The US Court of Appeals for the Federal Circuit reversed a district court’s judgment that the challenged claims were invalid for obviousness. The Court also vacated judgments in separate actions that had been entered based on collateral estoppel, concluding that the district court erred in its evaluation of the factual record in its obviousness analysis. Millennium Pharmaceuticals, Inc. v. Sandoz Inc., Case Nos. 15-2066; 16-1008; -1009; -1010; -1109; -1110; -1283; -1762 (Fed. Cir., July 17, 2017) (Newman, J).

Millennium is the exclusive licensee of the patent at issue, which relates to a chemical compound described as a boronate ester of bortezomib and D-mannitol and also claims a lyophilized compound. Millennium developed the patented product under the brand name Velcade®, and it became “a cancer treatment that changed the decades-old standard of care for multiple myeloma and has saved thousands of lives. The [US Food and Drug Administration] approved Velcade® in record time, despite its novel structure and mechanism of action.”

Sandoz filed abbreviated new drug applications (ANDAs) admitting infringement and seeking to invalidate various claims of the patent. The district court held the asserted and challenged patent claims invalid, based on its finding that they were the inherent result of an allegedly obvious process, i.e., lyophilizing bortezomib in the presence of the bulking agent mannitol. Regarding the patent owner’s evidence of secondary considerations, the district court found that Millennium did not establish unexpected results or long-felt need. Millennium appealed after the district court entered a final judgment in separate actions arising from ANDAs filed by Apotex and Teva based on collateral estoppel arising from the district court’s judgment of invalidity of the asserted patent claims in the Sandoz action. The Federal Circuit consolidated the appeals.

Reversing the district court, the Federal Circuit found clear error in the district court’s obviousness analysis. The Court noted that there was no teaching or suggestion in the prior art of the claimed compound (a mannitol ester of bortezomib), and that moreover there was no reference or combination of references that showed or suggested a reason to make the claimed compound in order to solve the problems of instability and insolubility so as to release bortezomib (the lead compound) at an effective rate in the bloodstream, all critical to effective use for treating multiple myeloma. The Court noted that none of the experts presented by the many defendants testified awareness of prior art to fill any of the gaps in terms of teaching or suggesting the patented Velcade® product. Rather, the Court found that the undisputed facts only showed failed attempts to achieve a stable formulation having the necessary properties of solubility and dissociation in the bloodstream, as did the claimed compound. The Federal Circuit explained that neither the requisite motivation nor reasonable expectation of success required to arrive at a determination of obviousness was found in the prior art.

Similarly, the Federal Circuit explained that the district court erred in its reasoning regarding inherency of the outcome, finding that the claimed compound was not inevitable: “[t]he inventor’s own path itself never leads to a conclusion of obviousness; that is hindsight. What matters is the path that the person of ordinary skill in the art would have followed, as evidenced by the pertinent prior art.” Here, the Court found no evidence that anyone “foresaw or expected” that the reaction between bortezomib and mannitol “would have the long-sought properties and advantages” of the claimed invention.

The Federal Circuit also concluded that the district court erred in its examination of secondary considerations of unexpected results and long-felt need. As to unexpected results, the Court found that the district court should have acknowledged the unrebutted evidence that the D-mannitol ester of bortezomib exhibited unexpected results compared with bortezomib, including unexpectedly superior stability, solubility and dissolution. As to long-felt need, the Court noted that there was no dispute that there was a long-felt need for a product to treat multiple myeloma, since available treatments prior to Velcade® gave poor remission rates and low survival rates.