After a bench trial, the US District Court for the District of Delaware found several Hospira patents covering a diluted, “ready-to-use” composition of dexmedetomidine obvious in view of the concentrated prior art product—but found that a claim requiring dexmedetomidine to be stable was not inherent or obvious, and was infringed by Amneal’s abbreviated new drug application (ANDA) submission as a matter of law. Hospira, Inc. v. Amneal Pharmaceuticals, Case No. 285 F.Supp.3d 776 (D. Del.,Jan. 22, 2018) (Andrews, J).

In December 1999, Hospira obtained US Food and Drug Administration (FDA) approval for its original Precedex product containing the sedative dexmedetomidine. Precedex was and is sold in a 2 mL glass vial containing 100 μg/mL of dexmedetomidine hydrochloride. Before being administered, Precedex concentrate must be diluted to an appropriate concentration per instructions on the Precedex label.

Hospira owned a compound patent covering dexmedetomidine that expired in 2013. Shortly before its compound patent expired, Hospira received approval for a “ready-to-use” formulation of dexmedetomidine (Precedex premix) containing 4 μg/mL of dexmedetomidine in 20, 50 or 100 mL vials. Hospira obtained several patents covering the Precedex premix formulation and methods of using it. These patents included limitations related to specific concentrations of a “ready-to-use” formulation of various volumes stored in a sealed glass container.

In 2015, Amneal filed an ANDA seeking FDA approval for a generic version of Precedex premix. Hospira filed suit alleging that the approved product infringed Hospira’s patents.

At trial, Amneal argued that the patents were obvious in view of the original Precedex product and label, and the knowledge of one of skill in the art. Hospira admitted that many of the claim limitations (including those related to dexmedetomidine concentration and total volume) would be met by diluting the original Precedex product in accordance with the instructions on its label. However, Hospira argued that one of ordinary skill would not be motivated to prepare a “ready-to-use” formulation and would not have a reasonable expectation of success in using a sealed glass container to store the formulations.

The court disagreed. Specifically, the court pointed to prior art articles showing that physicians had a preference for ready-to-use formulations, and that one hospital had even created its own ready-to-use Precedex syringes. In addition, the court noted that glass was the go-to material for containers for small-volume injections, and that the original Precedex product was sold in a glass vial. Thus, the court found all but one of the asserted patents obvious.

The remaining patent required that the formulation exhibit no more than a 2 percent decrease in dexmedetomidine concentration after storage for five months. Amneal argued that this limitation was obvious and pointed to testing of Precedex premix to show it was stable for five months. However, the court found that because Amneal did not provide any scientific explanation confirming the inherency, the examples Amneal pointed to were not enough. Thus, the remaining patent was found valid.

The court next turned to infringement. The only disputed question was whether Amneal’s product exhibited the required stability. Hospira argued that Amneal infringed as a matter of law because Amneal’s ANDA specified that the approved product’s dexmedetomidine concentration would remain within 90 percent of its original concentration for the entirety of its two-year shelf life. The court agreed. Since approval of Amneal’s ANDA (allowing Amneal to manufacture a product exhibiting no more than a 10 percent decrease in concentration after two years) would allow Amneal to manufacture a product exhibiting no more than a 2 percent decrease in concentration after five months, Amneal infringed as a matter of law. This was true even though the court found that as a matter of fact, Hospira did not prove that the stability data submitted for Amneal’s product showed that the product actually exhibited no more than a 2 percent decrease in concentration after five months.