Par Pharm., Inc. v. TWi Pharms., Inc.

Case Name: Par Pharm., Inc. v. TWi Pharms., Inc., Civ. No. CCB-11-2466, 2015 U.S. Dist. LEXIS 97977 (D. Md. July 27, 2015) (Blake, J.)

Drug Product and Patent(s)-in-Suit: Megace^® (megestrol acetate); U.S. Patent No 7,101,576 ("the '576 patent") 

Nature of the Case and Issue(s) Presented: Par sued TWi alleging infringement of the ’576 patent. After a five-day bench trial, the trial court concluded that the patent was obvious and invalid. On appeal, the Federal Circuit vacated the trial court’s judgment of invalidity and remanded the case for further analysis. In the Federal Circuit’s view, the trial court incorrectly applied Federal Circuit law on inherency in the context of obviousness. "There were simply no findings of fact addressing the question of whether TWi had presented evidence sufficient to demonstrate that the claimed food effect limitations necessarily are present in the prior art combinations—that is, whether "a reduction in particle size naturally results" in (i) "’no substantial difference in Cmax’ between the fed and fasted states" (as in claim 1), and (ii) a "’difference in Cmax’ between the fed and fasted states that is within an enumerated percentage difference" (as in claim 4). The remand court found that TWi has shown that the asserted claims are invalid as obvious and not enabled.

Why TWi Prevailed: The court first addressed the scope of issues on remand. With respect to obviousness, only the inherency analysis concerning the food-effect limitations was subject to further evaluation. Moreover, the Federal Circuit’s mandate allowed the remand court to consider TWi’s other invalidity arguments. Therefore, the parties addressed two arguments on remand: (i) invalidity based on obviousness; and (ii) invalidity based on a lack of enablement.

To prove that a claim limitation is inherent in the prior art, TWi must show by clear and convincing evidence that the limitation at issue is necessarily present, or the natural result of the combination of elements explicitly disclosed by the prior art. The court found that the prior art disclosed that a skilled artisan, in creating a nanosized formulation of Megace oral suspension, would have used particle sizes in the 100-400 nm range. And TWi had proven that megestrol nanoparticles within that size range would necessarily reduce the food effect so that the Cmax difference would be well under the claimed "less than about 60%" limitation. This was evidenced by various formulations from the ’576 patent examples, Par’s Megace ES formulation itself, TWi’s stipulation that its ANDA product meets the asserted claims. Supporting these formulations was TWi’s expert who explained the causal relationship between nanosizing and food-effect reductions. Par’s primary counter-argument was that mere examples of megestrol formulations within the claimed particle-size range that meet the food-effect limitations cannot, alone, prove an inherent property. The remand court disagreed for two reasons. First, Par had not pointed to any authority requiring TWi to show that the claimed food-effect limitations are inherent in every formulation claimed by the ’576 patent. To be sure, "in the obviousness context, examples are enough." Second, Par also failed to present sufficient evidence to either rebut TWi’s examples or prove that there are formulations within the relevant particle-size range that do not exhibit the claimed food-effect reductions. Thus the asserted claims were obvious.

TWi's second invalidity argument concerned the lack of enablement of the full scope of the claimed particle size range. The remand court concluded that TWI had proven that a skilled artisan would not be able to make and use, without undue experimentation, multiple portions of the claimed particle-size range, i.e., "less than about 2000 nm." Specifically, TWi proffered evidence showing that formulations below 100 nm and above 750 nm could not achieve the claimed food-effect limitations. Bolstering TWi's evidence was the fact that only a narrow subrange of 121-129 nm of the claimed particle size range was actu lly successfully tested for the purposes of the '576 patent. And the upper end of the claimed range is much closer to the particle-size range of the prior art that clearly did not achieve the claimed food-effect reductions. Par argued that it presented affirmative evidence showing that the entire range was enabled. Par combined the testimony of two of its experts to support this argument. But the two independent propositions proffered by Par’s two experts "have no bearing on the ultimate legal question: whether the specification enables a union of the two…." Thus, TWi has proven that over two-thirds of Par’s claimed particle-size range is not enabled.