluded from patentability 

Nor can a procedure using other embryonic stem cells, known as pluripotent cells, be patented where it first requires the destruction or modification of the embryo  

Mr Oliver  Brüstle holds a patent, filed in December 1997, which concerns isolated and purified neural precursor cells,  produced from human  embryonic stem cells used for the treatment of neural defects.  According to information provided by Mr Brüstle, the first clinical applications have already been developed, in particular for patients suffering from Parkinson’s disease. On the application of Greenpeace eV, the Bundespatentgericht ... declared Mr Brüstle's patent invalid, in so far as it related to procedures allowing precursor cells to be obtained from human embryonic stem cells. The Bundesgerichtshof ... decided to stay [appeal] proceedings and refer questions to the Court of  Justice on the interpretation, in particular, of the term  "human embryo", which is left undefined by Council Directive 98/44 ...

The questions concern, essentially, whether the exclusion of the human embryo from patentability concerns all stages of life from the fertilisation of the ovum or whether other conditions must be satisfied, such as the attainment of a certain stage of development.  

As a preliminary, the Advocate General ... makes the point that the Court is being called upon for the first time to consider the concept of ‘use of embryos for industrial or commercial purposes’ contained in Directive 98/44.  Having stated at the outset his awareness of the extreme sensitivity of that question and the importance of the philosophical, moral, human, economic and financial issues at stake, the Advocate General begins his legal analysis by stating that, since the directive pursues the  objective of establishing effective  and harmonised legal protection of biotechnological  inventions, the embryo needs to be given an autonomous definition in EU law.  That analysis is supported by the first interpretations by the Court in its case-law concerning that directive.  

After pointing out the major divergences existing between the legislation of the Member States and the impossibility, in the current state of scientific knowledge, of using a criterion of that nature capable of being recognised by all the Member States, the Advocate General fixes upon the wording of the directive, which, in Article 5(1), protects ‘the human body, at the various stages of its formation and development'. 

He then observes that totipotent cells, appearing after fusion of the gametes and existing in that form only for the first days of development, have the essential characteristic of carrying within each of them the capacity to develop into a complete human being.  Thus those cells, since they represent the first stage of the human body which they will  become must be legally classified as embryos, the patentability of which must be excluded.  This definition therefore covers unfertilised ova into which a cell nucleus from a  mature cell has been transplanted  and unfertilised ova whose division has been stimulated by parthenogenesis in so far as totipotent cells would be obtained in those ways.  

Similarly, the blastocyst stage of development, reached around five days after fertilisation, must also be classified as an embryo, since, according to the Advocate General, the principle of human dignity, to which the directive refers, is a principle which must be applied not only to an existing human person, to a child who has been born, but also to the human body from the first stage in its development, i.e. from fertilisation. By contrast, pluripotent embryonic stem cells,  taken in isolation, do not  fall within the definition of an embryo, since, individually, they are no longer capable of developing into a complete human being.  They can 'only' differentiate themselves into various organs forming parts of the human body.  It is those cells which are  concerned by the invention concerned by Mr Brüstle's patent, their removal from the embryo taking place at the blastocyst stage.  

However, it is not possible to ignore the origin  of these embryonic stem cells. The fact that they come from some stage in the development of the human body is not in itself a problem, provided only that their removal does not result in the destruction of that human body at the stage of its development at which the removal is carried out.  In the opinion of the Advocate General, it must therefore be agreed that inventions relating to pluripotent stem cells can be patentable only if they are not obtained to the detriment of an embryo, be that it's destruction or its modification. To make an industrial  application of an invention using embryonic stem cells would amount to using human embryos as a simple base material, which would be contrary to ethics and public policy.  

In conclusion, the Advocate General considers that an invention cannot be patentable where the application of the technical process for which the patent is filed necessitates the prior destruction of human embryos or their use as base material, even if the description of that process does  not contain any reference to the use of human embryos. The Advocate General observes, however, that the patentability of uses of human embryos for industrial or commercial purposes is not prohibited under the directive where it  concerns only inventions for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it – for example to correct a malformation and improve its chances of survival.                                                 

Note: in March 2010, the UK's Intellectual Property Office gave interested parties a ludicrously short FIVE DAYS to make their comments, ahead of an Opinion which has been published exactly one year to the day since their comments were sought. The Kat insists that we can all do better, giving more time to interested parties to think about what they are going to say as well as getting it typed up, generally beautified and checked for umlauts.