Pfizer Inc. v. Mylan Pharms. Inc.

Defendants’ lead-compound analysis failed to persuade the court that the patents-in-suit were invalid, and even had that argument been successful, the court found that Defendant did not establish that modifying the lead compound to the claimed prodrug would have been obvious.

October 20, 2017

GENERICally Speaking

Case Name:Pfizer Inc. v. Mylan Pharms. Inc., No. 15-79-GMS, 2017 U.S. Dist. LEXIS 125634 (D. Del. Aug. 9 2017) (Sleet, J.) 

Drug Product and Patent(s)-in-Suit: Toviaz® (fesoterodine fumarate extended-release tablets); U.S. Patents Nos. 6,858,650 (“the ’650 patent”), 7,384,980 (“the ’980 patent”), 7,855,230 (“the ’230 patent”), 7,985,772 (“the ’772 patent”), and 8,338,478 (“the ’478 patent”)

Nature of the Case and Issue(s) Presented: Pfizer sells Toviaz, which is approved for the treatment of overactive bladder with symptoms of urinary incontinence, urgency, and urinary frequency. After Mylan filed an ANDA with the FDA seeking approval to market a generic product, Pfizer sued Mylan for patent infringement. Mylan stipulated to infringement of the asserted claims, and challenged those claims on the basis of obviousness.

Fesoterodine is a prodrug of 5-hydroxymethyl tolterodine (“5-HMT”). Tolterodine, which had been studied for the treatment of overactive bladder, is metabolized to 5-HMT. In Mylan’s view, a POSA would be motivated to find a prodrug of 5-HMT (specifically, fesoterodine) with better absorption properties than tolterodine. The court disagreed.

Why Pfizer Prevailed: Mylan failed to meet its burden to show that a POSA would have accepted 5-HMT as a lead compound. Further, even if a POSA had selected 5-HMT as a lead compound, the court found that Mylan did not establish that modifying 5-HMT to make a prodrug of it would have been obvious. Moreover, the court found that, assuming a POSA was motived to create a prodrug of 5-HMT, fesoterodine would not be the obvious choice.

The court found that Mylan’s review of the prior art, which concluded that 5-HMT was at the forefront of overactive bladder research, was too limited. Pfizer’s expert identified a number of other research strategies that were being used. Accordingly, at least other lead compounds would be considered. Further, the court concluded that the metabolism and the side effects of tolterodine and 5-HMT were similar, and so a POSA would consider the two together, not just 5-HMT alone.

Even were it to accept Mylan’s argument that 5-HMT was a lead compound, the court found that Mylan had not established that modifying it to improve its absorption would have been obvious to a POSA. It reached this conclusion by determining that a POSA would expect the oral absorption of 5-HMT to be good—it satisfies the Lipinski Rule of Five. The court also expressed skepticism at Mylan’s reliance on the development of a prodrug, stating that the prodrug approach is a “last resort.”

Next, assuming arguendo that a POSA would have been motivated to create a prodrug of 5-HMT, fesoterodine would not be the obvious choice. The court found many problems with Mylan’s approach: it only considered ester-prodrugs, ignoring non-ester prodrugs; it proposed a modification of only one group, but there were at least three other groups where modification was possible; and the phenolic isobutyryl ester of 5-HMT it considered was only one of more than 7,000 options having two to six carbon atoms. Further, the court emphasized the unpredictable nature of prodrug development.

Finally, the court found the ’650 patent, which claims salt forms of fesoterodine, non-obvious. The court determined that the salt formation process was highly unpredictable. It observed that all but one of the more than 70 fesoterodine salts the inventor first synthesized resulted in oils. It then recounted the story of the inventor’s discovery of fesoterodine hydrochloride hydrate, calling that “fortuitous.”

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