By Thomas Long, J.D.
Although a district court erred in requiring proof that skilled persons would have been motivated to select everolimus over prior art treatments, it correctly found that they would not have reasonably expected success in using the compound to treat advanced renal cell carcinoma.
The federal district court in Wilmington, Delaware, did not err in holding that three challenged claims of a patent for methods of using the compound everolimus to treat advanced renal cell carcinoma were not invalid as obvious in light of prior art, the U.S. Court of Appeals for the Federal Circuit has decided. In a patent infringement suit brought by patent holders Novartis Pharmaceuticals Corp. and Novartis AG (collectively, “Novartis”)—which used everolimus as the active in ingredient in a brand-name drug, Afinitor—generic drug manufacturer West-Ward Pharmaceuticals International Ltd. failed to prove a person of ordinary skill (POSA) would have reasonably expected success in using everolimus for treatment of advanced renal cell carcinoma as of the priority date of the patent-in-suit. Although the district court erred in holding West-Ward to a heightened standard by requiring West-Ward to prove that a POSA would have selected everolimus over other prior art treatment methods, the appellate court agreed with the district court’s ultimate conclusion as to the claims’ validity (Novartis Pharmaceuticals Corp. v. West-Ward Pharmaceuticals International Ltd., May 13, 2019, Stoll, K.).
Patent-in-suit. West-Ward’s predecessor in interest, Roxane, filed an Abbreviated New Drug Application (ANDA) seeking to engage in the commercial manufacture, use, and sale of generic versions of Afinitor. Novartis filed suit for infringement in response. The parties stipulated that the ANDA infringed claims 1–3 of U.S. Patent No. 8,410,131 (“the ’131 patent”); West-Ward asserted that those claims were invalid as obvious. The ’131 patent covers methods of administering the compound everolimus to inhibit the growth of advanced renal cell carcinoma (RCC) tumors. Advanced RCC is a cancer of the kidneys that has spread to other parts of the body. As of February 19, 2001—the priority date of the ’131 patent—advanced RCC was known to be unpredictable and difficult to treat. The only approved drug for treating advanced RCC was the immunostimulant interleukin-2, which was associated with poor response rates and toxicity in patients. Everolimus belongs to a class of compounds called mTOR inhibitors. While the prior art in February 2001 disclosed that other mTOR inhibitors had shown some effectiveness in RCC patients in clinical trials, there was no data on the efficacy of everolimus to treat any type of cancer, let alone to treat advanced RCC.
Prior art. West-Ward argued that claims 1–3 of the ’131 patent would have been obvious to a POSA over one of two journal articles regarding clinical trials using the mTOR temsirolimus (“Hidalgo 2000” or “Hutchinson”) and one of two everolimus patents (U.S. Patent No. 5,665,772 or U.S. Patent No. 6,004,973), in view of the general knowledge in the art. According to West-Ward, knowledge in the art about the molecular biology of advanced RCC, the antitumor activity of mTOR inhibitors, temsirolimus clinical trial results, and safe dosing ranges for everolimus would have provided a POSA with a reasonable expectation of success of effectively treating advanced RCC with everolimus.
Motivation to combine. After reviewing the prior art, the district court found that a person of ordinary skill “would have been motivated to pursue everolimus as one of several potential treatment options for advanced solid tumors, including advanced RCC.” The district court then continued its analysis on motivation to combine and concluded that West-Ward “failed to prove by clear and convincing evidence that a POSA would have been motivated to select everolimus.” The district court erred in applying this heightened standard, the Federal Circuit said. However, the appellate court agreed with the district court’s ultimate determination on validity, discerning no clear error in the district court’s finding that a person of ordinary skill would not have reasonably expected success in using everolimus to treat advanced RCC as of February 2001. Federal Circuit precedent did not require that a particular combination must be the preferred, or the most desirable, combination described in the prior art in order to provide the requisite motivation to combine. Therefore, the district court should not have required West-Ward to prove that a POSA would have selected everolimus over other treatment methods. The Federal Circuit explained that the “would have selected” standard was appropriate in cases involving “lead compounds,” or starting points for further development efforts, but this was not such a case. Nor was it a case involving prior art that showed a range of options and a claim limitation that fell within that range, which also would call for an analysis of whether the prior art would have motivated the selection of the claimed composition from the prior art ranges.
In this case, the ’131 patent claimed methods of using everolimus to inhibit growth of solid tumors, including in patients having advanced RCC. It did not claim the everolimus compound itself, but rather methods of using the compound. The proper inquiry, the Federal Circuit said, was whether a person of ordinary skill would have been motivated to modify the prior art disclosing use of temsirolimus to treat advanced RCC with the prior art disclosing everolimus. The district court answered this question affirmatively, and that should have ended the analysis regarding motivation to combine.
Reasonable expectation of success. The district court did not err, however, in finding that a POSA would not have had a reasonable expectation of success in using everolimus to treat advanced RCC. The district court found that West-Ward’s asserted prior art combination—Hidalgo 2000 or Hutchinson in view of the ’772 patent or ’973 patent in view of the knowledge in the art—failed to provide clear and convincing evidence of a reasonable expectation of success. The district court’s decision was based on expert testimony to support subsidiary findings that (1) the temsirolimus clinical test data had diminished weight due to the tests’ small sample sizes and focus on safety rather than efficacy; (2) everolimus and temsirolimus had different pharmacological properties; and (3) the molecular biology of advanced RCC was not completely understood, particularly the role mTOR activity played in it. The Federal Circuit said that it could discern no error in these findings and therefore affirmed the determination that claims 1–3 of the ’131 patent would not have been obvious in view of the asserted prior art.
This case is No. 2018-1434.
Attorneys: Christina A. L. Schwarz (Venable LLP) for Novartis Pharmaceuticals Corp. and Novartis AG. David Zimmer (Goodwin Procter LLP) for West-Ward Pharmaceuticals International Ltd.
Companies: Novartis Pharmaceuticals Corp.; Novartis AG; West-Ward Pharmaceuticals International Ltd.
MainStory: TopStory Patent FedCirNews
Interested in submitting an article?
Submit your information to us today!Learn More
IP Law Daily: Breaking legal news at your fingertips
Sign up today for your free trial to this daily reporting service created by attorneys, for attorneys. Stay up to date on intellectual property legal matters with same-day coverage of breaking news, court decisions, legislation, and regulatory activity with easy access through email or mobile app.