2,226,784 – tadalafil– CIALIS
The claims at issue in this NOC proceeding were to tadalafil (CIALIS) for the treatment of ED in men, specifically by oral administration -. As discussed yesterday, de Montigny J rejected Mylan’s utility attack.
The second substantive issue was obviousness type double-patenting over the 2,181,377 patent. Smooth muscle tissue, including heart and vascular muscles, as well as penile tissue, is relaxed by the so-called NO/cGMP pathway, with the end result that increased concentration of cGMP causes the smooth muscle tissue to relax . Relaxation of penile tissue induces an erection. A class of enzymes known as PDEs break down cGMP. A compound that inhibits PDE can therefore prevent the breakdown of cGMP, resulting in increased concentration of cGMP, relaxation of the smooth muscle tissue, including penile erectile tissue. This was all known before sildenafil and tadalafil were discovered to treat ED. The ‘377 patent is a compound claim to tadalafil, and it discloses that tadalafil is a potent and selective PDEV inhibitor. The essential obviousness argument in this proceeding (as well as in various earlier proceedings regarding sildenafil), was that the information regarding the NO/cGMP pathway, combined with the knowledge that tadalafil was a selective PDEV inhibitors, made it obvious that tadalafil would be effective in treating ED.
The main legal question on this issue turned on the fact that the ‘377 patent, which revealed that tadalafil is a selective PDEV inhibitor, was not published until 27 July 1995, two weeks after the claim date of the ‘784 patent (14 July 1995). Thus the ‘377 patent could not be raised in a straight obviousness argument, because under s 28.3 obviousness is assessed in light of information disclosed before the patent's claim date.
Mylan therefore relied on obviousness-type double patenting. The key contested legal issue was whether the date for assessing obviousness type double-patenting should be the priority date of the ‘784 patent or the priority date of the ‘377 patent -. That is, in assessing whether the ‘784 patent is obvious in light of the ‘377 patent, should the art that arose after the ‘377 date, but prior to the ‘784 date, be taken into account?
de Montigny J held that the priority date of the earlier, ‘377 patent, was appropriate, for two main reasons. First:
 If, as Mylan would have it, the relevant date was to be the priority date of the second patent (in this case, July 14, 1995), the obviousness-type double patenting analysis would morph into a pure obviousness analysis, with the added benefit that the timing requirements of section 28.3 of the Patent Act would be circumvented.
This strikes me as a very strong point. The judicially created obviousness type double-patenting cannot be used to do an end-run around a clear statutory provision.
His second point was that the rationale for the doctrine of obviousness type double-patenting is to prevent evergreening of the earlier patent by a claim to subject matter which makes no further inventive contribution . Consequently, the question is “whether the claims of the ‘784 Patent disclose novelty or ingenuity over the ‘377 Patent” . If it does, then the later expiry date of the second patent is not impermissible evergreening, but a reward for a further inventive contribution. That point also strikes me as compelling.
Having decided that the appropriate date was the ‘377 priority date, de Montigny J held that it was clear that there was no obviousness type double-patenting. The fact that tadalafil was a PDE inhibitor, and was useful for relaxing smooth muscle tissue, did not make it obvious that it would be useful for treating ED, because prior to the sildenafil patent and related publications, everyone had thought that relaxing smooth muscle tissue would cause ED, rather than treat it, by generally lowering the patient’s blood pressure . The breakthrough that lead to the realization that tadalafil (and sildenafil) could be used to treat ED was the discovery that the the main PDE activity in human penile tissue is due to a particular type of PDE, PDEV, so that oral administration of PDEV would relax penile tissue but not vascular tissue . That was far from obvious at the priority date of the ‘377 patent.
While important, the question of the appropriate date for assessing obviousness type double-patenting was not determinative, because de Montigny J also held on the facts that the use of tadalafil to treat ED would not have been obvious over the ‘377 patent and the common general knowledge even at the priority date of the ‘784 patent , for essentially the same reason: the state of the art had not changed significantly in the interim, and even at that later date it was still thought that oral administration of any PDE inhibitor, including a PDEV, inhibitor, would result in systemic hypotension.