IP Law Daily, PATENT—D. Del.: Exelixis’ cancer treatment patents asserted against MSN Laboratories are not invalid, (Oct 16, 2024)

By Cheryl Beise, J.D.

MSN stipulated infringement of three patents; another asserted patent was not infringed.

After a four-day bench trial, the federal district court in Wilmington, Delaware, has ruled that certain claims of four patents owned by Exelixis, Inc., which claimed cabozantinib malate salts compositions for the treatment of various cancers were not invalid for obviousness, lack of written description, or obviousness-type double patenting. The court also found that MSN Laboratories did not infringe the asserted claim of one patent. MSN already had stipulated to infringement of the asserted claims of the other three patents (Exelixis, Inc. v. MSN Laboratories Private Limited, No. 1:22-cv-00228-RGA (D. Del. Oct. 15, 2024)).

Exelixis sells Cabometyx for the treatment of kidney cancer, liver cancer, and differentiated thyroid cancer and Cometriq for the treatment of metastatic medullary thyroid cancer. The active pharmaceutical ingredient (API) in Cabometyx and Cometriq is the (L)-malate salt of cabozantinib. MSN submitted Abbreviated New Drug Application (ANDA) No. 213878 to the U.S. Food and Drug Administration (FDA), seeking approval to manufacture and sell a generic version of Cabometyx.

Exelixis, Inc. brought a patent infringement action against MSN Laboratories Private Limited and MSN Pharmaceuticals, Inc. (together, MSN), asserting claim 3 of U.S. Patent No. 11,298,349 (the ’349 patent). The '349 patent is directed to a pharmaceutical composition of cabozantinib (L)-malate that includes certain classes of excipients and is free of a harmful genotoxic impurity. In a second suit, Exelixis asserted a group of patents that shared the same specification—claim 4 of U.S. Patent Nos. 11,091,439 the ’439 patent), claim 3 of U.S. Patent No. 11,091,440 (the ’440 patent), and claim 2 of U.S. Patent No. 11,098,015 (the ’015 patent) (collectively, the Malate Salt Patents). The Malate Salt Patent claims require a cabozantinib malate salt that is crystalline. The Malate Salt Patents and the ’349 patent have been listed in connection with Cabometyx in the FDA’s Orange Book.

The two infringement actions were consolidated. MSN disputed infringement of claim 3 of the ’349 patent and argued the claim was invalid as obvious. MSN stipulated to infringement of the Malate Salt Patents, but contended they were invalid for lack of written description and obviousness-type double patenting. The court held a four-day bench trial in October 2023 and issued this trial opinion.

The ’349 patent—infringement. The issue of infringement turned on whether the as granulated corn starch derivative known as GRASTAR MSN added to its ANDA products was a “glidant.” A glidant is a material that improves the flow of a drug powder mixture. MSN argued that GRASTAR was a dilutant rather than a glidant. The court explained that whether GRASTAR acts as a glidant in a particular pharmaceutical composition depends on the pharmaceutical composition. In this case, the court concluded that Exelixis failed to meet its burden to show GRASTAR served as a glidant in MSN's ANDA products, because it did not show by a preponderance of the evidence that GRASTAR improved flow. Accordingly, MSN did infringe the ’349 patent.

The ’349 patent—obviousness. At issue was the “essentially free” limitation of claim 3 of the ’349 patent. MSN argued that making a cabozantinib (L)-malate API essentially free of the 1-1 impurity would be obvious to a POSA. The court rejected MSN’s argument that the Brown prior art reference inherently discloses a cabozantinib (L)­ malate API essentially free of the 1-1 impurity. The court also found that a POSA would know from FDA guidance that the 1-1 starting material is genotoxic it would not have been obvious for a POSA to modify the Brown process to obtain a formulation of cabozantinib (L)-malate essentially free of the 1-1 impurity.

Malate Salt Patents—written description. The court found that the Malate Salt Patents claimed a genus of crystalline cabozantinib (L)-malate. Because all crystalline cabozantinib malate share the same chemical name and formula, the court determined a POSA would be able to identify whether the structure of a polymorph is crystalline and a POSA could distinguish between crystalline and amorphous cabozantinib. Citing GlaxoSmithKline LLC v. Banner Pharmacaps, Inc., 744 F.3d 725 (Fed. Cir. 2014) and Merck Sharp & Dahme, LLC v.Mylan Pharms. Inc., 2022 WL 22855168 (N.D. W.Va. Oct. 26, 2022), the court determined this evidence was sufficient to satisfy written description, and did not need to determine the size of the genus and whether Exelixis disclosed a representative number of species.

Malate Salt Patents—obviousness-type double patenting. MSN argued that Claim 4 of the ’439 patent is invalid for obviousness-type double patenting of Claim 5 of the ’473 patent. The issue was whether a POSA would have recognized that crystalline cabozantinib (L)-malate is a pharmaceutically acceptable salt of the cabozantinib compound.

The court agreed with MSN that a POSA would be motivated to make a salt of cabozantinib, but a POSA would not be motivated to use malic acid to form a salt of cabozantinib because there was no evidence of a reasonable likelihood of success in obtaining a crystalline salt using malic acid. The court found that MSN did not meet its burden of proving by clear and convincing evidence that it would be obvious for a POSA to treat kidney cancer with the malate salt of cabozantinib.

The Case is No. 1:22-cv-00228-RGA.

Judge: Andrews, R.

Attorneys: Jack B. Blumenfeld (Morris, Nichols, Arsht & Tunnell LLP) and William F. Lee ((Wilmer Cutler Pickerinh Hale and Dorr LLP) for Exelixis, Inc. Dominick T. Gattuso (Heyman Enerio Gattuso & Hirzel LLP) and George C. Lombardi (Winston & Strawn LP) for MSN Laboratories Private Ltd. and MSN Pharmaceuticals, Inc.

Companies: Exelixis, Inc.; MSN Laboratories Private Ltd.; MSN Pharmaceuticals, Inc.

Cases: Patent DelawareNews