Recent legislative changes and court rulings have resulted in a simpler and more coherent approach to the patenting of new dosage regimens in
To what extent should the law of patents restrict the freedom of physicians and surgeons to treat their patients? This is a question which has been debated in many legal systems, particularly as regards protecting novel and inventive dosage regimens. Within Europe a rather untidy middle ground had developed, resulting in only patchy protection being available to patentees and requiring the use of different (but somewhat arbitrary) forms of highly technical language to obtain such patents in different countries. Recently, however, movements within the legislature and decisions of various leading European tribunals have heralded the introduction of a clearer, more coherent and somewhat more patentee-friendly climate.
To understand the legal issues surrounding dose regimens, one must start with a consideration of the basic policy reasoning underlying patent protection. The starting point is that anything which is new, inventive and has industrial application can be patented. This is, of course, subject to certain exceptions. One of these exclusions arises from concerns over the possibility of the patent system restricting the ability of physicians and surgeons to treat their patients. With this in mind many countries have had provisions in their patent law which bar the obtaining of patents covering surgical techniques and the manner in which physicians administer treatments.
In the original European Patent Convention (EPC) this was reflected in the labyrinthine provisions of Articles 52 and 54, the relevant parts of which were worded as follows:
52 (1) European patents shall be granted for any inventions which are susceptible of industrial application, which are new and which involve an inventive step.
(4) Methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practiced on the human or animal body shall not be regarded as inventions which are susceptible of industrial application within the meaning of paragraph 1. This provision shall not apply to products, in particular substances or compositions, for use in any of these methods.
54 (5) The provisions of paragraphs 1 to 4 shall not exclude the patentability of any substance or composition, comprised in the state of the art, for use in a method referred to in Article 52, paragraph 4, provided that its use for any method referred to in that paragraph is not comprised in the state of the art.
Read literally, the combination of these provisions had the effect that (a) methods of treatment by surgery or therapy and diagnostic techniques were unpatentable due to a deemed lack of industrial application; but that (b) the patentability of a claim to a substance for use in such a method was not barred, provided that the substance had not been patented for any therapeutic use before. Thus, although methods of treatment could not be patented as such, claims to a particular substance for a therapeutic use were allowable – at least in relation to the first such use.
Protecting The Second Medical Use
Although approaches originally differed around Europe, a body of case law arose which interpreted these provisions as also allowing claims (in effect) to second and subsequent medical uses of a particular substance, so long as the appropriate form of drafting was used. One could not claim the use of the drug to treat the second disease, because that would offend against the restriction in the final clause of Art 54(5). What one could do, however, was adopt so-called ‘Swiss-form’ language. This required a patent claim drafted in the form ‘the use of substance X in the preparation of a medicament for the treatment of disease Y’. Thus it is (linguistically at least) the form of the medicament which is protected, rather than the use itself. Although rather a triumph of form over substance, and initially not accepted by several parties to the EPC, the use of Swiss-form claims for second medical uses became broadly accepted across Europe.
Difficulties With Dosage Regimens
Difficulties still lay, however, where the intention was to patent a new dose regimen for the same disease state as was already treated by the product – for example, changing the size, frequency or timing of the delivery of the drug. In the UK, in what was then seen to be the seminal case of Bristol-Myers Squibb v Baker Norton (BMS, a decision in 2000), the Court of Appeal appeared to hold that the restrictions on patentability prevented the grant of a patent for a new dosage regimen for an ‘old’ disease.
The BMS case concerned the anti-tumour drug Taxol (paclitaxel), which was at that time well-known to be under investigation for the treatment of various cancers, and in particular ovarian tumours. Due to problems with severe hypersensitivity reactions, the drug was delivered with premedication and initially over a period of 24 hours (coming down to a minimum of six hours if there was no adverse reaction). In addition, the drug was, in common with many chemotherapeutic agents, known to have the side-effect of causing neutropenia (a fall in the neutrophil count).
The patent was in Swiss form and claimed, in effect, Taxol and premedication used for the manufacture of a medicament for a cancer treatment to be delivered over three hours or less. Thus the drug was used for the same disease, but delivered over a much shorter time period. Interestingly, and indeed surprisingly, it was found that this manner of delivery led to significantly reduced neutropenic side-effects.
When considering this patent, the decision of the Court of Appeal was generally understood to take the following steps. The drug was known. Its use for the treatment of cancer was known. The only ‘new bit’ was the three-hour or less infusion time. But that was a method of treatment falling within Article 52(4) of the EPC, so had to be excluded from consideration. The patent was therefore held to be invalid. As a consequence of this decision it was understood to be the law, in the
Dose Regimens Decisions
Despite the
A somewhat middle ground position was adopted by the German Bundesgerichtshof (Federal Supreme Court) in its Carvedilol II decision (2006). Carvedilol (generic) is a beta-blocker used to treat congestive heart failure. The patent in this case sought to protect a new regimen for the dosage of this drug, which essentially involved stepping up the dose in a certain prescribed manner over certain time periods. The main form of claim advanced by the patentee was in the form "the use of carvedilol for the manufacture of a medicament for reducing mortality due to congestive heart failure… wherein the medicament is administered [according to the specific regime]".
The Bundesgerichtshof held that such a claim was not barred per se, as it claimed the medicament, not the method itself. The Court went on to decide, however, that because of the exclusion relating to methods of treatment it would have to disregard the administration steps when considering the novelty and inventiveness of the claimed invention. On this basis the claim was held to be invalid.
The Court did, however, also go on to consider an alternative claim with the wording "the use of carvedilol for the manufacture of a medicament for reducing mortality due to congestive heart failure… wherein the medicament is prepared for administration [according to the specific regime]". Here the Bundesgerichtshof held that the latter element of the claim was a description of a physical dose form with particular characteristics making it suitable for the regimen, rather than a claim to that regimen itself. In a claim phrased in this manner, it was therefore held, the tailoring of the dosage form to that regimen was something that could be taken into account in assessing the novelty and inventiveness of the patent – although in this case the claim was revoked for lack of inventive step in any event.
At different times, however, other EPC states adopted yet further approaches, leaving what can only be described as a bit of a mess. Inconsistent decisions led to differing protection being provided throughout the EPC states, and furthermore with differing technical wording being required in different jurisdictions – exactly what the EPC sought to avoid. Nonetheless the nation states ploughed their own furrows, albeit with some lack of enthusiasm about these variations being expressed by the Courts from time to time.
Recent Retrenchments
Recently, however, three lines of attack have been opened on these inconsistencies – by amendments to the EPC in 2000, a new decision of the Court of Appeal in the
As regards the EPC, which is ultimately the governing legislative document for each of the EPC countries, the convoluted former wording of Articles 52 and 54 has been replaced with the much clearer new Articles 53 and 54:
53 European patents shall not be granted in respect of:
(c) methods for treatment of the human or animal body by surgery or therapy and diagnostic methods practiced on the human or animal body; this provision shall not apply to products, in particular substances or compositions, for use in any of these methods.
54(4) Paragraphs […] 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 […] 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.
Articles 53(c) and 54(4) preserve the exclusion on claiming methods of treatment, while still allowing claims to the use of drugs in such treatment. They therefore maintain the status quo as regards first medical uses. Although this is a policy decision which leaves very little in the remaining scope of the exclusion, it is at least now worded in a much clearer manner.
Article 54(5) confirms that claims may also be made in relation to "specific" uses, thereby introducing a provision expressly allowing second and subsequent medical uses.
There was initially some debate as to whether Article 54(5) also allowed claims to new dosage regimens for old diseases. This question came before the Enlarged Board of Appeal of the EPO in a case known as Kos Life Sciences (19 February 2010). This concerned a patent application seeking protection for the use of oral nicotinic acid for the treatment of hyperlipidaemia, under a regimen of once a day dosing prior to sleep.
The use of oral nicotinic acid for treating hyperlipidaemia was known, and the novelty and inventiveness was said to reside in the specified dosage regimen. As such this case raised head on the issue of whether the amended EPC allowed claims to new regimens for treating old diseases. In its decision, the Enlarged Board of Appeal confirmed that the changes made by EPC 2000 were not intended to (and did not) affect its previous practice of granting use-led claims relating to dosage regimens; save that the former convoluted Swiss-form wording would be swept away for the much simpler formulation "the use of X to treat Y".
As regards the
In Actavis the Court took the opportunity to scrutinise the BMS decision very closely, concluding that it did not quite mean what everyone had thought it had meant (and furthermore that, very unusually, they would have felt able to depart from it as a precedent in any event). The Court held that there was no a priori reason why a patent claim should not be directed at a new and inventive use of a known drug to treat a known disease, reversing the previous understanding of UK law (and bringing the UK into line with the EPO). In that case the invention was the use of finasteride in low-dose oral form for the treatment of a type of male pattern baldness. Its use for the treatment of this type of baldness at a much higher dose was known of, but nonetheless the patent was held to be allowable under Article 52 EPC (in the pre EPC 2000 form), as well as both novel and inventive.
Falling Into Line ?
There is a great deal to be said in favour of these recent steps taken by the legislature, the European Patent Office in Kos and the UK Court of Appeal in Actavis. Given these decisions, and the greater clarity of the wording in the EPC 2000, it is expected that there will now be a general falling into line across the EPC states.
There are those who will celebrate this consolidation, or shift, of the law, while others, no doubt, will feel this to be an unwise step into the realm of the physician. Some will view claims to dosage regimens as providing justified protection to innovative advances, while others will foresee it being used to provide unwarranted line extensions to innovator companies.
The truth, as is often the case, is likely to lie between these positions. While, as was commented on by both the Court of Appeal in Actavis and the Enlarged Board of Appeal in Kos Life Sciences, there is no doubt that many new dosage regimens will lack any degree of invention, it is also inevitable that bad patents will be granted and will need to be weeded out. But where research leads to a dose regimen which is truly innovative, and which provides real benefits to patients, why, it might be asked, should patentees not be rewarded for their efforts?
Whatever one’s stance on these policy decisions, what was truly to be criticised in the former position was the inconsistency of protection across
Mark Chacksfield
Barrister