After nearly five years of litigation with Par and Alkermes, TWi can finally launch its generic version of Megace ES® (megestrol acetate). On remand from the Federal Circuit following an initial finding of invalidity, the District of Maryland held that the asserted claims are invalid for obviousness and lack of enablement, and denied the plaintiffs’ motion for a preliminary injunction pending appeal.
By way of background, the asserted claims were directed to methods of increasing body mass using megestrol acetate with particle sizes less than 2000 nm wherein there is “no substantial difference” in Cmax when given in a fed state or a fasted state. In February 2014, the district court found the claims obvious because all elements of the claims were explicit in the prior art except for the food effect limitation. For that claim limitation, the district court found that although not explicit in the prior art, it was an inherent property of the otherwise-obvious nanosized formulation.
As we previously wrote, in December 2014 the Federal Circuit vacated and remanded based on the district court’s inherency finding. Inherency, according to the Federal Circuit, can only apply to obviousness when the claim limitation is the “natural result” of the combination of prior art elements. The Federal Circuit remanded for consideration of whether TWi had shown that the “natural result” of the prior art combination would have “no substantial difference” in Cmax, and for consideration of whether the claims are enabled for the claimed particle sizes of up to 2000 nm.
On remand, the district court found that megestrol nanoparticles within the claimed size range would necessarily reduce the food effect. In addition to expert testimony, the district court relied on an example in the specification, Par’s own product, and TWi’s accused ANDA product, finding that because these formulations contain particles within the claimed range and meet the food effect limitation, the range necessarily reduces food effect.
The district court noted that TWI was not required to show that the claimed food effect limitations are inherent in every formulation claimed. “In the obviousness context, examples are enough.” And, Par failed to show evidence that there are formulations within the relevant particle size range that do not exhibit the claimed food effect reductions.
The district court found that a person of ordinary skill would not be able to make and use multiple portions of the claimed particle size range without undue experimentation. The claims were to particle sizes less than 2000 nm. However, the evidence showed that particle sizes below 100 nm and above 750 nm cannot achieve the claimed food effect limitations. Thus, the district court held “no amount of experimentation would have allowed a skilled artisan to achieve broad portions of the claimed particle size range because scientific phenomena made that practically impossible.”
After the district court issued its invalidity opinion, Par filed an appeal to the Federal Circuit and moved for an injunction pending appeal. The district court denied the motion. The district court found that Par is less likely to be irreparably harmed absent an injunction because Par began selling an authorized generic version of Megace ES. “Par – and not Twi – created the very risk of price erosion it fears.” The district court also found that Twi is more likely to be harmed by an injunction because the Megace ES market has shrunk. “Forcing Twi to wait even longer than the 11 months it has already waited since receiving FDA approval would increase the likelihood Twi would derive no revenue – and not merely delayed revenue – from its generic product.”
It remains to be seen whether the Federal Circuit will endorse the district court’s inherency findings as meeting the often difficult burden required for inherency in obviousness. However, this case demonstrates that inherency in obviousness is possible and can be shown by the examples in the patent, the branded product, and the generic product. This case also serves as a reminder that lack of enablement should be considered as a defense to infringement of claims involving ranges.