Chinta & Fratangelo LLP

Megestrol Nanoparticle Formulation Claims – Not Inherently Obvious (at least not yet)

Contact the author: Andrew Berks

Case citation: Par Pharmaceutical Inc. v. TWi Pharmaceuticals, Inc., No. 2014-1391 (Fed. Cir. 12/3/2014) (O’Malley, Wallach, Hughes, opinion by O’Malley)

In this dispute, Par is in the role of innovator drug company—they make a product called “Megace ES” which is a nanoparticle formulation of megestrol acetate, a drug useful for treating cachexia (wasting syndrome) in AIDS patients. A prior formulation, Megace OS, is micronized. Megace ES is asserted to have the critical advantage over the micronized formulation of much less variability in bioavailability based on whether the patient had a recent meal. Par has an Orange Book-listed patent on Megace ES, US7101576, at issue in this case.

TWi filed an Abbreviated New Drug Application (ANDA) with a paragraph IV certification alleging the claims of the ‘576 patent were invalid. This decision only considered the obviousness arguments. The claim discussed in the opinion recites a method of increasing body mass in a patient suffering from anorexia, cachexia, or loss of body mass, with a nanoparticle megestrol formulation wherein there is no significant difference in the Cmax (maximum blood concentration of the drug) with regard to the fed/fasted state of the patient.

The district court found the claims obvious based on an inherent obviousness argument. The Federal Circuit panel vacated and remanded, objecting to the inherency arguments.

In the summary of the district court holdings, TWi showed that megestrol was known to have poor bioavailability, but failed to prove that Megace OS had a known bioavailability problem or a known food effect in the prior art. The court concluded that TWi proved that all elements of the claimed invention were disclosed in the prior art. However, with regard to the food effect limitation of the claim, of bioavailability based on the whether the subject had a recent meal, the prior art did not explicitly disclose the food effect as claimed. The district court agreed with TWi that the  reduced food effect of Megace ES was “an inherent result” of nanosized megestrol, even if it was previously not known in the prior art that a food effect existed. Slip op. at 9–10. The district court also found that Par had a motivation to combine references disclosing bioavailability of megestrol and nanoparticle drug formulations. The district court also found that objective indicia of obviousness, including evidence of unexpected results and long-felt need, did not overcome the obviousness arguments.

In the analysis of the substantive obviousness arguments, the Federal Circuit panel says the parties agreed that all limitations of the claim were disclosed in various prior art references, except the specific food effect limitation. But with regard to TWi’s argument that the food effects are an inherent property of the formulation disclosed by an obvious combination of prior art elements, the panel was very concerned about the application of an inherency analysis in the obviousness context. Inherency is rooted in the law of anticipation and the opinion says its application to obviousness “must be carefully circumscribed.” Slip op. at 14. Inherency has been recognized previously as supplying missing claim limitations in the obviousness context. Id. However, in an obviousness analysis, an inherency argument has a heightened standard that must be the natural result flowing from the operation as disclosed in prior art references. Slip op. at 15. The panel concludes that the district court relied on  probabilities or possibilities to find the claims inherently obviousness, and therefore failed to meet this burden.

The panel also found that the district court did not require TWi to present evidence to prove inherency to the heightened obviousness standard, so the panel vacated the district court’s inherency analysis and remanded for the district court to determine whether TWi has clear and convincing evidence that the food effect as claimed is necessarily present in the prior art formulation. Slip op. at 17.

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