Adrenalin® (epinephrine injection)

Case Name: Par Pharm., Inc. v. Hospira, Inc., No. 2020-1273, 2020 WL 6846347 (Fed. Cir. Nov. 23, 2020) (Circuit Judges Dyk, Taranto, and Stoll presiding; Opinion by Taranto, J.) (Appeal from D. Del., Bataillon, J.)

Drug Product and Patent(s)-in-Suit: Adrenalin® (epinephrine injection); U.S. Patents Nos. 9,119,876 (“the ’876 patent”) and 9,295,657 (“the ’657 patent”)

Nature of Case and Issue(s) Presented: In 2017, Hospira filed an ANDA seeking permission to market a generic version of Par’s Adrenalin® epinephrine injection. Par sued Hospira under 35 U.S.C. § 271(e) alleging that Hospira’s proposed ANDA product infringed the ‘876 and ‘657 patents. Hospira argued that its proposed ANDA product would not meet several limitations of the asserted claims. After a bench trial, the district court found that the ANDA product would infringe the asserted claims. Hospira appealed to the Federal Circuit, and the court affirmed the infringement determination.

Why Par Prevailed: The district court found that Hospira’s ANDA product met the three claim limitations disputed at trial, which are reproduced below:

(i) about 6 to 8 mg/mL of a tonicity regulating agent; (ii) about 0.01 to 0.4 mg/mL of a transition metal complexing agent; and (iii) about 0.001 to 0.010 mL/mL of a pH lowering agent.

On appeal, Hospira argued that the district court committed clear error in finding that its proposed ANDA product contained a tonicity regulating agent, transition metal complexing agent, and pH lowering agent in the claimed amounts.

First, Hospira argued that the district court clearly erred because its ANDA specified a concentration of 9 mg/mL of sodium chloride, a tonicity regulating agent, which is outside of the claimed range of “about 6 to 8 mg/mL.” The Federal Circuit disagreed. The Federal Circuit explained that the outer reaches of the word “about” can be a matter for claim construction, but here, the parties agreed that “about” had its plain and ordinary meaning of “approximately.” The relevant issue for the court to consider was therefore what a POSA would reasonably understand to come within the claimed range. Under Federal Circuit precedent, the district court was correct to determine whether, as a matter of fact, the accused product would fall within the “about” range by considering the purpose of the upper limit of the range. The district court credited Par’s expert witness’s testimony that the purpose of both ends of the claimed range was to avoid both hypertonicity and hypotonicity of the solution, and that a concentration of 9 mg/mL would be acceptable to meet that goal. The expert further testified that there was nothing critical to the exact numbers of the claimed range.

Next, Hospira argued that the district court erred in finding its ANDA product contained “about 0.01 to 0.4 mg/mL of a transition metal complexing agent.” Hospira argued that the district court should have focused its analysis on the product Hospira was likely to sell, not on the ANDA specification. The Federal Circuit disagreed, explaining that the infringement statute for ANDAs, 35 U.S.C. § 271(e)(2), states that submission of an ANDA is an act of infringement if the ANDA is “for a drug claimed in a patent or the use of which is claimed in a patent.” Thus, the Federal Circuit has held that what a generic asks for and receives approval to market, if within the scope of a valid claim, is an infringement. On the other hand, the Federal Circuit reasoned that when an ANDA is silent with respect to a claim limitation, then the infringement analysis is guided by what the generic is likely to sell. In the end, the Federal Circuit concluded that because the ANDA stated that its product satisfied ICH Q3D guidelines relating to transitional metal impurities, it was sufficient to support the district court’s finding that the claim limitation was met.

Finally, Hospira argued that the district court erred in finding that its proposed ANDA product would contain “about 0.001 to 0.020 mL/mL of a pH lowering agent” because the district court counted both hydrochloric acid and citric acid. Specifically, Hospira argued that citric acid could not be counted as a pH-lowering agent because it is already included in the buffer system that counts toward meeting the claim limitation relating to a pH-raising agent. The Federal Circuit explained that Hospira did not make or preserve a claim construction argument that an acid (a pH lowering agent) could not also be a part of an agent that also serves to raise pH. The patent specification discusses a buffer system made up of an acid and a base. Thus, the Federal Circuit rejected Hospira’s argument that citric acid molecules must be allocated between the pH lowering agent limitation and the pH raising agent limitation, and affirmed the district court’s finding that Hospira’s ANDA product fell within the claimed range.