Saturday, 30 June 2012

Interpretative Spotlight: “Active”

The patent proprietor filed an appeal against the decision to revoke the patent under consideration.

Claim 1 of the main request read:
Use of fluprostenol isopropyl ester as the sole active ingredient for the manufacture of a medicament for topical application for the treatment of glaucoma and ocular hypertension. (my emphasis)
The Board found this claim to comply with A 123(2):

[3] A 123(2) stipulates that the European patent may not be amended in such a way that it contains subject-matter which extends beyond the content of the application as filed. According to the established jurisprudence of the boards of appeal, this content encompasses what can be directly and unambiguously deduced from the explicit and implicit disclosure of the application as filed in its entirety.

[3.1] As a first step, the meaning of the expression “active ingredient” has to be clarified. According to the respondent, it comprises every compound having any activity. Such a definition does not appear to be suitable in view of the fact that virtually every compound interacts with its environment somehow and therefore shows some sort of activity. Such a meaning of active ingredient would restrict claim 1 to the use of IEP as such, i.e. to the use of IEP in the absence of any additional compounds including excipients or preservatives, and this is clearly not how the skilled person would read the sole claim of the main request.

Taking into consideration that the skilled person makes a distinction between active ingredient on the one hand and excipients on the other hand, it might be argued that active ingredient encompasses every compound having any pharmacological activity including pharmacological activities not related to those defined in the claim. However, such an interpretation amounts more or less to the same restriction of the claim as the former definition. The appellant cited water, which may be used for treating dehydration, or sodium chloride, which is suitable for treating sodium deficiency, as examples of compounds having a pharmacological activity. The skilled person would not associate the exclusion of these compounds with the feature “as the sole active ingredient”. As a consequence, this definition is not correct either.

The board concludes that “active” in the feature “as the sole active ingredient” implies an activity in relation to the treatment defined in the Swiss-type claim. As a consequence, the feature “as the sole active ingredient” excludes further compounds characterised by a pharmacological activity which mitigates or otherwise influences the symptoms of glaucoma and ocular hypertension. It does not, however, exclude further compounds such as preservatives, co-solvents and viscosity building agents.

In this context, it is noted that some ocular preservatives such as boric acid may also be used as active ingredients for the treatment of inflammations, which in combination with conjunctival hyperemia and edema are known side effects of prostaglandins used in the treatment of ocular hypertension including FIE (see page 2, lines 13-15, and page 32, lines 1-12, of the original application). However, the fact that such preservatives may be able to lessen some side effects possibly caused by FIE does not make them active ingredients in the sense of the claim. These preservatives are not excluded from the claim of the present main request in view of the fact they do not have any activity in connection with glaucoma and ocular hypertension.

The board therefore concludes that the Swiss-type claim according to the main request relates to a medicament for topical application which, apart from FIE, does not comprise additional compounds which are able to treat glaucoma and ocular hypertension. Further compounds such as e.g. the preservatives, co-solvents and viscosity building agents mentioned above are not excluded.

[3.2] The board notes that the feature “fluprostenol isopropyl ester as the sole active ingredient” is not as such mentioned in the original application. The original application cites FIE as one of the preferred, albeit not the most preferred, active ingredients (see page 4, lines 14-17, and page 7, lines 4-8), but does not specify expressis verbis that it should be used as the sole active ingredient. In fact, the general description does not explicitly disclose monotherapy for any of the active agents therein; it merely says that certain cloprostenol and fluprostenol analogues as well as compounds according to general formula (IV) are useful in treating glaucoma and ocular hypertension (see page 4, lines 22-26, and page 7, lines 10-11). Original claim 16 concerns the “use of a compound of formula (IV) … for the manufacture of a medicament for topical application for the treatment of glaucoma and ocular hypertension”. These passages encompass both monotherapy and combination therapy and therefore cannot serve as a basis for the feature “fluprostenol isopropyl ester as the sole active ingredient”.

However, the evaluation of the overall content of a patent application also requires an analysis of the examples disclosed therein. The original application comprises nine examples.

Examples 1 to 4 concern the synthesis of some active ingredients and are therefore irrelevant in this context. Examples 5 and 6 deal with pharmacological assays of some active ingredients including FIE (compound B) in which the intraocular pressure lowering effect (example 6) and development of hyperemia as an unwanted side effect (example 5) were examined on the basis of animal models. Examples 7 and 8 also describe animal models in which the intraocular pressure lowering effect of some active ingredients not including FIE are studied. Although not relating to pharmaceutical formulations, as was correctly pointed out by the respondent, these examples nevertheless reveal that the active ingredients disclosed in the original application are suitable for monotherapy.

Example 9 discloses eight pharmaceutical formulations for topical use for lowering the intraocular pressure. Although different active ingredients are used (various cloposterol derivatives in formulations 1-3, 5 and 7-8; FIE in formulation 4; and 13,14-dihydrofluprostenol in formulation 6), these formulations have one thing in common, namely that a sole active ingredient in the sense as defined above was used.

[3.3] To summarise: the general part of the description does not explicitly refer to the use of a sole active ingredient but includes both monotherapy and combination therapy. All the formulations of example 9 comprise a sole active ingredient, there is not a single formulation exemplifying combination therapy. The concept of monotherapy is confirmed by examples 5 to 8, in which the suitability of the active ingredients as sole active agents in terms of pharmacological effects and side effects is shown.

The board concludes therefrom that monotherapy, i.e. the use of a sole active ingredient, constitutes the preferred form of administration in the original application. This preference is not restricted to FIE but concerns all the active ingredients disclosed in the original application and therefore has general character. FIE was selected from a list of compounds, and in particular from a list of six particularly preferred active ingredients (see page 7, lines 4-8) and combined monotherapy (as the sole active ingredient), which constitutes de facto the only administration form envisaged in the original application. Under these circumstances, the board concludes that the feature “fluprostenol isopropyl ester as the sole active ingredient” is not the result of two selections from different lists, as basically only one selection, i.e. the selection of FIE from a list of six preferred active ingredients, has to be made in order to arrive at the feature mentioned above. As a consequence, the requirements of A 123(2) are met.

The case was then remitted to the first instance for further prosecution.

To download the whole decision (T197/08), click here.

The file wrapper can be found here.