A Critical Analysis of the (Non)-Patentability of Diagnostic Methods and Consequences For BRCA1 Gene Type Patents in Europe

DR SVEN J.R. BOSTYN*

Assistant Professor of Commercial and Intellectual Property Law, Maastricht University, Law Faculty, Private Law Department, The Netherlands

Bio-medical technology and biotechnology have become increasingly important in our society. Advances in the unravelling of the human genome, developing knowledge about hereditary diseases, and the never-ending search for cures for these diseases have made biotechnology part of our daily life. Nevertheless, it is still a subject which is capable of causing considerable turmoil, emotionally or rationally. This has everything to do with the fact that this research is dealing with our genetic blue-print, and, to that extent, it personally affects us all. Because of its very specific nature, it is also a very media-sensitive subject. Consequently, new developments are quickly reported in the media. But unfortunately, as often happens with media-sensitive but difficult issues, there is no room for nuance. Easily understandable catchwords and appealing comparisons must do the job. If that recipe is applied to patenting biotechnological inventions, the cocktail becomes very risky. Two difficult fields, namely biotechnology and patent law, have to be explained to the general public, and that appears to be difficult to achieve. Add to that the fact that some pressure groups have specialised in these subjects, and one had better refrain from drinking the cocktail. There are plenty of examples to mention: the Harvard cancer-mouse, Dolly the cloned sheep, herbicide- or pesticide-resistent plants, genetically manipulated soya, the patenting of a number of DNA sequences, and in the more recent past cloning techniques, stem cells, ¹ and so on. The subject of this article is another example of a patent with a high publicity level, that is, the BRCA1 gene patents. ² These patents have stimulated thinking both in the academic and the medical communities for a number of reasons, and in this respect it is probably somewhat different from the other examples already mentioned.

Basically, the objections against biotechnological patents fall into two major categories. On the one hand, there is the objection that genetic information should never be patented, as it is already present in nature, and is thus not an invention. ³ In this same line of thought, there is also the objection that human genetic information, or even human body parts for that matter, should not be subject to an (intellectual) property right. This movement for some time ran into difficulty, especially when in Europe an EU Directive was passed which allowed the patentability of human genetic information⁴ as long as it is not patented in its natural state, that is, in the human body. An action to declare Directive 98/44/EC null and void was finally dismissed by the European Court of Justice. ⁵ But recent developments in the field of human cloning, stem cell research and the patents discussed in this article have given this movement a new lease of life. And it would not be surprising if their popularity increased dramatically in the near future, since there are respectable scientists among their members. From the point of view of patent law, their viewpoint is untenable, since they refuse to accept some of the fundamental features of the patent system. And above all, it may be observed that, in the author’s view, their negative attitude against patenting DNA-related inventions is, at least for some of these people, less inspired by fundamentalist ideas about property rights and human bodies, than by a more justified concern about the effects these patents might have on healthcare and scientific research. The latter idea actually belongs to the second category of people who oppose patents on DNA-related inventions. According to this line of thought, patents on this type of invention should not be granted, for a number of reasons. First of all, the patent, being a monopoly with a monopoly price, will have an effect on the costs of healthcare. Second, due to the patent right, scientific research could be hampered. In the author’s view, this category of opponents is not fundamentally opposed to patents on biotechnological inventions, but is very much concerned about scientific research and welfare effects.

The BRCA1 gene patents are an important challenge in this respect, because of their broad scope. This article will analyse the BRCA1 gene patents in the light of this growing concern about scientific research and affordability of the healthcare system. Presenting the details of these patents is the start of the analysis in this article. It will continue with comment on a number of issues presented by these patents. A prime issue is the question of patentability of this type of diagnostic method. This will also embrace analysis of the patentability of DNA sequences in the first place. A second issue relates to the scope of protection claimed by the patents. These patents claim an extensive variety of diagnostic and predictive test methods related to breast and ovarian cancer. Questions could be asked in respect of the sufficiency of the disclosure in relation to the embodiments or methods claimed. A third problem to address is the price level of the diagnostic methods brought onto the market by the patent-holder. A fourth issue concerns access to the patented information for research and commercial purposes. This problem also includes questions concerning licensing policies of patent-holders of this type of patents. Even though this article focuses on a single type of patents, I believe that this patent is illustrative for a generation of patents that will be granted in the future, and this wider perspective makes the analysis more valuable for future policy decisions, be it at the level of the patent offices or the legislator.

The BRCA1 Gene Patents in more Detail

Before going into the patent law issues surrounding the BRCA1 (breast cancer 1) gene patents, it may be interesting to consider first some background information about the patent, which sets it better in the perspective of the patent system. According to the abstracts of both patents,

(Non-) Patentability of Diagnostic and Medical Treatment Methods

The BRCA1 gene patents thus claim a variety of diagnostic and predictive test methods. To the extent that the predictive methods are also capable of having a diagnostic effect, they can also be considered to be diagnostic methods. In Europe, medical treatment methods are considered non-patentable. This is true not only for the pure treatment method for a disease, but also for diagnostic methods applied on the human body. ¹⁵ The question to be answered is thus whether the claimed methods could fall under the exclusion of Article 52(4) EPC.

The official rationale for this exclusion is laid down in the text of the provision, namely that inventions in this field are deemed not to be industrially applicable. But a glance at present-day practice in the medical sector and the fact that in the revised EPC the provision has been moved to another section of the Convention, ¹⁶ shows that the real rationale must be a different one. The reasoning behind the exclusion boils down to the argument that these treatment methods were excluded because it was considered ‘unethical’ in a sense, from the point of view of society, to allow patent protection for this type of inventions, ¹⁷ for the simple reason that it could create a class system of healthcare. If medical treatment methods were patented, they could become more expensive, which excludes part of the population from enjoying the best available treatment method for their medical condition. Medical treatment methods should be freely available to all those who wish (or need) to use them. By granting a patent, a physician or surgeon can only apply the method after having obtained a licence from the patent-holder. If he does not apply for a licence, he commits a patent infringement. Not everyone shares this position, however. The proponents of patent protection for medical treatment methods argue that there is no reason to exclude medical treatment methods from patentability. The availability of the method is not necessarily a problem, because most countries contain a compulsory licensing scheme in their patent Acts, ¹⁸ which allows a user of a patented invention to use it without committing a patent infringement if the patent-holder refuses to grant a licence, under specific conditions. ¹⁹

In the United States, no such prohibition on patentability of medical treatment methods exists. ²⁰ However, the rationale mentioned above has also been used in the United States to amend the US Patent Act, an argument which became stronger after a case where an ophthalmologist who applied a patented medical treatment was sued for patent infringement. ²¹ In consequence, a Bill was introduced which contained provisions very similar to Article 52(4) EPC. ²² The Bill was never passed, however. Another solution was that a patent infringement committed by a medical practitioner in a hospital to which he is professionally affiliated in respect of a medical activity, would not be subject to payment of damages to the patent-holder. ²³ There is no express prohibition on market players to patent medical treatment methods, but the patent will be of little value, because an infringement under the conditions laid down in the Patent Act will not have any financial consequence. This will presumably discourage possible inventors from filing a patent application relating to medical treatment methods.

In order to be able to answer the question as to whether the diagnostic and screening methods of the BRCA1 gene patents are excluded from patentability, a diagnostic method must be defined in more detail. Until recently, the prevailing view in Europe was based on a strict interpretation of the concept ‘diagnostic method’. Case T385/86²⁴ reflects this opinion. According to the Technical Board of Appeal in this case, only those diagnostic methods are to be excluded from patentability ‘whose results immediately make it possible to decide on a particular course of medical treatment. Methods providing only interim results are thus not diagnostic methods in the meaning of Article 52(4), first sentence EPC, even if they can be utilised in making a diagnosis.’ ²⁵ The Board reasoned that:

However, a recent case could shed a different light on this issue. In Case T964/99, ²⁷ the Technical Board of Appeal clarified its policy vis-à-vis the (non)patentability of diagnostic methods:

The expression ‘diagnostic methods practised on the human or animal body’ in Article 52(4) EPC or the equivalent expressions ‘Diagnostizierverfahren, die am menschlichen oder tierischen Körper vorgenommen werden’ and ‘méthodes de diagnostic appliquées au corps humain ou animal’ in the other two official languages should not be considered to relate to methods containing all the steps involved in reaching a medical diagnosis. According to the principle, well established in the case law of the Boards of Appeal, that the EPC has to be interpreted in good faith in accordance with the ordinary meaning to be given to the terms of the treaty in their context (Article 31(1) Vienna Convention on the Law of Treaties), Article 52(4) EPC is meant to exclude from patent protection all methods practised on the human or animal body which relate to diagnosis or which are of value for the purposes of diagnosis.²⁸

According to the Technical Board of Appeal in this case, the interpretation given in Case T385/86 can be said to be too restrictive, thus leaving most methods to be patentable. The Board is of the opinion that ‘the expression “diagnostic methods practised on the human or animal body” in Article 52(4) EPC … should not be considered to relate to methods containing all the steps involved in reaching a medical diagnosis.’ ²⁹ The straightforward meaning of the word ‘diagnosis’ would be ‘methods pertaining to, or of value for the purposes of, diagnosis’. Within this meaning, any medical activity concerning the gathering of information in the course of establishing a diagnosis qualifies as a diagnostic method. ³⁰ The Board concludes then that ‘Article 52(4) EPC is meant to exclude from patent protection all methods practised on the human or animal body which relate to diagnosis or which are of value for the purposes of diagnosis’.³¹

It must be clear, however, that even under the new policy, the methods envisaged are methods which are practised on the human body. This means that methods which are applied outside the human body (ex vivo), on a blood or other sample, do not at first glance fall under this definition. Consequently, the exclusion of patentability of diagnostic methods does not touch the tests of the patents in question. The methods of the BRCA1 gene patents are definitely valuable for purposes of diagnosis, and from that point of view, they could be covered by the above-mentioned decision, but the fact that they are performed outside the human body (ex vivo methods) excludes them from falling under the rule formulated in Case T964/99.

Two questions should be asked in this connection. First, would it be preferable to have also ex vivo diagnostic methods excluded from patentability, that is, the broad exclusionary approach, or second, would it be a preferred strategy to broaden the definition of diagnostic methods to embrace also methods which make use of human genetic information, that is, a DNA probe or the like, applied on samples taken from the human body, the narrow exclusionary approach? Exclusion from patentability of this type of tests, namely ex vivo tests aimed at screening and diagnosis of genetic diseases, could be considered, irrespective of the nature of the exclusion, in view of the possible negative consequences if they are considered patentable, comparable to the arguments used in the context of medical treatment methods. The patented tests cannot be used without the permission of the patent-holder, and if the patents are broad, there are no alternative tests left for the future user. In the case of the BRCA1 gene patents this has been the case, combined with a high price charged for the tests based on the patents and an exclusive licensing scheme developed by Myriad Genetics. The specific nature of this type of screening and diagnostic tests is that the core substance used is the DNA of interest, and there are no alternatives to be used to test the same genetic disorders. This argument brings us close to the reasoning used in excluding medical treatment methods. The broad exclusionary approach, that is, excluding all ex vivo diagnostic methods from patentability, would have serious effects for present patent practice. ³² Many patents have already been granted for diagnostic test methods. The methods which are the subject of this article are specific in the sense that they use material for which no alternative exists, the BRCA1 gene DNA. That is a different situation from that where the method developed is one of many tests, implying available alternatives. For DNA tests the situation is different because this is the core of the test. A solution could be envisaged according to which the types of methods used in the BRCA1 gene patents are excluded from patentability, without embracing all possible ex vivo diagnostic methods.

It must be clear that both alternatives require an amendment of the current patent laws. But even though excluding ex vivo diagnostic methods can be envisaged in various forms, it remains to be evaluated whether this would be a good solution for society at large. From a point of view of healthcare, exclusion from patentability would probably be a good idea in the short run. By not providing patent protection for this type of methods, all interested parties will be able to develop alternative methods without patent infringement threats, and due to the competition the price will automatically be lower than the monopoly price level of patented methods. But one has to look also to the long-term effects. And in that context, it remains to be seen whether the long-term effects would be more detrimental for the level of investments made to develop new diagnostic methods. If, because of the exclusionary provision in patent law, there is no prospect of obtaining patent protection for an invention which is also commercially valuable and which requires a substantial amount of investment if the diagnostic method and its components have all been developed independently, a number of innovators may choose not to invest any longer in this type of research. Or the results may be kept secret, which equally can lead to high prices as long as the secret lasts, and has an additional drawback that society cannot benefit from the knowledge acquired by the innovator. In the past, there have also been those who claim that medicaments ought to be excluded from patentability. We have product patent protection for medicaments, and countries who did not have it in the past, have seen their pharmaceutical industry booming after introducing product patent protection. Patents thus create social welfare. The present situation is, as has already been emphasised, different from traditional chemistry for the reason that the building blocks used and patented in the patent are unique and there is no alternative. It is in that perspective that the debate ought to be seen, and in that perspective alone I would like to invite legislators to start this debate.

No Product Patents for DNA Sequences?

Another option which has been suggested is to prohibit the patentability of (partial) DNA sequences under product claims. ³³ I doubt whether such a drastic solution is to be preferred. Prohibiting patents for DNA sequences as products will not prevent patents of the BRCA1 gene type being granted, which covers in patent EP 699754 only method claims. The Nuffield Council on Bioethics has suggested that it would be preferable to prohibit product patent protection for DNA sequences, but that it would not be desirable to abolish patent protection for diagnostic and screening methods. ³⁴ To the extent that one fears a reduction of investment for the development of new diagnostic methods due to lack of patent protection, ³⁵ there can be a similar fear that no investments will be made any longer in gene research for lack of patent protection. I do not plead for such a solution. In my view, patent protection should remain available for DNA sequences, if all patentability criteria are fulfilled. It is to be admitted, however, that under the present state of the art, patent protection for DNA sequences will be more limited than before. This has to do with the fact that sequencing is automatised, and in many cases it does not require any inventive activity to come up with a DNA sequence. ³⁶ But for those cases where there is still inventive activity required, and definitely in case of selected sequences with known functions, ³⁷ patent protection should be available.

The problem remains that very broad patents relating to DNA have a major influence on further research, because it is impossible to avoid such a patent if one seeks to make new developments based on that specific DNA sequence. This is not a problem as such, as it is possible to pay a licensing fee for use of the DNA sequence. It becomes more problematic if the patent covers a plethora of applications and functions, which in an extreme case could be (partly) unevidenced. Patent law has instruments to counter these overbroad claims, such as opposition and appeal proceedings in which the patent can be (partly) invalidated. ³⁸ However, this still requires costly and time-consuming legal action. In view of the major impact for society and the fact that gene patents cannot be invented around to create new developments on that specific gene, I would suggest in this context putting more emphasis on the function of the DNA which is described. Under Article 5(3) of Directive 98/44/EC, the industrial application must be mentioned in the patent application. A strict interpretation of this requirement can in the author’s view be defended. Probably, we ought to move towards purpose-bound product patent protection for DNA sequences, that is, only the specific purpose or function described credibly in the patent application would fall within the scope of the patent. That would allow other inventors to patent other specific purposes they have invented, although admittedly the latter would be an invention dependent on the first patent. If Article 5(3) of Directive 98/44/EC is interpreted in this way, it would not necessarily require additional statutory or EPC amendments, even though it would probably be wise to clarify this interpretation in the Implementing Regulations of the EPC. It must be admitted, however, that such a solution would derogate from the common understanding of product patent claims, namely, claims protecting the substance claimed, irrespective of the processes used, and irrespective of the use intended, the so-called absolute product patent protection. However, it cannot be said that limiting patent protection to the specific purpose mentioned in the application is completely unknown under European patent law. Under European patent law, it is seen in the case of first medical indication claims for known chemical substances. ³⁹ It is a matter of technique whether one allows second and further purpose-bound product patents for the same sequence with a different function, ⁴⁰ or whether for the subsequent purpose one has to use the so-called Swiss claim formulation which is used in Europe for second and further medical indication claims, ⁴¹ which could then read as ‘the use of a substance X for the manufacture of a product to achieve function Y’. Purpose-bound product protection would have as a result that the DNA sequence as such, for all possible uses, can no longer be claimed, but only the DNA sequence linked to a specific use. Inevitably, there will be overlap and dependency situations, but that is not in any way different from what we know under the current patent system.

Over-broad claims in patent applications will also remain with us for some time. Focusing on the scope of protection of the BRCA1 gene patents shows that the scope is broad indeed. In both patents together, approximately 50 diagnostic and predictive test methods are claimed, thus embracing most of these methods conceivable. And in the author’s view, that could be the strongest argument against these very patents. But focusing on the scope of protection presumes that patent protection is available for the methods in question. Consequently, when discussing scope of protection issues here, it is to be assumed that patent protection is available for those inventions. ⁴² Over-broad claims do not necessarily mean that no patents ought to be granted for inventions in that specific field. Over-broad claims are not desirable because the fundamental underlying principle of the patent system, the quid pro quo, is not being fulfilled. Society is prepared to provide a monopolistic, exclusionary right to the inventor if he is prepared to share with the public the details of his invention. Patents create social welfare in various forms, but one of them is the knowledge provided to us by the patent which in turn can be used for further technological development. Technological development can be hampered if the scope of the patents granted is not in conformity with the details given to the public. ⁴³

The patent system thus has a set of rules to tackle over-broad patent claims. One of the most important instruments in this context is the enablement or disclosure requirement, according to which the invention is to be described in the patent application in such a way that the man skilled in the art is capable of carrying out the invention without undue burden or inventive activity. ⁴⁴ If a patent applicant cannot make it credible that the embodiments or methods he claims are sufficiently described, then these elements or the whole patent will be rejected. Speculative claims can be tackled with this requirement. In the author’s view, it would be a sound policy to be apply the disclosure requirement rigorously. ⁴⁵ If the invention is the application of a general principle, applicable to an unlimited number of embodiments, the patent applicant can be satisfied with describing only some examples. However, if the invention is the application of a specific technology or method, without an underlying principle, then the applicant should describe all the different embodiments or methods he claims. ⁴⁶ And following US case law in this respect, the disclosure has to be commensurate with the scope claimed, in other words, broad scope will require detailed description. ⁴⁷⁴⁸

Applying this principle to the BRCA1 gene patent, the following conclusions may be drawn. The principle claimed is the diagnostic and predictive testing methods. However, in reality, various technologies or techniques are claimed to achieve that diagnostic or predictive effect. To the extent that these various technologies are clearly described, there is no problem, and the patent as granted can continue to exist. Society has received in return for the monopoly grant a description of the invention which is sufficient for the man skilled in the art to use the details of that invention for further technological development. If these various techniques are not sufficiently clearly described, there is a problem of lack of disclosure. That would mean that if such a case is established, the patent is to be (partly) invalidated. Patent protection cannot be granted for those techniques claimed without being sufficiently described. If that is the conclusion drawn, those other techniques are available to others to use without committing a patent infringement. If on the contrary it is argued that those techniques do not need to be described in detail because they are well known in the state of the art, the patents run a serious risk of being revoked for lack of inventive step. An invention cannot be inventive if the methods claimed consist of principles well known in the state of the art.

The BRCA1 gene patents have also brought up a number of other issues. It has been said that research could be at risk because of the patents. The argument is that due to the patent, researchers in the field of cancer research would not be able to make use of the patented invention without obtaining permission from the patent-holder. In this view, this could have a stifling effect on research. At least in Europe, these fears are theoretical, since most European countries have statutory provisions allowing the use of a patented invention without the permission of the patent-holder for research purposes. ⁵⁰ To the extent that the sequence is available or can be cloned in a laboratory of interest, a patent on the sequence will not prevent research institutions from continuing their research. The same is true for use of the diagnostic and screening methods, to the extent that the use is limited to research and no commercial purposes are involved. Fundamental scientific research is thus not put in jeopardy because patents such as the BRCA1 gene patents are being granted. That is exactly the aim of the research exemption, that is, to ensure that fundamental research, which is considered to be crucial in the advancement of technology, remains unhampered.

A number of arguments against the BRCA1 gene patents relate to the price level of the products brought on the market and the accessibility of the diagnostic tests. These arguments are partly related to the issue of licensing or users’ rights of the patented invention.

It is claimed that the price charged for the diagnostic methods is far too high, and consequently it appeared to be proved that patents for this type of inventions ought not to be granted. In the author’s view, such reasoning lacks consistency. It is indeed true that patent monopolies allow monopoly prices. And it may be true that in this particular case, the patent-holder has decided to pursue an aggressive commercial policy. But the mere fact that a patent-holder tries to recoup the investment as quickly as possible by charging excessive prices is as such not an argument against patentability of this type of inventions. It is simply the commercial policy of a patent-holder who presumably does not care too much about long-term strategy, since aggressive commercial policies are generally not popular among competitors, which the patent-holder will probably be licensing from in the future. In my view it is anti-social behaviour, but that in itself is no reason to burden the patent system with it. It is the role of the government to intervene in these cases. One can think of a scheme where the government fixes the maximum prices that may be charged for diagnostic methods. Fixing maximum prices is also common practice in European countries for the classical pharmaceutical products. In view of cost-cutting in healthcare systems, such a solution seems to be desirable. Regulatory government intervention is also justified in this case because of public health concerns and protection.

Another problem is the availability of tests on the market. A patent-holder is free to decide whom he will license the patented invention to. That means that he can decide to license exclusively to one user, which would then imply that that single user has a quasi monopoly on using the method, besides the patent-holder. Patents, being monopolies, give the right to patent-holders to use their monopoly as they see fit, as long as they comply with the law. Competition law does not by definition prohibit such a strategy. Competition law only penalises the abuse of monopolies, not the mere use of them. In the context of DNA-related inventions, questions could be asked, however. It has already been mentioned earlier that the specific nature of many DNA related patents implies that it is impossible to come up with alternatives for the patented invention, because the core of the invention is the DNA sequence, which will always be necessary for any alternative use or method one desires to develop. In view of this specific nature, exclusive licences might unduly limit the functioning of the market, and thus competition, or could even endanger public health. One could then also consider regulatory adjustments to competition law rules, prohibiting the grant of exclusive licences in this field. In Europe, this should be done by amending Block Exemption Regulation 240/96/EC, which is in the process of being revised in any event. ⁵¹ Such a solution is not as drastic as it might seem at first sight. Under current competition law, exclusive licences are only allowed for a limited period of time and in specific circumstances, ⁵² while in other specific circumstances they are even prohibited. ⁵³

In the context of availability of the patented methods, it has also been argued that compulsory licences should be granted readily to force access. Compulsory licensing has been developed by the legislator as a last resort remedy in case the patent-holder refuses to grant a licence to any user who requests one. ⁵⁴ This is definitely not the case with the BRCA1 gene patent, where the patent-holder has been granting licences, albeit exclusive licences. In other words, the mere fact that the patent-holder uses an exclusive licensing scheme can never be an argument for a compulsory licensing scheme. On the contrary, at first sight compulsory licensing is not even an option here. The rule that a non-exclusive licence has to be requested before the compulsory licensing scheme is put in action can be set aside in case of national emergency. ⁵⁵ National health threats could be an example. In my view, the BRCA1 gene patent case would not trigger this exception.

A last resort could be compulsory licensing on the basis of abuse of monopoly, or anti-competitive behaviour. This is not easy to establish however, because one of the very features of intellectual property protection, and thus of patent protection, is that competition is excluded by law. One might think in this context of an ‘essential facilities’-like doctrine. ⁵⁶ The ‘essential facilities’ doctrine starts from the premise that a company holds a facility which is essential for others to operate in a specific market, and the holder of the facility has a dominant position in that market. The doctrine further holds that in certain circumstances, the owner of such a facility may be obliged to grant access to those others for them to be able to operate in that market. Applied to intellectual property rights, the question is then to what extent the owner of an intellectual property right-protected product, process or service, can be obliged to license it to another person or entity to allow them to operate in that specific market. Even though the ECJ has never expressly used the term ‘essential facility’ in its case law, it has implicitly applied the doctrine in a very limited number of cases. In the so-called Magill case it was held in this context that:

And in the Bronner case the criteria for establishment of abuse under Article 82 in cases relating to the exercise of an intellectual property right were further clarified, being that (1) refusal of access to the facility is likely to eliminate all competition in the relevant market, (2) such refusal is not capable of being objectively justified, and (3) the facility itself is indispensable to carrying on business, inasmuch as there is no actual or potential substitute in existence for that facility. ⁵⁸ It is thus clear that the mere exercising of intellectual property rights does not amount to an abuse. That also implies that, in principle, a patent-holder is free to decide with whom he wishes to enter into a licensing agreement. Applied to Myriad and its BRCA1 gene patents, the following can be concluded. Myriad, the patent-holder, has never refused to license its patented invention. It has merely used a restrictive licensing policy, with a limited number of exclusive licensees. Thus, in the author’s view, even if one wanted to apply the doctrine to this case, which would require the invention to be categorised as an essential facility, which is not completely evident at first sight, then the conditions for abuse are not being fulfilled. It can thus be doubted whether the essential facilities doctrine is applicable to the present case. A second argument why the essential facility is not so easy to apply to the present case is the fact that the doctrine applied to intellectual property rights has been developed for those rights, that is, copyright, where no statutory compulsory licensing scheme existed. Under patent law, a compulsory licensing scheme is laid down in the statute of almost all European countries. That scheme contains the rule that if the patent holder refuses to grant a licence, or in other words, refuses to deal, a compulsory licence can be granted. There are thus already safeguards laid down in the patent Acts, which are not present for other IPRs. Admittedly, the conditions under which the licence may be granted are not expressly laid down in the statute, and to that extent the case law of the ECJ and CFI might be a useful tool, with the limitations I have expressed, however.

Invoking compulsory licensing can easily have negative effects as well. If a patent-holder faces a compulsory licence, which is an unpredictable process, and thus has no control whatsoever over the market, and consequently no control over the price level and subsequently over the possibility of recouping his investments, he could decide to refrain from applying for a patent and keep his invention secret, or stop working on developments altogether. In both cases, society would be worse off than it would be with patents. It has to be remembered that the patent system is based on a balance, that is, the patent-holder shares the details of his invention with the public, and in return he obtains a monopoly. The knowledge made available is useful for subsequent innovators. As the law stands today in most countries in Europe, there are not sufficient grounds in the law applied to the BRCA1 gene patents to grant such a compulsory licence.

The BRCA1 gene patents have caused a new and heated debate about the patentability of DNA-related inventions. Thousands of DNA-related patents are granted every year, and they pass almost without comment, because these inventions have a positive effect on the knowledge we need to acquire in order to win the battle against hereditary diseases, the patent claims are not over-broad and the patent holders act in an understanding manner when it comes to licensing and price strategy. The patent system has provided sufficient evidence that it has worked satisfactorily for the dissemination of technological knowledge and the advancement of technology, and in the field of medicine, to achieve a better level of medicine. Even though we will never be able to prove beyond doubt whether the same inventions would have been made without a patent system, there is a presumption that the existence of a patent system has been able to create the necessary financial resources to pursue the costly R&D, and has made a considerable amount of technological knowledge available to the public. A patent system creates social welfare and is thus beneficial for society. ⁵⁹ However, no system is perfect, and there will always be mistakes. But in the author’s view, unfortunate patents, such as the BRCA1 gene patents, which might turn out to be over-broad and thus revocable, and the commercial strategy followed by the patent-holder may not be a reason to overhaul the complete patent system, which is built on a well considered balance between the inventor on the one side, and his competitors and society on the other.

The BRCA1 gene patents have opened our eyes, however, for a number of more fundamental questions in the context of the relationship between patent law and healthcare, which require thorough scrutiny by policy-makers in the future. As a patent lawyer, I am not against patenting biotechnological inventions. But even patent lawyers have to realise that the increasing number of patents for DNA-related inventions will have an effect on the costs of healthcare, and in my view the question must be asked to what extent we are prepared and able to pay the rising cost of cures. This question becomes even more urgent if we consider that a large number of diseases will be solely dependent on biotechnological treatments in the future. In other words, to what extent are we still capable of keeping up the quid pro quo principle of patent law? In society we have choices to make. If it seems that no cures can be made available without patent protection because of the huge investment required in R&D, it is for us to choose whether we are prepared to pay more for better healthcare, or pay less for less healthcare. I think it is unrealistic to think that we can receive the best level of healthcare, top-level treatment of high technological sophistication, without being prepared to pay for it. You can’t have your cake and eat it. With governments having relatively low budgetary capabilities, it is up to the public to pay some part of the treatment. Proponents of healthcare systems that are universally available at moderate prices have got stuck in a past with little sophistication in healthcare. Present-day healthcare is inevitably more expensive. If we choose not to pay for it any longer, the level of sophistication and consequently the level of healthcare will be reduced. I think that most people would opt for the best healthcare achievable.

Some of the problems presented by the BRCA1 gene patent can in my opinion be solved within the current patent rules we have, such as the broad scope with the disclosure requirement, and the possible lack of inventive step with that respective requirement. Other issues such as accessibility can be solved through the research exemption within the patent system, and the prices charged can be solved through regulatory efforts by the government and rules of competition law. There is thus no need to create a completely new patent system. On the contrary, I think it would be a bad idea to alter a well functioning system for the convenience of those who oppose a specific patent, or patents for that matter, if the problems cannot be solved substantially by the patent system, when there are good solutions available in other areas of law. But I also think it would be a sound intellectual exercise, when talking about the patentability of gene-related inventions, to undertake a cost-benefit analysis, not only in terms of purely financial implications for both industry and the medical sector, but also in terms of patients’ accessibility to healthcare. This article has suggested a number of solutions which could be used to tackle some of the current problems surrounding the patenting of DNA-related inventions. I have already mentioned the scope of protection remedies. I also think that it is worth analysing whether it would be preferable to limit patent protection to the specific purpose or function mentioned in the patent application. Excluding ex vivo diagnostic methods from patentability would be a far-reaching conclusion, which requires further analysis, and would in any event require an amendment of the patent laws. Compulsory licensing is in my view a last resort, only to be used in case the patent-holder refuses to provide access to the invention, and the grounds for invoking it can in practice be tackled, in the context of cost levels, by regulatory price control.

E-mail: s.bostyn@pr.unimaas.nl.

1. See T.M. Spranger, ‘Legal Status and Patentability of Stem Cells in Europe’, 21 Biotechnology Law Report, 2002, at 105 onward; M. Herdegen, ‘Die Patentierbarkeit von Stammzellenverfahren nach der Richtlinie 98/44/EG’, GRUR Int., 2000, at 859 onward.

2. As a matter of fact, there are various patents granted and applied for in Europe in connection with the BRCA1 gene. The most famous patents are those granted to Myriad Genetics, EP 699754, granted 10 January 2001, and EP 705903, granted 23 May 2001. Both patents are currently subject to opposition proceedings at the EPO. Interestingly enough, there is also a recent European patent application filed for three coding sequences of the BRCA1 gene, together with predictive test methods and gene therapy methods, EP 1126034 A: Coding sequences of the human BRCA1 gene, published 22 August 2001.

3. For a general discussion of this issue, which is now considered by patent law specialists to be past the discussion stage, and further references, see S.J.R. Bostyn, ‘The Patentability of Genetic Information Carriers, The new E.U. Directive 98/44 on the legal protection of biotechnological inventions’, Intellectual Property Quarterly (IPQ), 1999/1, at 2 onward.

4. EC Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions, OJ L 213/13, 30/07/1998, Article 5.

5. Judgment of the ECJ of 9 October 2001, Kingdom of the Netherlands/Council and European Parliament, C–377/98.

6. Claim 1-12 of patent EP 699754 (containing 29 claims). Claim 1: ‘A method for diagnosing a predisposition for breast and ovarian cancer in a human subject which comprises determining whether there is a germline alteration in the sequence of the BRCA1 gene coding for a BRCA1 polypeptide having the amino acid sequence set forth in SEQ.ID.NO:2 or a sequence with at least 95% identity to that sequence, said alteration being indicative of a predisposition to said cancer.’ Claim 2: ‘A method for diagnosing a lesion of a human subject for neoplasia associated with the BRCA1 gene locus which comprises determining in a sample from said lesion whether there is an alteration in the sequence of the BRCA1 gene coding for a BRCA1 polypeptide having the amino acid sequence set forth in SEQ.ID.NO:2 or a sequence with at least 95% identity to that sequence, said alteration being indicative of neoplasia.’ Claim 3: ‘A method as claimed in claim 2 wherein said lesion is a breast or ovarian lesion.’ Claim 4: ‘A method as claimed in any one of claims 1 to 3 wherein the sequence of the BRCA1 gene in said sample is compared with the sequence of one or more wild-type BRCA1 gene sequences selected from the sequence set forth in SEQ.ID. No. 1 from nucleotide 120 to nucleotide 5708 and wild-type allelic variants thereof.’ Claim 5: ‘A method as claimed in any one of claims 1 to 3 wherein the level and/or sequence of an expression product of the BRCA1 gene in said sample is investigated.’ Claim 6: ‘A method as claimed in claim 5 wherein said expression product is mRNA.’ Claim 7: ‘A method as claimed in claim 6 wherein mRNA of said sample is contacted with a BRCA1 gene probe under conditions suitable for hybridization of said probe to an RNA corresponding to said BRCA1 gene and hybridization of said probe is determined.’ Claim 8: ‘A method as claimed in any one of claims 1 to 4 wherein a BRCA1 gene probe is contacted with genomic DNA isolated from said sample under conditions suitable for hybridization of said probe to said gene and hybridization of said probe is determined.’ Claim 9: ‘A method as claimed in claim 7 or claim 8 wherein said probe is a mutant, allele specific probe.’ Claim 10: ‘A method as claimed in claim 5 wherein said expression product is the polypeptide encoded by the BRCA1 gene in said sample.’ Claim 11: ‘A method as claimed in claim 10 wherein said polypeptide is detected by immunoblotting or immunocytochemistry.’ Claim 12: ‘A method as claimed in claim 10 wherein binding interaction is assayed between the BRCA1 gene protein isolated from said sample and a binding partner capable of specifically binding the polypeptide expression product of a mutant BRCA1 allele and/or a binding partner for the BRCA1 polypeptide having the amino acid sequence set forth in SEQ.ID NO:2.’ Patent EP 705903 contains another 18 claims relating to different methods of using the BRCA1 gene for diagnosis and determining predisposition.

7. See Claims 1 to 13 of patent EP 705903.

8. According to Article 52(4) EPC, ‘Methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body shall not be regarded as inventions which are susceptible of industrial application within the meaning of paragraph 1. This provision shall not apply to products, in particular substances or compositions, for use in any of these methods.’

9. In the 2000 revision of the EPC, this provision, with almost identical contents, has been moved to Article 53, dealing with exceptions to patentability. The reference to lack of industrial applicability has been removed, however. See Document MR/3/00/Rev.1. e.

10. For example, R. Moufang, ‘Methods of Medical Treatment Under Patent Law’, 24 IIC, 1993, at 31 onward.

11. For example, for the Netherlands, see Article 57 Dutch Patent Act 1995 (licence granted by the Secretary of State), Article 58 (licence granted by the judge), Article 59 (licence granted in the interest of the state). For the United Kingdom, see section 48 onward of the UK Patent Act 1977.

12. See, for example, D. Thums, ‘Patent Protection For Medical Treatment – A Distinction Between Patent and Medical Law’, IIC, 1996, at 442; R. Moufang, Note 17 above, at 48; S.A. Miller, ‘Should Patenting of Surgical Procedures and Other Medical Techniques by Physicians Be Banned?’ 36 IDEA, 2/1996, at 270 onward.

13. See, for example, J.K. Flanagan, ‘Gene Therapy and Patents’, 80 JPTOS, 1998, at 739 to 775.

14. For more details, see S.A. Miller, Note 19 above.

15. HR 1127 Bill, 3 March 1995, Medical Procedures Innovation and Affordability Act.

16. 35 USC §287(c)(1) to (4) as amended by §616 PL 104 to 208, 30 September 1996 (35 USC §100 onward represents the United States Patent Act) . According to this provision, the term ‘medical activity’ means the performance of a medical or surgical procedure on a body, but shall not include (i) the use of a patented machine, manufacture, or composition of matter in violation of such patent, (ii) the practice of a patented use of a composition of matter in violation of such patent, or (iii) the practice of a process in violation of a biotechnology patent. The term ‘medical practitioner’ means any natural person who is licensed by a state to provide the medical activity described in subsection (c)(1) or who is acting under the direction of such person in the performance of the medical activity. The term ‘related health care entity’ shall mean an entity with which a medical practitioner has a professional affiliation under which the medical practitioner performs the medical activity, including but not limited to a nursing home, hospital, university, medical school, health maintenance organisation, group medical practice, or a medical clinic. The term ‘professional affiliation’ shall mean staff privileges, medical staff membership, employment or contractual relationship, partnership or ownership interest, academic appointment, or other affiliation under which a medical practitioner provides the medical activity on behalf of, or in association with, the healthcare entity.

17. T385/86, Non invasive measurement/Broker, Decision of Technical Board of Appeal 3.4.1, 25 September 1987, OJ EPO, 1988, at 308.

18. T385/86, Headnote 1.

19. T385/86, at 3.2 of the reasons.

20. T964/99, Device and method for sampling of substances using alternating polarity/CIGNUS, Decision of Technical Board of Appeal 3.4.1, 29 June 2001, OJ EPO, 2002, at 4.

21. T964/99, Headnote 1 and 2.

22. T964/99, at 4.1 of the reasons.

23. T964/99, at 4.2 of the reasons.

24. T964/99, at 4.4 of the reasons (original emphasis).

25. Interestingly, the Nuffield Council on Bioethics is not in favour of excluding all diagnostic methods from patentability: see The Ethics of Patenting DNA: a discussion paper, Nuffield Council on Bioethics, London, 2002, at 53.

26. Ibid., at 62.

27. Ibid., passages referred to above.

28. The Nuffield Council on Bioethics has stated that it is important that patent protection remains available for diagnostic and screening methods to guarantee incentives for further research in this field, see above.

29. See also S.J.R. Bostyn, Enabling Biotechnological Inventions in Europe and the United States. A study of the patentability of proteins and DNA sequences with special emphasis on the disclosure requirement, Eposcript Series, no. 4, EPO (European Patent Office), München, 2001, at 142.

30. For the selection inventions concept applied to gene sequence inventions, see ibid., at 141.

31. See further below, ‘Scope of Patent Claims’.

32. See Article 54(5) EPC: ‘The provisions of paragraphs 1 to 4 shall not exclude the patentability of any substance or composition, comprised in the state of the art, for use in a method referred to in Article 52, paragraph 4, provided that its use for any method referred to in that paragraph is not comprised in the state of the art.’

33. Until now, under European patent law, only purpose-bound product patents are possible for the first medical indication of known substances. Nothing prevents the patent offices or legislators to decide that for DNA sequence invention, only purpose-bound patent protection is possible.

34. The claim formulation to circumvent the exclusion for new medical applications of products already known in the state of the art, which requires a use or method claim, has been developed in Case G0005/83, Second medical indication/EISAI, OJ EPO, 1985, at 64. Claims need to be formulated as follows: ‘Use of substance X for the manufacture of a medicament for the treatment of disease Y.’ This claim formulation can obviously also be used for method claims for a first medical indication.

35. In opposition and appeal proceedings, it is often claimed, in first instance, that the invention is not patentable, and in second instance, if that line of argumentation is not followed by the Board or court, other arguments relating to the patentability requirements and scope of protection are being used. In that sense, the lines of reasoning developed in this article are not out of the ordinary.

36. Note 36 above, at 42 onward.

37. Article 83 EPC: ‘The European patent application must disclose the invention in a manner sufficiently clear and complete for it to be carried out by a person skilled in the art.’ 35 USC § 112: ‘The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.’

38. Note 36 above, at 292.

39. Ibid., at 297.

40. See, for example, In re Fisher, 427 F.2d at 833, 166 USPQ 18, at 24 (CCPA 1970); In re Vaeck, 947 F.2d 488, 20 USPQ2d 1438, at 1445 (CAFC 1991); Amgen, Inc. v Chugai Pharmaceutical Co. Ltd, and Genetics Institute, Inc. , 927 F.2d 1200, at 1213 to 1214, 1991 US App. LEXIS, 3481, 18 USPQ 2d (BNA) 1016 (CAFC 1991).

41. I do not recommend following the position of US case law in respect of the written description requirement, however, which is rather confusing at the moment, witness the recent Enzo Biochem case, where the CAFC held that they erred in an earlier decision in the same case: see, Enzo Biochem, Inc. v Gen-Probe Incorporated, and Chugai Pharma USA, Inc. and Chugai Pharmaceutical Co., Ltd, and Biomerieux, Inc., and Becton Dickinson and Company, and Biomerieux SA, 2002 U.S. App. LEXIS 14328 (CAFC 2002), decided 15 July 2002, overruling the previous case between the same parties, decided 2 April 2002, 285 F.3d 1013, 2002 US App. LEXIS 5642 (CAFC 2002). See for this in more detail, S.J.R. Bostyn, ‘The Quest for the Holy Grail? Ideal Scope of Protection and the Disclosure Requirement for Biotechnological Inventions in a Harmonized Patent System: A European Perspective’, 5 Journal of World Intellectual Property, 2002, November at 1013 onward.

42. This again has to be seen in the context of what has been said above, namely assuming that other options mentioned in this article are not considered feasible or desirable.

43. In most patent Acts, the provision is based on Article 27(b) CPC, which never entered into force: ‘[The rights conferred by a Community patent shall not extend to:] (b) acts done for experimental purposes relating to the subject-matter of the patented invention.’ Germany, §11 Nr. 2 PatG: ‘Die Wirkung des Patents erstreckt sich nicht auf … Handlungen zu Versuchszwecken, die sich auf den Gegenstand der patentierten Erfindung Beziehen’; United Kingdom, Patents Act 1977, section 60(5)(b): ‘An act which, apart from this subsection, would constitute an infringement of a patent for an invention shall not do so if … (b) it is done for experimental purposes relating to the subject-matter of the invention’; France, Code de la Propriété Intellectuelle, Article L. 613 to 615: ‘Les droits conférés par le brevet ne s’étendent pas … (b) aux actes accomplis à titre expérimental qui portent sur l’objet de l’invention brevetée.’

44. Commission Regulation (EC) 240/96 of 31 January 1996 on the application of Article 81(3) (ex 85(3)) of the Treaty to certain categories of technology transfer agreements, OJ, 1996, L31/2. Admittedly, this Regulation deals with concerted practices issues, and not with dominant position issues, which are covered by Article 82 EC Treaty. But that does not take away the gist of the argument that solutions could be found to avoid exclusive licensing practices, which besides Article 81 consequences, in the context of intellectual property rights, will also have Article 82 consequences.

45. See, for example, Article 1 and 2 Reg. 240/96/EC.

46. For example, grant-back licences of improvements. In case of severable improvements the licence may not be exclusive, since the licensee, who has developed the severable improvement, must be able to benefit from his own improvements in a way which allows him to reap the most benefit. See Article 2(1)(4) Reg. 240/96/EC.

47. For the Netherlands, see Article 57 Dutch Patent Act 1995 (licence granted by the Secretary of State (in Dutch = Minister)), Article 58 (licence granted by the judge), Article 59 (licence granted in the interest of the state). For the United Kingdom, see section 48 onward, UK Patent Act 1977.

48. I use the TRIPs provision as an example (Agreement on Trade-Related Aspects of Intellectual Property Rights, Including Trade in Counterfeiting Goods, Marrakesh Agreement Establishing the World Trade Organization, 15 April, 1994, Annex 1C). Article 31 TRIPs says in the relevant part: ‘Where the law of a Member allows for other use 7 of the subject matter of a patent without the authorization of the right holder, including use by the government or third parties authorized by the government, the following provisions shall be respected: (a) authorization of such use shall be considered on its individual merits; (b) such use may only be permitted if, prior to such use, the proposed user has made efforts to obtain authorization from the right holder on reasonable commercial terms and conditions and that such efforts have not been successful within a reasonable period of time. This requirement may be waived by a Member in the case of a national emergency or other circumstances of extreme urgency or in cases of public non-commercial use. In situations of national emergency or other circumstances of extreme urgency, the right-holder shall, nevertheless, be notified as soon as reasonably practicable. In the case of public non-commercial use, where the government or contractor, without making a patent search, knows or has demonstrable grounds to know that a valid patent is or will be used by or for the government, the right holder shall be informed promptly … (k) Members are not obliged to apply the conditions set forth in subparagraphs (b) and (f) where such use is permitted to remedy a practice determined after judicial or administrative process to be anti-competitive. The need to correct anti-competitive practices may be taken into account in determining the amount of remuneration in such cases. Competent authorities shall have the authority to refuse termination of authorization if and when the conditions which led to such authorization are likely to recur.’

49. For a general overview of the essential facilities doctrine, see: J. Temple Lang, ‘Defining Legitimate Competition: Companies’ Duties to Supply Competitors and Access to Essential Facilities’, 18 Fordham International Law Journal, 1994, at 437 onward; D. Ridyard, ‘Essential Facilities and the Obligation to Supply Competitors’, ECLR [1998] at 438 onward; Treacy, ‘Essential Facilities – Is the Tide Turning?’ ECLR [1998] at 501 onward; V. Korah, ‘The Interface Between Intellectual Property and Antitrust: The European Experience’, 69 Antitrust Law Journal, 2002, at 801 onward.

50. Joined Cases C–241/91 P and C–242/91 P, Radio Telefis (RTE) and Independent Television Publications Ltd (ITP) v Commission, ECR [1995] I–0743, paragraphs 49, 50 and 54.

51. Case C–7/97 Oscar Bronner GmbH & Co. KG v Mediaprint Zeitungs- und Zeitschriftenverlag GmbH & Co. KG ECR [1998] I–17791, paragraph 41.

52. I have already explained this in more detail: see Note 36 above at 23 to 64, passim, and Note 48 above.

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