Protection and enforcement of second medical use claims
Second medical use claims have become the second most important claim category – next to product claims – for therapeutics. Second medical use claims provide the required protection for originator companies to recoup research investments in therapeutic advances based on known chemical entities. They are also regularly used for lifecycle management purposes to provide additional protection after the expiry of patents that provide product protection for the drug of interest. Given the importance of second medical use claims in the protection of both new and established blockbuster drugs, this is an area of constant legal activity – which is reason enough to keep up to date with developments at the European Patent Office (EPO) and in a key European jurisdiction for pharmaceutical litigation – Germany.
Obtaining second medical use protection at the EPO
In Europe, the EPO is the pre-eminent patent examination and granting authority for inventions in the pharmaceutical and biotech sector, given that pan-European protection is of particular importance in this field. The EPO generally accepts second medical use claims in the format ‘Compound X for use in the treatment of disease Y’. Other similar wordings are also accepted and nicely summarised in the EPO Guidelines for Examination (see G-VI 7.1.2). The above-cited wording is based on Article 54(5) of the European Patent Convention (EPC), which provides the statutory basis for second (or further) medical use claims at the EPO. According to Article 54(5), a substance or composition – but not a device – of the prior art “for any specific use” in a method referred to in Article 53(c) of the EPC is novel if the specific use is not disclosed in the prior art. Article 53(c) excludes from patentability methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practised on the human or animal body. Thus, a compound for any specific use in a method of treatment is novel if this use is not part of the prior art. In this way, the EPC explicitly provides purpose-limited product protection for inventions that can be protected by neither a product claim, due to lack of novelty, nor a method claim, due to exclusion from patentability.
Second medical uses in applications with a filing or earliest priority date of January 29 2011 or later can be claimed only according to the above-cited purpose-limited product claim language in accordance with Article 54(5) of the EPC. So called ‘Swiss-type’ claims of the format ‘Use of compound X for the manufacture of a medicament for therapeutic application Z’, which were previously accepted by the EPO, are no longer admissible. However, if the application has a filing or earliest priority date before January 29 2011, Article 54(5)-type claims and Swiss-type claims may be used, even in the same claim set, since they are considered to relate to different subject matter (T1021/11). Based on this interpretation, pursuing both claim types in the same application – as long as the application pre-dates January 29 2011 – is generally advisable.
Based on the interpretation that Swiss-type claims and Article 54(5)-type claims pertain to different subject matter, the Technical Boards of Appeal have also stated in at least two independent decisions (T1780/12 and T0015/14) that two patents may be obtained by the same applicant with the same effective date, one claiming a second medical use in Swiss-type format, the other in Article 54(5)-type format. Since these claim formats relate to different subject matter, obtaining two such patents does not amount to double patenting. The Technical Boards of Appeal also ruled that Swiss-type claims and Article 54(5)-type claims do not have the same scope of protection (T250/05).
The boards of appeal have been particularly busy determining what renders a second medical use claim novel over the prior art. According to Article 54(5), it can be “any specific use” that is not disclosed in the prior art and falls under the exclusion of Article 53(c). In the seminal Decision G2/08 it was decided that “any specific use” is not limited to the treatment of a new illness. Rather, a different treatment of the same illness may also be novel (eg, if a different dosage regime is used). Dosage regime claims typically relate to specific amounts of the compound or a specific administration schedule that is associated with a useful technical effect. The mode of administration (eg, intramuscular versus subcutaneous injection) may also constitute a novel specific use.
It is further established practice that the use of a known compound in the treatment of the same disease may represent a novel therapeutic application if it is carried out on a new group of subjects which is distinguished from the former by its physiological or pathological status. However, the new patient group should not overlap with the patient group of the prior art.
Applicants are often interested in obtaining second medical use protection for a new mechanism of action in the treatment of the same disease with the same compound. However, this is typically possible only if the new mechanism of action corresponds with a new clinical situation that can be distinguished from the situation of the prior art (eg, prophylaxis instead of treatment or bactericidal effect instead of inhibition of bacterial toxin). On the other hand, case law holds that the mere identification of an underlying mechanism of action cannot confer novelty on a known use.
Established case law requires that the therapeutic effect mentioned in the claim be made plausible by the patent application as filed. While in exceptional cases this requirement may be fulfilled without the presentation of experimental results (T920/10), in most cases experimental results should be filed with the original application in support of the claimed therapeutic effect. At the date of filing, the claimed compound must not necessarily have already been tested in clinical trials, let alone have been approved as a drug. However, preferably, animal data in a relevant disease model should be filed to support the therapeutic effect. If animal data is not available, even in vitro data may be sufficient to render a therapeutic effect plausible if there is a clear and accepted established relationship between the observed physiological activities and the disease. In each individual case a balance must be struck between the requirement for sufficient disclosure of the therapeutic effect – potentially delaying application filing – and the need for early filing.
Broad functional definitions of the compound for use in a therapeutic application are problematic before the EPO, but not in Germany and other jurisdictions. For instance, in Decision T1151/04 the underlying patent was revoked due to the broad functional definition of the compounds in question as “activity lowering effectors of dipeptidyl peptidase IV (DP IV) or DP IV-like enzyme activity”. No structural feature of the DP IV inhibitors was recited in the claims. The board found that the subject matter was not sufficiently disclosed. Additional structural limitations should therefore always be included in the application as potential fall-back positions.
The overwhelming majority of second medical use patents in Europe are granted by the EPO (rather than national patent offices). However, in general, second medical use applications may also be filed with individual national patent offices. National patent applications are examined and granted according to the national patent laws. Further, revocation proceedings – during which the validity of the granted patent is assessed, even of the national parts of a European patent – must be brought before the national courts (until the Unified Patent Court (UPC) begins operations). In these cases, national courts apply and interpret the EPC. Questions of infringement are presently also dealt with by the national courts. Thus, with respect to the allowability, validity and infringement of second medical use claims in Europe, the situation in individual states must also be factored in.
Validity of second medical use claims in Germany
Purpose-limited product claims and medical use claims have long been available in Germany. In the past, both the German Patent Act and the EPC excluded methods of treatment from patentability based on the legal fiction that such methods lack industrial applicability. EPO case law provided a way around this exclusion through Swiss-type claims (G5/83) directed to use for manufacturing a medicament, which was considered industrially applicable. In contrast, German courts resorted to the concept of ‘manifest preparation’. According to this legal concept, the subject matter of a use claim extends beyond the literally recited use and includes the preparation of a product for the claimed use. Following this interpretation, use claims of the type ‘Use of compound X for the treatment of disease Y’ also included the manifest preparation of the compounds for the treatment of the disease as part of the claimed subject matter. Therefore, German courts considered medical use claims to be industrially applicable and thus allowable.
Today, the situation with regard to the validity and allowability of second medical use claims as judged by German courts and the German Patent and Trademark Office is to a large degree in sync with EPO practice. This is true for German patent applications dealt with under the German Patent Act and German parts of European patents dealt with under the EPC. The wording of the relevant statutes in the Patent Act and the EPC is virtually identical. The Patent Act also acknowledges novelty for specific uses in a method of treatment and diagnosis of compounds or compositions if the specific use is not part of the prior art. The Patent Act also excludes methods of treatment and diagnosis from patentability.
In 2007 the Federal Court of Justice decided (Carvedilol II) that the specification of a dosage regime in a Swiss-type claim is not amenable to industrial application, since it is a fundamental part of the medical practitioner’s activity; therefore, according to the court, a dosage regime cannot confer novelty on the claimed subject matter. However, in two more recent decisions (Collagenase I and II) the court opined that – at least for purpose-limited product claims in the sense of Article 54(5) of the EPC and Section 3, Paragraph 4 of the Patent Act – a new dosage regime or other modalities (eg, mode of administration and patient sub-group) may confer novelty. With these decisions, German case law is converging with EPO practice with regard to what constitutes a specific use that confers novelty on a second medical use.
An important difference between German case law and EPO practice with regard to the validity and allowability of second medical use claims is that German courts are more favourable when it comes to the broad functional definition of compounds in the context of second medical use claims. For instance, in a case concerning a patent of the same family as the above-referenced European DP IV patent, the Federal Court of Justice considered the broad functional definition ‘inhibitor of the enzyme activity of DPIV’ allowable (in contrast to the EPO Board of Appeal). Thus, in certain cases it might be an interesting option for applicants to file a German national patent application in parallel with the European application or to branch off a German utility model from the European application to increase the likelihood of a broader scope of protection, at least in Germany.
Enforcement of second medical use claims in Germany
For the assessment of infringement of second medical use claims, the German courts have also applied the concept of manifest preparation. Established case law holds that a drug manufacturer can be held liable for direct infringement if it produces the compound recited in the second medical use claim in such a way that it is manifestly prepared for the claimed therapeutic use. For example, a product is manifestly prepared for a particular therapeutic use if how it should be used is evident from the product itself (eg, from the formulation, dosage, packaging or patient information leaflet). Mere general statements (eg, advertising) that are not directly linked to the product in question have not been considered by the courts to constitute manifest preparation. Thus far, the courts have decided only on cases concerning Swiss-type second medical use claims that expressly recite the manufacturing process of the medicament. As such, the manifest preparation (manufacturing) is – unsurprisingly – considered an infringing act. The question remains as to how the courts will treat an Article 54(5)-type claim that recites only the therapeutic use and the compound, but no manufacturing step.
According to earlier – and controversial – German case law, the indirect infringement of a second medical use claim presupposes that the compound is offered or supplied for the purposeful arrangement of the compound. However, the offer or supply for immediate use in the therapeutic method was not considered to constitute indirect infringement (Ribavirin 2004). Explicitly deviating from this case law, in a more recent decision the Hamburg Regional Court granted a preliminary injunction against multiple generic companies in the much-discussed Pregabalin/Lyrica litigation involving Pfizer’s patent on a neurophatic pain medication. In this case, the court granted the injunction based on indirect infringement as the generic companies had participated in public tenders for rebate contracts with insurers without clarifying that the skinny-labelled generic version (not mentioning the patented neurophatic pain application) could not be prescribed to patients for the patent-protected indication. Again, this decision concerned a Swiss-type claim and it remains to be seen how this will play out with Article 54(5)-type claims. In addition, the appeal against the decision is pending (meanwhile, the Pfizer patent has been revoked at first instance by the Federal Patent Court).
While the courts have not yet decided on the infringement of an Article 54(5)-type claim, the Federal Court of Justice recently made some important comments in this regard in its Pemetrexed decision. The court essentially equated the subject matter of Swiss-type claims and Article 54(5)-type claims, holding that, in substance, they are both purpose-limited product claims. With this position, the Federal Court of Justice stands in direct opposition to EPO case law, according to which Swiss-type claims and Article 54(5)-type claims relate to different subject matter and have different scopes. This equation of Swiss-type claims and Article 54(5)-type claims may suggest that the German case law which so far has been based on Swiss-type claims will also be applied to Article 54(5)-type claims.
With many stakeholders involved, a complex legal landscape and significant advances in the pharmaceutical and biopharmaceutical sciences, the area of second medical use claims will keep practitioners on their toes for years to come. With the UPC system on the horizon (planned to start as early as 2017), another facet should come into play very soon. There is no way of predicting how the UPC will interpret the validity and infringement of Swiss-type and Article 54(5)-type second medical use claims – so stay tuned.
Grünecker Patent Attorneys and Attorneys-at-Law
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Markus Grammel joined Grünecker in 2012 and works as a German patent attorney in the biotechnology department. He graduated with a diploma in biology from the Technical University of Munich and a PhD from the Rockefeller University in New York. During his diploma studies, he conducted research at the Max-Planck-Institute of Biochemistry in Martinsried and the Ludwig Institute for Cancer Research in Melbourne, and studied at the Hong Kong University of Science and Technology. Mr Grammel has experience in drafting and prosecuting patent applications in a variety of technical fields, including biotechnology and pharmaceutical chemistry, and is regularly involved in opposition and appeal proceedings. His practice further includes opinion work for all patent-related IP matters.
Heike Vogelsang-Wenke joined Grünecker in 1987 and co-heads its biotechnology department. She has a strong background in biotechnology (with diplomas in both chemistry and biology) and molecular biology (the subject of her PhD). She has built up extensive experience drafting and prosecuting patent applications before the European and German patent offices. Her practice focuses on opposition and appeal proceedings and she routinely represents opponents and patentees in multi-party proceedings. Her practice also includes representing clients in invalidation proceedings before the German Federal Patent Court and the German Supreme Court, as well as in infringement proceedings before the German federal district and appeal courts. Her main technical expertise is in pharmaceutical chemistry, biochemistry, immunology, virology and general recombinant DNA technology.