Last week Judge Gregory Sleet of the District of Delaware rejected the generic defendants obviousness challenge of Pfizer’s molecule patent for Toviaz®.

The defendants based their obviousness defense on the selection of 5-HMT, a metabolite of tolterodine, as a “lead compound.”  Tolterodine was already approved to treat overactive bladder as of the critical date.  The defendants then argued that it would have been obvious to POSAs to modify that metabolite to arrive at the claimed prodrug: fesoterodine.  The court rejected this argument at every turn.

First, Judge Sleet found that a person of ordinary skill would not have chosen 5-HMT and tolterodine as her only lead compounds.  The defendants argued that that because tolterodine did not cause the adverse side effect of dry mouth that other overactive bladder drugs caused, a person of skill in the art would focus on developing its metabolite rather than other types of lead compounds.  The court rejected this approach as “myopic” and found that a person of skill would have considered a number of lead compounds rather than focusing on just 5-HMT and tolterodine.

Next, the court found that using a prodrug approach to modify 5-HMT would not have been obvious.  The defendants argued bioavailability problems with tolterodine would have motivated POSAs to modify 5-HMT rather than tolterodine.  However, the court found that there were three prior art publications showed that the pharmacokinetics of tolterodine did not produce significant differences in patient outcomes, which would have informed POSAs that tolterodine did not have had a bioavailability problem.  Defendants’ expert analyzed these publications and determined that they were flawed, but the court held that this post hoc analysis did not indicate that a person of ordinary skill would have simply disregarded these references.  Moreover, Judge Sleet found that a person of skill would not have been motivated to develop a prodrug of 5-HMT because the oral absorption properties of 5-HMT were unknown and POSAs view prodrugging as a “last resort.”

Finally, the court found that it still would not have been obvious to pursue the final chemical structure of fesoterodine.  The court found that there would be over 7,500 options for modifying the 5-HMT molecule to create a 5-HMT prodrug, and found that this “sheer number of possible combinations” indicated that it would not have been obvious to create fesoterodine.

For all of these reasons, the court held that the asserted claims were not invalid.  This case highlights the obstacles ANDA-filers must overcome when challenging compound patents.  That said, the Court’s very stringent lead compound analysis may be labile to appellate challenge, as it effectively reads out many compounds from the prior art by effectively requiring the defendant to prove that the identified lead compound was the single best compound in the market.  But—in a case handled by the attorneys at Carlson Caspers—the Federal Circuit has previously confirmed that to be inconsistent with KSR v. Teleflex.  Altana Pharma AG v. Teva Pharms. USA Inc., 566 F.3d 999, 1008 (Fed. Cir. 2009) (rejecting patentee’s argument “that the prior art must point to only a single lead compound for further development efforts,” because “that restrictive view of the lead compound test would present a rigid test similar to the teaching-suggestion-motivation test that the Supreme Court explicitly rejected in KSR”).