Federal Circuit Affirms Invalidity of Entecavir Patent As Obvious

We discussed the Bristol-Myers Squibb Co. v. Teva Pharmaceuticals, Inc. in a previous post, in which a Judge Burke of the District of Delaware found the patent for the hepatitis B drug entecavir (the active ingredient in Baraclude) obvious.  Last week, the Federal Circuit affirmed.

There were two main issues on appeal, the selection of a “lead compound” and the motivation to modify the lead compound to arrive at entecavir with an attendant expectation of success.  The alleged lead compound at issue was 2’-CDG, which differs from entecavir at one position:

The Federal Circuit found that there was ample evidence to support the district court’s finding that 2’-CDG was a suitable lead compound, in no small part because Bristol-Myers’s own expert admitted that “medicinal chemists during the relevant time frame were actually treating and using 2′-CDG as a lead compound” to search for new antivirals at the time.  And, three prior art references demonstrated as much.

The Federal Circuit also found that the trial record likewise supported the motivation to modify 2’-CDG to arrive at entecavir, and an expectation of success in making that change.  Importantly, a prior art reference demonstrated that making the change to a similar structure to that of the lead compound resulted in increased potency.  And here, again, Bristol-Myers’s expert made critical concessions that the prior art reference “would not dissuade” the skilled chemist from making the change and that the prior art “could have led” the skilled chemist to seek new antivirals.  The fact that the prior art suggested increased potency served as the basis for the finding of the expectation of success.

This case was a perfect confluence of factors for the defendant generic company Teva.   The prior art included a close compound which could justifiably be selected as a lead compound, and additional art taught the exact modification to produce the patented molecule from the lead compound.  Also, Teva’s counsel was able to elicit significant admissions from Bristol-Myers’s expert about the significance of that prior art.  This case shows that with strong prior art and the proper expert support, obviousness cases in the compound case are winnable.