January 22, 2018

Case Name: Hospira, Inc. v. Amneal Pharms. LLC, No. 15-cv-697, 2018 U.S. Dist. LEXIS 9307 (D. Del. Jan. 22, 2018) (Andrews, J.) 

Drug Product and Patent(s)-in-Suit: Precedex®(dexmedetomidine HCl); U.S. Patents Nos. 8,242,158 (“the ’158 patent”), 8,338,470 (“the ’470 patent”), 8,455,527 (“the ’527 patent”), and 8,648,106 (“the ’106 patent”)

Nature of Case and Issue(s) Presented: At issue were ready-to-use injectable formulations of the compound dexmedetomidine. Hospira’s original Precedexproduct (100 µg/mL dexmedetomidine HCl), also known as Precedexconcentrate, has been sold since 1999 in 2 mL glass vials. Prior to administration, the Precedexconcentrate is diluted to an appropriate concentration, as described on the product label. In 2013, Hospira received FDA approval for 50 mL and 100 mL glass bottles of a ready-to-use 4 µg/mL formulation of dexmedetomidine HCl.

The ’158 patent, the ’470 patent, and the ’527 patent were directed to a 4 µg/mL ready-to-use dexmedetomidine formulation disposed in a sealed glass container. The ’106 patent was directed to a dexmedetomidine formulation that exhibits less than a 2% decrease in concentration when stored in a glass container for five months (the “no more than about 2% decrease limitation”).   

Why Hospira Prevailed: Amneal argued that the ’106 patent was obvious because the no more than about 2% decrease limitation was inherent in a 4 µg/mL ready-to-use dexmedetomidine formulation in normal saline disposed within a sealed glass container. Judge Andrews explained, however, that Amneal offered no expert testimony concerning the scientific principles underlying its inherency argument and relied on only two examples of stability data covering the claimed 4 µg/mL dexmedetomidine concentration. Judge Andrews further explained that stability data for a 4 µg/mL dexmedetomidine formulation could not be inferred from the label for the Precedex concentrate. As a result, Amneal failed to prove obviousness by clear and convincing evidence.

Amneal further argued that the ’106 patent was indefinite because the specification discloses concentration measurements performed under long-term and accelerated conditions, but the asserted claim did not specify which condition to use when measuring the no-more-than-about-2%-decrease limitation. Although true, Judge Andrews explained that the examples describing accelerated conditions never measured the no-more-than-about-2%-decrease limitation. Instead, this limitation was only measured after long-term storage, and thus the ’106 patent was not invalid as indefinite, as a person of ordinary skill would know to measure under long-term storage conditions.

Judge Andrews further explained that the ’106 patent was infringed as a matter of law based on statements concerning stability that were found in Amneal’s ANDA.

With regard to the remaining patents, Amneal was successful in overcoming its burden of proof that all of the patents-in-suit were invalid. Judge Andrews concluded that a POSA would have been motivated to develop a ready-to-use dexmedetomidine formulation based on the 2010 Precedexlabel, which disclosed instructions for diluting the Precedexconcentrate for intravenous administration. Further, a prior-art article described that certain hospital pharmacies were routinely making premixed 10 mL syringes of 4 µg/mL dexmedetomidine available to physicians for clinical use. Hospira argued, however, that a POSA would not have had a reasonable expectation of success because the prior art did not explicitly disclose a diluted 4 µg/mL dexmedetomidine formulation in a sealed glass container. And although Hospira presented evidence that its inventors expressed concern about using glass as a container material, Judge Andrews found this evidence unpersuasive as Hospira presented no publically available data suggesting that the formulation would be unstable in a glass container. This conclusion was bolstered by the fact that Precedexconcentrate was available in a glass vial.

Concerning secondary considerations, Judge Andrews explained that the evidence of commercial success had little probative value because a patent covering the dexmedetomidine molecule precluded competitors from entering the market until after Hospira filed its applications for the patents-in-suit. Moreover, upon product launch, Hospira marketed the Precedexpremix at a ten percent discount by comparison to the predecessor Precedexconcentrate. As a result, Judge Andrews found little evidence of commercial success and concluded that the asserted claims of the ’158 patent, the ’470 patent, and the ’527 patent were invalid as obvious.