Millennium Pharma v. Sandoz (Federal Circuit 2017)
As part of a brand-generic pharma battle, the district court invalidated a set of Millennium’s patent claims covering its Velcade drug used to treat multiple myeloma. The district court held that the claims (covering the chemical compound active ingredient) were obvious as the inherent result of an obvious process.
In particular, the claims cover a freeze dried (“lyophilized”) version of the compound “D-mannitol N-(2- pyrazine) carbonyl-L-phenylalanine-L-leucine boronate.” The active portion of the compound is the boronate (bortezomib), which was known to work but was unstable. Researchers tried and failed to create liquid formations and so turned to freeze-drying. To achieve that end, mannitol was added to the compound in a way formed a chemical bond with the boronate – leading to dramatic improvement in stability. When a patient ingests the new drug (a “prodrug”), the body breaks-down the compound and allows the active ingredient to work.
The boronate portion was known in the prior art for its medical use and the mannitol portion was a known bulking agent. The process of freeze-drying was also known. However:
No reference taught or suggested reacting bortezomib with mannitol, and no reference hinted that … an esterification reaction might occur during lyophilization. No reference taught or suggested that the product of such lyophilization would be a new chemical compound that would solve the problems that had inhibited development of bortezomib in oncology.
In its decision, the district court recognized that the resulting compound was likely unexpected, but focused on the process of getting to that result – holding that the claimed compound was simply the “natural result” inherent to the lyophilized process and that it would have been obvious to try the process on boronate + mannitol. On appeal, the Federal Circuit has reversed.
The easy part of the decision for the district court focused-in on the motivation to combine boronate and mannitol. The district court found that an Adams Patent “pointed directly to mannitol” for the combination. However, according to the Federal Circuit, “the Adams Patent’s fail[s] to mention mannitol.”
In my view, this easy-part is sufficient for the patentee to win, and my preference would be for the court to delete the rest of its muddled opinion – and instead rest its case on the lack of the motivation to combine. The remainder of the decision is somewhat difficult to follow because it jumps back and forth dancing around but never answering the basic question: If the combination would have been obvious to try, would its natural result also be considered obvious? At times, the court appears to agree that obviousness would follow, while other sections of the opinion suggest the compound would not have been obvious since its actual structure was so unexpected.
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A patent claim is obvious when, “if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.” Here the appellate panel focused the question to: “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.”
On the topic of inherency in particular, the court seems to have simply strung together several loosely related sentences. Take the following pair as an example:
Sandoz argues that although lyophilization in the presence of mannitol produced an unexpected result, the result was “inevitable” and thus “inherent,” and thus not “inventive.” However, invention is not a matter of what the inventor intended when the experiment was performed; obviousness is measured objectively in light of the prior art, as viewed by a person of ordinary skill in the field of the invention . . .
In the end, the reversal makes sense, but the law created is somewhat of a mess.
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 Millennium Pharm., Inc. v. Sandoz Inc., No. 12-1011, 2015 WL 4966438 (D. Del. Aug. 20, 2015); U.S. Patent No. 6,713,446.
 35 U.S.C. 103.