©2018. Published in Landslide, Vol. 10, No. 3, January/February 2018, by the American Bar Association. Reproduced with permission. All rights reserved. This information or any portion thereof may not be copied or disseminated in any form or by any means or stored in an electronic database or retrieval system without the express written consent of the American Bar Association or the copyright holder.
Is the natural result of a known process considered inherently obvious? Patent practitioners might quickly jump to the conclusion that any natural result of an arguably known and/or obvious process is itself inherently obvious and unpatentable. The Federal Circuit’s ruling in Millennium Pharmaceuticals, Inc. v. Sandoz this past summer, however, demonstrates this is not always the case.1
Indeed, the Federal Circuit in Millennium sent an important message that the existence of inherent disclosures may not necessarily be enough to render a patent claim obvious. The claimed invention in Millennium concerned a chemical compound known as bortezomib. Bortezomib is used in the treatment of patients with multiple myeloma and mantle cell lymphoma who have received at least one prior therapy, and Millennium Pharmaceuticals markets it under the brand name Velcade.2 Although bortezomib was known and described in a prior art patent, it had not achieved FDA approval by the time the patent-in-suit was applied for.3 It was previously known that bortezomib suffered from instability, rapid degradation in liquid formulations, and insolubility. After many failed attempts to develop a viable liquid formulation that resolved the issues in bortezomib, the patent applicants developed a promising formulation. This formulation was prepared by lyophilization (freeze-drying) using a known bulking agent, mannitol.4 The formulation was the subject of U.S. Patent No. 6,713,446 (’446 patent) and ultimately became the formulation for Velcade.
Three generic drug manufacturers filed abbreviated new drug applications seeking approval for a generic version of Velcade. In response, Millennium filed suit in the District of Delaware. At trial, the closest and sole prior art was found to be an earlier patent filed by Millennium’s predecessor claiming the bortezomib compound, and both parties agreed that bortezomib was the proper lead compound for the obviousness analysis.5 Both parties also agreed that the Velcade compound provided unexpected properties that solved the problems of bortezomib.6 The generic defendants argued that lyophilization would have been an obvious process to stabilize bortezomib. Specifically, the generic defendants argued it was a “standard” formulation method that a formulator would have considered.7 They further argued that there were “only ‘half a dozen or so’ . . . ‘pharmaceutically acceptable bulking agents’” with the “most prominent” being mannitol, and thus it would have been obvious to lyophilize bortezomib with mannitol.8 According to the generic defendants, if the court finds freeze-drying with mannitol to be obvious, then the patent is necessarily invalid because the claimed formulation “is the inherent result of that combination.”9 To further support their position, the generic defendants argued that Millennium had also admitted to inherency by claiming an invention date based on when the inventors made the claimed formulation. Because the alleged invention date was before the resulting ester formation was first identified, the generic defendants argued that Millennium had “conceded as a matter of law that the ester is the ‘natural result’ of freeze-drying bortezomib with mannitol.”10 Millennium, however, maintained that it would not have been obvious to a person of ordinary skill in the art to try lyophilization because “lyophilization would not necessarily address the instability of bortezomib.”11 Millennium also argued that a person of ordinary skill in the art would have avoided modifying bortezomib for fear of disturbing its chemical properties.12
Persuaded by the generic defendants’ expert witness, the district court found that lyophilization was “well-known in the field of formulation and often utilized when a liquid formulation provided limited success,” and thus attempting a lyophilized formulation of bortezomib would have been routine to a person of ordinary skill in the art.13 The district court further found that the prior art pointed directly to mannitol and that it would have been obvious to use mannitol as a bulking agent as it was among a “finite number of identified, predictable solutions.”14 And following the generic defendants’ reasoning, the district court found that the claims were “the inherent result of an allegedly obvious process, viz., lyophilizing bortezomib in the presence of the bulking agent mannitol” and thus invalid.15
On appeal, the Federal Circuit criticized the lower court, concluding that “[t]he district court clearly erred in its obviousness analysis.”16 The Federal Circuit found “no teaching or suggestion in the references to produce the claimed mannitol ester” and that “[n]o reference shows or suggests ester formation at freeze-drying conditions, or that any such ester might solve the problems” of bortezomib.17 The Federal Circuit also found that “[n]o reference provides a reason to make the mannitol ester of bortezomib.”18 The Federal Circuit was not convinced by the generic defendants’ argument that the claimed invention was obvious simply because lyophilization was a generally known process and mannitol was a known bulking agent used for lyophilization. While the Federal Circuit agreed that mannitol and lyophilization were both known, it determined that “nothing on 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.”19 Moreover, the Federal Circuit found that “[n]o reference supports the district court’s conclusion that skilled formulators would be motivated to create a mannitol ester to improve bortezomib’s stability and solubility.”20 The Federal Circuit also found persuasive Millennium’s argument that a person of ordinary skill in the art would have avoided creating an ester with mannitol.21
Even though it found no motivation to combine, the Federal Circuit went further and held that “[t]he district court . . . clearly erred in its consideration of inherency.”22 The Federal Circuit explained that the “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.”23 Because the inventor’s path is irrelevant in an obviousness analysis, the Federal Circuit dismissed the district court’s finding that Millennium had conceded that the claimed invention was the natural result of freeze-drying bortezomib with mannitol. In following the path of a person of ordinary skill in the art, the Federal Circuit found that “[n]o 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.”24 Thus, the Federal Circuit suggests that in order to show inherency, one must demonstrate the prior art references show both (1) a reason for conducting a particular experiment, and (2) an expectation of the resulting product. Results that are unforeseeable and serendipitous are not enough to satisfy inherency.
Finally, the Federal Circuit concluded that the district court erred in its consideration of the objective indicia of unexpected results and long-felt need. The Federal Circuit found that Millennium presented persuasive evidence of unexpected results and that the claimed invention met a long-felt but unmet need.25
Given the Federal Circuit’s decision in Millennium, a patent owner can take a bit of solace that not all discoveries based on a supposed “natural result” are unpatentable. An invention may still survive patent challenges despite being a “natural result” of a well-known formulation method if it can be shown that a person of ordinary skill in the art would not have foreseen, expected, or intended such result.26 Even if a discovery may appear to be obvious, inherency cannot be based on hindsight reconstruction by merely following the inventor’s path.27 Millennium certainly demonstrates that the unforeseeable and unexpected nature of discoveries plays an important role in an invention’s ability to survive patent challenges.
1. 862 F.3d 1356 (Fed. Cir. 2017).
2. Millennium Pharm., Inc. v. Sandoz, No. 12-1011-GMS, 2015 WL 4966438, at *1 (D. Del. Aug. 20, 2015).
3. Millennium, 862 F.3d at 1361.
4. Id. at 1362.
5. Millennium, 2015 WL 4966438, at *5; see also Millennium, 862 F.3d at 1364.
6. See Millennium, 862 F.3d at 1364.
7. Millennium, 2015 WL 4966438, at *6.
8. Id. at *7.
9. Id. at *6–8.
10. Id. at *8.
11. Id. at *6.
12. See Millennium, 862 F.3d at 1366.
13. Millennium, 2015 WL 4966438, at *6.
14. Id. at *7.
15. See Millennium, 862 F.3d at 1362–63.
16. Id. at 1364.
20. Id. at 1366.
21. Id. at 1366–67.
22. Id. at 1367.
25. Id. at 1367–69.
26. Id. at 1367 (“‘The mere fact that a certain thing may result from a given set of circumstances is not sufficient’ to render the result inherent.”).
27. Id. (“The inventor’s own path itself never leads to a conclusion of obviousness; that is hindsight.”).