Abraxis Bioscience, Inc. v. Mayne Pharma (USA) Inc. (Fed. Cir. 2006)

    By Donald Zuhn --

In an appeal from a District Court judgment of infringement of U.S. Patent Nos. 5,714,520; 5,731,355; and 5,731,356, the Federal Circuit reversed the District Court's claim construction and finding of literal infringement, and affirmed the District Court's finding of infringement under the doctrine of equivalents.

The patents at issue relate to an improved formulation of a general anesthetic and sedative containing propofol (2,6-diisopropylphenol), in which an antimicrobial agent has been added.  AstraZeneca Pharmaceuticals LP (AstraZeneca), the original assignee of the patents at issue, had discovered that microbial contamination of its propofol composition had led to an increase in post-operative infections, which necessitated that a patient's infusion device be changed at least every 6-12 hours.  The inventors of the patents at issue discovered that by adding preservatives to its propofol composition, the microbial contamination could be retarded such that a patient's infusion device need be changed only once every 24 hours.  In particular, the inventors discovered that the preservative disodium edetate was unexpectedly effective in retarding microbial growth in the propofol composition.  Abraxis Bioscience, Inc. (Abraxis) subsequently acquired all rights to the patents at issue.

Seeking to develop a generic formulation of AstraZeneca's improved propofol composition, ESI Lederle (ESI) began a research effort aimed at identifying an antimicrobial agent that would work as well as the edetate in AstraZeneca's propofol composition.  ESI's research efforts led to the identification of the calcium trisodium salt of diethylenetriaminepentaacetic acid (calcium trisdoium DTPA) as a suitable antimicrobial additive, and ESI was granted U.S. Patent No. 6,028,108 (the '108 patent) for a propofol composition containing calcium trisodium DTPA.  Following issuance of the '108 patent, Wyeth Pharmaceuticals, Inc. (Wyeth), of which ESI was a division, notified AstraZeneca that it was seeking FDA approval for ESI's propofol composition.  AstraZeneca responded by filing a patent infringement action against Wyeth and ESI.  Mayne Pharma (USA), Inc. (Mayne) subsequently acquired the Abbreviated New Drug Application (ANDA) for ESI's propofol composition, and AstraZeneca filed a second patent infringement action against Mayne.  Ultimately, Mayne was substituted for Wyeth and ESI in the first action, and the two actions were consolidated.

In its Markman ruling, the District Court construed three contested terms, including the term "edetate" (i.e., the antimicrobial agent recited in the asserted claims).  The District Court noted that the patentees defined "edetate" in the patents at issue as "EDTA and derivatives thereof," and thus, construed the term "edetate" as meaning "EDTA as well as compounds structurally related to EDTA regardless of how they are synthesized."  Following a bench trial, the District Court determined that Mayne's propofol composition infringed the asserted claims of the patents at issue both literally and under the doctrine of equivalents.

With respect to the District Court's construction of "edetate," the Federal Circuit noted that the District Court had adopted a broad definition of the term "derivatives" in arriving at a construction of "edetate" that encompassed structural analogs of EDTA as well as synthetic derivatives.  The Federal Circuit determined, however, that the instrinsic evidence failed to support a construction of "edetate" that would encompass structural analogs of EDTA.  For example, while the patents at issue list several derivatives of EDTA that are suitable for the invention, the Federal Circuit observed that none of these derivatives are structural analogs.  The Federal Circuit concluded, therefore, that "the listing of EDTA salts as '[p]articular derivatives of use in the present invention,' coupled with the statements regarding the uniqueness of edetate as the only successful antimicrobial agent, and the patentees' description of EDTA salts as advantageous, preferable, and 'exceptional,' limit the term 'derivatives' to EDTA salts or compounds that maintain the EDTA free acid structure."  Thus, the Federal Circuit determined that the District Court had erred in adopting a broad definition of the term "derivatives," and held that "the proper construction of 'edetate' is EDTA and derivatives of EDTA, such as salts, but not including structural analogs."

With respect to the District Court's finding of literal infringement, the Federal Circuit noted that Abraxis had conceded during oral argument that calcium trisodium DTPA is not a salt of EDTA, and further, that calcium trisodium DTPA is not a derivative of EDTA, since it cannot be synthesized from EDTA in a laboratory.  The Federal Circuit concluded that because neither EDTA nor any of its salts or derivatives was present in Mayne's propofol composition, the District Court had erred in finding that Mayne's propofol composition infringed the patents at issue.

In affirming the District Court's finding of infringement under the doctrine of equivalents, the Federal Circuit rejected three arguments proffered by Mayne in support of its position that the District Court had erred in finding that calcium trisodium DTPA was an equivalent of edetate.  Mayne first asserted that the District Court, in applying the function-way-result test, had improperly defined the "way" in which edetate works.  The Federal Circuit, however, agreed with the District Court's determination that the "way" in which both calcium trisodium DTPA and edetate "function" to retard microbial growth is by metal ion chelation.  Mayne next asserted that because the patentees chose to narrowly claim their invention, it was impermissible as a matter of law to extend the meaning of edetate to calcium trisodium DTPA by equivalence.  The Federal Circuit, however, determined that "[c]ontrary to Mayne’s assertion, the inventors did not clearly disavow other polyaminocarboxylates, including DTPA, by claiming edetate," and further that "[t]here is no evidence that the patentees made a clear and unmistakable surrender of other polyaminocarboxylates, or calcium trisodium DTPA in particular, during prosecution."  Finally, Mayne asserted that the lack of known interchangeability between calcium trisodium DTPA and edetate as an antimicrobial agent indicated that the substitution of calcium trisodium DTPA for edetate was a substantial change.  With respect to Mayne's last argument, which the Federal Circuit stated was largely premised on Mayne's ability to secure a patent for its own propofol composition, the Federal Circuit concurred with the District Court's determination that "the separate patentability of Mayne’s generic formula did 'not outweigh the substantial evidence of equivalence between Mayne’s calcium trisodium DTPA and the claimed edetate.'"

Abraxis Bioscience, Inc. v. Mayne Pharma (USA) Inc. (Fed. Cir. 2006)
Panel: Circuit Judge Lourie, Senior Circuit Judge Plager, and Circuit Judge Rader
Opinion by Circuit Judge Lourie