Exelixis, Inc. v. MSN Labs. Private Ltd.

Case Name: Exelixis, Inc. v. MSN Labs. Private Ltd., No. 19-2017-RGA-SRF, 2023 WL 315614 (Consol.) (D. Del. Jan. 19, 2023) (Andrews, J.) 

Drug Product and Patent(s)-in-Suit: Cabometyx® (cabozantinib (S)-malate); U.S. Patents Nos. 7,579,473 (“the ’473 patent”) and 8,877,776 (“the ’776 patent”)

Nature of the Case and Issue(s) Presented: Cabometyx is a tyrosine kinase inhibitor (“TKI”) indicated for the treatment of various cancers. The ’473 patent claims cabozantinib compounds, including cabozantinib (S)-malate and cabozantinib (L)-malate. The ’776 patent claims a particular crystalline form of cabozantinib (L)-malate called Form N-2. MSN argued that the ’473 patent was obvious and that it did not infringe the ’776 patent.

Why Exelixis prevailed: The court found that the ’473 patent was not invalid. The court disagreed with MSN’s lead compound analysis, finding that a POSA would not have been motivated to select Kirin’s Example 5 as the lead compound. Further, even if Example 5 was selected, the court found that a POSA would not have found it obvious to modify Example 5 to reach cabozantinib.

As part of the lead compound analysis, MSN argued that a POSA would have been motivated to inhibit c-Met to treat cancer,” and, in turn, would have selected Kirin Example 5 as the lead compound. Exelixis responded by arguing that there were more than 20 different kinase targets, and that a POSA would not have selected c-Met. But the court found that a POSA would have selected c-Met and that Kirin was the only publication that disclosed small molecule inhibitors.

Kirin disclosed 333 exemplary compounds and provided an “IC50 value” of representative potency for each compound. MSN argued that after excluding compounds with known toxicity, the most potent remaining exemplary compounds include a malonamide (Example 269) with two urea compounds and a different malonamide (Example 5). MSN further contended that POSA would have deprioritized the urea compounds because they would “not provide an opportunity for irreversible inhibition.”

The court disagreed, concluding that it was hindsight to deprioritize the 14 compounds that were more potent than Example 5. The court also explained that Kirin prioritized certain molecules for in vivo examination and that Example 5 was not one of those molecules.

Even if Example 5 of Kirin was selected as the lead compound, the court found that it would not have been obvious to modify the described molecule to reach cabozantinib. More particularly, the court found that a POSA would have been concerned that the proposed modification would have unpredictable effects and that a POSA would not have been motivated to pursue an irreversible inhibitor.

Next, the court found that MSN did not infringe the ’776 patent. MSN argued that it uses Form S of cabozantinib. Exelixis argued that MSN nevertheless infringed because Form S is unstable and, over time, converts to Form N-2. The court disagreed that Exelixis had met its burden to show infringement. Exelixis’s expert tested MSN’s expired, three-year-old samples and did not detect From N-2. Further, Exelixis detected Form N-2 only after subjecting MSN’s API and finished dosage form to accelerated conditions. But the court explained that Exelixis failed to demonstrate that the accelerated conditions were representative of MSN’s manufacture or storage conditions.