As you certainly know, G 2/08 has opened the door to dosage regime patents by finding that “where it is already known to use a medicament to treat an illness, A 54(5) does not exclude that this medicament be patented for use in a different treatment by therapy of the same illness”. However, the Enlarged Board (EBA) also added that patentability was “subject to compliance with the other provisions of the EPC, in particular novelty and inventive step”, and this might prove fatal to many dosage regime claims, as it did in the present case.
The patent proprietor filed an appeal against the revocation of the opposed patent by the Opposition Division (OD). Claim 1 of the sole request before the Board read:
Use of valaciclovir or a pharmaceutically acceptable salt thereof in the manufacture of a medicament for oral administration for the suppression of recurrent genital herpes in a human host and for administration to said human host at a once daily dose of 500 mg of the valaciclovir or the salt thereof. (additions to claim 1 as granted are underlined).
A 123, A 83, A 84 and A 54
[2] The board has no reason to disagree with the findings of the OD with respect to A 123(2) and A 54.
Claim 1 of the request as amended with regard to claim 1 as granted has its basis in the application as filed in original claim 1, redrafted in second medical use format. Oral administration is disclosed as a preferred embodiment [… in] the application as originally filed and all parts of the description are directed to oral dosage forms, in particular all examples and every specific disclosure in the overall text. The 500 mg dosage is disclosed as one of three embodiments in original claim 2 and on page 3, line 1.
The claim thus fulfils A 123(2).
The OD’s point of view with respect to the claimed dosage regimen is in line with the decision of the EBA G 2/08. Therefore, the board also does not deviate from the OD’s conclusion on novelty.
By introducing of the amendments with regard to claim 1 as granted, the scope of the claim is narrowed. The requirements of A 123(3) are fulfilled.
Claim 1 of the request, relating to well-defined features such as a dosage of 500 mg or once daily administration, is clear and concise.
Based on these features, it can be carried out by the person skilled in the art.
Claim 1 of the request thus fulfils the requirements of A 84 and A 83.
A 56
[3.1] The subject-matter of claim 1 of the patent in suit relates to the
(a) use of valaciclovir in the manufacture of a medicament
(b) for oral administration
(c) for the suppression of recurrent genital herpes in a human host
(d) at a once daily dose
(e) of 500 mg.
[3.2] Document D5 represents the closest state of the art.
The disclosure of this document relates to the
(a) use of aciclovir in the manufacture of a medicament […],
(b) for oral administration […]
(c) for the suppression of recurrent genital herpes in a human host […]
(d) at a twice or four times daily dose […],
and discloses
- that there is another active compound that can replace aciclovir […] because of its improved pharmacokinetic profile, with the result that for treatment of herpes zoster and genital herpes advances were achieved “with simpler thrice daily (zoster) and twice daily (genital herpes) oral regimes compared with the five times daily dose frequency recommended for oral aciclovir, and without compromise to the excellent safety profile which characterizes acyclovir” […] and
- that for treatment of herpes zoster instead of 800 mg aciclovir five times daily, 1000 mg valaciclovir was administered thrice daily […] and for treatment of acute genital herpes instead of 200 mg aciclovir five times daily, 1000 or 500 mg valaciclovir twice daily was used […].
[3.3] There is no evidence on the file of the patent in suit that the use of valaciclovir for administration to a human host at a once daily dose of 500 mg according to amended claim 1 in suit exhibits an unexpected improvement over any dosage to be derived from the better bioavailability of valaciclovir. The dosage can be derived from the above-mentioned parallels and the recommended twice or four times daily administration of aciclovir for suppression of genital herpes given that, after oral administration, valaciclovir is readily absorbed and then undergoes almost complete (99%) hydrolysis to aciclovir […] such that the active substance after administration of valaciclovir is aciclovir anyhow.
Example 12 consequently indicates that administration of valaciclovir in a dosage of 250, 500 or 1000 mg once daily shows better results with a rising amount of the compound. 500 mg is an arbitrary choice from these alternatives.
[3.4] In the absence of evidence indicating a particular effect of the dosage of 500 mg, the problem to be solved has to be defined as
the provision of an alternative use of valaciclovir for the preparation of a medicament for oral administration for the suppression of recurrent genital herpes in a human host.
[3.5] With regard to example 12 of the patent in suit, the board is satisfied that this problem is solved by the use of valaciclovir according to claim 1 of the main request.
[3.6] In line with the overall aim of document D5 of reducing the frequency of administration […], it is outlined in context with suppression that it was “well recognised in medicine that, for prophylaxis, once daily regimens are optimal and ensure better compliance” […] and that the higher bioavailability of aciclovir from valaciclovir ensures that plasma aciclovir levels exceed the in vitro IC50 for clinical HSV (herpes simplex virus) strains with once- or twice daily dosing regimens […].
Thus, based on the recommended twice or four times daily administration of aciclovir for suppression of genital herpes from the state of the art, only a “frequency” of once daily administration of valaciclovir is to be derived for this suppression therapy from document D5.
The dose, as the single remaining feature of claim 1 of the request on file, can be determined from routine experiments without any inventive effort.
[3.7] Consequently, the board concludes that the subject-matter of claim 1 of the main request does not involve an inventive step (Article 56 EPC).
[4] Under these circumstances, the additional arguments of the appellant cannot hold.
As set out under point [3] of this decision, the teaching of document D5 establishes that valaciclovir would also allow reduction of administration frequency in suppression of herpes genitalis, given that figure 3 sets out “simulated plasma aciclovir concentration profiles following multiple oral doses of valaciclovir or acyclovir” taken from document D8. Therefore, the overall consequence of document D5 remains the same in view of the considerations on plasma levels of aciclovir according to document D8.
Even document D16 casts no doubt on the conclusions from the content of document D5, because it relates to aciclovir therapy (while document D5 starts from the new opportunities arising from the superior characteristics of valaciclovir) and because, even there, a once daily therapy for suppression of herpes genitalis was not excluded but was set out as a possibility in particular circumstances […]. […]
The appeal is dismissed.
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