First published in European BioPharmaceutical Review, June 2010

A feature of patent litigation in the English Courts is that it often produces a wave of cases in a particular technological field before another field takes over.  So it was with genetic engineering, surgical stents and mobile telecoms.  What field of technology will feature in the next wave of patent litigation?  Many commentators have their eyes on stem cells where the race is on to bring new clinical applications to the marketplace and the field is awash with patents.

As with all of the fields of technology mentioned above, patent disputes only tend to arise when they are commercially rational – i.e., when money is to be made by third parties trying to grab a piece of the lucrative market.  We are not yet at this stage with stem cell technologies but we are not far away either.  For example, the website of ReNeuron (a company based in Guildford, UK) indicates it will soon be recruiting for a phase 1 clinical trial of its ReN001 stem cell therapy for disabled stroke patients.  If ReNeuron’s therapy shows promise in the clinic, we can expect a flurry of activity in the marketplace.

So what are the key issues which may arise in future litigation concerning patents for stem cells in research and therapies which are necessarily filed at an early stage of research and development?

Morality

On 25 November 2008[1], the Enlarged Board of Appeal of the European Patent Office (the “EBA”) ruled on the issue of patentability of stem cell cultures.  The case involved a patent application filed by Wisconsin Alumni Research Foundation (“WARF”) in 1995 which described a method for obtaining embryonic stem cell cultures from primates, including humans.  The claims covered human embryonic stem cell (“hESC”) cultures and it was accepted that at the filing date of the patent application the only disclosed starting point for the creation of these hESC cultures was the use (involving their destruction) of human embryos.

Under European patent law, patent protection is denied to inventions, the commercial exploitation of which would be contrary to “ordre public” or morality.  A fair test is whether the public in general would regard the invention as to be so abhorrent (rather than merely controversial) that the grant of patent rights would be inconceivable.  The relevant law provides a specific example: “the use of human embryos for industrial or commercial purposes”.  However, there is nothing which directly addresses the patentability of hESCs.

In its decision, the EBA held that an invention which necessarily involves the use and destruction of human embryos cannot secure patent protection.  Such prohibition applies to the invention in the context of its commercial exploitation rather than being limited to what an applicant has chosen to explicitly write into the patent’s claims.

Significantly, the EBA clearly stated that its decision was “not concerned with the patentability in general of inventions relating to human stem cells or human stem cell cultures.”

In light of this decision, the UK Intellectual Property Office reconsidered its patent examination practice in the area of stem cells which have been isolated from human embryos and processes involving these cells. 

The practice note issued on 3 February 2009 indicates the following:

(i) Processes for obtaining stem cells from human embryos – not patentable;

(ii) Human totipotent cells having the potential to develop into an entire human body – not patentable;

(iii) Human embryonic pluripotent stem cells not having the potential to develop into an entire human body, and which can be grown in culture and the cell lines stored in cell banks – patentable provided that they satisfy the normal requirements for patentability and at the filing or priority date, the invention could be obtained by means other than the destruction of human embryos.

Additionally, the German Federal Court of Justice has recently referred questions to the Court of Justice of the EU including one on the interpretation of the term “human embryos” and whether it includes all stages of development of human life beginning with the fertilisation of the egg.  It remains to be seen whether the CJEU will take a similarly restricted approach as the EBA.  In any event, the ruling could be determinative of the validity of many applications claiming the use of human stem cells.

Industrial Application

It is a requirement of patentability under European law that a claimed invention is susceptible of industrial application.  For example, a new chemical cannot be patented unless it has some use, e.g. as a pharmaceutical or an intermediate, even though the utility may not form part of the patent claim.  Similarly in biotechnology, attempts to patent gene or partial gene sequences of unknown or speculative utility such as ESTs or SNPs will fall foul of this principle. 

The issue of industrial application often arises because of the inherent tension which exists between being the first in the race to file patent applications against ensuring that those patent applications contain enough explanatory information to pass muster.  File too late and you may be beaten to the punch by your competitors.  File too early and you may not be in a position to describe a utility for your invention. 

The UK case of Eli Lilly and Co v Human Genome Sciences Inc[2] (“HGS”) did not relate to stem cell technology but rather to recombinant DNA and proteins involved in mediating the inflammatory response.  Nevertheless, the principles which arose in that case are of direct relevance to the UK stem cell industry. 

The HGS patent application disclosed the nucleotide and amino acid sequence of a novel member of the TNF ligand superfamily (named Neutrokine-α).  By analysing the nucleotide sequence of a cDNA clone using bioinformatics, HGS identified the sequence as corresponding to a new TNF ligand.

The English Judge identified several important principles that can be used to assess the industrial applicability of inventions: 

a)      ‘Industry’ must be construed broadly. It includes all manufacturing, extracting and processing activities of enterprises that are carried out continuously, independently and for commercial gain.  It need not necessarily be conducted for profit and a product which is shown to be useful to cure a rare or orphan disease may be considered capable of industrial application even if it is not intended for use in any trade at all.

b)       Industrial applicability must be derivable by the skilled person from the patent specification read with the benefit of the common general knowledge.

c)      The specification must disclose a practical way of exploiting the invention in at least one field of industrial activity. Is there a sound and concrete basis for recognising that the contribution could lead to practical application in industry?  There remains a need to disclose in definite technical terms the purpose of the invention and how it can be used to solve a given technical problem.

d)       The requirement will not be satisfied if what is described is merely an interesting research result that might yield a yet to be identified industrial application.  A speculative indication of possible objectives that might or might not be achievable by carrying out research is not sufficient.  Similarly, it should not be left to the skilled reader to find out how to exploit the invention by carrying out a research programme.

e)       the purpose of granting a patent is not to reserve an unexplored field of research for the applicant nor to give the patentee unjustified control over others who are actively investigating in that area and who might eventually find ways actually to exploit it.

f)        If a substance is disclosed and its function is essential for human health then the identification of the substance having that function will immediately suggest a practical application. But if the function of that substance is not known or is incompletely understood, and no disease has been identified which is attributable to an excess or a deficiency of it, and no other practical use is suggested for it, then the requirement of industrial applicability is not satisfied. This will be so even though the disclosure may be a scientific achievement of considerable merit.

g)       Using the claimed invention to find out more about its own activities is not in itself an industrial application.

The above principles also highlight the overlap between the legal requirement of industrial application and that of inventive step[3] and sufficiency of description[4].  There needs to be at least a prospect of a real as opposed to a purely theoretical possibility of exploitation and this should be derivable from the patent description if it is not already obvious from the nature of the invention or from the background art.  The requirements all reflect the basic principle of the patent system that exclusive rights can only be granted in exchange for a full disclosure of the invention. 

The HGS specification contained mere speculation about how Neutrokine-α might be useful, it did not teach the skilled person how to solve any technical problem and its teaching as to the range of applications of the Neutrokine-α, although plausible, was “miles away from being able to say that any particular use was plausible in the sense of being taken, by the reader, to be reasonably so.  In reality one was faced with a research program to see which, if any, of the possible uses of the Neutrokine-α or its antagonists was real.”

It was also noted that the application was filed at a time when the field was very active and rapid advances were being made in terms of the public availability of gene sequences and how they might be searched.  HGS had filed its application very promptly, perhaps in anticipation of the discovery of Neutrokine-α by others in the field.  In essence, HGS had “secured broad protection over an unexplored technical field without providing an adequate compensating benefit to the public.”   It was not relevant that evidence published subsequently confirmed some of the speculation stated within it (although this was taken into account by the EPO).

This case illustrates the fundamental drawback of filing broad and speculative applications at an early stage in the development of a new invention when it may not be possible to provide the full disclosure required.  The case provides a cautionary tale for those looking to file patents in the rapidly expanding field of stem cell technology where it may take time to establish enough evidence to confirm any plausible advantages and utility. 

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[1] WARF/Stem cells (G2/06)



[2] [2008] EWHC 1903 (Pat); upheld unanimously by the Court of Appeal [2010] EWCA Civ 33 9 although conflicting with equivalent EPO decision T 0018/09.



[3] An aspect of the test for inventive step is that the disclosure in the patent should bring some contribution to the stock of human knowledge.

[4] The test for sufficiency of description is whether the specification discloses the invention clearly enough and completely enough for it to be performed by a person skilled in the art or in other words that the invention could be put to practical use without undue effort by the skilled person.