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Clean sweep for Mylan in low-dose tadalafil NOC application

On February 2, 2015 Justice de Montigny released his Judgment and Reasons in a second prohibition application started by Eli Lilly involving Mylan’s proposed tadalafil products (for our discussion of  Justice de Montigny’s first decision, see here.)

The prohibition application involved Canadian Patent No. 2,226,684 directed to a pharmaceutical unit dosage form of tadalafil comprising about 1 to about 20 mg of tadalafil for the treatment of sexual dysfunction.  The 684 patent discloses that this dose range was effective and “minimizes or eliminates the occurrence of adverse side effects”, including vision abnormalities, flushing, including in patients undergoing nitrate therapy.

Promise of the Patent

Lilly argued, based on the wording of the claims, that the patent only promised that the claimed formulations were efficacious in the treatment of ED.  Mylan, on the other hand, argued that the patent promises that the claimed doses provide an improvement over sildenafil by reducing the three side effects to clinically insignificant levels. Further, these advantages are not provided by higher doses.

Justice de Montigny refused to read down the promise as proposed by Lilly, holding that such an interpretation “would fly in the face of the clear language of the 684 Patent, which explicitly promised much more than a marginal improvement over sildenafil.” In largely accepting Mylan’s construction of the promise of the 684 Patent, Justice de Montigny held:

[100] On the basis of the foregoing, I am therefore prepared to hold that the promise of the ‘684 Patent is not merely to lower the incidence of adverse side effects as compared to sildenafil, but to minimize them significantly or even to eliminate them. This is true for all three side effects that are the focus of the ‘684 Patent, but more particularly with respect to the co-administration of tadalafil with nitrates; this is the inescapable conclusion that one must draw from the statement that a contraindication is unnecessary when tadalafil is administered as a unit dose of about 1 to about 20 mg.

Applying this promise, Justice de Montigny held that the utility of 1-20 mg of tadalafil had not been demonstrated or soundly predicted when administered to patients also taking nitrates. The only test that had been done with nitrates was a on a group of 22 healthy volunteers, which would not be representative of the general population suffering from erectile dysfunction. In coming to this conclusion, Justice de Montigny also relied on the current CIALIS product monograph in which CIALIS is contraindicated for patients taking nitrates.

Anticipation

Justice de Montigny agreed with Mylan that the 1 to 20 mg dosage range claimed in the 684 Patent was anticipated by a prior disclosure that 0.2 to 400 mg of tadalafil was effective for treating erectile dysfunction.  Since the reduced side effect profile is not part of the claimed invention but is merely a result of the invention, the prior patent anticipated the asserted claims.

Obviousness

Justice de Montigny held that it was more or less self evident that lower and narrower doses of tadalafil claimed in the 684 Patent would be effective in treating erectile dysfunction and would result in a reduced side effect profile. Where the inventor’s actual course of conduct deviated markedly from the ordinary course of drug development by starting with an unusally high dose, the inventors cannot later  claim to have “surprisingly” found that they could have used a lower dose.

A copy of Justice de Montigny’s Judgment and Reasons may be found here.