IP Law Daily, PATENT—D. Del.: Astellas’ sustained-release mirabegron formulation patent survives invalidity challenges, (Apr 16, 2025)

By Saurabh Kashyap, B.A., LL.B., LL.M.

Generic manufacturers failed to prove invalidity on enablement, written description, or indefiniteness grounds.

The federal district court in Delaware ruled in favor of Astellas Pharma Inc. in its long-running Hatch-Waxman litigation against Zydus Inc. and Lupin Inc., upholding the validity of Astellas’ U.S. Patent No. 10,842,780 (the ’780 patent) covering a sustained-release formulation of mirabegron used to treat overactive bladder. On remand from the Federal Circuit, the court found that the defendants failed to prove invalidity under 35 U.S.C. §112 on grounds of lack of enablement, inadequate written description, or indefiniteness. The court was also persuaded by Astellas' expert evidence, which demonstrated that the patented hydrogel-based system could be prepared using routine pharmaceutical formulation methods known in the art (Astellas Pharma Inc. v. Zydus, Inc., No. 1:20-cv-01589-JFB-EGT (D. Del. Apr. 15, 2025)).

Background. The plaintiff, Astellas Pharma Inc., is a global pharmaceutical innovator and the developer of Myrbetriq®, a mirabegron tablet used to treat overactive bladder symptoms. Mirabegron is a beta-3 adrenergic agonist, and the sustained-release formulation mitigates adverse effects associated with rapid absorption in immediate-release forms.

The defendants, Zydus Inc. and Lupin Inc., are U.S. subsidiaries of international generic pharmaceutical companies. The defendants submitted Abbreviated New Drug Applications (ANDAs) to market generic versions of Mirabegron. Astellas sued both companies under 35 U.S.C. §271(e)(2), alleging that their proposed generics would infringe the '780 patent.

The patent-in-suit claims hydrogel-based oral dosage forms of mirabegron with a defined dissolution profile: no more than 39% released after 1.5 hours and at least 75% after 7 hours under USP Apparatus 2 testing at 200 rpm in a specified dissolution medium. The claims include both structural and functional limitations and aim to reduce food effects, improve tolerability, and enable once-daily dosing.

Following a bench trial, the district court initially invalidated the ’780 patent under 35 U.S.C. §101, reasoning that the claims impermissibly covered a natural law implemented by conventional steps. The Federal Circuit reversed that ruling in Astellas Pharma Inc. v. Sandoz Inc. , 117 F.4th 1371 (Fed. Cir. 2024), holding that the district court had improperly ruled on an unpled theory of invalidity. On remand, the court considered only the parties’ §112-based challenges—enablement, written description, and indefiniteness—resolving them in Astellas’ favor.

Enablement. The court concluded that the patent satisfies the enablement requirement under §112(a), relying heavily on the testimony of Astellas' expert, Dr. Peter Little. Dr. Little explained that sustained-release hydrogel formulations were well understood in 2008, and a person of ordinary skill in the art (POSA) could produce the claimed formulations with minimal trial and error by following the patent's teachings and applying known scientific principles.

According to Dr. Little, a POSA could design a formulation meeting the specified dissolution profile in as few as five experiments by selecting from disclosed ingredient classes and adjusting polymer viscosity. The patent included working examples, target dissolution rates, and detailed ingredient lists. The court rejected Zydus’s argument—based on Dr. Chambliss’s testimony—that the POSA would face an unmanageable number of possible combinations (over 1.5 million), emphasizing that the experimentation would not be undue because it would be guided by established relationships between polymer structure and drug release.

The court also distinguished the Supreme Court’s ruling in Amgen Inc. v. Sanofi, 598 U.S. 594 (2023), which invalidated genus claims requiring undue experimentation. Here, it held, Astellas claimed a narrow genus defined by both structural and functional limitations and provided sufficient guidance to make and use the invention without unreasonable effort.

Written description. The court found that Astellas satisfied the written description requirement by disclosing representative species and articulating a clear structure-function relationship. The patent detailed three working formulations—Examples 2, 8, and 9—that used polyethylene oxide (PEO) as the hydrogel-forming polymer and met the dissolution specifications. These examples included all structural and functional claim elements.

While Zydus argued that the disclosure was too narrow and relied only on PEO, the court concluded that the examples represented the broader genus and that the POSA would understand how to substitute other polymers like HPMC or HPC based on known viscosity characteristics. Dr. Little testified that POSAs knew how to tune viscosity to control dissolution rates—which the court found credible and consistent with the patent specification and prior art.

The court also found that the structure-function relationship was sufficiently described to show Astellas’s possession of the claimed invention. Citing Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010) (en banc), it emphasized that written description is context-dependent and that the combination of examples and teaching on polymer behavior satisfied the statutory requirement.

Indefiniteness. Zydus's final defense focused on indefiniteness, arguing that hydrogel polymers degrade over time, altering the dissolution profile. It contended that without a specific testing time frame, the exact product might infringe when fresh but not when expired, making the claim scope indefinite under Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898 (2014).

The court rejected this argument, holding that the POSA would understand to evaluate dissolution rates using freshly prepared tablets or ones tested under standard industry conditions. It credited Dr. Little’s testimony that industry practice and FDA guidance instruct testing prior to expiration and that degradation is a routine variable accounted for in pharmaceutical development.

The court also found no ambiguity in the claim terms “no more than 39%” and “at least 75%,” ruling that they provide clear, objective boundaries for infringement analysis. As a result, it held the claims met the definiteness standard of informing skilled artisans about the scope of the invention with reasonable certainty.

Expert testimony and credibility. The court found both experts—Dr. Little for Astellas and Dr. Chambliss for Zydus—qualified and credible, but ultimately favored Dr. Little’s testimony where their conclusions diverged. It emphasized that both experts agreed on the predictability of hydrogel systems and the fact that sustained-release formulation was an established field by 2008.

The court rejected Dr. Chambliss’s contention that the patent’s examples were tested at 50 rpm rather than the claimed 200 rpm, noting that discovery included spreadsheets showing actual test conditions aligned with the claim language. It also dismissed Zydus’s assertion that PEO degradation rendered the claims indefinite, pointing to well-established testing protocols in the pharmaceutical industry.

Conclusion. Having rejected all three validity challenges, the district court upheld the ’780 patent, finding that Zydus and Lupin failed to prove invalidity by clear and convincing evidence. The ruling clears the path for continued enforcement of Astellas’ sustained-release mirabegron patent, though infringement and damages issues remain for trial.

The Case is No. 1:20-cv-01589-JFB-EGT.

Judge: Bataillon, J.

Attorneys: Daniel M. Silver (McCarter & English, LLP) for Astellas Pharma Inc. Alexis Stombaugh (Young, Conaway, Stargatt & Taylor LLP) for Zydus Pharmaceuticals [USA], Inc.

Companies: Astellas Pharma Inc.; Zydus Pharmaceuticals (USA), Inc.

Cases: Patent DelawareNews