(rs)So the specification would be understood to contemplate expressing particle size distributions both by number and by volume. The claimants contend that this means the claim is truly ambiguous and insufficient. I do not agree. The claimants’ submission overlooks the common general knowledge of the skilled formulator. The skilled formulator prefers volume, knows that the two approaches are possible but also knows that they give radically different results. So if the claim expressly called for a volume distribution the reader would not be surprised. It is their preferred approach. Equally a claim which expressly called for a number distribution would be readily understood. However, the one thing the skilled reader would think would be decidedly odd would be the idea that the inventors intended that the boundary of the claim could be determined by either or both approaches. That makes no sense. It would be readily apparent to the skilled reader that such a construction made the claim hopelessly ambiguous. They would think the inventors must have meant one or the other, no rational formulator would cover both. One can always be converted into the other albeit this can introduce significant error.
(rt)Of course it would have been a simple matter to clear this up by stating expressly which distribution was being referred to and one possibility is that the draughtsman was deliberately being vague and trying to hedge their bets by allowing for either. I do not think that is what has happened nor do I think the reader would think that is what has happened.
(ru)The skilled reader would reject, at least provisionally, the idea that the claim covers both or either, and ask which of the two kinds of distribution is the one the inventors must have meant. Only if they could not answer that question would the claim be ambiguous. However, the conclusion is simple. A volume distribution is the one preferred in the pharmaceutical industry and for good reason. Given that ultimately what one wants to deliver to the patient is tadalafil molecules rather than particles as such, it makes sense to think of the distribution that way. That is consistent with the use of laser scattering to produce a volume distribution for the API. The skilled reader would see that the only reason a number distribution is determined at the end with microscopy is because there is no alternative. It could always be converted albeit with errors. Reading the document as a whole and in the light of the common general knowledge the skilled reader might well start with a doubt about it but they would arrive at one answer. The claim requires a volume distribution. I reject this ground of insufficiency.
Infringement - 092
(rv)The only distinct infringement issue relates to claim 19 and the SmPC. Since the claimed limit is 20 mg/day, it would be infringed if it was valid. The question of quia timet infringement actions relates as much to 092 as to 181 and the answer is the same.
(rw)I find that:
i)At least claim 7 of the 181 patent is valid and infringed;
ii)All the claims of the 092 patent are invalid.
Annex 1 – relevant claims of the 181 patent
In addition to claim 1, the relevant claims of the 181 patent are:
2. The dosage form of claim 1 comprising 2.5mg of the compound in unit dosage form.
3. The dosage form of claim 1 comprising 5mg of the compound in unit dosage form.
6. The dosage form of any of claims 1 through 3 for use in treating a condition where inhibition of PDE5 is desirable.
7. The dosage form of claim 6 wherein the condition is a sexual dysfunction.
10. Use of a unit dose containing 1 to 5 mg of a compound having the structure [of tadalafil] for the manufacture of a medicament for administration up to a maximum total dose of 5 mg of said compound per day in a method of treating sexual dysfunction in a patient in need thereof.
12. The use of Claim 10 or 11, wherein the unit dose contains 2.5 mg of the compound.
13. The use of Claim 10 or 11, wherein the unit dose contains 5 mg of the compound.
Annex 2 – relevant claims of the 092 patent
2. The free drug particulate form of claim 1 wherein at least 90% of the particles have a particle size of less than about 25 microns.
3. The free drug particulate form of claim 1 wherein at least 90% of the particles have a particle size of less than about 15 microns.
4. The free drug particulate form of claim 1 wherein at least 90% of the particles have a particle size of less than about 10 microns.
8. A pharmaceutical composition comprising:
(a) a free drug form of a compound having the formula of [tadalafil] and pharmaceutically-acceptable salts and solvates thereof, in which the compound is present as solid particles not intimately embedded in a polymeric co-precipitate; and
(b) one or more pharmaceutically-acceptable carriers, diluents, or, excipients.
wherein the composition exhibits a Cmax of 180 to 280 micrograms/litre or an AUC (0-24) of 2280 to 3560 microgram hour/litre, measured using a 10 milligram dose of the compound.
9. The composition of claim 8 wherein the composition exhibits a Cmax of about 180 to about 280 micrograms/litre and an AUC (0-24) of 2280 to 3560 microgram.hour/litre.
12. A free drug particulate form according to any one of claims 1 to 4 for use in a method of treatment.
13. Use of particles of a free drug particulate form according to any one of claims 1 to 4 or a pharmaceutical composition according to any one of claims 5 to 7 for the manufacture of a medicament for the treatment of sexual dysfunction.
14. The use of claim 13 wherein the sexual dysfunction is male erectile dysfunction.
15. The use of claim 13 wherein the sexual dysfunction is female sexual arousal disorder.
16. Use of a pharmaceutical composition according to claim 8 or 9 for the manufacture of a medicament for the treatment sexual dysfunction.