Adams Respiratory Therapeutics, Inc. v. Perrigo Company (Fed. Cir., August 5, 2010)
Panel: Linn, Moore (author), Friedman
By Jason Rantanen
Adams holds patent number 5,372,252, which covers an extended release formulation containing guaifenesin (an expectorant used to thin, loosen, and help expel mucus that causes congestion). Perigo sought FDA approval for a generic version of Adams' product, Mucinex®. After construing the claims, the district court granted summary judgment of noninfringement. Adams appealed that decision.
The claim terms in dispute related to pharmacokinetic parameters. These parameters are used to characterize the rate and extent of absorption of the active pharmaceutical ingredient ("API"). The primary term at issue, Cmax, indicates the maximum concentration of the API following dosing.
The parties' main dispute was over the meaning of the term "equivalent" in the context of "provides a Cmax in a human subject equivalent to the Cmax obtained when the first of three doses of a standard immediate release formulation having one third the amount of guaifenesin is dosed." For purposes of FDA approval, a formulation is considered to be bioequivalent if, among other things, its Cmax is within 80% to 125% of the value with which it is being compared at a 90% confidence interval. The district court agreed with Perrigo that "equivalent" should be construed to mean equivalent under the FDA bioequivalence guidelines.
On appeal, Adams challenged the requirement of a 90% confidence interval, arguing that it makes sense when seeking FDA approval, but not when proving infringement.
The Federal Circuit agreed with Adams. In doing so, it rejected Perrigo's argument that the inventors had expressly defined "equivalent" as te FDA's bioequivalence guidelines. Rather, the court construed Adams' reference to the FDA guidelines as referring specifically to the 80-125% range, not to the requirement of a 90% confidence interval. According to the court:
Requiring a 90% confidence interval would inappropriately raise the bar for establishing infringement. Adams must show that it is more likely than not that Perrigo's ANDA product will have a Cmax within the 980-125% range. Adams is not required to show that Perrigo's product will meet this requirement 9 times out of 10.
Slip Op. at 8.
Comment: This interpretation opens up a box of statistical worms, and I suspect that down the line the court may regret its venture into probability theory. For the time being, however, it gives parties useful language to quote when attempting to prove infringement (and perhaps invalidity) via clinical results.
A ≈ B ≈ C therefore A ≈ C
Adams also appealed the district court's ruling that it impermissibly compared the accused product to Mucinex. Adams' argument was that because the accused product was bioequivalent to Mucinex, and Mucinex was bioequivalent to a standard immediate release ("IR") product, then the accused product had a Cmax equivalent to the IR product.
The Federal Circuit agreed that, under the circumstances of this case, Adams' argument was sufficient to preclude summary judgment of noninfringement. The court cautioned, however, that "[i]f Adams had relied on the mere fact of bioequivalence of the two sets of products (and no PK data or Cmax values, that would not be enough to survive summary judgment." Slip Op. at 11. Here, however, Adams presented actual PK data and Cmax values, which a fact-finder could look at when assessing equivalence between the accused product and an IR product.
The court also addressed the meaning of the term "bioavailable" in the context of the '252 patent. The dispute hinged on whether the phrase "fully bioavailable in the subject's stomach" meant "both release and availability in the stomach for absorption, wherever that absorption might occur."
Perrigo argued that because "bioavailable" is commonly understood to mean absorption, thus requiring the guaifenesin to be absorbed in the stomach. Because guaifenesin is primarily absorbed in the small intestine, this construction would preclude a finding of infringement.
The court rejected the proposed construction as inconsistent with the specification: "Although the specification never expressly defines bioavailable, it uses the term when describing the availability of the drug for absorption, not the actual absorption." Slip Op. at 14. The court further noted that Perrigo's construction would exclude the preferred embodiment, which "is rarely, if ever, correct and would require highly persuasive evidentiary support."
Doctrine of Equivalents
Finally, Adams argued that the district court erroneously precluded it from relying on the doctrine of equivalents with respect to a dependant claim requiring that the total amount of guaifenesin released in to the patient be at least 3500 hr*ng/mL. The panel concluded that the use of a numerical limit did not preclude Adams from arguing that an amount of 3494.38 hr*ng/mL was equivalent to 3500 hr*ng/mL.