Tadalafil – USA

On Apr. 18, 2018, Court of appeal for the federal circuit affirmed PTAB’s decision & found patents covering tadalafil formulation obvious over certain prior arts.

ICOS Corporation appealed the PTAB’s inter partes review (“IPR”) decisions holding claims 1–32 of U.S. Patent No. 7,182,958 and claims 1–11 of U.S. Patent No. 6,821,975 would have been obvious over PCT Application WO 97/03675 (“Daugan”), PCT Application WO 96/38131 (“Butler”), U.S. Patent No. 4,721,709 (“Seth”), and Wadke, et al. The ’958 patent is directed to pharmaceutical formulations containing micronized tadalafil. The ’975 patent is directed to micronized tadalafil in a free-drug particulate form. Actelion Pharmaceuticals Ltd. (“Actelion”) filed two petitions for inter partes review. The first, IPR2015- 00561, alleged claims 1–32 of the ’958 patent would have been obvious & second, IPR2015-00562, alleged claims 1–11 of the ’975 patent would have been obvious.

In the ’958 IPR, the Board found a motivation to combine Butler’s teaching that tadalafil has poor solubility with Seth’s teaching that compounds with low solubility generally also have a slow dissolution rate, and with Seth and Wadke’s teachings that reducing particle size through micronization can increase dissolution rate. It found there was a reasonable expectation of success in combining the teachings of these references, and rejected ICOS’ claim of unexpected results. In the ’975 IPR, the Board found Daugan, Butler, Seth, and Wadke disclose every limitation of the challenged claims. It found the general knowledge that tadalafil is poorly water soluble would have motivated an ordinarily skilled artisan to micronize it to improve its absorption and an ordinarily skilled artisan would have had a reasonable expectation of success in doing so. Based on these facts, in each instance, the Board concluded that the claims would have been obvious. ICOS appealed.

On appeal, ICOS challenged the Board’s findings that there was a motivation to micronize tadalafil, that a skilled artisan would have had a reasonable expectation of success in doing so, and that Daugan teaches the claimed combination of excipients. Federal circuit however, said that substantial evidence supports the Board’s findings that the prior art discloses the compound tadalafil, the micronization of drugs to less than about 40 microns, and a motivation to combine these teachings. Actelion’s expert testified that even if tadalafil’s absorption was solubility-limited, a skilled artisan would still have considered particle size reduction useful for increasing dissolution rate and improving absorption. Court further said that substantial evidence also supports the Board’s finding that an ordinarily skilled artisan would have combined the claimed excipients recited in claims.

Federal circuit finally rejecting ICOS challenges held that the prior arts provided a motivation to combine the elements in the manner claimed, and there was a reasonable expectation of success & found no error in the Board’s conclusions of obviousness. Federal circuit therefore affirmed the Board’s conclusion that claims 1–32 of the ’958 patent and claims 1–11 of the ’975 patent would have been obvious.