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The patent system has evolved over many centuries and has proven successful in stimulating innovation that is of benefit to society, or as Abraham Lincoln put it: “The patent system added the fuel of interest to the fire of genius.” Patents on microorganisms, such as baker's yeast, were already granted in the 19th century; however, only at the end of the 20th century, with the rise of genetic engineering, was patent law applied more broadly to living organisms. Today, genetically modified microorganisms, plants and animals are patentable in many jurisdictions, including the US, Japan and Europe. Still, many intuitively reject the concept of “patents on life”. The recent public debate about synthetic biology and “artificial life” (e.g. Craig Venter's minimal genome bacterium) has reignited this discussion. Other areas where patents are in the spotlight are breeding methods for plants and animals as well as human embryonic stem cells. What is patentable in Europe and on what legal basis? How is the law keeping pace with the rapid developments in the field? How are ethical and moral objections taken into account? While addressing these questions, this article aims to summarise some of the recent developments in European patent law in life sciences and biotechnology.

“The patent system added the fuel of interest to the fire of genius.”Abraham Lincoln

The EPC

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

The European Patent Convention (EPC) is the legal basis for the granting of patents in its 38 member states [1]. The EPC is an international treaty created that the European Patent Organisation (EPOrg) and its executive body, the European Patent Office (EPO). Although all European Union (EU) member states are also EPC member states, the EPOrg is politically and financially independent from the EU and covers a broader territory. The EPC contains patentability criteria that apply to all fields of technology, namely novelty, inventive step and industrial application. A European patent application must further satisfy the general requirements of clarity and sufficiency of disclosure. The claims must in particular find support in the description.

For inventions in the medical and biotechnological area, a number of specific provisions exist. Plant and animal varieties and essentially biological processes for the production of plants and animals (Art. 53(b) EPC) and methods for treatment of the human or animal body by therapy or surgery and diagnostic methods practised on the human or animal body (Art. 53(c) EPC) are excluded from patentability [2]. Based on older European patent law traditions, inventions, the commercial exploitation of which would be contrary to “ordre public” or morality are also excluded from patentability (Art. 53(a) EPC). This excludes patenting of inventions that the public in general would regard as so abhorrent that the granting of patent rights would be inconceivable. Letter bombs or anti-personnel mines, but also biological-weapons, would be obvious examples.

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The EU Biotech Directive

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

A specific set of rules on the patentability of biotechnological inventions was adopted by the European Union in 1998 following an almost 10-year-long debate in various political bodies: the EU Directive 98/44/EC [3]. The member states of the EPC decided to incorporate these rules into its regulations. Since EPC members that are also members of the EU had to implement the Directive into their national law, this was considered the best way to achieve a harmonised legal framework for patenting biotechnology in Europe. In the following years a considerable body of case law interpreting and refining the patentability criteria for biotechnological inventions has emerged from the technical boards of appeal and the Enlarged Board of Appeal of the EPO (EBoA) [4].

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DNA and proteins

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

The EU Biotech Directive and the rules in the EPC derived from it clearly set out that biological material (i.e. material containing genetic information and capable of reproducing itself or being reproduced in a biological system) is patentable when isolated from its natural environment or produced by means of a technical process even if it previously occurred in nature (Rule 27(a) EPC). This means that for example genes, DNA, RNA, proteins, viruses or cells can be patented even though they might have existed before in nature. An element isolated from the human body or otherwise produced by means of a technical process may also constitute a patentable invention, even if the structure of that element is identical to that of a natural element. The human body itself, at the various stages of its formation and development, and the simple discovery of one of its elements, including the sequence or partial sequence of a gene are, however, not patentable (Rule 29(1) EPC). This excludes also human germ cells and human embryos from patentability (98/44/EC Recital 16). Also the output of high-throughput genome sequencing, which usually results in mere discoveries, is thus not patentable.

The most important requirement after having established novelty is inventive step, i.e. that the invention is not obvious over the prior art [5]. For a new gene sequence in most cases this can only be proven by assigning a non-obvious function to it. This function can be physiological or artificial such as in a diagnostic application or in an industrial process. Simply deducing a function on the basis of structural homology with a known gene or protein is usually considered obvious and thus not inventive. The provision of variants or fragments of a known sequence (e.g. alternative splice forms) can only be considered inventive if a specific unexpected effect can be linked to the new form, which distinguishes it from the known one. An argument based on “structural non-obviousness”, i.e. that the structure could not be predicted from prior art, will not be accepted in European proceedings. Theoretically also the process by which a gene or protein is isolated or its structure is determined could give rise to an inventive step in particular when major hurdles had to be overcome. This is nowadays only rarely the case given the advancement of technology in this field.

A vague and speculative possible use of a new protein or gene encoding it is not enough to patent it.

As a further requirement, the industrial application of a sequence or partial sequence of a gene must be disclosed in the patent application (Art. 57 and Rule 29(3) EPC). This was substantiated in a number of decisions from the technical boards of appeal of the EPO [4]. In summary, it was found that the application has to be practical and provide some profitable use or commercial benefit, which should be derivable directly from the description coupled with common general knowledge. A vague and speculative indication of possible uses that might or might not be achievable is not sufficient. For a new protein or RNA and the gene encoding it, merely identifying the structure of it, without attributing a clear role, or suggesting any practical use, is not enough. The requirements of a plausible and specific possibility of exploitation can be at the biochemical, cellular or biological level.

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Antibodies, antisense, RNAi

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

Nucleic acids and proteins are patentable. This also includes antibodies, antisense oligonucleotides, short interfering RNA and the like. Where a novel and inventive protein is disclosed, usually antibodies, antisense molecules and siRNA against this protein or its encoding mRNA can be claimed and will equally be considered novel and inventive. In most cases it is not necessary to show by way of examples that such molecules have indeed been made because it is assumed that their generation is a routine task for the skilled person. On the other hand, when a protein is already known, antibodies, antisense or siRNA against this protein, even if novel, will usually be considered as obvious, because their generation involves no inventive skill. In such a case it would have to be shown that a specific molecule or a group of molecules defined by common features shows an unexpected effect, for example higher binding efficiency or increased inhibition.

The attempt of some applicants to generally claim “inhibitors”, “modulators” or “binding entities” to a target such as an extracellular receptor will normally be rejected because these terms are unclear. Moreover, it is not possible to determine if everything falling under the scope of such claims would be novel as known compounds could have the claimed activities without having been recognized. Also the so-called “reach-through” claims with which applicants try to cover every result of a screening method are not permissible because they are unclear, not sufficiently disclosed (the compounds are not yet known) and novelty cannot be established.

Surgical methods

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

Methods of treatment by surgery are excluded from patentability. The definition of what “surgery” actually encompasses is, however, not trivial and has generated a large body of case law from the technical boards of an appeal [4]. In decision G1/07 the EBoA found that the term should not be construed too broadly in view of today's technical reality [6]. Although no definition that would delimit the exact boundaries of a treatment by surgery could be given, it was stated that a method that comprises or encompasses an invasive step representing a substantial physical intervention on the body, which requires professional medical expertise to be carried out and which entails a substantial health risk even when carried out with the required professional care and expertise, is excluded from patentability.

This means that methods practiced on the human or animal body even if they are of invasive nature do not necessarily have to be excluded from patentability. It has to be analysed on a case-by-case basis if the method would involve a considerable health risk for the patient. Minor and routine operations e.g. intramuscular injections or the taking of (small) blood samples are usually not considered “surgical” and thus not excluded.

Dosage and dosage regimen

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

Although methods of treatment by therapy are excluded from patentability under the EPC, the compounds or compositions for such use (i.e. medicaments) can be patented. The EPC in its revised form (EPC 2000 in force since 13 December 2007) contains the possibility to formulate “use limited product claims”, which restrict the protection of a product to either a general medical use (“compound X for use in medicine”) or a specific further medical use (“compound Y for use in a method of treatment for disease Z”). This means that a known compound that has not been used in medicine before can be patented for such use and even if the use for the treatment of one disease is known, a patent can be granted for the treatment of another disease (e.g. acetylsalicylic acid for the treatment of blood clotting as compared to the treatment of headache).

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Recently the question was referred to the EBoA of the EPO whether the formulation of a novel dosage or dosage regimen (how often per day/per week) can render a claim novel when the same compound was already known for the treatment of the same disease. The EBoA in decision G2/08 (OJ EPO 10/2010) concluded that this is indeed the case. This enables pharmaceutical companies to protect the considerable investment that goes into research and clinical trials for improved formulations and dosage regimens. To be patentable the new finding also has to be non-obvious, i.e. an inventive step has to be present. Usually this involves showing an unexpected effect of the new dosage regimen, for example when the prior art held that a medicament was only effective at a certain dosage and now the applicant has unexpectedly found that the medicament is effective at a smaller dosage with fewer side effects.

A known medicament can be patentable when it is unexpectedly found to be effective at a smaller dosage with fewer side effects

In the same decision, the EBoA declared the definitive abolition of the so-called “Swiss-type” claims for second or further medical use applications (“use of compound X for the preparation of a medicament for the treatment of disease Y”). Accordingly, applications with a priority or filing date as of 29 January 2011 may only contain claims in the new format (Notice from the EPO, OJ EPO 10/2010).

Patient groups

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

Personalized medicine and pharmacogenomics are widely believed to represent the future of medicine [7]. With regard to patents the question arises if the selection of a specific patient group can render a previously known medicament novel. This has in principle been acknowledged in a number of decisions from the technical boards of appeal (T19/86, T893/90, T233/96 and T1399/04). Two criteria have been developed that such patient groups have to fulfil, namely (i) that they are clearly distinguishable from the group of patients previously treated by physiological and/or pathological features and (ii) that there is a functional relationship between the features distinguishing the patient group from the patient group treated according to the prior art and the pharmacological effect achieved by the active compound of the manufactured medicament, e.g. greater efficacy or less side effects.

Human embryonic stem cells

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

Rule 28(c) of the EPC, which comes from Directive 98/44/EC, excludes “uses of human embryos for industrial or commercial purposes” from patentability. Since this legislation was drafted before human embryonic stem cells were known, further interpretation of this rule was required to determine if and how it applied to such cells. The first guidance to interpretation was provided by decision G02/06 of the EBoA (OJ EPO 5/2009), which held that “products which could be exclusively obtained by a process which involved the destruction of a human embryo are excluded from patentability” even if the claims did not contain any reference to human embryos [8].

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Further guidance was provided by judgement C-34/10 of the European Union Court of Justice (EUCJ) in October 2011, which found that the exclusion applied for all products for which a human embryo was destroyed or used as a starting material at whatever stage of the process leading to said product [9]. This means that even inventions based on established cell lines of human embryonic stem cells are excluded from patentability because at some stage a human embryo was used for their production [10], [11]. The EPO is not directly bound by this judgement because it is not an organ of the EU and only 27 of its 38 member states are also members of the EU. The EPO is currently analysing, if and how the judgement will be taken into account in its examination practice.

Plants and animals

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

Article 53(b) EPC excludes plant and animal varieties and essentially biological processes for their production from patentability. The reason for the exclusion of varieties is the existence of the international system of plant variety protection, UPOV (Union internationale pour la protection des obtentions végétales), of which all EPC member states are also members. The legislator wanted to avoid double protection in this area and thus excluded varieties from patent protection. “Essentially biological processes” were excluded to keep breeders free from patents in their traditional work of breeding plant varieties. However, science has advanced rapidly in this area and many technologies could not be anticipated when the law was drafted. Examples are genetic engineering and genetically modified organisms.

In decision G1/98 (OJ EPO 3/2000) the EBoA ruled that while varieties were excluded from patentability, broader genera of plants or animals could be patented if the technical teaching of the patent application (for example genetic engineering) was applicable to such a broader class. More recently the EBoA in combined decisions G2/07 and G1/08 found that processes for the production of plants that included the steps of crossing and selection were considered “essentially biological” and thus excluded from patentability even if the crossing and selection steps were preceded or followed by other steps of a technical nature [12]. This ruling also excludes methods of marker assisted breeding from patentability. Questions regarding the patentability of plants or animals resulting from such “essentially biological processes” are likely to be referred to the EBoA in the near future [13].

A further requirement with regard to the patenting of animals finds its basis in Article 53(a), which excludes inventions, the commercial exploitation of which would be contrary to “ordre” public and morality from patentability. In Rule 28(d) this is further specified to exclude processes for modifying the genetic identity of animals which are likely to cause them suffering without a substantial medical benefit to man or animal, and also animals resulting from such processes. In the famous “Oncomouse” decision (T315/03, OJ EPO 1/2006) the competent board of appeal found that the generation of a mouse cancer model indeed fulfilled the required test and was thus patentable.

With the implementation of the EU Biotechnology Directive and a constantly developing case law reflecting technical advancement the EPO is in a good position to react to the needs of technology and society.

Summary and outlook

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

Biotechnology is a fast advancing technology, while patent law in an international framework such as the EPC with its 38 member states is designed to be generally applicable to new developments in every technical field. The EPC contains exclusions with regard to morality, agriculture and medicine, which come into play when deciding on sensitive issues such as the patenting of human embryonic stem cells, plant varieties or animal models. With the implementation of the EU Biotechnology Directive 98/44/EC the legislator created some further technology specific rules. A constantly developing case law can rapidly reflect technical and other changes. The combination of both puts the EPO in a good position to react appropriately to the needs of technology and society. With the possible advent of the European Unitary Patent, which would include 25 of the EPC's member states it can be expected that the judicial systems of the EU and the EPC will grow even closer together [14].

Acknowledgements

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES

I am indebted to my colleagues Siobhán Yeats, Eleni Kossonakou and Ashok Chakravarty for their most valuable comments.

The present article is based on personal considerations by the author and does not necessarily reflect the official position of the EPO on the subject.

REFERENCES

  1. Top of page
  2. The EPC
  3. The EU Biotech Directive
  4. DNA and proteins
  5. Antibodies, antisense, RNAi
  6. Surgical methods
  7. Dosage and dosage regimen
  8. Patient groups
  9. Human embryonic stem cells
  10. Plants and animals
  11. Summary and outlook
  12. Acknowledgements
  13. REFERENCES