The patented problem AstraZeneca solved was retarding microbial growth in sustained intravenous application of a general anesthesia and sedative. The chosen anti-microbial additive was edetate.

In November 1989, AstraZeneca launched in the United States an original pharmaceutical composition used to induce and maintain general anesthesia and sedation in patients. The product was marketed and sold under the trade name DIPRIVAN® for treatment in humans and RAPINOVET® for veterinary use. The composition consists of an injectible oil-in-water emulsion containing propofol, or 2,6-diisopropylphenol, as its active ingredient.

Typically, DIPRIVAN® is administered to patients by infusion, which involves the use of a “giving set.” ’520 patent, col.2 ll.56-61. A giving set involves connecting a reservoir containing the propofol emulsion with the patient’s vein via the appropriate tubing. In 1990, AstraZeneca became aware that patients using DIPRIVAN® were increasingly suffering from post-operative infections. It was determined that the infections were linked to the microbial contamination of fluids contained in the DIPRIVAN® giving set. As a result, the Food and Drug Administration (“FDA”) imposed a requirement that the giving sets be “changed at least every 6 or 12 hours dependent on the presentation being used.” Id., col.3 ll.2-3.

AstraZeneca researchers began developing an improved formulation that would allow giving sets to be changed less frequently. The inventors of the patents in suit recommended the use of preservatives in DIPRIVAN®. They experimented with a number of preservatives, but discovered that most were ineffective. The inventors ultimately discovered that one preservative in particular, disodium edetate, was unexpectedly effective in retarding microbial growth in the propofol formulation without disrupting the oil-in-water emulsion for at least twenty-four hours. AstraZeneca subsequently developed an improved version of the original DIPRIVAN® formulation consisting of edetate, as well as all of the ingredients in the original formulation. The original DIPRIVAN® formulation and the improved formulation have identical anesthetic properties.

ESI Lederle, another company, learned of the DIPRIVAN® infection problem, and discovered calcium trisodium DTPA as an effective mircobial retardant. The hat trick was coming up with a different but similar agent that evaded the expensive process of FDA-mandated clinical and safety trials.

In selecting that compound, Dr. George considered a number of factors. Dr. George stated in a memorandum that the “product must be approvable as an ANDA without clinical or safety studies . . . [and] must match the reference product characteristics and stability profile” of AstraZeneca’s improved formulation. J.A. at A3662. Dr. George also noted that since calcium trisodium DTPA is “structurally similar to edetate, product stability is predicted to be unaffected.” Id. ESI determined that calcium trisodium DTPA produced the same characteristics and stability profile as improved DIPRIVAN®. Ultimately, calcium trisodium DTPA was chosen as the final antimicrobial additive.

The defendant, Mayne Pharma, was an indirect assignee of 6,028,108, ESI's patent. AstraZeneca initiated its lawsuit upon receiving a notice letter from Mayne Pharma that they intended to make and sell the generic version developed by ESI.

The district court construed the claim term edetate as including structural analogs.

The court construed three contested terms. Only one term, “edetate,” is at issue in this appeal. This term was construed by the district court as “EDTA as well as compounds structurally related to EDTA regardless of how they are synthesized.” Id. at 417... Based on the district court’s construction of “edetate” as encompassing structural analogs of EDTA, the court found that Mayne’s generic propofol formulation literally infringed claims 1 and 3-14 of the asserted patents, and claim 38 of the ’520 patent. Additionally, the court determined that Mayne’s formulation infringed claims 1-14, 16-32, and 34 of the asserted patents, and claims 38 and 39 of the ’520 patent under the doctrine of equivalents.

In construing “edetate,” the court noted that the patentees defined “edetate” in the specification as “EDTA and derivatives thereof.” ’520 patent, col.4 ll.51-52. The court proceeded to define the term “derivatives” by adopting a broad definition, specifically one that encompasses structural analogs of EDTA as well as synthetic derivatives. The district court found that that broad definition of “derivatives,” and thus “edetate,” was most consistent with the use of the term in the specification.

In its claim construction, the CAFC did a more careful reading of the specification, and decided that the derivatives claimed had been specifically listed, thus eliminating structural analogs as within that scope.

As this court recognized in Phillips, “claims ‘must be read in view of the specification, of which they are a part.’” 415 F.3d at 1315 (quoting Markman, 52 F.3d at 979). We further stated that “the specification ‘is always highly relevant to the claim construction analysis. Usually, it is dispositive; it is the single best guide to the meaning of a disputed term.’” Id. (internal citations omitted). Here, the specification leads us to the conclusion that the patentees intended a more narrow meaning for the term “derivatives” than the definition adopted by the district court.

We first note that the part of the specification describing “edetate” reads:

By the term “edetate” we mean ethylenediaminetetraacetic acid (EDTA) and derivatives thereof, for example the disodium derivative is known as disodium edetate. In general suitable edetates of this invention are those salts having lower affinity for EDTA than calcium. Particular derivatives of use in the present invention include trisodium edetate, tetrasodium edetate and disodium calcium edetate.

’520 patent, col.4 ll.51-57 (emphases added). Thus, the inventors listed several derivatives of EDTA that are suitable for the invention. Notably, all of these derivatives are salts of EDTA, none are structural analogs.

Abraxis argues, and the district court agreed, that the EDTA salts merely serve as examples of “derivatives” and thus “may not be used to limit a claim term.” AstraZeneca, 352 F. Supp. 2d at 413. We disagree. When reading these statements in the context of the entire specification, it is evident that the listing of various EDTA salts defines the term “derivatives.” At the very least, “derivatives” does not include structural analogs.

Thus, on appeal, ESI evaded literal infringement, but was not so lucky with infringement under the doctrine of equivalents.

“Infringement may be found under the doctrine of equivalents if every limitation of the asserted claim, or its ‘equivalent,’ is found in the accused subject matter, where an ‘equivalent’ differs from the claimed limitation only insubstantially.” Ethicon Endo-Surgery, Inc. v. U.S. Surgical Corp., 149 F.3d 1309, 1315 (Fed. Cir. 1998). An accused device that “performs substantially the same function in substantially the same way to obtain the same result” as the patented invention may infringe under this doctrine. Graver Tank & Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 608 (1950).

In a well-reasoned opinion, the district court concluded that calcium trisodium DTPA and edetate were equivalent after finding that the differences existing between the two were insubstantial. In reaching this conclusion, the court performed a function-way-result analysis.

“What constitutes equivalency must be determined against the context of the patent, the prior art, and the particular circumstances of the case.” Graver Tank, 339 U.S. at 609. As the Supreme Court instructed, “[e]quivalence, in the patent law, is not the prisoner of a formula and is not an absolute to be considered in a vacuum.” Id. Here, the district court properly assessed the “way” edetate works by referring to the patent and the evidence presented at trial.

The court correctly determined that calcium trisodium DTPA performs substantially the same function in substantially the same way to achieve the same result as edetate. Indeed, that conclusion is consistent with the findings made by the district court that calcium trisodium DTPA was specifically chosen for the generic propofol formulation because of its structural similarities to edetate and the likelihood that it would match the product characteristics and stability profile of Abraxis’ improved DIPRIVAN® formulation.

The CAFC brushed aside the argument of prosecution estoppel.

Contrary to Mayne’s assertion, the inventors did not clearly disavow other polyaminocarboxylates, including DTPA, by claiming edetate. There is no evidence that the patentees made a clear and unmistakable surrender of other polyaminocarboxylates, or calcium trisodium DTPA in particular, during prosecution. See Cordis Corp. v. Medtronic AVE, Inc., 339 F.3d 1352, 1363 (Fed. Cir. 2003) (noting that a “clear and unmistakable surrender of subject matter” is required to find estoppel by argument).

What about ESI getting its own patent?

Lastly, we reject Mayne’s argument that the lack of known interchangeability between edetate and DTPA as an antimicrobial agent mandates the conclusion that the accused product does not infringe under the doctrine of equivalents. Mayne’s theory is largely premised on the fact that Mayne was able to receive a patent on its generic propofol formulation. In fact, the absence of known interchangeability underscores that the patent applicant had no reason to foresee and claim DTPA in this combination. As stated in Warner-Jenkinson, known interchangeability is only one factor to consider in a doctrine of equivalents analysis. It aids the fact-finder in assessing the similarities and differences between a claimed and an accused element. Warner-Jenkinson, 520 U.S. at 37 (“[a] skilled practitioner’s knowledge of the interchangeability between claimed and accused elements . . . tells the fact-finder about the similarities or differences between those elements”). As discussed above, the court made factual findings that insubstantial differences exist between calcium trisodium DTPA and edetate, and further found 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.” Nov. 2, 2005 Opinion, slip op. at 39. We see no clear error in that finding.