Natural Phenomenon Takes Back Seat to Analysis

In a recent decision of the CAFC entitled Millennium Pharmaceuticals, Inc. v. Sandoz Inc., et al, a consolidated appeal of cases 2015-2066, 2016-1008, 2016-1009, 2016-1010, 2016-1109, 2016-1110, 2016-1283, and 2016-1762, decided July 17, 2017, Judge Newman writing the opinion for a unanimous panel reversed a decision of the District Court for the District of Delaware holding the patent (US 6,713,446) on the cancer drug Velcade® invalid for obviousness. That drug had been used clinically to successfully treat multiple myeloma and mantle cell myeloma.

The active moiety in Velcade® was the compound D-mannitol N-(2-Pyrazine)carbonyl-L-phenylalanine-L-leucine boronate. That compound arose as a result of a yearlong quest to solve the instability problem with solutions of the non-sugar containing bortezomib compound. When the inventor of the ‘446 patent (a scientist at the NCI and the University of Kansas) lyophilized bortezomib in the presence of mannitol he obtained the aforesaid boronate which had covalently incorporated the mannitol producing a new compound. This compound proved to be not only stabile on storage and in solution but also when administered to a subject functioned as a prodrug for bortezomib. No prior art was presented that taught or suggested a compound whose structure presented a basis for an obvious rejection using standard analysis of a pharmaceutical compound claim.

In the District Court case, Judge Sleet accepted the expert testimony provided on behalf of the defendants to the effect that lyophilization was a well-known technique in the pharmaceutical arts that had been used before to overcome stability problems with active agents in solution. Additionally, Judge Sleet further accepted the evidence that sugars such as mannitol were known conventional additives for use in carrying out lyophilizations. He then found the in situ formation of the covalent mannitol prodrug new compound to be a ”natural phenomenon” resultant from using the obvious procedure with an obvious adjunct and held the ‘446 patent invalid.

Judge Newman gave short shrift to the need for deference to a trial court’s judgment on trial issues involving expert testimony. She applied tried and true obviousness standards for evaluating the effect of prior art disclosures when applied to novel product claims, thereby limiting newly minted concepts based on amorphous “natural phenomenon” analysis in stating:

“The prior art contains no teaching or suggestion of this new compound, or that it would form during lyophilization. Sandoz identifies no reference or combination of references that shows or suggests a reason to make the clamed compound. No reference teaches or suggests 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 blood-stream, all critical to effective use for treating multiple myeloma.” (Decision at page 10).

George M. Gould is Counsel in the Gibbons Intellectual Property Department.
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