The Circuit issued only one precedential patent case this week, reversing a determination of obviousness as to a Millennium Pharmaceutical patent covering its blockbuster cancer drug Velcade®, thus extending the life of patent coverage beyond that of an older patent expiring this year. In Millennium v. Sandoz, the panel reviewed the doctrines of inherent disclosure, teaching away, hindsight, unexpected result and long felt need and ruled the claimed invention to be nonobvious because the prior art did not teach that lyophilization of bortezomib in the presence of mannitol would form a new chemical compound, or that this new compound would solve the previously intractable problems of bortezomib formulation.
Millennium Pharmaceuticals, Inc. v. Sandoz Inc., Fed. Cir. Case 2015-2066, -1008, -1009, -1010, -1109, -1110, -1283, and -1762 (July 17, 2017)
A district court finding of obviousness is reversed as to a Millennium patent covering its blockbuster cancer drug Velcade® in consolidated patent appeals involving Sandoz, Apotex and Teva. As stated by the panel, the issue on appeal is whether a person of ordinary skill, seeking to remedy the known instability and to produce an efficacious formulation of bortezomib, would obviously produce the D-mannitol ester of bortezomib, a previously unknown compound.
It is not disputed that Velcade provided unexpected properties, solving the problems that accompanied bortezomib. Sandoz argues that lyophilization was generally known in formulating pharmaceutical products. It states that bulking agents were known for use in lyophilization, and that mannitol was a known bulking agent. However, the panel concludes that the prior art does not teach or suggest that lyophilization of bortezomib in the presence of mannitol would produce a chemical reaction and form a new chemical compound, or provide a reason to make this specific new chemical compound, or that this new compound would solve the previously intractable problems of bortezomib formulation.
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.” Millennium offered persuasive evidence that the chemical modification of bortezomib would have been unattractive to a person of ordinary skill for fear of disturbing the chemical properties whereby bortezomib functions effectively as an anti-cancer agent; in particular, a person of ordinary skill would have noted that the ester blocks a portion of the bortezomib molecule. Dr. Adams, the principal inventor in an expiring Millennium patent also covering Velcade testified that he was surprised when he learned that such a multiplicity of mannitol esters did not form with bortezomib.
The district court also clearly erred in its consideration of inherency. Millennium conceded that the ester is the “natural result” of freeze-drying bortezomib with mannitol. However, the 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.
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. No expert testified that they foresaw, or expected, or would have intended, the reaction between bortezomib and mannitol, or that the resulting ester would have the long-sought properties and advantages.
The panel also finds that the court erred in its examination of the objective indicia of unexpected results and long-felt need. 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. Although Sandoz now argues that the bortezomib glycerol ester is “generically” encompassed by the Adams Patent, glycerol ester is not specifically disclosed in the Adams Patent or elsewhere. The panel therefore concludes that the district court should have acknowledged the unrebutted evidence that the D-mannitol ester of bortezomib exhibited unexpected results compared with bortezomib, including unexpectedly superior stability, solubility, and dissolution.
The existence of a long-felt but unsolved need that is met by the claimed invention is further objective evidence of non-obviousness. 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.
Apotex, Teva, and Millennium agreed that, since the judgment in the Sandoz case is reversed, the dismissal of the litigation between Millennium and Apotex and Teva should be vacated and remanded so that Apotex and Teva have an opportunity to present their case
Comment: It is rare to see an obviousness case discuss inherency, hindsight, teaching away, unexpected result and long-felt need, but this case has it all. The conclusion reached by the panel appeared preordained when the panel stated the issue on appeal to be “whether a person of ordinary skill, seeking to remedy the known instability and to produce an efficacious formulation of bortezomib, would obviously produce the D-mannitol ester of bortezomib, a previously unknown compound.”
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