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Second Medical Use Claims Revisited

by Dr. Markus Engelhard, Boehmert & Boehmert, München,  Germany

Background

In scenarios where a compound per se is already known but a specific medical use is not, it is possible to nevertheless obtain a patent for such a medical use, provided it fulfills the usual patentability requirements. This has been and continues to be practice at the European Patent Office (EPO) which has granted so-called second medical use claims for over thirty years (see decisions of the Enlarged Board of Appeal of the European Patent Office (G1/83, G5/83 and G6/83). According to the European Patent Convention, methods of treatment of the human body are not patentable but substances or compositions for the use in any such methods are. Historically, the EPO first endorsed the practice of claiming new medical uses of known substances in the so-called “Swiss-type” format, which is the “use of compound/substance X for the manufacture of a medicament/pharmaceutical composition for the treatment of disease Y”. Later on, the EPO’s Enlarged Board of Appeal switched to the so-called “EPC 2000 format”, namely “substance/composition comprising compound X for treating or preventing disease Y” or “substance/compound X for treating disease Y” (decision by the Enlarged Board of Appeal G2/08).

There is considerable body of case law from the European Patent Office with respect to the patentability of such claims, with all decisions essentially dealing with the question under which circumstances patents may be granted in respect of second medical use inventions. Second medical use patents are considered an important asset of/for pharmaceutical manufacturing companies, given that they allow to protect pharmaceutical inventions even when product protection as such is no longer available. Such second medical use patents may thus provide an incentive for investment and research and development into pharmaceutical inventions, as they promise a return on investment for pharmaceutical manufactures, provided such second medical use patents can be successfully enforced. At the same time, however, a fair balance must be struck between the interests of investing innovator companies versus the public’s interest in access to affordable medicines and in the prevention of an abuse of the patent system to provide evergreening patent protection.

In comparison to the abundance of decisions dealing with the patentability of second medical use claims, until recently, there have been surprisingly few decisionsdealing with such claims in infringement proceedings. In the following, we shall briefly review the situation with respect to the interpretation and the enforcement of second medical use patents in Germany.

Although Swiss-type claims are no longer granted by the EPO, there are nevertheless still numerous second medical use patents with such claim format existing, and the decisions that are dealing with the enforcement of second medical use claims are at present exclusively concerned with such Swiss-type claims.

The Ribavirin Cases

Claim 1 of EP 0 903 148 relates to the use of ribavirin for the manufacturing of a medicament for the treatment of patients having chronic hepatitis C infection, wherein the ribavirin is administered in combination with interferon alpha for a specified time period and the patient is characterized by specific features, such as viral load and HCV genotype. The alleged infringer marketed ribavirin capsules together with a package leaflet, wherein the treatment of hepatitis C patients was mentioned only in the context of a ribavirin monotherapy or as a combination therapy with interferon alpha but the specific patient group was not mentioned. The District Court of Düsseldorf came to the conclusion that there is no direct patent infringement of the claim because there was no “evident or manifest preparation” for the patented subject matter. Because the package leaflet lacked a disclosure of important features, such as the specific patient group to be treated, the package leaflet could not be considered an “evident or manifest preparation” for the patented subject matter. The principle of an “evident or manifest preparation” (stemming from various earlier patentability decisions of the Federal Court of Justice, such as “Benzolsulfonylharnstoff”, “Sitosterylglycosid”, “Hydropyridin” and others) is based on the notion that patent infringement effectively occurs already in the manufactured product itself, for example the packaging, the label, the package leaflet, the summary of product characteristics (SmPC), the confectioning or the dosage of the product units sold,the rationale being that the manufacturer has effectively performed all the relevant acts for infringement of the claim, by manufacturing the drug and labelling it accordingly such that the patented medical use will inevitably and automatically follow.

In a related case also concerning ribavirin, again dealing with the use of ribavirin for the manufacture of a medicament for the treatment of HCV infections in combination with interferon alpha in yet further specific groups (EP 0 956 861 B1), the alleged infringer had, again, avoided a specification of the specific patient groups, but had nevertheless advertised the drug for, inter alia, the patented use in flyers, marketing materials and various advertisements. The Court came to the conclusion that such acts of advertising for the patented use did not constitute a direct patent infringement, as the marketing material and the advertisements were not directly linked to the product and therefore did not form part of an “evident or manifest preparation”. The Court also denied an indirect infringement because the defendant did not offer the drug for an act of manufacturing as would be required by the claim language.

Hence, according to this established, albeit sometimes debated, line of case law, a pharmaceutical manufacturer can be held liable for patent infringement if it produces and markets the respective drug in a manner that can be considered an “evident preparation” of the product for the patented use. Hence, if no such link from the product to the patented use can be unequivocally established, then a German Court following this reasoning will not find for direct or indirect infringement. As a consequence, under this case law, a carving out of patented indications from the product leaflet to produce a “skinny labeling” is possible. As a result thereof, the patentee may not enjoy protection from a potential cross-label use of the drug.

It should be noted that all of these decision have been in relation to claims of the Swiss-type, and not in relation to claims of the more recent EPC 2000-format (see above). Because of their nature being more on the product-side (as opposed to the Swiss-type claims which are more on the use/method side), there is the possibility that the hurdle for successfully establishing an “evident preparation” may be lower, such that for example marketing materials would be more directly attributed to the respective drug and could thus also form part of such “evident and manifest preparation”. However, no such case has been decided yet.

Indirect Infringement and the Pregabalin Injunctions of the District Court of Hamburg

According to Section 10 of the German Patent Act (indirect infringement), it is forbidden for any third party without the consent of the patent owner to supply or offer to supply means relating to an essential element of the invention for using the invention, where the third party knows or it is obvious from the circumstances that such means are suitable and intended for using the invention. Hence, an indirect infringement of a second medical use claim according to German Patent Law requires that a drug manufacturer must have known or it must have been obvious from the circumstances that the manufactured drug is suitable and intended to be used for the patented second medical use.

Hence, such an indirect infringement typically only may come into play, where the alleged infringer has already avoided to include the patented indication in its package leaflet and/or advertising materials. The finding of an indirect infringement then relies on the patentee being able to show that either the alleged infringer knew or that it was obvious from the circumstances that the means provided by the alleged infringer were suitable and intended for using the invention. Hence, also because of such subjective requirement(s), a finding of indirect infringement heavily relies on the circumstances of the individual case and the evidence that the patentee may be able to provide.

The cases decided by the District Court of Hamburg related to Warner Lambert’s patent EP 0 934 061 which was directed at the use of pregabalin for the preparation of a pharmaceutical composition for treating pain. The pain was further specified in claim 3 to be neuropathic pain. Product protection for pregabalin per se had expired in 2013, and Warner Lambert marketed its drug (“Lyrica®”) for the indications epilepsy, generalized anxiety disorders (GAD) and neuropathic pain. However, apart from the aforementioned EP 0 934 061 protecting the use of pregabalin for treating pain, there are no second medical use patents protecting the indications epilepsy and generalized anxiety disorders. Hence, there are patented and non-patented indications. In the cases in question, the defendant(s) marketed their pregabalin with skinny labels restricted to the non-patented indications, but they joined a tender for pregabalin which was not limited to the patent-free indications epilepsy and GAD. The defendant(s) concluded a rebate agreement for pregabalin with a public health insurance company. Under German law, public health insurance companies may offer rebate agreements to pharmaceutical companies via public tenders. The rebate agreement typically entitles the contracted pharmaceutical company to be the exclusive supplier of the respective drug for patients insured by the health insurance company, if such drug is prescribed by the physician. Typically, the physician prescribes a medicinal product under its brand name or its International non-proprietor name (INN) with details of strength, dosage form and package size, but not with a particular indication for the respective patient. By default, the branded product is prescribed “aut idem” which means that the branded product may be substituted (“aut idem” meaning “or the same”) by the same but cheaper drug from another manufacturer, unless “aut idem” is crossed out. The physician is, however, also under budgetaryconstraints, so (s)he will likely not cross out “aut idem”. Furthermore, in accordance with German law, every product with the same particulars as the prescribed (branded) medicinal product must be dispensed if both products are authorized in (at least) one identical medical indication. The pharmacist dispensing the medicine has an obligation to substitute the prescribed medicine by a product for which a rebate agreement exists or to dispense one of the three cheapest products that meet the requirements. If the pharmacist does not do so, (s)he will not get reimbursed from the health insurance company. The pharmacist’s software is fed with all rebate agreements, but does not include any details regarding patent indications, and points to the cheapest substitute.

Under this set of circumstances, the District Court of Hamburg found that the defendant(s) indeed did supply means relating to an essential element of the invention for exploiting the invention, and the defendant(s) knew, or it was obvious from the circumstances that such means are suitable and intended for using the invention. Hence, the Court concluded that a participation as a bidder in an unlimited tender (i. e. without limiting such participation to the non-patented indications epilepsy and general anxiety disorders) constitutes an indirect patent infringement on the participating bidder’s side. According to the Court it is obvious and foreseeable that the dispensing pharmacist will substitute the patented (and typically more expensive) originator drug by the (cheaper) generic drug for all indications, irrespective of their patent protection.

Therefore, according to this body of caselaw, a skinny labelling alone does not guarantee a finding of non-infringement, if other circumstances, such as the entry into an unlimited rebate agreement provide an indication that the drug and its way of distribution is suitable and intended to be used in a patented manner.

Conclusion

It remains to be seen how this will develop further in the future. As of now, insofar as the pregabalin cases have not become final and were challenged to the higher instance, the Upper District Court has not issued a decision yet. It emerges however that second medical use claims and their interpretation by the Courts cannot be solved by mere reference to patent law. Rather, a wider picture and a further reaching approach must be adopted striking a fair balance between the justified interest of innovator companies to be able to get a return of investment also for their significant second medical indication inventions and the likewise justified interest of the public in affordable medicines coupled with the equally justified interest of pharmaceutical generic companies to not be obstructed with a plethora of second medical use patents that clearly were filed for the sole purpose of evergreening patent protection way beyond the innovator’s real contribution to the health system. Such further reaching approach must deal with the fact that the decision for an off-label use, and hence the decision for a possibly patent infringing act,effectively seems to lie at present only with the treating physician. Furthermore, in the future it should be questioned whether the dispensing pharmacist should not be made aware of the indication for which the physician prescribes the respective drug so as to be able to choose the right product that is not running the risk of infringing a patent. This should be mirrored in a possible redesign of the pharmacist’s software to also include information on patented indications and patent-free indications.

Clearly, the field of second medical use claims is currently evolving, and there are likely to be many more interesting decisions and developments to come.

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