October 20, 2017

Case Name:  Millennium Pharms., Inc. v. Sandoz Inc., Nos. 2015-2066, 2016-1008, -1009, -1010, -1109, -1110, -1283, -1762, 2016 U.S. App. LEXIS 12702 (Fed. Cir. July 17, 2017) (Circuit Judges Newman, Mayer, and O’Malley presiding; Opinion by Newman, J.) (Appeal from D. Del., Sleet, J.) 

Drug Product and Patent(s)-in-Suit: Velcade® (bortezomib); U.S. Patent No. 6,713,446 (“the ’446 patent)

Nature of the Case and Issue(s) Presented:  Millennium is the exclusive licensee of ’446 patent, issued Mar. 30, 2004 and assigned to the United States. Millennium developed the patented product for treatment of oncology disease, particularly multiple myeloma and mantle cell lymphoma. Appellees all filed ANDAs seeking to market generic bortezomib, admitting infringement, and seeking to invalidate various claims of the ’446 patent. The district court held that claims 20, 31, 49, and 53 of the ’446 patent were invalid, and this appeal ensued. The Federal Circuit held that, in finding invalidity the district court erred, and reversed.

Why Millennium Prevailed:  The question was whether a person of ordinary skill, seeking to remedy the known instability and insolubility and to produce an efficacious formulation of bortezomib, would obviously produce the D-mannitol ester of bortezomib, a previously unknown compound. The prior art contained no teaching or suggestion of this new compound, or that it would form during lyophilization. Appellees identified no reference or combination of references that showed or suggested a reason to make the claimed compound. No reference taught or suggested that such a new compound would have the long-sought properties of stability and solubility, and sufficiently dissociate to release bortezomib at an effective rate in the bloodstream, all critical to effective use for treating multiple myeloma.

The Federal Circuit also held that the district court erred in crediting appellees’ dismissal of secondary considerations of non-obviousness. Millennium presented expert testimony that the lyophilized mannitol ester of bortezomib yielded unexpected results as compared to bortezomib, viz., greatly improved stability, solubility, and dissolution, which the district court did not credit. Additionally, the district court’s conclusion that the lyophilized mannitol ester of bortezomib did not meet a long-felt need was both perfunctory and clearly erroneous. There is no dispute that there was a long-felt need for a product to treat multiple myeloma, for treatments prior to Velcade gave poor remission and low survival rates. Although it was agreed that bortezomib was the effective product in the body, bortezomib alone was not an available product. Appellees offered no evidence of successful solution of the problems that had barred bortezomib from clinical approval. Finally, the district court clearly erred in attributing Velcade’s commercial success to bortezomib alone, as bortezomib was not a viable commercial product and had been denied FDA approval because of its instability. The D-mannitol ester was responsible for Velcade’s successful results, for the D-mannitol ester was necessary to provide the required solubility and stability.