United States Court of Appeals for the Federal Circuit 

06-1118 

ABRAXIS BIOSCIENCE, INC. (formerly known as 

 ASTRAZENECA PHARMACEUTICALS LP 

and ASTRAZENECA UK LTD.), 

Plaintiffs-Appellees, 

v. 

MAYNE PHARMA (USA) INC. 

(formerly known as Faulding Pharmaceutical Company), 

 Defendant-Appellant. 

 Denise L. Loring, Ropes & Gray LLP, of New York, New York, argued for 

plantiffs-appellees. With her on the brief were Sona De and Herbert F. Schwartz; and 

Robert J. Goldman, of Palo Alto, California. 

 Charles A. Weiss, Kenyon & Kenyon LLP, of New York, New York , argued for 

defendant-appellant. With him on the brief were Thomas J. Meloro and Richard L. 

DeLucia. Of counsel on the brief was Jules E. Goldberg, Reed Smith, LLP, of New 

York, New York. 

 

Appealed from: United States District Court for the Southern District of New York 

Judge William H. Pauley, III 
United States Court of Appeals for the Federal Circuit 

06-1118 

ABRAXIS BIOSCIENCE, INC. (formerly known as 

ASTRAZENECA PHARMACEUTICALS LP 

and ASTRAZENECA UK LTD.), 

 Plaintiff-Appellee, 

v. 

MAYNE PHARMA (USA) INC. 

(formerly known as Faulding Pharmaceutical Company), 

Defendant-Appellant. 

_____________________ 

DECIDED: November 15, 2006 

_____________________ 

Before LOURIE, Circuit Judge, PLAGER, Senior Circuit Judge, and RADER, Circuit 

Judge. 

LOURIE, Circuit Judge. 

Mayne Pharma (USA), Inc. (“Mayne”) appeals from the decision of the United 

States District Court for the Southern District of New York granting judgment of 

infringement of U.S. Patents 5,714,520 (“the ’520 patent”), 5,731,355 (“the ’355 patent”), 

and 5,731,356 (“the ’356 patent”), both literally and under the doctrine of equivalents, in 

favor of AstraZeneca Pharmaceuticals LP and AstraZeneca UK Ltd. (collectively 

“AstraZeneca”). AstraZeneca Pharms. LP v. Mayne Pharma (USA) Inc., No. 02-7936, 

03-6487 (S.D.N.Y. Nov. 2, 2005) (“Nov. 2, 2005 Opinion”). Because the district court 

erred in its construction of “edetate,” which was the basis upon which it found literal 

infringement, we reverse the court’s claim construction and the court’s finding of literal 
infringement. However, because the court did not clearly err in determining that the 

accused product infringes under the doctrine of equivalents, we affirm the district court’s 

judgment. 

BACKGROUND 

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 

06-1118 2
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. Nov. 2, 2005 Opinion, slip op. at 4. 

In March 1995, the inventors applied for a patent on their improved DIPRIVAN®

formulation. In December 1995, AstraZeneca also filed a supplemental New Drug 

Application (“NDA”) on the new formulation. It was approved on June 11, 1996, and 

AstraZeneca was granted three years of marketing exclusivity for the improved 

DIPRIVAN® formulation. AstraZeneca also requested the FDA to withdraw approval on 

the original DIPRIVAN® formulation, and in 1998, the FDA granted the request. 

Abraxis Bioscience, Inc. (“Abraxis”) is the assignee of the three asserted patents 

that cover the improved formulation.1

 The ’520 patent, entitled “Propofol Composition 

Containing Edetate,” was issued on February 3, 1998. The ’355 and ’356 patents, both 

entitled “Pharmaceutical Compositions of Propofol and Edetate,” were issued on March 

24, 1998 from divisional applications based on the ’520 patent application. All three 

patents share a common specification. The asserted claims of the patents are claims 1-

14, 16-32, and 34 of each patent, as well as claims 38 and 39 of the ’520 patent. 

 1

 On August, 11, 2006, Abraxis was substituted as plaintiff-appellee in this 

action for AstraZeneca after acquiring all rights, title, and interest in the ’520, ’355, and 

’356 patents and NDA No. 19-627. 

06-1118 3
In 1995, scientists at ESI Lederle (“ESI”) learned of the reports of infection 

relating to original DIPRIVAN®.

2

 ESI also learned that AstraZeneca reformulated its 

composition by adding an antimicrobial agent, and decided to develop a similar generic 

formulation. Dr. Martin Joyce of ESI led those development efforts. After reviewing 

AstraZeneca’s ’520 patent, Dr. Joyce and his colleagues screened antimicrobial agents 

in an effort to replace the edetate in the improved DIPRIVAN® formulation with a 

different agent. Id., slip op. at 8-9. Dr. Mary George, a senior formulator at ESI, 

advised the formulation group that the calcium trisodium salt of 

diethylenetriaminepentaacetic acid (pentetate), which is also referred to as DTPA, was 

a promising candidate as an antimicrobial agent.3 

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 

 2

 Abbreviated New Drug Application (“ANDA”) No. 76-452 relates to the generic 

propofol emulsion. ESI, a division of Wyeth Pharmaceuticals, Inc. (“Wyeth”), originally 

filed this ANDA and was the party responsible for developing the generic formulation. 

Baxter Healthcare Corporation subsequently acquired ESI from Wyeth, as well as the 

generic propofol product. Mayne acquired the application from Baxter and became the 

applicant of record for ANDA No. 76-452. Mayne was substituted as defendant in this 

action for Wyeth and ESI on February 3, 2003. 

3

 Throughout this opinion, we will refer to this compound as calcium trisodium 

DTPA. 

06-1118 4
improved DIPRIVAN®. Nov. 2, 2005 Opinion, slip op. at 9. Ultimately, calcium 

trisodium DTPA was chosen as the final antimicrobial additive. 

ESI filed a patent application on its pharmaceutical composition and was later 

granted U.S. Patent 6,028,108 (“the ’108 patent”) on February 22, 2000. On June 28, 

2002, ESI filed ANDA No. 76-452 on its generic propofol formulation. ESI included a 

Paragraph IV Certification asserting that the patents in suit were invalid, unenforceable, 

or would not be infringed by its generic propofol formulation. Pursuant to 21 U.S.C. 

§ 355(j)(2)(B)(ii), Wyeth notified AstraZeneca by letter dated August 20, 2002 that it was 

seeking FDA approval for its generic propofol formulation and that it intended to 

commercially manufacture, use, or sell a 20 ml vial product. AstraZeneca filed the first 

of two patent infringement actions against Wyeth and ESI on October 4, 2002. 

Thereafter, Mayne, as the indirect assignee of ESI, sent AstraZeneca a notice letter 

dated July 15, 2003 informing AstraZeneca of its intent to commercially manufacture, 

use, or sell its generic propofol formulation in 50 ml and 100 ml vials. AstraZeneca 

initiated the second lawsuit based on this notice letter, and both actions were 

consolidated. 

The district court issued a Markman ruling on December 28, 2004. AstraZeneca 

Pharms. LP v. Mayne Pharma (USA), Inc., 352 F. Supp. 2d 403 (S.D.N.Y. 2004). 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. After 

holding an eleven-day bench trial, the court entered judgment in favor of AstraZeneca, 

concluding that the filing of Mayne’s ANDA No. 76-452 infringed the asserted claims of 

06-1118 5
the patents in suit. 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. Mayne timely appealed. We have 

jurisdiction pursuant to 28 U.S.C. § 1295(a)(1). 

DISCUSSION 

Claim construction is an issue of law, Markman v. Westview Instruments, Inc., 52 

F.3d 967, 970-71 (Fed. Cir. 1995) (en banc), that we review de novo. Cybor Corp. v. 

FAS Techs., Inc., 138 F.3d 1448, 1456 (Fed. Cir. 1998) (en banc). The district court’s 

determination of infringement, in contrast, is a question of fact that we review for clear 

error. Centricut, LLC v. Esab Group, Inc., 390 F.3d 1361, 1367 (Fed. Cir. 2004). A 

determination of infringement requires a two-step analysis. “First, the court determines 

the scope and meaning of the patent claims asserted, and then the properly construed 

claims are compared to the allegedly infringing device.” Cybor, 138 F.3d at 1454 

(citations omitted). “A finding is ‘clearly erroneous’ when although there is evidence to 

support it, the reviewing court on the entire evidence is left with the definite and firm 

conviction that a mistake has been committed.” United States v. U.S. Gypsum Co., 333 

U.S. 364, 395 (1948). 

06-1118 6
I. 

Claim Construction

Central to the disposition of this appeal is the construction of the term “edetate,” 

which is a limitation in each of the asserted claims. Claim 1 of the ’520 patent is a 

representative claim. It reads, in pertinent part, as follows: 

1. A sterile pharmaceutical composition for parenteral 

administration which comprises an oil-in-water emulsion in 

which propofol dissolved in a water-immiscible solvent, is 

emulsified with water and stabilized by means of a 

surfactant, and which further comprises an amount of 

edetate sufficient to prevent a no more than 10-fold increase 

in growth of each of Staphylococcus aureus ATCC 6538, 

Escherichia coli ATCC 8739, Pseudomonas aeruginosa 

ATCC 9027 and Candida albicans ATCC 10231 for at least 

24 hours as measured by a test . . . . 

’520 patent, col.11 ll.33-41 (emphasis added). 

The district court construed “edetate” as “EDTA as well as compounds 

structurally related to EDTA regardless of how they are synthesized.” AstraZeneca, 352 

F. Supp. 2d at 417. 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.4

 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. 

 4

 Relying on the declaration of Michele M. Winneker, the court stated that a 

structural analog is “a compound that has the same structural components as the lead 

compound,” even if it cannot practically be prepared from that lead compound. 

AstraZeneca, 352 F. Supp. 2d at 414 n.6. The court further stated that a synthetic 

derivative, in contrast, is a compound that “is synthesized from that lead compound” by 

one or more chemical reactions. Id. 

06-1118 7
Mayne argues that the district court erred by adopting an overly broad definition 

of “edetate,” particularly by including structural analogs as “derivatives.” Mayne 

contends that that definition is unsupported by the intrinsic evidence. Mayne asserts 

that based on the intrinsic evidence, the correct construction of “edetate” is “the salts or 

anions of EDTA.” 

Abraxis responds that the district court correctly construed “edetate” to include 

structural analogs of EDTA. In defining the term “derivatives,” Abraxis asserts that the 

district court properly adopted the broader definition, particularly in light of certain 

statements in the specification. 

“Words of a claim ‘are generally given their ordinary and customary meaning.’” 

Phillips v. AWH Corp., 415 F.3d 1303, 1312 (Fed. Cir. 2005) (en banc). A patentee, 

however, can “act as his own lexicographer to specifically define terms of a claim 

contrary to their ordinary meaning.” Chef Am., Inc. v. Lamb-Weston, Inc., 358 F.3d 

1371, 1374 (Fed. Cir. 2004) (citation omitted). To a person of ordinary skill in the art, 

the term “edetate” can refer to the common name of an EDTA salt, namely, a salt of 

ethylenediaminetetraacetic acid.5 J.A. at A6624. That term could also refer more 

generally to “[a]ll anions derived from [EDTA].” Id. at A6796. As the district court 

properly concluded, however, the patentees acted as their own lexicographers by 

defining “edetate” in the specification. In particular, the patentees stated that: “By the 

term ‘edetate’ we mean ethylenediaminetetraacetic acid (EDTA) and derivatives thereof 

. . . .” ’520 patent, col.4 ll.51-52. The district court correctly noted that a plain reading of 

that statement indicates that “edetate” includes “EDTA and derivatives of EDTA.” 

 5

 As noted in the specification, EDTA stands for ethylenediaminetetraacetic acid. 

’520 patent, col. 4 ll. 51-52.

06-1118 8
AstraZeneca, 352 F. Supp. 2d at 413 (citing Webster's Third New International 

Dictionary 2372 (1993) for the definition of “thereof”). We disagree, however, with the 

district court’s definition of “derivatives.” Under the district court’s construction, 

structural analogs of EDTA fall within the literal scope of the claim. The intrinsic 

evidence, however, fails to support that conclusion. 

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 

06-1118 9
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. 

Earlier in the specification, the patent discloses that considerable effort had been 

spent experimenting with a number of known preservatives including, among others, 

benzyl alcohol, sodium methyl hydroxybenzoate, sodium metabisulphite, and sodium 

sulphite. ’520 patent, col.4 ll.22-28. The patentees noted that none of those 

preservatives met their requirements. Instead, after extensive experimentation, the 

universe of potential antimicrobial agents was narrowed down to one particular agent, 

i.e., edetate. The patentees explained: 

We then investigated the possible use of other agents which 

might have the action that we sought. We unexpectedly 

found that edetate, which is not regarded as a broad 

spectrum antimicrobial agent was the only agent that would 

meet our requirements. 

Id., col.4 ll.28-33 (emphasis added). That statement indicates that edetate possessed 

particular chemical properties that allowed it to work as an effective antimicrobial agent 

and that the term “derivatives” was not intended to extend broadly. 

The patentees further proceeded to describe their experimentation. They noted: 

As can be seen from the experimental section, sodium

calcium edetate has some advantages over other additives 

but disodium edetate is exceptional. Accordingly, most 

preferably the edetate is disodium edetate. 

Id., col.4 ll.64-67 (emphases added). That statement again emphasizes the significance 

of the patentees’ discovery that edetate, or more particularly EDTA salts, worked as 

successful antimicrobial agents. Notably, in the experimental section which that 

statement references, the patent lists five different agents including sodium 

06-1118 10
metabisulphite, sodium sulphite, hydroxybenzoates, sodium calcium edetate, and 

disodium edetate dehydrate. As noted above, three of those agents had already been 

rejected by the patentees as suitable agents. Significantly, the two remaining agents, 

sodium calcium edetate and disodium edetate dehydrate, which the patentees described 

as advantageous, preferable and “exceptional,” are EDTA salts. 

We thus conclude 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. Those statements 

are inconsistent with a definition of “derivatives” that includes structural analogs that can 

encompass a large number of non-derivative compounds. That definition fails to 

recognize that the patentees’ discovery focused on the unexpected effectiveness of 

edetate and its salts as antimicrobial agents. 

Abraxis argues that a narrow definition is unsupported by the specification, 

particularly in light of the patentees’ statement that “[t]he nature of the edetate is not 

critical, provided that it fulfils the function of preventing significant growth of 

microorganisms for at least 24 hours in the event of adventitious extrinsic 

contamination.” Id., col.4 ll.57-61. But, when read in context, that statement does 

support a narrow construction. It appears in the specification directly after the listing of 

the various EDTA salts that the patentees identified as suitable edetates. Thus, the 

statement that the “nature of the edetate is not critical” only connotes that the choice of 

which particular agent to use, i.e., EDTA or any EDTA salt, itself is not of critical 

06-1118 11
importance, as long as the agent chosen can adequately prevent microbial growth. 

Contrary to Abraxis’ suggestion, that sentence does not support a broad construction for 

“derivatives.” 

Abraxis also relies on another statement in the specification in support of its 

definition for “derivatives.” Abraxis points to the patentees’ use of the term “derivatives” 

in the context of silicone. The patent identifies “dimethicone” and “simethicone” as 

“silicone derivative[s].” Id., col.3 ll.40-41. Those compounds are not synthetic 

derivatives of silicone, but are structural analogs. Abraxis contends that using the term 

in that manner to broadly describe a class of antifoaming agents supports a broader 

definition for “derivatives” in the context of “edetate.” We disagree. That term was used 

to describe a general class of antifoaming agents as disclosed in another patent. That 

is far removed from the pointed discussion in the specification identifying the 

“derivatives” of “edetate.” Thus, the passing reference to silicone derivatives fails to 

overcome our conclusion that the patentees narrowly defined edetate “derivatives” to 

mean EDTA and its salts. 

In light of the foregoing analysis, despite the district court’s thorough analysis and 

review of the patent, we conclude that the district court erred by adopting a broad 

definition of the term “derivatives.” Based on the specification, “derivatives” does not 

include structural analogs. Accordingly, the proper construction of “edetate” is EDTA 

and derivatives of EDTA, such as salts, but not including structural analogs. 

II. 

Literal Infringement

Having determined the correct claim construction of “edetate,” we next consider 

literal infringement. Literal infringement requires that each and every claim limitation be 

06-1118 12
present in the accused product. Frank's Casing Crew & Rental Tools, Inc. v. 

Weatherford Int’l, Inc., 389 F.3d 1370, 1378 (Fed. Cir. 2004). All of the asserted claims 

require “edetate,” i.e., EDTA or derivatives of EDTA. Thus, the issue before the court is 

whether calcium trisodium DTPA is a derivative of EDTA. 

As Abraxis conceded during oral argument, DTPA is not a derivative of EDTA 

since it cannot be synthesized from EDTA in a laboratory, and it is certainly not a salt of 

EDTA. Abraxis’ expert admitted that synthesizing DTPA from EDTA cannot be 

performed in a laboratory, but stated that it “can easily be done on the blackboard.” J.A. 

at A727. However, theoretical blackboard constructs do not necessarily make a 

structural analog a derivative. Abraxis itself conceded that DTPA is only a structural 

analog of EDTA, and thus qualified only as an EDTA “derivative” under the district 

court’s claim construction. Consequently, in light of our claim construction and Abraxis’ 

own admissions, we conclude that the district court was clearly erroneous in finding that 

Mayne’s product literally infringes the asserted claims of the patents in suit, because 

neither EDTA nor any of its salts or derivatives is present in the accused formulation. 

III. 

Doctrine of Equivalents

Unlike claim construction, a matter of law reviewed de novo, infringement under 

the doctrine of equivalents is a factual determination that we review for clear error. 

Centricut, LLC v. Esab Group, Inc., 390 F.3d 1361, 1367 (Fed. Cir. 2004). Thus, 

notwithstanding our disagreement with the district court’s conclusions regarding claim 

06-1118 13
construction and literal infringement, we will affirm its decision on infringement under the 

doctrine of equivalents.6

 

“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 EndoSurgery, 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). 

On appeal, Mayne advances three main arguments in support of its position that 

the court clearly erred in finding that calcium trisodium DTPA is an equivalent of 

edetate. First, Mayne argues that the court clearly erred in its analysis with regard to 

the “way” prong of the function-way-result test by improperly defining the “way” in which 

edetate works. Secondly, Mayne argues that it was impermissible as a matter of law for 

the meaning of edetate to extend to calcium trisodium DTPA by equivalence because 

the patentees chose to narrowly claim their invention. According to Mayne, the 

patentees chose to use the restrictive term “edetate” in claiming their invention, rather 

than broader terms such as “polyaminocarboxylates” or “metal ion chelators,” and thus 

are now precluded from extending patent protection to cover compounds beyond 

 6

 While our modified claim construction directly affects the outcome of our literal 

infringement analysis, the outcome of the doctrine of equivalents issue is not similarly 

affected, as discussed below. 

06-1118 14
edetate.7

 Third, Mayne asserts that the lack of known interchangeability between 

calcium trisodium DTPA and edetate as an antimicrobial agent indicates that the 

substitution of calcium trisodium DTPA is a “substantial” change weighing against a 

finding of equivalence. 

Abraxis responds that the district court properly analyzed the differences 

between edetate and calcium trisodium DTPA under the function-way-result test, and 

correctly determined that the differences between them are insubstantial, and thus the 

two are equivalent. Secondly, Abraxis argues that it is not estopped from asserting that 

calcium trisodium DTPA is an equivalent of edetate. Lastly, Abraxis asserts that the 

known interchangeability of one element for another is just one of several factors to be 

considered in a doctrine of equivalents analysis. According to Abraxis, the district court 

correctly found that that factor was insufficient to outweigh the substantial evidence 

supporting the conclusion that edetate and calcium trisodium DTPA are equivalent. 

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 functionway-result analysis. The court identified the “function” of edetate as “retard[ing] 

microbial growth in propofol oil-in-water emulsions.” Nov. 2, 2005 Opinion, slip op. at 18. 

The court then defined the “way” that edetate worked as by metal ion chelation and 

found that the result achieved was “retard[ing] microbial growth to the extent required by 

the microbiological test set forth in the claims.” Id., slip op. at 19. Based on the 

 7

 EDTA and DTPA belong to a broad class of structurally analogous compounds 

known as polyaminocarboxylic acids. Nov. 2, 2005 Opinion, slip op. at 13. Compounds 

belonging to this group have several amino groups and several acetic acid or carboxylic 

acid (COOH) groups. 

06-1118 15
evidence of record, the court found that calcium trisodium DTPA similarly retards 

microbial growth in an oil-in-water emulsion by metal ion chelation to retard the growth 

of the microorganisms to the extent required by the test set forth in the claims. 

Mayne asserts that the district court clearly erred in defining the “way” as metal 

ion chelation.8

 Mayne contends that the proper definition of “way” is a narrower one, 

i.e., one that incorporates the specific metal ions that are chelated, the strength of the 

bonds that are formed during chelation, and the stability constants. Because Abraxis 

did not proffer evidence at trial that established those additional factors, Mayne argues 

that the “way” prong of the three-pronged test was unsupported by substantial evidence. 

We disagree. “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 record evidence 

supports the conclusion that the “way” in which both edetate and calcium trisodium 

DTPA perform as an antimicrobial agent is by metal ion chelation. Indeed, the patent 

specification describes edetates as “metal ion sequestering agent[s].” ’520 patent, col.4 

ll.33-35. Moreover, Mayne itself argued to the FDA that calcium trisodium DTPA is an 

 8

 Mayne also raises arguments on appeal concerning the function and result 

prongs of this test. Those arguments, however, are not properly before the court 

because Mayne failed to raise them below. Indeed, Mayne conceded that the dispute 

with respect to the doctrine of equivalents was limited to the “way” prong of the analysis. 

See J.A. at A1204 (“We agree, function and result aren’t the issue here [with respect to 

the Graver Tank analysis]. Calcium trisodium [p]entetate is antimicrobial and it does 

achieve the result of killing those four microbes.”). As such, those arguments are 

deemed waived and will not be addressed on appeal. 

06-1118 16
effective antimicrobial agent in its generic propofol formulation because “of its ability to 

chelate divalent metal ions.” J.A. at A1907. 

The court made fact-findings that calcium trisodium DTPA also inhibited microbial 

growth by chelating metal ions. In reaching this conclusion, the court credited the 

testimony of several experts at trial including Dr. Weiner, Dr. Tierno, and Dr. Knapp, all 

of whom testified about metal ion chelation and the use of calcium trisodium DTPA as a 

metal ion chelator to inhibit microbial growth. Additionally, the court relied on an expert 

report by Dr. Kille that was included in Mayne’s FDA submission. The Kille report 

explained that calcium trisodium DTPA is effective as an antimicrobial agent “as a result 

of its ability to chelate divalent metal ions that are essential for many biological 

processes.” J.A. at A1907. We thus conclude that the district court did not clearly err in 

defining “way” as metal ion chelation and in finding that that is the “way” in which 

calcium trisodium DTPA functions as an antimicrobial agent. 

Secondly, we reject Mayne’s argument that, as a matter of law, it is 

impermissible for the meaning of edetate to extend to other polyaminocarboxylates by 

equivalence. Mayne contends that by claiming their invention narrowly, i.e., by limiting 

the claim to edetate, Abraxis is barred from capturing DTPA, or any other 

polyaminocarboxylate, as an equivalent. Mayne cites Tanabe Seiyaku Co. v. United 

States International Trade Commission, 109 F.3d 726 (Fed. Cir. 1997) in support of this 

argument. In Tanabe, we affirmed the International Trade Commission’s ruling of 

noninfringement under the doctrine of equivalents. The patent, which covered a method 

for preparing a pharmaceutical composition used for the treatment of various 

cardiovascular diseases, claimed, inter alia, five specific base-solvent combinations. 

06-1118 17
One claimed combination was potassium carbonate and acetone. Id. at 729. The 

accused product used a potassium carbonate and butanone combination, instead of 

acetone. We found that replacing acetone with butanone, a structurally similar 

compound, was a substantial change and thus not equivalent. 

In reaching that conclusion, we noted that the inventor chose to specifically 

define his invention in the claims, the specification, and prosecution history in terms of 

the five base-solvent combinations. We noted that a person of skill in the art would 

know that the inventor could have claimed a broader term such as “ketone,” which 

would have encompassed butanone, but decided to limit the claims to acetone. We 

further noted that the inventor distinguished his invention over prior art while 

prosecuting its foreign counterparts by arguing that the five base-solvent combinations 

yielded unexpectedly good results. Therefore, by describing the invention in that 

“sharply restricted nature” and by making arguments during prosecution that 

emphasized the importance of the five particular base-solvent combinations, we found 

that the inventor effectively disclaimed subject matter beyond the five combinations. Id.

at 732. Thus, a competitor reading the patent and file wrapper would reasonably 

believe that butanone was not part of the invention. 

That is not the situation here. 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 

06-1118 18
find estoppel by argument). Indeed, the district court found that “the antimicrobial 

activity of calcium trisodium DTPA was unforeseeable during prosecution.” Nov. 2, 

2005 Opinion, slip op. at 37-38. Mayne itself acknowledged the unforeseeability of 

DTPA while prosecuting its own patent. Id. at 38. Thus, a person of ordinary skill in the 

art reading the patent would not conclude that by claiming “edetate,” the patentees 

surrendered or waived coverage of all polyaminocarboxylates, including DTPA, as an 

equivalent, particularly in light of the unforeseeability of calcium trisodium DTPA as an 

equivalent. See Warner-Jenkinson, 520 U.S. 17, 37 (1997) (rejecting petitioner’s 

argument that equivalents should be limited to known equivalents at the time of patent 

issuance, and not extend to after-arising equivalents); see also Kinzenbaw v. Deere & 

Co., 741 F.2d 383, 389 (Fed. Cir. 1984) (“[t]he doctrine of equivalents is designed to 

protect inventors from unscrupulous copyists and unanticipated equivalents”) (citing 

Graver Tank, 340 U.S. at 607) (emphasis added). We thus reject Mayne’s contention 

that, as a matter of law, the district court erred by determining that calcium trisodium 

DTPA is an equivalent of edetate. 

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 

06-1118 19
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. 

In sum, we conclude that the district court’s conclusion that Mayne’s generic 

propofol formulation infringes the patents in suit under the doctrine of equivalents was 

not clearly erroneous. 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. Thus, Mayne fails to demonstrate that that finding amounted 

to clear error. 

We have considered Mayne’s remaining arguments and find them unpersuasive. 

Moreover, in light of our conclusion, we need not address Mayne’s arguments with 

respect to the claims requiring disodium edetate. Accordingly, the court’s judgment of 

infringement on this basis is affirmed. 

06-1118 20
CONCLUSION 

For the foregoing reasons, we reverse the district court’s claim construction as to 

the term “edetate” and the court’s finding of literal infringement. The district court’s 

finding of infringement under the doctrine of equivalents, however, is affirmed. 

AFFIRMED. 

06-1118 21