Astrazeneca Ab, Aktiebolaget Hassle, Kbi-E, Inc., Kbi, Inc., and Astrazeneca Lp v. Mutual Pharmaceutical Company, Inc.
Docket: 04-1100
Court: Court of Appeals for the Federal Circuit; September 30, 2004; Federal Appellate Court
Astrazeneca AB, Aktiebolaget Hassle, KBI-E, Inc., KBI, Inc., and Astrazeneca LP filed a lawsuit against Mutual Pharmaceutical Company, Inc. for patent infringement under 35 U.S.C. § 271(e)(2) after Mutual submitted an Abbreviated New Drug Application (ANDA) for extended-release felodipine tablets, which Astrazeneca claimed infringed U.S. Patent No. 4,803,081 (the '081 patent). The United States District Court for the Eastern District of Pennsylvania ruled in favor of Astrazeneca, granting motions for summary judgment on both the infringement and validity of the patent. The appellate court found that the district court misconstructed claims of the '081 patent by not adequately considering its specification and prosecution history, particularly limiting "solubilizer" to surfactants. Consequently, the appellate court reversed the judgment on infringement and remanded for a noninfringement ruling, while affirming the validity of the patent. Astrazeneca markets extended-release felodipine tablets under the name PLENDIL(R) and holds two patents related to this product, with the '081 patent still in effect. Mutual filed its ANDA for generic felodipine in June 2000, which was approved by the FDA in 2004.
Mutual timely appealed to the court, which has jurisdiction under 28 U.S.C. § 1295(a)(1). Oral arguments were heard on August 5, 2004. Mutual contests the district court's rulings on claim construction, infringement, and validity, with its challenge to validity hinging on the court affirming the district court's claim construction. If the court were to adopt Mutual's narrower interpretation of the claims, they would not be deemed invalid.
The '081 patent includes sixteen product claims and one process claim, with Astrazeneca asserting claims 8, 12, 14, 15, and process claim 17. The primary claim of interest is claim 1, which describes a solid preparation for extended release of a poorly water-soluble active compound using a specific solubilizer and a release-controlling system. Claim 17 outlines the process for creating such a preparation.
The dispute revolves around the term "solubilizer," generally understood by experts to refer to surfactants, co-solvents, and complexation agents. However, Mutual argues that "solubilizer" should be limited to surfactants based on the patent's specification. Since Mutual's ANDA sought approval for extended-release felodipine tablets that used a co-solvent, it claims this does not constitute infringement under § 271(e)(2). The district court rejected this argument, affirming that "solubilizer" encompasses all three chemical types based on common understanding and definitions, and found no intrinsic evidence in the patent limiting this definition.
Claim construction is reviewed de novo, emphasizing that claims delineate the patent's exclusionary rights and the challenge is to ascertain their meaning and scope.
Evidence intrinsic to a patent, particularly its specification and the inventors' written description, serves as the primary source for determining the meaning of patent claims. This principle has been consistently upheld in patent law, with courts generally agreeing that the specification should clarify the claims. The patent is viewed as an integrated document, where claims outline the invention as described in the specification. Claim construction aims to ascertain how an ordinary artisan would interpret the claims alongside the specification. While extrinsic evidence can aid understanding of the relevant art, it should only be considered after determining the ordinary meaning of the claim terms from the intrinsic record. An explicit definition by the patentee or a clear disavowal of scope can override the presumption favoring dictionary definitions.
In the case at hand, the key question is whether the intrinsic evidence or the ordinary meaning of "solubilizer" should guide the claim construction. The parties agree that the extrinsic meaning is broad, with Astrazeneca advocating for this interpretation. However, it is determined that the intrinsic evidence necessitates a narrower definition for "solubilizer," thus requiring a reversal of the district court's claim construction, regardless of Astrazeneca's preferred methodology.
The '081 patent specification relates to pharmaceutical extended release preparations for active compounds with low solubility, particularly substituted dihydropyridines. Its objective is to create solid preparations that enhance bioavailability and ensure extended release of these compounds, which often face dissolution challenges and variable absorption rates. Substituted dihydropyridines, like nifedipine and felodipine (the latter having a solubility of only 0.5 mg/l), are highlighted as examples. To address these solubility issues, the invention utilizes surfactant solubilizing agents, which improve drug absorption by forming micelle structures that prevent precipitation upon dilution with water or intestinal juice.
The invention aims to provide a formulation that maintains a prolonged and consistent drug absorption rate while ensuring high bioavailability. It specifies the use of solubilizers, primarily non-ionic surface-active agents containing polyethylene glycol derivatives, such as polyethoxylated fatty acids and alcohols. Preferred solubilizers include various commercial products, notably Cremophor(R) RH 40.
Additionally, the active compound-solution mix is designed for incorporation into controlled release systems, such as hydrophilic gels, beads with rate-controlling membranes, or tablets with porous matrices. The preferred controlled release mechanism involves using a hydrophilic swelling matrix, like HPMC, to regulate the release of the drug and solubilizer micelles effectively.
The specification includes five detailed examples of drug formulations related to the invention. Mutual argues that the term "solubilizer" is limited to surfactants, a position supported by the specification. The inventors are determined to have acted as their own lexicographers, as the "Description of the Invention" specifies that suitable solubilizers are identified in subsequent text, explicitly defining them as "semi-solid or liquid non-ionic surface active agents." Astrazeneca claims these definitions refer merely to preferred embodiments; however, the specification uses definitive language, suggesting a clear redefinition of the term. The lack of a formal lexicographic statement does not negate this, as definitions can be established by implication through the reading of the patent documents.
Furthermore, the specification disavows nonsurfactant solubilizers. The implicit disavowal is reinforced by descriptions of micelle structures, which are integral to the invention. The drug's inclusion in a micelle structure formed by the solubilizer is highlighted, with surfactants being the only solubilizers known to create micelle structures in aqueous environments. Other solubilizers or co-solvents are criticized for potentially causing undesirable precipitation when diluted, further underscoring the specification's emphasis on surfactants as the preferred solubilizers.
Astrazeneca argues that the statements in the patent specification merely describe preferred embodiments. They assert that a clear disavowal of claim scope necessitates explicit language such as "my invention does not include...," but the court clarifies that such formalism is not necessary. If the invention's summary emphasizes a feature and criticizes alternatives lacking that feature, it can indicate a disavowal of those alternatives. Citing cases like SciMed Life Systems and Teleflex, the court notes that limitations can be inferred from the written description without explicit disavowal language.
The specification details preferred solubilizers, identifying semi-solid or liquid non-ionic surface active agents, especially those containing polyethyleneglycols. It lists specific preferred solubilizers, including commercially available products like Cremophor and Myrj, all of which Astrazeneca agrees are surfactants. Furthermore, all working examples in the specification utilize these surfactants. This consistency supports the conclusion that the term "solubilizer" within the claims should be interpreted to mean surfactants, thus limiting the claim scope accordingly. The court determines that the specification of the '081 patent effectively restricts the ordinary meaning of "solubilizer" to surfactants.
The prosecution history of the '081 Patent reveals critical insights into the claim construction of the term "solubilizer." During prosecution, the patent applicants responded to a rejection by clarifying that the definition of "solubilizer" is limited to "semi-solid or liquid non-ionic surface active agents," indicating they acted as their own lexicographers. They pointed out that only one component from the cited prior art, specifically U.S. Patent No. 4,673,564 to Kawata et al., could qualify as a "nonionic solubilizer" in their context, which they equated with surfactants. The applicants emphasized that none of the prior art disclosed the use of nonionic surfactants to create solid preparations with extended release, further reinforcing their limitation of "solubilizer" to surfactants.
The conclusion drawn is that the district court's claim construction was erroneous; the term "solubilizer" must be restricted to surfactants. Consequently, Mutual's extended-release felodipine tablets, which utilize a co-solvent instead of a surfactant, cannot literally infringe on the '081 patent. Astrazeneca's request for remand to consider the doctrine of equivalents is rejected, as the specification's disavowal of nonsurfactant solubilizers precludes applying this doctrine to reclaim surrendered claim coverage. This is supported by precedents indicating that a patentee cannot use the doctrine of equivalents to regain coverage of clearly excluded structures.
The judgment of infringement is reversed, and the case is remanded for a judgment of noninfringement. Mutual acknowledges that the '081 patent is not invalid if "solubilizer" is defined to include only surfactants. The court concludes that "solubilizer" is limited to surfactants, affirming the district court's ruling on invalidity in favor of Astrazeneca. The court's decision is affirmed in part, reversed in part, and remanded, with costs awarded to the appellant. Notably, the parties did not present expert testimony on the meaning of "solubilizer" during the Markman hearing, agreeing on its general understanding. The court emphasizes the importance of interpreting claims in conjunction with the specification without improperly adding limitations. It references the need to discern whether the specification implies a requirement for a limitation in all embodiments or only in some. Future considerations on claim construction law may be forthcoming, as indicated by a related en banc rehearing case. The court also cites the standard for demonstrating intent to restrict claim scope through clear disavowal in the specification.
