By Reza Mollaaghababa
In a recent decision, the Court of Appeals for the Federal Circuit (CAFC) affirmed decisions in two inter-partes review (IPR) proceedings that patents owned by ICOS Corporation directed to tadalafil formulations (used in the erectile dysfunction drug, Cialis, and the pulmonary arterial hypertension drug, Adcirca) were invalid as obvious. (CAFC Decision Nos. 17-1071 and 1018, April 18, 2018.)
The challenged claims were directed to a pharmaceutical formulation comprising micronized tadalafil – the active ingredient of the drugs. The challenger, Actelion Pharmaceuticals, argued that the claims were obvious in view of the teachings of four prior art references: Daugan, Butler, Seth and Wadke. In particular, the challenger argued that Daugan disclosed tadalafil and the excipients included in the claims, Butler disclosed that tadalafil was poorly water soluble, Seth disclosed that micronization was a frequently used method for improving the rate of dissolution of poorly soluble hydrophobic drugs, and Wadke disclosed that it was generally recognized that poorly soluble drugs will be more readily bioavailable when administered in a finely subdivided state preferably in a 10-40 micron range. The challenger hence argued that it was obvious to combine the references with a reasonable expectation of success.
The Patent Trial and Appeal Board found that, while Seth recognized disadvantages to micronization, those disadvantages would not have stopped ordinarily skilled artisans from using the technique, and held that there was a reasonable expectation of success in combining the teachings of these references. (IPR2015-00561 and IPR2015-00562.)
The CAFC held that substantial evidence supported the Board’s findings. The CAFC did not agree with ICOS’ argument that the prior art taught away from micronization. In particular, the CAFC indicated that although Butler disclosed coprecipitation as a solution to tadalafil’s poor solubility, the Board had credited Actelion’s expert’s testimony that Bulter did not suggest that micronization would not work but rather it had chosen a different solution. Further, while Seth recognized problems with agglomeration when micronizing, the Board had similarly credited Actelion’s expert’s testimony that there were recognized solutions in the art for the agglomeration problem. Moreover, the Board determined that Wadke did not teach a sequential approach that favored coprecipitates over micronization but instead described two alternative approaches.
The outcome of these cases appears to demonstrate that “teaching away” arguments have a low probability of success before the Board in defending challenged claims. The fact that a reference points out the disadvantages associated with a particular approach may not be sufficient to persuade the Board that the reference teaches away from that approach. For example, the Board may find that the reference simply compares alternative approaches but does not dissuade one of ordinary skill from using the less advantageous approach, or the Board may find that there are known solutions to overcome the cited disadvantages.