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.
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.
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