Astra Aktiebolag v. Andrx Pharmaceuticals, Inc.

Citation: 84 F. App'x 76Docket: Nos. 03-1101 to 03-1106, 03-1131, 03-1132, to 03-1136, 03-1171, 03-1172, 03-1173

Court: Court of Appeals for the Federal Circuit; December 10, 2003; Federal Appellate Court

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The United States District Court for the Southern District of New York ruled that U.S. Patent Nos. 4,786,505 and 4,853,230 are valid and were infringed by Andrx Pharmaceuticals, Genpharm, and Cheminor Drugs. Conversely, the court found that Kremers Urban Development Co. and Schwarz Pharma did not infringe these patents. The court affirmed its decisions regarding claim construction, validity, infringement, and evidentiary issues. Astra owns the patents, which pertain to a drug delivery system featuring an enteric coating that protects omeprazole from stomach acid. Claim 1 of the '505 patent details a pharmaceutical preparation with a core region containing omeprazole and an alkaline compound, an inert subcoating, and an outer enteric coating. Claim 1 of the '230 patent similarly describes a preparation with an alkaline core, an inert subcoating, and an enteric coating that enhances stability. The generic companies sought FDA approval for omeprazole formulations and claimed the patents were invalid, prompting Astra to sue for infringement. After a lengthy bench trial, the district court issued a detailed opinion confirming the patents' validity and infringement by the specified companies while ruling against KUD-Co. Andrx, Genpharm, and Cheminor appealed the infringement and validity decisions, with Astra cross-appealing the non-infringement ruling for KUD-Co and certain evidentiary matters. The appellate court has jurisdiction over the case.

A court assesses patent infringement by first construing the claims and then applying them to the accused product or process. Claim construction is conducted without deference, while obviousness is a legal question reviewed de novo, and factual findings are examined for clear error. Anticipation is treated as a factual question also reviewed for clear error, and evidentiary rulings are reviewed for abuse of discretion.

In the case at hand, Andrx, Genpharm, and Cheminor contest the district court's definitions of several terms, including 'alkaline reacting compounds,' 'subcoating,' 'disposed on,' 'materials,' 'effective amount,' and 'pH buffering alkaline compound.' Conversely, Astra seeks a broader interpretation of 'alkaline reacting compounds.' The court upheld the district court’s constructions. 

The term 'alkaline reacting compound' was defined as a pharmaceutically acceptable alkaline substance with a pH greater than 7 that stabilizes omeprazole by maintaining a micro-pH of at least 7 around the particles. The court found no error in this definition. The term 'subcoating' was interpreted as a physically conforming layer beneath the enteric coating, distinct from a gelatin capsule, emphasizing its form-fitting nature. The court clarified that while 'separating layer' pertains to the function of the subcoating, it does not expand its definition beyond structural implications. 

Lastly, 'disposed on' was correctly construed by the district court to merely indicate the location of the layer without imposing additional structural or methodological limitations.

The district court appropriately interpreted the term "materials" in the context of the patents, clarifying that the plural form does not necessitate multiple compositions, but rather ensures grammatical consistency with "layers." There is no intrinsic evidence supporting a narrower definition that would limit subcoatings to more than one material. Regarding "effective amount," the court rejected Astra's claim that the ARC is merely an excipient applicable only to omeprazole, emphasizing that the ARC is not an inert adhesive but an alkaline substance that stabilizes the active drug, thus affecting both the drug and the ARC in terms of dosage. In defining "pH buffering alkaline compound," the court noted that the terms used in the patent are interchangeable and that an average skilled formulator would not interpret "pH-buffering" in its traditional chemical sense based on the patent's context. Although the district court may have erred in referencing a previous case to justify a "substantially" addition to claim limitations, this error did not impact the overall claim construction or its implications for infringement. On the issue of validity, the appellees' argument that claims are anticipated by prior art involving a gelatin capsule was rejected, affirming the district court’s ruling. The obviousness claims were based on several prior patents and publications, with the court confirming that certain references were not considered public "printed publications," a conclusion stemming from factual determinations relevant to patent law.

Genpharm does not contend that Up-to-Date qualifies as a printed publication but references Thomas & Betts Corp. v. Litton Sys. Inc. to argue its relevance for demonstrating the level of skill in the art. However, the comparison is flawed since the cited case involved additional testimonial support regarding the state of the art at the time. The district court's finding that Up-to-Date does not reflect the level of skill was not clearly erroneous. Cheminor's reliance on Astra's characterization of TC-5 as a 'general publication promoting the use of TC-5' is insufficient, as it does not definitively indicate that TC-5 is a 'generally available' publication necessary for printed publication status. Moreover, Cheminor fails to differentiate the legal standards for prior art between the U.S., Europe, and South Africa based on Astra's statements during patent prosecution in those regions. The district court dismissed Hager's Handbook as merely cumulative to other vague statements, noting its lack of specific information regarding subcoating limitations like water solubility. The court found that EP ’495 describes a formulation with an enteric coating but does not provide motivation for adding a subcoating, and that GB ’403 lacks specificity about sub-coating materials. The ’099 patent, while mentioning a water-soluble PVP subcoating, does not indicate its relevance to omeprazole formulations. Genpharm’s infringement argument relies solely on claim construction errors, and since the court affirms the district court's construction, Genpharm's noninfringement claim fails. Cheminor also contests Astra's evidence regarding the microenvironment pH of its product but provides no testing or data to counter Astra’s findings. Cheminor’s expert supported Astra’s position, confirming that the core region provides an alkaline environment for omeprazole, with tests indicating a pH of about 9, corroborating Astra's expert's conclusions.

The district court found that the meglumine in Astra's formulation creates a micro-pH greater than 7, leading to a conclusion that Cheminor's product infringed Astra's patent. In contrast, Andrx's formulation does not utilize a direct subcoating but contains a water-soluble polymeric film made from HPMCP salt, which results from a reaction between disodium hydrogen phosphate and HPMCP in its enteric coating. The court analyzed extensive evidence, including Dr. Davies's testing, which confirmed the presence of HPMCP salt in the formulation. The district court deemed Andrx's expert Dr. Gardella's tests insufficient because they focused solely on core pellets and not on the complete formulation. Andrx argued that Astra did not prove the subcoating's solubility, highlighting that talc was a significant part of the subcoating. However, the court found that the presence of insoluble particles does not prevent the overall disintegration of a soluble film. The evidence indicated that the HPMCP salt is soluble and contributes to the film's disintegration in water, supported by additional disclosures from GB ’403 regarding similar formulations. The district court's finding of infringement was upheld as it was based on preponderant evidence, and Astra did not concede that talc negated the infringement claim. The patent specifications also allow for talc in the separating layer. The court affirmed the district court's ruling, reinforcing the conclusion of infringement.

The trial court's findings are supported by a preponderance of evidence, following an extensive trial. Astra's cross-appeal challenges the district court's determination that KUD-Co does not infringe on Astra's claims. The court found Astra failed to provide adequate evidence that KUD-Co’s product, particularly the hydroxypropyl methylcellulose (HPMC) component, contains an Alkaline Release Component (ARC). Astra argues that the HPMC includes an alkaline material meeting the ARC requirement but does not identify any ARC within the core. Astra claims that demonstrating a pH greater than 7 near the omeprazole particles is sufficient to infer the presence of an ARC in the core. The court disagrees, affirming that the claims explicitly necessitate an ARC. The district court's conclusion that Astra's evidence is insufficient to prove the existence of an ARC in KUD-Co’s formulation is not clearly erroneous. Additionally, Astra argues the district court improperly allowed KUD-Co to present evidence for its non-infringement theory related to a 'size-reduction step' and excluded Astra’s expert rebuttal testimony. The district court provided a sound rationale for these evidentiary rulings, indicating no abuse of discretion occurred. The plaintiffs in the case include various Astra entities.