No. 2010-1246 (Fed. Cir. 8/5/2010) (Linn, Moore, Friedman, opinion by Moore).This case highlights several important issues in an ANDA litigation.
Background
Adams owns the ‘252 patent for controlled release guaifenesin. Adams markets Mucinex® which is the preferred embodiment of the ‘252 patent. Slip op. at 3. Perrigo filed an ANDA seeking to market 600 mg guaifenesin extended release tables, with a paragraph IV certification to the ‘252 patent. Adams sued Perrigo for patent infringement. After construing the claims, the district court granted Perrigo summary judgement of noninfringement. Adams then appealed. The Federal Circuit panel reversed the grant of summary judgement and remanded.
The meaning of “Equivalent”
The independent claim at issue was claim 24, which required equivalence in Cmax between the claimed extended release product and sequential doses of an IR formulation. The district court construed “equivalent” according to the guidelines in the Orange Book, as a Cmax within 80% to 125% of the reference drug with a 90% confidence interval. Adams challenged the requirement of the 90% confidence interval, without explaining the significance of this point. The panel holds that the specification did not define “equivalent” as the same as the FDA bioequivalence guidelines, and bifurcates the permissible range of Cmax and the confidence interval, holding that confidence interval reflects the FDA concern that a generic drug consistently match the performance of the reference drug. Slip op. at 8. (See comment below on this point).
Summary Judgement on Equivalence Reversed
The opinion discusses whether a commercial embodiment of an invention can be properly compared to an accused device, concluding that such a comparison may be appropriate. “Our case law does not contain a blanket prohibition against comparing the accused product to a commercial embodiment.” Slip op. at 10. Then, contrary to the claim construction analysis of the word “equivalant,” the opinion relies on a 90% confidence interval to support Adams proposition that Perrigo is infringing. Slip op. at 9–10. Adams presented “PK” and Cmax data, so the panel held that a reasonable fact finder could conclude that Perrigo’s product was equivalent to Adam’s product. Summary judgement for Perrigo was therefore reversed on this ground.
Construction of “Bioavailable”
The district court construed “immediate release form which becomes fully bioavailable in the subject’s stomach” to mean “a form intended to rapidly release in the stomach substantially all of the active pharmaceutical ingredient for absorption.” Slip op. at 13. The panel agreed with this construction, since it was stated to be consistent with the usage of “bioavailable” in the specification. Slip op. at 14. By contrast, Perrigo’s proposed construction was stated to improperly exclude the preferred embodiment in the specification. The panel upheld the district court’s denial of summary judgement on the construction of this phrase.
Numerical Ranges and the Doctrine of Equivalents
The opinion has a substantial review of the use of numerical ranges in a doctrine of equivalents analysis. Slip op. at 17–18. The claim limitation was an AUC of “at least” 3500 hr*ng/mL. The accused product had a maximum value of 3493.38 hr*ng/mL, which was within 0.189% of the claimed value. Slip op. at 15–16. Perrigo argued that the claim limitation of “at least” was an absolute lower limit. Adams responded that the real issue was substantiality. The court concludes that specific numeric ranges do not foreclose the doctrine of equivalents, and that the words “at least” do not change the analysis. Slip op. at 18. Two previous cases, Quantum Corp. v. Rodime, PLC, 65 F.3d 1577 (Fed. Cir. 1995) and Lantech, Inc. v. Keip Machine Co., 32 F.3d 542 (Fed. Cir. 1994), each discuss the use of “at least,” but the panel says neither case supports Perrigo’s position that “at least” forecloses the application of the doctrine of equivalents. Slip op. at 19. The panel holds that the proper analysis is whether the accused value is insubstantially different from the claimed value. Id.
Comments
The bifurcation of the range of Cmax values necessary for bioequivalence from the confidence interval is playing fast and loose with statistics, and (in my view) is technically incorrect. The range of values and the confidence interval are organically related concepts that are intertwined. Specifying a numerical range without a confidence interval is practically meaningless, and there was no good explanation for not importing the FDA values into the claim construction, even if the exact language was omitted from the literal text of the specification or claims. If the language was omitted from the spec, that omission can also be interpreted as a written description problem.
On the other hand, the discussion of numeric values in a doctrine of equivalents analysis was very helpful.