In Millenium Pharmaceuticals Inc., v. Sandoz Inc., 2015-2066, 2016-1008, 2016-1009, 2016-1010, 2016-1283, 2016-1762 (Fed. Cir. July 17, 2017), the Federal Circuit pulled no punches in overruling the Districts Court’s finding of patent invalidity for U.S. Patent No. 6,713,446 (446 Patent), exclusively licensed by Millennium. The case related to Velcade®, used in chemotherapy for the treatment of multiple myeloma. Such was the drug’s effectiveness that it “changed the decades-old standard of care for multiple myeloma and has saved thousands of lives.
A collection of companies filed abbreviated new drug applications (ANDA’s), admitting infringement and seeking to invalidate several claims of the 446 Patent. The District Court for the District of Delaware found claims 20, 31, 49, and 53 invalid as obvious, and that there was no demonstration of unexpected results. Millenium appealed. In separate cases, ANDA’s were also filed by Apotex and Teva based on collateral estoppel from the District Court’s holding, and the Federal Circuit consolidated the Sandoz appeal with the Apotex and Teva cases. Judge Newman authored the Opinion.
Velcade® is an ester of bortezomib and mannitol produced during lyophilization (freeze drying), which acts as a “prodrug,” i.e., a compound that converts to or releases the active pharmaceutical ingredient upon administration to a patient. It was a new compound, exhibiting a dramatic improvement in dissolution and stability hitherto unknown in bortezomib compounds.
Federal Circuit Analysis
In addressing the reasoning behind the rulings, the Federal Circuit bluntly communicated its view that it was a ruling having questionable legal support, in a style that periodically approached the sarcastic. Some of the Federal Circuit’s findings with respect to the district court’s evaluation of the reference’s “teaching or suggestion” is summarized below.
|1. The district court did not find that the prior art taught or suggested that the claimed new compound would be formed, or taught or suggested making the claimed new compound by any method, or taught or suggested that this new compound would have the properties of stability, solubility, and dissociability that it exhibited.|
|2. No reference taught or suggested reacting bortezomib with mannitol, and no reference hinted that such an esterification reaction might occur during lyophilization.|
|3. 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.|
|4. 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.|
This is only a sampling. There were at least eight more analogous portions critical of the district court’s approach to teaching or suggestion.
Not surprisingly, the Federal Circuit concluded that the district court had committed clear error with regard to its obviousness analysis. However, the Federal Circuit wasn’t finished. On four additional occasions it concluded that clear error was present:
The district court also clearly erred in its determination that lyophilizing bortezomib with mannitol to form an ester was a “suitable option from which the prior art did not teach away.”
The district court also clearly erred in its consideration of inherency.
The district court clearly erred in attributing Velcade®’s commercial success to bortezomib alone, as bortezomib is 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 is necessary to provide the required solubility and stability.
We conclude finally that the district court clearly erred in its examination of the objective indicia of unexpected results and long-felt need.
The reasoning behind the district court’s conclusion with regard to the absence of unexpected results was founded in Millennium’s concession “that the ester is the ‘natural result’ of freeze-drying bortezomib with mannitol.” However, Sandoz itself had agreed that Millenium’s new product produced unexpected results but nevertheless argued that the unexpected results were inherent because of Millennium’s concession. The Federal Circuit rejected this reasoning.
The district court stated that Millennium “conceded as a matter of law that the ester is the ‘natural result’ of freeze-drying bortezomib with mannitol.” Dist. Ct. Op. *8. However, “[t]he inventor’s own path itself never leads to a conclusion of obviousness; that is hindsight. What matters is the path that the person of ordinary skill in the art would have followed, as evidenced by the pertinent prior art.” Otsuka, 678 F.3d at 1296.
The dismissive nature of the Federal Circuit’s opinion is highlighted by the sarcastic tone the opinion adopts when addressing the testimony of Sandoz’s experts.
None of the experts presented by the many defendants stated that they were aware of prior art to fill any of the gaps in teaching or suggestion of the Velcade® product-although they variously opined that this long-sought discovery was obvious. Sandoz’s expert Dr. Repta, who offered an opinion of obviousness, conceded that he had “never worked with any boronic acid compound and has not performed or supervised any lyophilization experiments since 1983.” *** Dr Repta cited seventeen references, none of which teaches or suggests the claimed new compound, or proposes lyophilization in the presence of mannitol to produce a new compound, or suggest that such new compound should be prepared in order to obtain the necessary stability, solubility, and dissociability for treatment of multiple myeloma.
I found the energy of the Federal Circuit’s opinion refreshing. The reason is that from time to time as I page through a Final Rejection I find myself thinking, “come on, there’s no motivation or suggestion there! Not even close!” or “this Examiner thinks EVERYTHING is inherent. Sometimes I then find a bit of solace in the notion that “if this were in front of a judge who actually understood Obviousness, they would toss this Final Rejection around the ring like Thunderlips did to Rocky.” This was just that kind of Opinion.
 Slip Op at 6.
 Id. at 4.
 Id. at 6.
 Id. at 7.
 Id. at 10.
 Id. at 11.
 Id. at 14-15 (emphasis added)
 Id. at 15. (emphasis added)
 Id. at 20. (emphasis added)
 Id. at 17. (emphasis added)
 Id. at 16.
 Id. at 12-13. (emphasis added)
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