Holding: Bioequivalence, on its own, is not sufficient to prove infringement of a claimed composition by the doctrine of equivalents under the function-way-result test. Bioequivalence merely shows the result portion of the test and the accuser still must prove that the accused product performs the same function and work in a similar way to the claimed invention.
Galderma owns patents for the drug Oracea®, which is sold to treat rosacea. These patents are directed to a pharmaceutical composition that is formulated to be 30 mg immediate release (IR) and about 10 mg delayed release (DR) doxycycline and methods of treatment using the composition. The IR portion releases substantially all of the doxycycline upon administration and the DR portion uses an enteric coating that prevents the release of the rest of the doxycycline while the pill is in an acidic stomach environment below pH 4.5. The enteric layer dissolves when the pill reaches the small intestine, which has a pH greater than 4.5.
Lupin filed an ANDA to market a 40mg doxycycline product that it claimed to be a bioequivalent of Oracea®. Lupin’s product is a capsule that contains 22 mg IR and 18 mg DR doxycycline and includes an enteric coating to allow for the delayed release. The enteric coating is the same polymer used in Oracea®, and is designed to dissolve above pH 5.5. Galderma sued Lupin’s ANDA product for infringement of US Patent No. 7,749,532 and US Patent No. 8,206,740.
Galderma alleged Lupin’s product had a weak enteric coat, resulting in about 8 mg of DR doxycycline to actually be an IR portion. Therefore, Galderma argued that Lupin’s product met the 30 mg IR/10mg DR limitation claimed in the asserted patents. Although the polymer used for the enteric coating was the same for both Oracea® and Lupin’s product, Galderma alleged that testing showed that Oracea has 30% weight gain due to its enteric coating while Lupin’s product only has a 18% weight gain. Additionally, Galderma argued that Lupin used methylene chloride in its coating process, resulting in a weaker enteric coating.
To prove its theory, Galderma presented expert testimony describing a two-stage, in vitro dissolution test at pH 1.1 and pH 4.5. This test showed the release of some of the doxycycline from the DR portion of the Lupin product at pH 4.5. Galderma further argued that pH 4.5 can be found in the stomach, thus some of the DR portion Lupin’s product would be release immediately upon ingestion. In rebuttal of Galderma’s expert testimony, Lupin presented evidence from a single-stage test that showed that the DR portion of Lupin’s capsules did not dissolve at pH 4.5. The District Court found that Lupin did not infringe the Galderma patents, stating that Galderma’s two-stage, in vitro test was not representative of in vivo behavior of the Lupin product.
The Federal Circuit upheld the district court’s decision, finding no clear error in the determination that Galderma’s in vitro test was not indicative of in vivo behavior of Lupin’s product. Galderma’s test was not reliable because the pH of a fasted stomach is typically between 1 and 2. The pH can rise slightly higher after the ingestion of water, but Galderma’s expert testimony stating that the pH of the stomach could rise to pH 4.5 was rebutted by the testimony of Lupin’s expert, who stated that a pH 4.5 better approximates the pH of the small intestine than the stomach. Therefore, reliable conclusions about the actual timing and location of the release of doxycycline by the Lupin product within the body could not be drawn from Galderma’s in vitro testing at pH 4.5. Further, the district court’s reliance on pH values and time cutoffs despite these limitations not being in the claims of the Galderma patents was not improper, as these features were limited to an analysis of whether Galderma’s two-stage dissolution test represented in vivo behavior of Lupin’s product.
The Federal Circuit also upheld the district court’s decision that there was no infringement under the doctrine of equivalents. The district court found that Galderma did not show infringement by the doctrine of equivalents under either the function-way-result test or the insubstantial differences test. The bioequivalence of the Lupin’s product with Galderma’s claimed composition only showed the result portion of the function-way-result test. Because Galderma’s in vitro test was not considered to represent in vivo conditions, Galderma did not prove that Lupin’s product performed substantially the same function in substantially the same way as the Galderma claims. Additionally, the district court found the 22 mg IR/18 mg DR composition of Lupin’s product to be substantially different from the 30 mg IR/10 mg DR composition of the claims in the asserted patents.
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