THESIS – MASTER INFORMATION LAW University of Amsterdam
Second-Class Protection
for
Second Medical Use Inventions
A study on the (im)possibility of enforcing second medical use patents.
AUTHOR: Menno G. Loos
DATE: January 2016
STUDENT NR: 10885234
Table of Contents
List of Abbreviations ... 4 Introduction ... 5 Relevance ... 6 Research Framework ... 6 Methodology ... 7 Hypothesis ... 7Chapter 1 – Factual Overview ... 9
1.1 Personalised Medicine ... 9
1.2 Personalised Medicine and Patent Law ... 10
1.3 Patentability ... 11
Europe ... 12
United States ... 16
1.4 Summary ... 18
Chapter 2 – Law and Practice ... 19
2.1 A Confusing Situation... 19
2.2 Product Label ... 20
2.3 Prescribing and Dispensing ... 21
2.4 Preference Policy ... 21
2.5 Summary ... 23
Chapter 3 - Scope and Infringement ... 24
3.1 InnovaThor v Generix ... 24 3.2 Europe... 25 3.2.1 United Kingdom ... 26 3.2.2 Germany ... 32 3.2.3 The Netherlands ... 35 3.3 United States ... 38 Direct Infringement ... 39 Induced Infringement ... 40 Contributory Infringement ... 40 Interim Summary ... 41
Exemplary Case – Eli Lilly v Teva ... 41
Outcome – InnovaThor v Generix ... 43
4.1 Patent System ... 45
4.2 Regulatory Framework ... 46
Adjustment of Prescribing Practice – Split Preference ... 46
Other ... Error! Bookmark not defined. Conclusion ... 52 List of Literature ... 54 Articles ... 54 Books ... 56 Legislation ... 57 United States ... 57 European Union ... 57 Jurisprudence ... 58 EPO... 58 United States ... 58 United Kingdom ... 59 Germany ... 59 The Netherlands ... 60 Miscellaneous... 60
Appendix A – Overview of different claims under EPC ... 63
List of Abbreviations
AIPPI Association Internationale pour la Protection de la Propriété Intellectuelle API Active pharmaceutical ingredient
Art. Article Dir. Directive
DNA Deoxyribonucleic acid EBA Enlarged Board of Appeal EMA European Medicines Agency EPC European Patent Convention EPO European Patent Office
FDA Food and Drug Administration INN International Non-proprietary Name MA Market authorization
NCE New Chemical Entity PIL Patient information leaflet PM Personalized Medicine R&D Research and development RNA Ribonucleic Acid
SmPC Summary of product characteristics SPC Supplementary Protection Certificate TBA Technical Board of Appeal
TRIPs Agreement on Trade Related Aspects of Intellectual Property Rights
UK United Kingdom
US United States
USPTO United States Patent and Trademark Office WTO World Trade Organisation
Introduction
The classic case of second medical use of a pharmaceutical compound concerns the situation in
which a drug is initially developed for a particular therapeutic purpose, and later research finds that the drug is also useful for another therapeutic area. The classic example is the drug acetylsalicylic acid (brought to the market as Aspirin); it was originally used as an antipyretic and analgesic, but it was subsequently found to be useful as an anticoagulant, and later as an anti-stroke medication and an anti-ischaemic. A more recent example relates to the series of chemical compounds named pyrazolopyrimidinone. They were well-known for treating heart and vascular disease. However, they gained even more popularity when Pfizer found that one of the compounds, sildenafil citrate, was also useful for treating erectile dysfunction. Marketed as Viagra, the product has been extremely successful with annual sales of billions of dollars.1
This kind of second medical use inventions is very much likely becoming wide spread and increasing in
amount under the influence of personalised medicine. In brief, personalised medicine is a medical model that aims to customise health care. Personalised medicine has significant influence on the development of health care products and health care in general. In particular, it influences the development of medical drugs. Stratification and thorough research of the human genome have led to the discovery of additional applications of existing medicines (second or further medical uses). The inventers of such personalised medicine products seek the protection of patents in order to secure their investments. Patenting of second or further medical uses of an existing drug results in a situation in which one medicine may contain multiple patents. One can imagine that this causes ambiguity, especially when each of these patents have different due dates; when may the medicine legitimately be used for which indication?
Patents protecting second medical uses prove difficult to enforce. This difficulty arises, to paraphrase Judge Arnold, out of a collision between the policy of incentivising important medical research by granting second medical use patents on the one hand and other policies and practices on the other hand.2 These other policies and practices consist of rules and practices of the medical sector about prescribing and dispensing medicines, and of rules regarding health care
1 These examples are derived from the AIPPI Q238 2014 Working Guidelines, point 14.
2 [2015] EWHC 72 (Pat) 21 January 2015 (Warner-Lambert v Actavis), par. 1: “This case arises out of a collision
between the policy of incentivising important medical research by granting second medical use patents on the one hand and other policies and practices which form part of the United Kingdom's healthcare systems (and in particular the English and Welsh systems) on the other hand.”
insurers. Such rules seem to work separately from the rules prescribed by patent law. It is this separation, or collision as Judge Arnold calls it, which makes it difficult for patentees to enforce their rights.
Relevance
Patent protection is of utmost importance for innovators. For it to be effective, innovators must be able to actually enforce their rights. Enforcing second medical use claims may also be difficult, as the need and practice for enforcement of such claims is a relatively new phenomenon. As substances (including medicines) have only been patentable since the late 1970s, many patents are now expiring, allowing other manufacturers to sell the substances. Innovators will therefore focus increasingly on obtaining second medical use patents. In addition, the number of second medical use inventions will increase under the influence of personalised medicine. Thus, with the future in mind, it is not only desirable, but necessary that second medical use patents are effectively enforceable.
Next to patentees there are other stakeholders involved, each with their own interests. Patients want to have access to the newest and best health care for a fair price. In the current situation it is questionable whether this is always the case. Furthermore, there are the patentees’ competitors, usually generic manufacturers. These competitors produce copies of existing medicines, for a price that is lower than that of the innovators. However, patents prevent generics from entering the market. Moreover, when they do enter the market, it is often uncertain whether they will be held liable for patent infringement. This uncertainty potentially further reduces the access to generic medicines. To make things complicated, governments and health insurers are generally interested in the good health of their citizens or customers, but are keen to reach this goal in the cheapest possible way. Next, health care providers are mostly interested in providing the best possible care. However, they cannot ignore financial realities, i.e. restrictions. Finally, there is the overall importance of innovation. Society in general benefits from innovation in health care which eventually results in better health of the population.
Research Framework
This thesis addresses the difficulty that surrounds the enforcement of second medical use patents. The research question that will be answered in this thesis is as follows:
“Is amendment of patent law or regulatory rules necessary with a view to arrive at an equitable system of enforcement of second medical use claims, taking into account also the rights and interests of third parties?”
In order to answer the research question, several sub-questions will be analysed. These questions are addressed in the order of occurrence in practice, i.e. first the framework of rules is sketched, followed by discussions on how the problematic situation arises, and subsequently on how courts deal with such situations. Finally solutions and remedies are proposed.
Chapter one concerns factual questions. It contains the essential facts and background knowledge required to comprehend the topic of this thesis: the enforcement of second medical use claims. Firstly, the meaning of personalised medicine and its relevance is discussed. Secondly, the relationship between personalised medicine and patent law is addressed. Lastly, an outline of the patentability of second medical uses in both Europe and the United States (US) is provided. This chapter includes a historical overview. Chapter two seeks to address the sub-question: “How does the regulatory system currently contribute to or prevent infringement of second medical use claims?” In Chapter three the following sub-question is addressed: “When does patent infringement for second medical use patents occur and what behaviour constitutes infringement?” In Chapter four several solutions and remedies are described. The sub-question that underlies this chapter is: “Is amendment of patent law required to come to an equitable solution, or should the solution be sought in amending regulatory law, or both?”
Methodology
The main research question and underlying sub-questions will be addressed through comparisons between the European patent system and that of the US. The comparisons are intended to distil useful insights and solutions from the different approaches of different countries and their legal culture. Within Europe the patent law of the United Kingdom (UK), Germany and the Netherlands will be considered, since patent law in Europe is not completely harmonised. The reason for choosing these countries is because they are the most developed when it comes to legislation and case law regarding the enforcement of second medical use claims.
Hypothesis
The background on which this thesis is based is that the patent law system and the regulatory system do not cooperate and even thwart each other. As a result, patents on second medical uses
are being infringed on a large scale. It is hypothesised that adaptation of the regulatory framework for second medical use patents will provide for an equitable system of enforcement which also takes into account the rights and interests of other stakeholders.
Chapter 1 – Factual Overview
This chapter provides essential facts and background knowledge in order to comprehend the issue that this thesis will deal with later on: enforcement of second medical use patents. Firstly, personalised medicine and its relevance will be discussed. Secondly, the relationship between personalised medicine and patent law is addressed. Lastly, an outline of the patentability of second medical uses in both Europe and the US will be provided.
1.1 Personalised Medicine
Personalised medicine is a medical model that aims to customise health care. It has become a common denominator for a variety of techniques and technologies. Most of these are based on so-called stratification strategies, i.e. technology strategies that aim at categorizing patients into a variety of patient groups, on the basis of which treatments targeted at those groups can be developed.3 Personalised medicine must be considered as an umbrella term not only related to the treatment of individual patients. However, with this approach, personalised medicine has the potential to drastically improve individual treatment and health care in general. Stratification of patients enables health care providers to tailor medical treatment methods, practices and products to the specific needs of a patient group and ultimately to an individual patient.
The premise that underlies the personalised medicine model is that no two individuals are the same. Each and everyone has a set of unique variations in his/her genome that can determine the individual’s reaction to treatment and medication. Since the genetic makeup of an individual can influence that person’s response to a drug, modern personalised medicine techniques have started to include genome sequencing. Sequencing can reveal mutations in DNA, which may result in variations in RNA and encoded proteins that are part of the pathobiology of diseases and responsiveness to drugs.
Given the above, one application of personalised medicine is to only prescribe those drugs to people who will respond (well) to them, based on their genetic profile. Differentiating as much as possible between patients, all the way up to the genetic makeup of the patient, makes it possible to adjust medical treatment or a drug specifically to a patient’s needs, resulting in the best possible treatment for that one patient or patient group. This is called pharmacogenomics.
Although pharmacogenomics is one of the most important applications of personalised medicine, it is not the only one. Treatment and medication may also be personalised on the basis of non-genetic biomarkers, such as the type of virus or the bacterial type of the infection.4 Because of the vast array of techniques and technologies that personalised medicine encompasses and the technical developments that succeed each other rapidly, it is clear that the definition of personalised medicine today may be obsolete tomorrow.5
Knowledge of the human genome, as well as the ability to link efficacy of drugs and treatment to specific genetic characteristics, has increased greatly. This development has already led, and will continue to lead, to a transition from population-based dosing and prescriptions to patient individualization, both in drug development and in clinical practice.6 This, however, should not be confused with the development of many new chemical entities and medical treatment methods. Personalised medicine is more probable to lead to research and development of new possible applications and improved versions of existing substances, also called “line extensions”.7
We face a future in which pharmacological agents and medical treatments are increasingly being tailored for specific subpopulations, with specific genomic characteristics. This will lead to medication usable for multiple indications and treatment methods having multiple applications.
1.2 Personalised Medicine and Patent Law
It is clear that research and development (R&D) of (new applications of) drugs and medical treatment methods are very time-consuming and costly. In pharmaceutics, total R&D costs of over $500 million and an average of 10 years for clinical trials and registration of only one product is not uncommon.8 In addition, innovators’ ongoing search for new products is a risky business. Although some research projects lead to spectacular breakthroughs in medicine (and come with great profits), many other pharmaceutical projects may fail.9 Moreover, once a product enters the market, it is relatively easy for other parties to copy that product. Copies of medicines,
4 Patrinos & Prainsack 2014, p. 611.
5 See for examples of definitions: Ingelman-Sundberg 2015, p. 152; S. Schleidgen et al. 2013; Redekop & Mladsi
2013, S4-S9.
6 Ingelman-Sundberg 2015, p. 152. 7 Van Overwalle 2000, p. 53.
8 Cf. Albrecht et al. 2015, p.3; Statement from NEFARMA (the Dutch association for innovative medicines), 2009
Visiedocument ‘Beschikbaarheid van nieuwe geneesmiddelen’. Accessible here:
http://www.nefarma.nl/stream/fz-visiedocument-beschikbaarheid-nieuwe-geneesmiddelen-12-2009.pdf 9 E.g., Adrian Looney (Pfizer, Inc.) stated at the AIPPI’s 2015 World Congress that Pfizer’s oncology products in
development suffer a 95% failure rate. B. Cordery, ‘Report from Rio (2): Personalised medicine’, Kluwer Patent Blog, 14 October 2015.
also called generics, can be made in less time and without the high costs the innovator had to incur. For this reason, patent protection is crucial.
The patent system aims to stimulate innovation. An inventor is rewarded with a patent right, a temporary monopoly, in exchange for the publication of his invention. This implies that, (among other things), the patent holder has the exclusive right to apply10 the patented invention during a certain period of time.11 In addition to the individual importance of patents for innovators as discussed above, the patent system in fact serves the public interest, although it is not immediately evident. A well working patent system will eventually lead to investments, innovation, technical progress, economic growth and prosperity.12 Nevertheless, patents have always been the subject of fierce criticism. This is especially the case for patents in the field of health care. The monopoly of the inventor is often seen as a limitation of the freedom to provide health care: patents would reduce the accessibility of health care, physically as well as financially.13
Innovators, mostly from the pharmaceutical industry, respond to this kind of criticism by stating that they have to recoup their investments and have to make profit in order to keep investing in R&D.14 Without the guarantee of an effective and efficient patent system, companies will not survive and innovation will come to a halt. According to them, patents are pivotal to the public health.15
It is this paradox that underlies every debate about patent law and medical inventions.
1.3 Patentability
The question as to whether inventions are patentable has been the subject of numerous lawsuits and has led to a vast body of jurisprudence. Obviously, the answer as to whether an invention is patentable depends on the subject of the invention, the way in which it is claimed and the country in which protection is sought. Here the issue of patentability is not exhaustively discussed, it merely serves as an overview intended to provide a better understanding of the problem as discussed below. Since there are significant differences between the patent systems of
Europe and the US, these systems are discussed separately.
10 See Art. 64 EPC and §60 UK Patents Act, §9 German Patent act, Art. 53 Dutch Patent Act and §271 US Patent
Act.
11 The term of protection shall be 20 years (art. 63(1) EPC and §154 A(2) US Patent Act). 12 Van Overwalle 2000, p. 33.
13 Ibidem.
14 See Albrecht et al. 2015, p.3.
15 See Cockburn & Long 2015, p. 739 and Statement from NEFARMA, accessible here: http://www.nefarma.nl/stream/jz-visiedocument-octrooirecht-mei-2011-pdf
Europe
The patent system of the European states is governed by the European Patent Convention (EPC),16 which is administered by the European Patent Office (EPO). A patent granted by the EPO consists of a bundle of national patents under the laws of the states in which protection is sought.17
The Enlarged Board of Appeal (EBA) is the EPO’s ultimate arbiter for the interpretation of the EPC. When interpreting European patent law, courts must seek uniformity in all contracting states. This implies that courts shall consider the jurisprudence of the boards of appeal of the EPO as well as that of courts in other contracting states.
The EPO does not make decisions on infringement matters; European patents fall within the jurisdiction of the national courts. However, as regards the validity of European patents, both the EPO, during opposition proceedings,18 and national courts, during nullity proceedings,19 may decide to revoke a European patent.
Several provisions are of specific relevance for this thesis. First of all, Article 52 EPC states the five requirements for patentability: (1) an invention, (2) that is belonging to a field of technology, (3) novel,20 (4) inventive21 and (5) susceptible of industrial application.22
Secondly, Article 53 EPC states exceptions to patentability. Relevant for this thesis is the exception of Article 53(c) EPC: European patents shall not be granted in respect of:
“methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body; this provision shall not apply to products, in particular substances or compositions, for the use in any of these methods.”
Products for the use in any of the methods mentioned in Article 53(c) EPC, which are patentable, are for example a stethoscope and medicines.
16 European Convention on the Grant of European Patents (1973). 17 Article 2 EPC.
18 Article 99 EPC. 19 Article 138 EPC.
20 Further elaborated in Article 54 EPC. 21 Further elaborated in Article 56 EPC. 22 Further elaborated in Article 57 EPC.
Fig. 1. Schematic overview of Article 53(c) EPC.
Lastly, Article 54 EPC is of great relevance. It deals with the requirement of novelty. It is this tricky criterion that led to important case law in the field of medical patents and amendments in the text of the convention. At first sight, a new application of an existing substance seems unpatentable since the substance is already part of the prior art. But this rankles, because the application of the substance is indeed novel. However, when one wants to emphasise the novelty of the way the substance is applied, one will most probably end up claiming a method for treatment. Since a method for treatment is not patentable under art. 53(c) EPC, a solution for this problem needs to be found.
Second Medical Use
Pharmaceutical research can be divided into two kinds: research on new chemical entities (NCEs)23 and research and development of new possible applications and improved versions of existing substances, so-called line extensions.24
The development of NCEs is becoming more difficult as more substances are added to the prior art. Therefore research and development priorities have shifted towards the development of line extensions.25
Pre EPC era
Until the late 1970s, substances (including medical drugs) were not patentable in most (European) countries, at least not directly.26 This meant that it was not possible to claim protection for a substance as such by means of a product claim (Substance X, consisting of…).
23 Hereafter also referred to as substances. 24 Van Overwalle 2000, p. 53.
25 Van Overwalle 2000, p. 38.
26 Van Nieuwenhoven Helbach, Huydecoper & Van Nispen 2002, p. 74; Van Overwalle 2000, p. 36; Schutjens
Protection was sought by claiming protection for the preparation of the substance, in the form of a process claim (Process Z for the preparation of substance X.). Such a patent also protected the
outcome of the claimed process. Via this detour the substance was indeed protected, however, enforcement was only possible when a substance was produced in the exact same way as was claimed. It should be noted that the scope of protection of a process claim is smaller than that of
a product claim. After all, in the case of a process claim, the patentee may only take action when the substance is prepared in exactly the same manner as the one defined in the claim. The form in which an invention is defined in the claims is thus of great importance for the scope of protection of the patent.
EPC 1973: 1977 – 2007
The Convention entered into force on 7 October 1977 for the first group of countries.27 Subsequently, other countries have joined the EPC.
Under Article 54(5) EPC first medical uses of substances were patentable by means of a product claim:
“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(4) EPC, provided that its use for any method referred to in that paragraph is not comprised in the state of the art.”
The first medical use claim was a purpose-limited product claim, in the sense that the use of the substance was limited to use in a method referred to in Article 52(4) EPC. However, in practice this claim granted protection for the entire method, without actual limitation to the first use.28 This was presumably the case because there was no provision for protection of second medical uses in the EPC 1973. Without a special provision for protection of a second medical use, such protection seemed to go against Article 52(4) EPC.29
When the EBA had the opportunity, it conceived a way out. The so-called Swiss-use claim was introduced in case G 5/83.30 This type of use claim allows for the protection of second (and subsequent) medical usage by targeting the use of a substance or composition for the
27 The Convention first entered into force on 7 October 1977 for the following countries: Belgium, Germany
(then West Germany), France, Luxembourg, the Netherlands, Switzerland and the United Kingdom, and on 1 May 1978 for Sweden.
28 See Van Nieuwenhoven Helbach, Huydecoper & Van Nispen 2002, p. 88; Ventose 2009, p. 64. 29 Kraβer, p. 277.
manufacture of a medicament for a specified (new) therapeutic application (Use of substance X for the manufacture of a medicament for treatment of Z).31 The claim is classified as a purpose-bound process claim. The construction is based on a legal fiction: the inventor did not invent a new process for preparation of a substance; rather the invention enables a new method of treatment. The novelty
of the invention is derived from the new application of the substance, not from the novelty of the substance. The words “manufacture of” are added to escape the exclusion of 52(4) EPC. The
EBA also settled the haziness with regard to first medical use claims of 54(5) EPC. First medical use claims are granted purpose-limited product protection when in a form that is technically adapted to a specified therapeutic purpose.32
EPC 2000: 2007 – today
The renewed Convention EPC 2000 came into force in December 2007. Article 54(4) and 54(5) EPC regarding the novelty were now amended to:
“(4) Paragraphs 2 and 3 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 53(c), provided that its use for any such method is not comprised in the state of the art.
(5) Paragraphs 2 and 3 shall also not exclude the patentability of any substance or composition referred to in paragraph 4 for any specific use in a method referred to in Article 53(c), provided that such use is not comprised in the state of the art.”
The adjusted Article now allowed for purpose-bound product claims. Before the EPC 2000 came into force, only Swiss-claims were allowed.33 Subsequently the new so-called EPC2000-claims were also allowed for second or further medical use inventions (Substance X for treatment of Z). After 28 January 2011, Swiss-claims were no longer allowed.34
31 G 5/83, point 19 of the reasons for the decision. This type of use claim is referred to as Swiss-claim because
the board relied on a statement of practice of the Swiss Federal Intellectual Property Office.
32 G 5/83, point 15 of the reasons for the decision.
33 Decision of the Administrative Council of 28 June 2001 on the transitional provisions under Article 7 of the
Act revising the European Patent Convention of 29 November 2000.
Under the current law the outcome of pharmaceutical research may be patented for three separate reasons.35
First, an NCE is developed. The patentability of an NCE is based on the pharmacological activity and is patentable under 52(1) EPC. Protection of such an invention is obtained via a product claim (Substance X, consisting of…) and protects the substance as such. This claim awards
the highest level of protection.36
Second, a specified medical application of a known substance is developed (‘first medical indication’). Such an invention is patentable under 54(4) and 53(c) EPC and claimed in a purpose-bound product claim (Substance X for the use as a medicament for…).
Third, a new specified medical application of a known substance with a known medical application is developed (‘second medical use’). Protection is granted under 54(5) and 53(c) EPC. Depending on the date of filing, the invention is claimed in the form of a Swiss-claim (Use of substance X for the manufacture of a medicament for treatment of Z) or an EPC2000-claim (Substance X for treatment of Z).37
The novelty of a second medical use invention may arise from the fact that a medicament is applied for a new indication,38 or to a different subpopulation,39 or a treatment renders a different technical effect,40 or a new mode of administration is applied,41 or a new dosage regime is applied.42
United States
The patentability of inventions is governed under §101 of the US Patent Act:43
“Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.”
35 See Appendix A for an overview. 36 Van Overwalle 2000, p. 54.
37 The EPC2000-claim confers a bigger scope of protection than the Swiss-claim. See T 1780/12, point 22 of the
reasons for the decision.
38 T 108/09.
39 T 19/86, T 893/90, T 233/96, T 1399/04, T 734/12 cf. T 708/02. 40 T 290/86.
41 T 51/93. 42 T 570/92.
Such an invention must still satisfy the remaining statutory criteria for utility, novelty44 and non-obviousness45 before the patent will be granted. Although the US Patent Act does not mention excluded subject matter, the days that “anything under the sun that is made by man is patentable”46 are long gone. In addition to the statutes, case law expressly recognises that there are three exceptions to the broad treatment of what constitutes patent-eligible subject matter: laws of nature, natural phenomena, and abstract ideas.4748
Unlike Europe, there is no statutory exclusion from patentability for medical treatment methods. This results in the allowance of claims to a method of treatment per se.49 Inventions are to be divided into four categories: a process, a machine, a composition and a manufacture.50 A process is synonymous with a method,51 and is merely a series of steps for carrying out a given task. There are three types of process patents typically related to the medical field: (1) medical procedures that do not require the use of any patented medical products, (2) methods for using a patented drug or device, and (3) techniques for isolating chemical compounds or building devices.52
Medical Treatment Methods
Since patents for medical treatment methods are allowed, one does not have to apply an artificial rule in order to patent a compound for another indication. One and the same compound may therefore feature in different medical treatment patents, as long as these methods each fulfil the patentability requirements.
US claims covering a second medical use take the form of a method (i.e. process) rather than a ‘use’ form.53 Some examples are set out below by way of comparison:54
44 Section 102 US Patent Act. 45 Section 103 US Patent Act.
46 From testimony of P. J. Federico in hearings on H.R. 3760 before Subcommittee No. 3 of the House
Committee on the Judiciary, 82d Cong., 1st Sess., 37 (1951), cited inDiamond v Chakrabarty, 447 U.S. 303, 309
(1980).
47 See Parker v. Flook,437 U.S. 584, 198 USPQ 193 (1978); Gottschalk v. Benson, 409 U.S. 63, 67, 175 USPQ 673,
674-675 (1973); Funk Seed Co. v. Kalo Co., 333 U.S. 127, 130, 76 USPQ 280, 281 (1948); O’Reilly v. Morse, 15 How. 61, 112-121 (1853); Le Roy v. Tatham,14 How. 155, 175 (1852).
48 This was also found again in more recent cases. Mayo, 566 U.S. Supreme Court(2012), Myriad, 569 U.S.
Supreme Court (2013), Alice 573 U.S. Supreme Court(2014).
49 AIPPI Q238 2014 Working Guidelines, point 26. 50 Saeh 2011, p. 7.
51 Section 100(b) US Patent Act. 52 M. Kubick 2010, p. 283.
53 See AIPPI Q238 2014 National Group: United States, question 1 and 2d). 54 AIPPI Q238 2014 Working Guidelines, point 31.
1.4 Summary
Under the EPC, further medical uses may be protected in a Swiss-claim or an EPC2000-claim. A Swiss-claim protects the use of a substance for manufacturing a medicament for treatment of a specific disease. This claim is thus classified as a purpose-bound process claim. An EPC2000-claim protects the use of a substance for treatment of a specific disease and is therefore to be classified as a purpose-bound product claim. The EPC2000-claim results in a broader scope of protection.
Under US law, a further medical use is considered to be a new treatment. Protection is granted in the form of a method of treatment claim.
Chapter 2 – Law and Practice
This chapter investigates how the regulatory system works and how it is connected to patent law. First an overview is provided of the scenery when second medical use patents are involved. This is followed by a discussion on label practice and prescribing and dispensing practice.
2.1 A Confusing Situation
The introduction of patentability of second and further medical indications makes things less clear. When the patent on a substance and the patent on the first medical indication of that substance expire (usually at the same time), anyone is allowed to produce and sell that medicine.55 However, a second medical use patent is frequently granted (years) after the granting of the patent on the substance and the first medical use. This results in a situation where on the one hand the patents on the substance (substance X) and the first medical use (indication Y) have expired, but where the patent on the second medical use (indication Z) is still valid. This is a situation that may lead to trouble because a generic company is now in fact allowed to produce and sell a generic, but only for indication Y (usually referred to as the ‘off-patent’ indication56), not for indication Z because it is still protected by a second medical use claim. It is this confused situation that makes it difficult to enforce second medical use claims.
55 These ‘copied’ medicines, comparable to the brand name counterpart in dosage form, strength, quality and
performance characteristics and intended use, are usually referred to as generic drugs or generics.
56 Not to be confused with ‘off-label use’. Off-label use is the use of drugs for an unapproved indication or in an
Fig. 2. Example of patent protection time frame. Here, a second medical indication patent is granted 10 years after the first medical indication was claimed.57
2.2 Product Label
In a situation where several indications of a drug are off-patent, while others are still protected by a further medical use patent, it is difficult for patentees to enforce their rights. This has everything to do with the regulatory framework, which seems to be entirely separate from the patent law framework.58
In every member state, an authority is entrusted with the task to grant market authorisations (MA) for a medicine. For European countries Article 11 of dir. 2001/83/EC provides that, for authorisations of generics, those parts of the summary of product characteristics (SmPC) of the reference product referring to indications or dosage forms which are still covered by patents need not be included.59 This enables generic suppliers to carve out indications which are protected by second medical use patents from their SmPCs, and hence their marketing authorisations and patient information leaflets (PILs).60 61 However, the online medicine database still shows the full product information, including patented indications.62 In practice this comes down to – and this is what Bostyn refers to63 – a situation in which the MA does not provide any information on whether an indication may be permissibly marketed, stocked, prescribed or delivered with regard to patent law. As the digital database is the leading information source for medical professionals, merely applying a carve-out seems insufficient to prevent a generic from being sold for the patented infringement.6465
57 This time frame is highly simplified. The period of clinical trials and registration is not taken into account, nor
is the situation where a supplementary protection certificate (SPC) is granted. Patents are being granted before the clinical trials. Medicines that succeed in clinical trials have to go through the registration process of the EMA or FDA in order to obtain market authorisation. This results in an ‘effective’ patent protection of 8-10 years in contrast to the depicted 20 years.
58 Bostyn 2015, p. 781.
59 Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community
code relating to medicinal products for human use. Cf. 21 U.S.C., Drug Price Competition and Patent Term Restoration Act, also referred to as the Hatch-Waxman Act, §355(j)(2)(A)(viii).
60 [2015] EWHC 72 (Pat) 21 January 2015 (Warner-Lambert v Actavis), par. 17.
61 A SmPC from which indications have been carved out is often referred to as a “skinny-label”.
62 This is at least the case in the Netherlands, but the situation is similar in other member states. The Dutch
market authority rolled out this policy in 2009, in order to provide for open access to information for prescribers and patients. See Schutjens 2015 and http://www.cbg-meb.nl/voor-mensen/voor-handelsvergunninghouders/inhoud/wettelijke-basis-van-geneesmiddelen/generiek-geneesmiddel.
63 Bostyn 2015, p. 781.
64 See also AIPPI Q238 2014 Resolution, p.4.
65 In this respect the term “cross-label use” also occurs. This is the situation where a certain drug is used for an
approved and patented indication that is not mentioned on the label instructions (possibly due to a carve-out), but is mentioned on the label instructions of another drug (usually the brand name).
2.3 Prescribing and Dispensing
The phenomenon of patent law is not an issue that pharmacists and other health care providers concern themselves with in daily practice. After a diagnosis, a doctor determines which active pharmaceutical ingredient (API) is needed.66 When prescribing, the international non-proprietary name (INN) is used.67 A pharmacist receives this prescription without the indication being noted.68 The pharmacist now searches for the specific API. It is possible that, for example, ten different manufacturers produce a medicine that features this specific API. The pharmacist could now choose one of the ten possibilities, since it is assumed that these ten options are equally effective as they all feature the same API.69
2.4 Preference Policy
Often health insurers implement so-called ‘preference policies’, which control the choices of a pharmacist. In a case where there are multiple medicines with the same pharmacological efficacy, the insurer chooses one medicine that will be reimbursed, i.e. there is one preferred medicine per API. This policy is called ‘label preference’.70
In order to determine which medicine to give preference to, insurers may organise a ‘tender’. In a tender, manufacturers are given the opportunity to bid on APIs. The manufacturer who offers to sell his medicine at the lowest price wins the tender. This implies that his medicine will be the only medicine reimbursed by the insurer when the associated API is needed. Other, more expensive, medicines are not reimbursed.71 This implies that a pharmacist is highly financially incentivised to prescribe the preferred medicine.
66 In the Netherlands the Standard of the Dutch General Practitioners Society is leading in the decision of which
API is prescribed for which diagnosis.
67 [2015] EWHC Civ 556 28 May 2015, par. 138 (Warner-Lambert v Actavis), par. 376.
68 There are some exceptions to this practice. For example in the Netherlands there are 23 medicines that need
to be prescribed together with the indication. See
http://knmg.artsennet.nl/Nieuws/Overzicht-nieuws/Nieuwsbericht/134105/Reden-van-voorschrijven-op-recept-en-labwaarden-uitwisselen.htm#23 .
69 As regards effectiveness, patient specific characteristics, such as comorbidity, side effects of certain
medicines and ease of use are also taken into account.
70http://www.mijnmedicijnvergoeding.nl/preferentiebeleid
71 An exception to this practice occurs when there is a medical necessity for a certain medicine. In such case
another, not the preferred, medicine must be reimbursed (See for example art. 2.8 (4) of the Dutch Health Insurance Decree).
It is clear that when a preferred medicine is determined by means of a tender, the decision to choose that medicine is only influenced by the price.72 The aim of preference policies is to let manufacturers compete on price, so that the total expenditure on medicines decreases.73
Next to tenders, an insurer may also determine the preferred medicine on another basis. For instance, a medicine may be picked from a public price list.74 This method leaves some additional room for factors other than price. Among the medicines with low prices, the insurer may now choose the medicine from a manufacturer who is best capable of supplying the market during the preference period.75
An insurer may also implement a ‘price preference’ policy. Under this policy the insurer sets a price up to which it is prepared to reimburse medicines, and leaves the pharmacist to decide which medicine to buy and at what price.76
In practice, whether or not under the influence of a preference policy, the pharmacist will select the most inexpensive medicine, usually a generic.77 Since the ten medicines are equally effective, the price becomes the decisive factor. No other factors are taken into account at this point.
Although it is possible for a pharmacist to check the indications for which each of the ten medicines are registered, this does not happen in practice. Since the pharmacist does not know for what indication the medicine will be used,78 checking the register does not afford any useful information since he/she will still not be able to determine whether prescribing a certain medicine will be permissible or not in the context of patent rights.79
72 See https://www.knmp.nl/praktijkvoering/bekostiging/preferentiebeleid and http://www.mijnmedicijnvergoeding.nl/index.php/over-medicijnen/preferentiebeleid.
73 See Ibidem. And see ACM Report, ‘Farmacie onder de loep’, 2015 p. 8. 74 In the Netherlands, the G-Standaard may be used.
75 See https://www.knmp.nl/praktijkvoering/bekostiging/preferentiebeleid
76 See http://www.mijnmedicijnvergoeding.nl/index.php/over-medicijnen/preferentiebeleid and http://www.nefarma.nl/website/visiedocumenten/visiedocument/preferentiebeleid
77 See AIPPI Q238 2014 National Group: Germany, question 3a(iii).
78 See AIPPI Q238 2014 National Group: Germany, question 3a(iii) and [2015] EWHC Civ 556 28 May 2015, par.
138 (Warner-Lambert v Actavis), par. 385.
79 However, there are two exceptions. First, a medicine may be prescribed along with the patient’s indication.
For example in the Netherlands there are 23 medicines that need to be prescribed together with the indication. See http://knmg.artsennet.nl/Nieuws/Overzicht-nieuws/Nieuwsbericht/134105/Reden-van-voorschrijven-op-recept-en-labwaarden-uitwisselen.htm#23 and
https://www.knmp.nl/patientenzorg/medicatiebewaking/reden-van-voorschrijven-en-labwaarden. Secondly, in some cases the pharmacist is able to deduce for what indication the medicine will be used from the dosage or mode of administration. In these cases a pharmacist is able to know whether he/she is dispensing a medicine permissibly with regard to patent law.
2.5 Summary
In practice, second medical use patents are not taken into account when it comes to the prescription of medicines. By issuing prescriptions exclusively based on the API, and not on the indication, it is highly probable that doctors unknowingly prescribe, and pharmacists dispense, medicines off-label and cross-label. The consequence of the current practice is that generics are being prescribed for a protected second medical use. Chapter three discusses whether such a case is to be classified as a patent infringement.
Chapter 3 - Scope and Infringement
This chapter seeks to determine the scope of protection of second medical use inventions and to address the infringement of these patented inventions. Despite great similarities between national provisions, the scope of protection and ruling on infringement differs between Europe and the US as well as within Europe. In order to address those differences, a fictional casus is provided. Subsequently the fictional outcome in different countries will be treated based on recent case law.
3.1 InnovaThor v Generix
In a member state of Eponia, InnovaThor develops a medicine for the treatment of a specific headache. This medicine consists of the substance ‘reparatum’. The substance and the medical indication are patented. Subsequently a market authorisation is granted and InnovaThor starts marketing its medicine under the brand name Repair®. Five years later InnovaThor discovers that reparatum is very effective to treat foot pain (a common ailment for which strangely enough no treatment has been developed yet). InnovaThor applies for patent protection of this second medical use of the substance reparatum. The second medical indication is added to the patent, claimed Swiss-style. Claim 3 reads:
“Use of reparatum for the manufacture of a medicine for treatment of foot pain.”
An independent market study shows that in 80% of the cases, Repair® is being sold for the indication of foot pain, and only in 20% of the cases for headache.
As soon as the patent protection of the substance reparatum and the first medical indication expire, Generix starts manufacturing a generic reparatum. The company quickly obtains a MA via article 10 of Directive 2001/83/EC. Before Generix starts marketing its generic reparatum, it requests the Central Authority for Carve-Outs (‘CACO’) to exclude the indication of foot pain from its SmPC and PIL (provided for under art. 11 of Directive 2001/83/EC), since this indication is still protected by InnovaThor’s patent. However, CACO exercises a policy in which it only carries out the carve-out on the physical SmPC and PIL. Health care professionals such as prescribers and pharmacists always use digital or online information. This implies that to practitioners the medicines Repair® and the generic reparatum are the same, as they both contain the API reparatum.
Furthermore, rules and regulations require that practitioners prescribe a medicine on the basis of the INN, without including the indication.
For one year this practice does not pose problems. The two products are being prescribed alongside each other. Repair® is being prescribed for headache and foot pain (since practitioners are used to prescribing Repair® for those indications) and more and more of Generix’s generic reparatum are being prescribed for headaches, since Generix advertises its product for this indication.
During that first year, the products are equally expensive. But then Generix lowers its product’s price, making it attractive for pharmacists to dispense the generic reparatum instead of Repair®. In addition, Generix enters into a rebate agreement with a health care insurer. Generix’s reparatum is now the preferred product when reparatum is needed (regardless of the indication). From now on, only Generix’s product would be reimbursed in many hospitals and general practices in case reparatum is prescribed. These developments cause a major change to the market. The sales of Generix’s product increase and the sales of Repair® drop.
From the sales figures it becomes clear that Generix’s product is not only being dispensed for the off-patent indication headache, but also for the protected indication foot pain. Thus, InnovaThor sues Generix on the basis of direct and indirect infringement of its second medical use claim.
3.2 Europe
Infringements of European patents are dealt with by national law.80 The provisions of the Patent Acts of the UK, Germany and the Netherlands each contain the following components with regard to the infringement of a process:
A person infringes a patent for an invention
• Where the invention is a process and he uses the process without consent of the proprietor, knowing that this use without consent would be an infringement.81
• Where the invention is a process, he offers any product obtained directly by means of that process.82
• When he supplies any of the means, relating to an essential element of the invention, for putting the invention into effect when he knows that those means are suitable and intended to put the invention into effect.83
80 Art. 64(3) EPC.
81 Section 60(1)(B) UK Patents Act, §9(2) German Patent Act, art. 53(1)(B) Dutch Patent Act. 82 Section 60(1)(C) UK Patents Act, §9(3) German Patent Act, art. 53(1)(B) Dutch Patent Act.
3.2.1 United Kingdom
A very similar situation was at issue stake in the case Warner-Lambert v Actavis. Warner-Lambert (hereinafter WL) marketed a medicine, pregabalin (Lyrica®), for three different indications. Two of the three indications were off-patent. One indication, treatment for pain relief, was protected by a further medical use patent. Actavis (hereinafter AC) applied for a market authorisation for a generic version of the drug, limited to the two off-patent indications, and marketed it under Lecaent®.
AC notified prescribers and pharmacists that Lecaent® was not to be used for the pain indication. Still, WL was concerned that the generic drug would be dispensed for the patented further medical use, because most prescriptions are written generically (i.e. by INN). WL also argued that, because the generic drug is usually cheaper than the patentee’s product, pharmacists have a financial incentive to dispense the generic version of the drug unless steps are taken to prevent this.
Warner-Lambert I
Since WL’s invention was claimed Swiss-style, WL sought injunctive relief on the basis of 60(1)(c) and 60(2) UK Patents Act.84 In first instance at the High Court of Justice, WL contended that Lecaent® is a product obtained directly by means of the process of claims 1 and 3 of WL’s patent.85 The dispute is based on whether the manufacture of pregabalin by AC would fall within the claims of WL’s patent.86
The indication of pain is claimed in claims 1 and 3 as follows:
“1. Use of [pregabalin] or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain.
3. Use according to Claim 1 wherein the pain is neuropathic pain.”87
It was held that in the UK the term “for” is traditionally interpreted as “suitable and intended for”.88 It is further common ground that Lecaent® is a product which is suitable for treating pain. But it remains unclear whether Lecaent® is a product obtained by use of pregabalin for the preparation of a pharmaceutical composition which is intended for treating pain.89 Therefore the meaning of this intention in the clause “suitable and intended for” must be determined. Whose intention was relevant?90 And what did the requirement of intention comprise?91
As submitted by AC, Judge Arnold held that WL’s claim is to a process of manufacture. It follows that the relevant intention thus must be understood as that of the person who carries out the process, i.e. the manufacturer.92
Concerning the requirement of intention, WL submitted “that it was sufficient for this purpose that Actavis intended to sell pregabalin and knew that pharmacists were likely to dispense it for treating (neuropathic) pain (…)”. AC contended that such knowledge is not sufficient and that what is required is a ‘subjective intention’ on their part that the pharmaceutical composition should be used for treating pain.93 This was accepted by the court.94 The mere
84 [2015] EWHC 72 (Pat) 21 January 2015 (Warner-Lambert v Actavis). 85 Ibidem, par. 94.
86 Ibidem, par. 95. 87 Ibidem, par. 15.
88 Ibidem, par. 97 with reference to [2014] EWHC 1094 (Pat) (Hospira UK Ltd v Genentech Inc), par. 58. 89 Ibidem, par. 98.
90 Ibidem, par. 99. 91 Ibidem, par. 100.
92 Ibidem, par. 99 and 96 with reference to Actavis v Merck, par. 75. 93 Ibidem, par. 100.
knowledge, or fact, that it is foreseeable that the product will be sold for the patented use, was considered to be insufficient to establish infringement.
As regards indirect infringement, it is common ground that the person at the end of the supply chain must have the intention to put the invention into effect.95 However, it seems difficult to prove indirect infringement of a Swiss-claim (Use of substance X for the manufacture of a medicament for treatment of Z). The end user is not likely to use substance X for the manufacture of a
medicament. The substance is merely used for treatment. After a medicament is manufactured, there are no other persons the chain of supply who will apply the claimed process. This is referred to as the absence of a downstream event beyond the manufacturer. Neither a doctor prescribing, nor a pharmacist dispensing or a patient using substance X use it for the manufacture of a medicament. They simply use it for treatment.
Arnold J. indeed held that there can only be indirect infringement “if there can be infringement by the person supplied or by a user further down the chain of supply (although it is not necessary for there actually to be an infringing act). This is not the case here, since no wholesaler or pharmacist will use Lecaent to prepare a pharmaceutical composition.”96 No indirect infringement was established.
Warner-Lambert II
In appeal of the preliminary decision, Judge Floyd held that he can see no reason why the skilled person would conclude that the word “for” implied subjective intent. 97 Infringement on the basis of 60(1)(b) UK Patents Act does therefore not require a subjective intention. In his judgment, the skilled person would understand that the patentee was using the word “for” in the claim to require that the manufacturer knows or can reasonably foresee the ultimate intentional use for pain, not that he has that specific intention or desire himself.98 Floyd J. thus considered that there are two mental elements involved in the claims:
1. Knowledge and foreseeability of the manufacturer about;
2. The intentional use by the end user.99
He agreed with WL’s attorney that a requirement of subjective intent will rob Swiss-claims of much of their enforceability. Such a requirement would mean that the patentee must
95 [2010] EWCA Civ 1260 (KCI Licensing Inc v Smith & Nephew plc), par. 53 (with references to [2010] EWCA Civ
1110 (Grimme Maschinenfabrik GmbH & Co KG v Scott)).
96 Ibidem, par. 113.
97 [2015] EWHC Civ 556 28 May 2015, par. 127. 98 Ibidem.
prove that it is AC’s wish or desire to sell some Lecaent® for pain relief.100 Answering the question of infringement under 60(1)(b) UK Patents Act, Floyd J. held that a manufacturer is infringing when he manufactures pregabalin when he knows or foresees that users will intentionally
administer it for pain relief.101
In contrast to Arnold J., Floyd J. did see reasons to allow the indirect infringement case to go to trial.102 Firstly, because “courts of two EPC member states considering the same question have held that, at face value, indirect infringement can arise in these circumstances”.103 Secondly, if there is “infringement of the process claim under §60(1)(b), then it follows that dealings downstream in the direct product of the process are also infringements under §60(1)(C). Although this may not add anything to the direct infringement case, it is wrong to strike it out as a viable additional cause of action.” 104 And finally, he considered that “it is arguable to say that when §60(2) speaks of ‘putting the invention into effect’, it may be legitimate to look not just at whether any one person is carrying out the invention in a sense which would give rise to liability of that person for an act of infringement. It may be that the invention is put into effect if pregabalin is manufactured by one person and supplied to another who intentionally uses it for the treatment of pain. In those circumstances, a person who supplies pregabalin with the requisite knowledge (i.e. that prescribed in §60(2) itself) does provide means suitable and intended to put the invention into effect, albeit by the combination of manufacturer and user, rather than by any one person alone. It may be that this is the reasoning which underlies the decisions in the Dutch and German cases which I have referred to.”105
Warner-Lambert III
In the proceedings on the merits, Arnold J. held (as he did earlier106) that “for” in a Swiss-claim should be interpreted as requiring an intention on the part of the manufacturer.107 Merely the foreseeability that the drug would be used for the patented indication is not enough, it also needs to be proved that the drug was intentionally administered for the patented use. He arrived at the
100 Ibidem, par. 126. 101 Ibidem, par. 129. 102 Ibidem, par. 135.
103 Ibidem, par. 136. Floyd J. refers to the cases Hamburg District Court, Case No. 327 O 140/15, decision of 2
April 2015 – (Warner-Lambert v Aliud) – Pregabalin and Court of Appeal of The Hague, 27 January 2015 (Novartis v Sun).
104 Ibidem, par. 137. 105 Ibidem, par. 138.
106 [2015] EWHC 72 (Pat) 21 January 2015 (Warner-Lambert v Actavis), par. 97.
conclusion that AC did not infringe on claims 1 or 3 of WL’s patent, as AC never intended
Lecaent® to be used to treat pain.108
As regards this intention, it was held that a doctor prescribing pregabalin generically would not have the necessary intent. Infringement must depend on what the manufacturer can foresee happening with his product. Because a doctor prescribes pregabalin generically (thus from any manufacturer), he would not be intending to prescribe Lecaent® in particular.109
A pharmacist dispensing any generic pregabalin by order of a prescription without the indication would for the same reason not have the necessary intent.110 Dispensation Lecaent® for pain relief in a case where the indication is given, would however prove the intention. The patient’s intention is irrelevant.111
When Arnold J. applied Floyd J.’s requirement of knowledge and foreseeability of the manufacturer about the intentional use by the end user, he came to the same conclusion as with his own approach: no infringement. He considered that it was not foreseeable to AC that Lecaent® would be intentionally administered for the treatment of pain because Lecaent® was marketed under a skinny label and because of the preventive actions AC took. Taking into account that only some Lecaent® (5% of the prescriptions) would be dispensed for pain and considering the actions AC undertook to prevent sales of Lecaent® for pain, it was concluded that AC did not infringe WL’s patent pursuant to §60(1)(c).112
Arnold J is ‘puzzled’, ‘baffled’ and simply does not understand Floyd J’s considerations on indirect infringement.113 He sticks to the position that a downstream event is necessary for the establishment of an indirect infringement. He does acknowledge that “Lecaent’s active ingredient is ‘means, relating to an essential element of the invention for putting the invention into effect”’. But it is not suitable for putting, or intended to put, the invention into effect because of the lack of a downstream event.114 He concludes that AC has not infringed claims 1 and 3 of WL’s patent pursuant to §60(2) UK Patents Act.
Outcome - InnovaThor v Generix
The case InnovaThor v Generix differs from the Warner-Lambert case for two reasons. First, Generix entered into a rebate contract, resulting in its product being the preferred medicine, 108 Ibidem. 109 Ibidem, par. 637. 110 Ibidem, par. 638. 111 Ibidem, par. 639. 112 Ibidem, par. 663-677.
113 [2015] EWHC 2548 (Pat) 10 September 2015 (Generics v Warner-Lambert), resp. par. 679, 681, 683. 114 Ibidem, par. 684.
regardless of indication. Secondly, Generix did not notify prescribers that its product is not to be used for the patented indication of foot pain. These two differences may lead to the establishment of infringement by Generix.
By applying a carve-out, Generix shows that it does not intend its product to be used for treatment of foot pain.115 However, it is questionable whether a skinny label alone means that it is no longer foreseeable for Generix that its product is being intentionally administered for treatment of foot pain. Besides, Generix entered into a rebate contract. This act should be assessed as a strong factor contributing to the intention of Generix.116 One of the conditions of the rebate contract is that Generix’ product will be prescribed for headache as well as for foot pain. Generix knows this. The rebate contract therefore means that Generix can no longer credibly argue that it is not foreseeable that its product will be administered intentionally for the indication of foot pain.
Commentary
The approach applied by Arnold J. implies that a carve-out, accompanied by a notice to prescribers and pharmacies, should be sufficient to prove the lack of a subjective intention of the generic manufacturer.117 Although the concept of a skinny label is conceived to allow generic manufacturers to market a medicine for off-patent use, it does not exempt manufacturers from any other reasonable responsibilities. A notice, warning prescribers and pharmacists, could be an embodiment of such reasonable responsibility. However, a skinny label together with a warning notice turned out to be insufficient in preventing Lecaent® from being prescribed or dispensed for the indication occurring in WL’s claims.
By applying a skinny label and warning prescribers and pharmacists, AC may have made it clear that it is not its subjective intention for Lecaent® to be used for the treatment of pain. However, AC did profit from the fact that its product was sold for the patented indication, at the expense of WL. It could be arguable that therefore the actions taken by AC should not be sufficient to escape liability.
It should be understood that there is some leeway between not having a subjective intention and the situation in which there is clearly no patent infringement. This implies that
merely the lack of a subjective intention should not absolve one from liability.
115 Cf. [2015] EWHC 2548 (Pat) 10 September 2015 (Generics v Warner-Lambert), par. 664. 116 See Blomme 2015, p. 93.
As discussed above and in the case at hand, a medicine is generally prescribed by reference to its generic name. This means that a notification is only effective when executed together with a different manner of prescribing. Because only when a pharmacist knows for what indication the generic pregabalin is prescribed, he/she is able to choose the appropriate medicine. Consequently, a pharmacist is capable of dispensing a medicine with respect to AC’s warning, resulting in the dispensation of Lyrica® when pregabalin is prescribed for pain relief.
Returning to the requirement of subjective intention, it must be concluded that this requirement does not serve to answer the question of liability. As in the present case, no subjective intention can be proven, while it follows from the facts that a generic is being sold for a patented use. Consequently, another requirement should be used, or the requirement must be treated differently.
3.2.2 Germany
Section 2a(2) of the German Patent Act contains a provision corresponding to Article 53(c) EPC. In contrast to what the EBA would later hold in its case G 5/83, the German Federal Supreme Court interpreted this section, then §5(2) German Patent Act, as not excluding the patentability of an invention entailing the use of a known substance for the treatment of a disease.118 This decision implied that medical use claims as defined under the EPC-2000, were allowed in Germany beginning in 1983. After G 5/83 (1984) was granted, medical use claims in Germany were formulated either as ‘direct’ medical use claims or as Swiss-claims. Remarkably, the Supreme Court held that the scopes of such direct use claims and Swiss-claims were to be interpreted in approximately the same way.119
According to the Supreme Court, this scope includes the mere application of the substance for the protected purpose and the ‘sinnfällige Herrichtung’ of the substance for that purpose.120 What this term means will likely remain a mystery for non-native German speakers, as many translations exist. Common translations include: displayed formulation, 121 obvious orientation,122 manifest arrangement,123 physical manifestation124 and evident preparation.125126
118 BGH , 20 September 1983 - X ZB 4/83 : BGH, “Hydropyridin”. Translation derived from F-J, Zimmer and S.M.
Zeman, ‘The Enforceability of Medical Use Claims in Germany’, 2006, p. 2. Accessible here:
http://www.grunecker.de/files/medicaluse.pdf
119 BGH , 20 March 2001 - X ZR 177/98 – Trigonellin.
120 See BGH , 20 September 1983 - X ZB 4/83 : BGH, “Hydropyridin”, at 216-217; OJ EPO 1/1984, p. 28, point 2
(Hydropyridine), with reference to Sitosteryl glycoside, IIC 14, 283 (1983) and Benzolsulfonylharnstoff, IIC 5, 42 (1987).
121 See Benyamini 1993, p. 84; OJ EPO 1/1984 (Hydropyridine), p. 29. 122 Benyamini 1993, p. 85.
According to the Supreme Court, the use of a substance can be susceptible of industrial application, because the sinnfällige Herrichtung of the substance for the therapeutic purpose in the invention could be performed in the industrial sector.127 This implies that a second medical use invention does not merely consist of elements not susceptible of industrial application, such as the doctor’s treatment, but also exist of elements that are susceptible of industrial application, grouped under the term sinnfällige Herrichtung. Such elements of sinnfällige Herrichtung may include the acts of formulation and confectioning of the medication, preparing ready-for-use packaging together with instructions and its dosage, product information, and the label.
The scope of a ‘German-claim’ is not confined to the use of a substance for manufacture. It also includes the use of the substance for treatment as such and acts of sinnfällige Herrichtung. Therefore, a German-claim must be considered as a purpose-bound product claim.128129
The German courts use the principle of sinnfällige Herrichtung when interpreting Swiss-claims. Such a sinnfällige Herrichtung is established when e.g. label instructions of a generic describe the patented use. Adding such label instructions constitutes a manifest arrangement for the claimed use, and may therefore confer liability for infringement.130131 However, this general principle was restricted in Ribavirin.132 It was held that there is no infringement in the case where a generic is used to treat 50% of a certain patient group, although the patient group is the subject of a second medical use patent. No manifest arrangement can be established when the purpose to treat the specific patient group is not mentioned in the label instructions.
With regard to infringement it was also held that the mere advertising of a medicine for the patented use in marketing materials, flyers and advertisements by sales people (even if they are employees of the generic manufacturer) does not constitute a manifest arrangement.133 The reason for this line of thought is that it is uncertain whether the recipient of the marketing
124 [2015] EWHC Civ 556 28 May 2015 (Warner-Lambert v Actavis), par. 75.
125 F-J, Zimmer and S.M. Zeman, ‘The Enforceability of Medical Use Claims in Germany’, 2006, p. 3. Accessible
here: http://www.grunecker.de/files/medicaluse.pdf
126 As there is no consistent translation, the original German wording is used.
127 OJ EPO 1/1984 (Hydropyridine), p. 29-30, with reference to Sitosteryl glycoside, IIC 14, 283 (1983). 128 BGH , 20 September 1983 - X ZB 4/83 : BGH, “Hydropyridin”, at 219.
129 Cf. T 1780/2 , point 22 of the reasons. The EPO considers Swiss-claims to have a narrower scope than
EPC2000-claims.
130AIPPI Q238 2014 National Group: Germany, question 3a).
131 Label instructions describing the patented use are treated as an element of “manufacture” as referred to in
a Swiss-claim.
132 Düsseldorf District Court, Case No. 4a 0 12/03, decision of 24 February 2004, GRUR-RR 2004, 193- Ribavirin. 133 Düsseldorf Court of Appeal, Case No. 2 U 54/11, decision of 31 January 2013 – Cistus Incanus; Düsseldorf
