By Linda O’Brien, J.D., LL.M.
In a patent infringement action by the developer of cancer treatment drug Velcade, the district court erred in finding that a person of ordinary skill would obviously make the new chemical compound in Velcade that solves the issue of providing an effective form of protein inhibitor bortezomib. Thus, the U.S. Court of Appeals for the Federal Circuit reversed and remanded a Delaware federal district court’s judgment of the patent’s invalidity (Millennium Pharmaceuticals, Inc. v. Sandoz Inc., July 17, 2017, Newman, P.).
Millennium Pharmaceuticals is the exclusive licensee of U.S. Patent No. 6,713,446 ("the '446 patent"). The '446 patent describes the new chemical compound D-mannitol N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronate, which is boronate ester of bortezomib ( a boronic acid) and D-mannitol (hydroxyl compound). Millennium developed a patented product for the treatment of oncology disease, under the brand name Velcade®. Sandoz filed a new drug application (ANDA) for the manufacture and sale of generic versions of Velcade and Millennium responded with a patent infringement suit. Sandoz stipulated to infringement and sought to invalidate certain claims of the '446 patent. The district court held that claims 20, 31, 49, and 53 of the '446 patent were invalid as obvious (the "Sandoz litigation"). In separate arising from ANDAs filed by Apotex and Teva, the district court entered judgment against Millennium based on collateral estoppel. Millennium appealed and the appeals in the Sandoz, Apotex, and Teva cases were consolidated.
The appellate court found that the district court erred in its evaluation of obviousness, and invalidity was not established. Bortezomib and its properties were previously known and described in U.S. Patent No. 5,780,454 (the "Adams patent"). Despite its known efficacy against various cancers, bortezomib never received FDA approval due to its instability. However, the inventor of the '446 patent produced a new lyophilized formulation that formed a new chemical compound—the claimed ester of bortezomib and mannitol, which released the active pharmaceutical ingredient upon administration to a patient. The ensuing drug was Velcade, the court explained.
The district court held that the claims were obvious because they were the inherent result of an obvious process. Here, the court noted, the question is whether a person of ordinary skill, seeking to remedy the known instability and insolubility of bortezomib, would obviously produce the D-mannitol ester of bortezomib, a previously unknown compound. The D-mannitol ester of bortezomib was a new compound with distinct chemical properties. The prior art contained no teaching or suggestion of the new compound or that it would form during lyophilization. Sandoz identified no reference or combination of references that showed a reason to make the claimed compound. No reference teaches or suggests that such a new compound would the long-sought after properties of stability and solubility.
Although mannitol is a known bulking agent and lyophilization was a known method of drug formulation, nothing in the record teaches or suggests that a person of ordinary skill should have used mannitol as part of a synthetic reaction to make an ester through lyophilization, the court noted. Furthermore, no prior art or reference supports the district court’s conclusion that a skilled artisan would have motivated to create a mannitol ester to improve bortezomib’s stability and solubility and would have had a reasonable expectation of success. None of the defendants’ experts stated that they were aware of prior art to fill in any gaps in teaching or suggestion of the Velcade product.
The district court also clearly erred in its consideration of inherency. According to the court, the mere fact that the ester may result in the freeze drying of bortezomib with mannitol was insufficient to render the result inherent. The inventor’s path itself never leads to a conclusion of obviousness since what was relevant was the path a person of ordinary skill in the art would have followed as evidenced by the pertinent prior art.
Attorneys: William F. Lee (Wilmer Cutler Pickering Hale) for Millennium Pharmaceuticals, Inc. Thomas J. Meloro (Willkie Farr & Gallagher LLP) for Hospira, Inc. George C. Lombardi (Winston & Strawn LLP) for Sandoz Inc. Paul Braier (Greenblum & Bernstein, P.L.C.) for Accord Healthcare, Inc. Gary Edward Hood (Polsinelli PC) for Actavis LLC. Tung On Kong (Rhodes Attorneys at Law P.C.) for Mylan Laboratories Limited and Agila Specialties Inc. Louis Harry Weinstein (Budd Larner, P.C.) for Dr. Reddy’s Laboratories, Ltd. and Dr. Reddy’s Laboratories, Inc. Rachel C. Hughey (Merchant & Gould P.C.) for Sun Pharmaceutical Industries Limited and Sun Pharma Global FZE. William A. Rakoczy (Rakoczy Molino Mazzochi Siwik LLP) for Apotex Corp. and Apotex Inc. Mark David Schuman (Carlson, Caspers, Vandenburgh, Lindquist & Schuman) for Teva Pharmaceuticals USA, Inc. Jay Philip Lessler (Blank Rome LLP) for Glenmark Pharmaceuticals Ltd., Glenmark Generics Ltd., and Glenmark Generics Inc. USA. Kevin Michael Nelson (Duane Morris LLP) for Wockhardt Bio AG and Wockhardt USA, LLC.
Companies: Millennium Pharmaceuticals, Inc.; Sandoz Inc.; Accord Healthcare, Inc.; Actavis LLC; Mylan Laboratories Limited; Agila Specialties Inc.; Dr. Reddy’s Laboratories, Ltd.; Dr. Reddy’s Laboratories, Inc.; Sun Pharmaceutical Industries Limited; Sun Pharma Global FZE; Apotex Corp.; Apotex Inc.; Teva Pharmaceuticals USA, Inc.; Glenmark Pharmaceuticals Ltd.; Glenmark Generics Ltd.; Glenmark Generics Inc. USA; Hospira, Inc.; Wockhardt Bio AG; Wockhardt USA, LLC.
MainStory: TopStory Patent FedCirNews
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