MILLENNIUM PHARMACEUTICALS, INC. v. SANDOZ INC

(Fed. Cir. July 17, 2017) (NEWMAN, Mayer, O’Malley)

This case arose out of an ANDA litigation between Millennium and a number of generic-drug companies who sought FDA approval of the generic counterparts of Velcade®, an oncology drug prescribed for multiple myeloma and mantle cell lymphoma. Millennium had sued the generic-drug companies over U.S. Patent 6,713,446 which claims the mannitol ester of bortezomib generated by lyophilizing bortezomib with mannitol. According to the district court, Millennium had conceded that the claimed mannitol ester was a natural result of lyophilizing bortezomib in the presence of mannitol. The district court then found the ‘446 patent claims obvious for being the inherent result of an allegedly obvious chemical process (that is, lyophilizing bortezomib in the presence of mannitol). On appeal, the Federal Circuit reversed the lower court’s finding of invalidity and entered judgment in favor of Millennium.

The Federal Circuit first stated that the issue in the case is whether a person of ordinary skill in the art seeking to remedy known instability and insolubility issues of bortezomib would have obviously produced the new ester compound. The Federal Circuit explained that although lyophilization was a known method of drug formulation, and mannitol was a known bulking agent used in lyophilization, nothing on the record taught or suggested (1) the new ester, (2) that the new ester would be formed during the lyophilization process, (3) a reason to make the new ester, or (4) that the new ester would remedy the known shortcomings of bortezomib.

The Federal Circuit found that the district court clearly erred in determining that the prior art did not teach away from application of the lyophilization process. The Federal Circuit also found that the district court erred in its consideration of inherency and its analysis of objective indicia of unexpected results and long-felt need. According to the Federal Circuit, the district court should have treated bortezomib as the closest prior art compound, and acknowledged the unrebutted evidence that the mannitol ester of bortezomib exhibited unexpected results as compared with bortezomib. The unexpected results included superior stability, solubility, and dissolution of bortezomib in the blood stream. These unexpected properties of an unexpectedly produced new compound, and the ensuing pharmaceutical efficacy and benefit, negated the district court’s ruling of obviousness. For these reasons, the Federal Circuit reversed the lower court’s obviousness determination and entered judgment upholding the validity of Millennium’s ‘446 patent.