Par Pharmaceutical, Inc. et al. v. TWI Pharmaceuticals, Inc.

Docket Nos. 2014-1391

December 3, 2014

Brief Summary: DC decision that pharmaceutical formulation would have been obvious vacated and remanded as being improperly reliant on inherency (to be relevant, “the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art”).

Summary: Par appealed DC finding that US 7,101,576 relating to the drug megestrol acetate for “increase[ing] the body mass in a human patient suffering from anorexia, cachexia, or loss of body mass” was invalid for obviousness. An oral micronized suspension of Megestrol has been used to treat wasting in cancer and AIDS patients, and marketed as “Megace OS” by Bristol-Myers Squibb. Par received marketing approval for a generic micronized megestrol formulation and continued to experiment with it to reduce the particle size to the nanometer range. It contracted with Alkermes (Elan) to use its “NanoCrystal” technology to do so. Par found this formulation did not show the “strong food effect” of Megace OS (meaning taking it with a meal showed a significantly higher rate and extent of absorption), which was important for patients with substantially reduced appetites. The PTO initially rejected Par’s claims to the nanosized formulation in view of prior art that discussed micronized megastrol formulation and Elan’s NanoCrystal technology. The claims were allowed after Par amended the claims to include three “wherein” clauses, the first requiring “no substantial difference in the Cmax…when…administered to the subject in a fed versus a fasted state” and the second requiring “the subject having no food within the at least the previous 10 hours”, and the third defining the “fed state…as the subject having a high calorie meal within approximately 30 minutes of dosing.” TWI filed an ANDA for nanosized megestrol with a paragraph IV certification. The DC concluded the ‘576 patent was invalid for obviousness because “TWi proved that all elements of the claimed invention were disclosed in the prior art…even though the prior art did not explicitly disclosed the food effect differences as claimed” since “[t]he claimed pharmacokinetic parameters with respect to a food effect…are inherent properties of the obvious nanoparticular formulation…even if it was previously not known in the prior art that a food effect existed.” It also concluded “that the known high viscosity and high interpatient variability of Megace OS would have motivated ‘a person skilled in the art to create a method of treatment using nanoparticles”, the prior art did not teach away from the nano-formulation, and the evidence of unexpected results unconvincing. The FC opinion first explained that it must first be determined “if all the elements of an invention are found in a combination of prior art references” (only then will the motivation to combine and reasonable expectation of success be considered (Medichem, S.A., FC 2006)). The FC panel agreed with the DC that TWi failed to clearly and convincingly prove that the food effect was known in the prior art but found error with its reliance on inherency. The opinion explained the inherency is only relevant to the obviousness analysis where “the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art” (Alcon, FC 2012; Kubin, FC 2009; Santarus, FC 2012 (“an obvious formulation cannot become nonobvious simply by administering it to a patient and claiming the resulting serum concentrations”); Kao, FC 2011 (limitation must add something “of consequence”)). And the DC, the opinion explained, ignored the “wherein” claim limitations and was therefore flawed. The FC panel did, however, agree with the DC conclusions that there was a motivation to combine (no error in finding “motivations beyond the food effect” (Allergan, FC 2013)) and a reasonable expectation of success (absolute certainty not required (O’Farrell, FC 1988)). The FC also agreed the DC correctly determined there was no teaching away in the prior art (Santarus, FC 2012; Kubin, FC 2009). It also concluded the DC correctly considered the secondary considerations. However, the DC decision was vacated and remanded based on the inherency issue.

This entry was posted in Generics / ANDA, Inherency, Obviousness. Bookmark the permalink.

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