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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
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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.
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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 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).
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.
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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 function-
way-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.
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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
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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.
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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.
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