October 21, 2019

October 21, 2019

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Federal Circuit Addresses Obviousness of Polymorphs in Grunenthal GmbH v. Alkem Labs. Ltd., No. 2017-1153 (Fed. Cir. Mar. 28, 2019)

For the first time, on March 28, 2019, the Federal Circuit addressed obviousness of polymorph claims based on a known approach to polymorph screening, finding no reasonable expectation of success.

In the case, Plaintiffs Grünenthal and Assertio Therapeutics, Inc. asserted U.S. Patent Nos. 7,994,364 and 8,536,130[1] against Defendants Alkem Laboratories Ltd., Hikma Pharmaceuticals International Ltd., Hikma Pharmaceuticals USA Inc., and Actavis Elizabeth, LLC. Both patents were listed in the Orange Book for NUCYNTA® ER, a tapentadol hydrochloride tablet used to treat pain.

Prior Art “Form B” Plus Byrn (1995) Did Not Provide a Reasonable Expectation of Success

The ‘364 patent is directed to the Form A polymorph of tapentadol hydrochloride. At trial, Alkem argued that prior art disclosure of crystalline Form B tapentadol hydrochloride, along with known approaches to polymorph screening rendered the claimed Form A obvious. To support a reasonable expectation of success, Alkem relied on a 1995 article by Stephen Byrn which disclosed a decision tree outlining a typical polymorph screen. The Federal Circuit affirmed the district court’s finding that there was no reasonable expectation of success.

The Federal Circuit treated Byrn as highlighting the variables involved in a polymorph screen, including the choice of solvent and variations in temperature, concentration, agitation and pH, and called its disclosure “insufficient guidance in discussing the wide array of conditions that could affect recrystallization and, therefore, the crystal structure of a resulting compound.”

Prior Art Reproduction Results Supported Unpredictability

The Federal Circuit also cited Alkem’s prior art reproduction to reject Alkem’s argument that, because claimed Form A is the most stable form, “any polymorph screening of a sample of tapentadol hydrochloride would result in Form A, either in whole or in part.” Alkem had attempted to show inherent anticipation by the prior art and, although its experts found Form A, they had not performed all steps of the prior art process. Plaintiffs’ experts performed all steps and found no Form A. Even though Alkem did not appeal the district court’s rejection of its anticipation argument, the Federal Circuit nonetheless reasoned that different results from the parties’ respective experts highlight the effects of the variables at play.

Following Grunenthal, Polymorph Challenges Become More Difficult

In view of Grunenthal, ANDA filers should expect that already difficult obviousness challenges to polymorph patents will be even more difficult. While the Federal Circuit rejected a per se rule—“Our decision today does not rule out the possibility that polymorph patents could be found obvious”—Grunenthal leaves little room to argue based on Byrn that the results of routine polymorph screens are expected. Grunenthal also highlights the dangers of relying on prior art reproductions that deviate from the prior art and underscores the need to craft a holistic invalidity strategy. Separately, given Grunenthal, ANDA filers have even more incentive to utilize non-infringing polymorphic forms where possible.

[1] The Federal Circuit affirmed the district court’s finding that Hikma and Actavis do not infringe the ‘130 patent in view of their respective carve-out statements under 21 U.S.C. § 355(j)92)(A)(viii). It did not address invalidity as to the ‘130 patent.

© Polsinelli PC, Polsinelli LLP in California


About this Author

Luke Shannon Intellectual Property Attorney

Luke Shannon believes that there is no “secret formula” for success; rather, success requires careful attention, informed analysis, and sensitivity to each client’s particular needs. He believes that each individual case presents unique strengths that can be leveraged against potential weaknesses. Luke’s industry experience and decade-plus of litigation practice allows him to identify and develop strengths and hedge against weaknesses in order to provide success to the client in the most cost-effective manner. His practice focuses on patent infringement suits arising under the Hatch-Waxman...

Taras A. Gracey Shareholder Chicago Polsinelli Biosimilars IP Patent Litigation

Taras Gracey is a trial lawyer with more than 20 years of courtroom experience. He has tried both jury and bench trials as well as handled numerous appeals in the Federal and Seventh Circuits. He has represented both patent owners and accused infringers in a broad spectrum of intellectual property disputes, focusing on pharmaceutical/Hatch-Waxman litigation and technology matters involving chipsets and display technologies. He also is versed in and has handled inter partes reviews (IPRs). Taras' litigation experience spans the country, including federal courts in California, Delaware, Illinois, New Jersey, New York, and Texas.

On the patent owner side, Taras has won a jury verdict of over $20 million in one technology case and obtained a $35 million settlement on the last day of trial in another. On the Hatch-Waxman side, he has successfully first-chaired numerous cases and was part of the team that invalidated Eli Lilly's patent on Prozac®, which the press called "the Mother of All Patent Challenges."