Source: https://casetext.com/case/astrazeneca-pharmaceuticals-v-mayne-pharma
Timestamp: 2019-04-22 14:54:53+00:00

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02 Civ. 7936 (WHP), 03 Civ. 6487 (WHP).
AstraZeneca Pharmaceuticals LP and AstraZeneca Pharmaceuticals UK Ltd. (collectively, "AstraZeneca") allege patent infringement by Mayne Pharma (USA) Inc. ("Mayne"), formerly known as Faulding Pharmaceutical Company. In particular, AstraZeneca accuses Mayne of infringing U.S. Patent Nos. 5,714,520 (the "`520 patent"), 5,731,355 (the "'355 patent") and 5,731,356 (the "'356 patent") (collectively, the "asserted patents") by filing Abbreviated New Drug Application ("ANDA") No. 76-452 with the United States Food and Drug Administration ("FDA").
This action arises under 35 U.S.C. § 271(e) and this Court has subject matter jurisdiction pursuant to 28 U.S.C. §§ 1331 and 1338(a). Venue is proper under 28 U.S.C. §§ 1391(b)-(c) and 1400(b). This Court conducted an eleven-day bench trial. Insofar as the Court exercises its prerogative as finder of fact to determine the weight and credibility of the evidence, the discussion herein is limited to the evidence that this Court credits. Further, this Court recites only those findings of fact that are relevant to its conclusions of law.
AstraZeneca owns the asserted patents. Those patents have a common specification and relate to a pharmaceutical composition of propofol and edetate. AstraZeneca alleges that by filing ANDA No. 76-452, Mayne infringed one or more claims of the asserted patents under 35 U.S.C. § 271(e)(2)(A). ANDA No. 76-452 was filed by ESI Lederle ("ESI"), formerly a division of Wyeth Pharmaceuticals, Inc. ("Wyeth") and later a division of Baxter Healthcare Corporation ("Baxter"). Mayne acquired ANDA No. 76-452 from Baxter and is now the applicant of record.
By letter dated July 15, 2003, Mayne notified AstraZeneca pursuant to 21 U.S.C. § 355(j)(2)(B)(ii) that it was seeking FDA approval for its amended ANDA No. 76-452, filed on July 7, 2003, to engage in the commercial manufacture, use or sale of its generic propofol emulsion in 50 and 100 mL vials. (JPTO ¶ VI.B.27.) On August 6, 2003, AstraZeneca filed the second action, No. 03 Civ. 6487 (WHP), alleging patent infringement by Mayne based on its July 15, 2003 notice. (JPTO ¶ VI.B.28.) This Court consolidated the actions on October 24, 2003.
The "giving set" is the tube that connects an intravenous needle to the bag containing the pharmaceutical composition administered to the patient.
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 wherein a washed suspension of each said organism is added to a separate aliquot of said composition at approximately 50 colony forming units per ml, at a temperature in the range 20° 25° C., whereafter said aliquots are incubated at 20° 25° C. and are tested for viable counts of said organism after 24 hours, said amount of edetate being no more than 0.1% by weight of said composition.
(PX 1, Col. 11, lines 33-48.) Claim 38 is identical to Claim 1 but includes the additional requirement that the edetate not destabilize the emulsion. Claims 2 and 20 specify that the edetate is disodium edetate, and Claim 34 specifies the amount of disodium edetate as 0.005%. (PX 1, Col. 11, line 33 — Col. 14, line 36.) Claims 3-14 specify the various constituents of the Claim 1 formulation, and Claims 16-19, 21-32 and 39 address the molar concentrations of edetate.
The asserted claims of the '355 patent are directed to "[a] method for producing anaesthesia in a warm-blooded animal which comprises parenterally administering" a sterile pharmaceutical composition of the type set forth in the claims of the '520 patent. The asserted claims of the '356 patent are directed to "[a] method for limiting the potential for microbial growth" in a sterile pharmaceutical composition of the type described in the claims of the '520 patent.
EDTA as well as compounds structurally related to EDTA regardless of how they are synthesized, and which can 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.
AstraZeneca Pharmas., LP v. Mayne Pharma (USA), Inc., 352 F.Supp. 2d 403, 419 (S.D.N.Y. 2004).
A Paragraph III Certification informs the FDA that the ANDA applicant is aware of a patent covering its formulation and that the applicant does not intend to market its product until the patent expires. See 21 U.S.C. § 355(j)(2)(A)(vii)(III).
DTPA is also known as pentetic acid or pentetate. Calcium trisodium DTPA is also known as pentetate calcium trisodium, calcium trisodium pentetate and more commonly as Ca-DTPA. See FDA, Pentetate calcium trisodium injection, atwww.fda.gov/cder/foi/label/2004/021749Ca-DTPAlbl.pdf. (See also PX 21 at FPC221291-92; PX 281 at FPC255811.) For ease of reference, this Court refers to Ca-DTPA as calcium trisodium DTPA.
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 wherein a washed suspension of each said organism is added to a separate aliquot of said composition at approximately 50 colony forming units per ml, at a temperature in the range 20°-25° C., whereafter said aliquots are incubated at 20°-25°C. and are tested for viable counts of said organism after 24 hours.
AstraZeneca contends that Mayne's filing of ANDA No. 76-452 on its generic propofol composition infringes Claims 1-14, 16-32 and 34 of each asserted patent as well as Claims 38 and 39 of the '520 patent. Each asserted claim includes "edetate." The parties principally disagree over whether Mayne's formulation contains the edetate recited in the claims. That is, the parties dispute whether the calcium trisodium DTPA in Mayne's generic propofol emulsion qualifies as the edetate in the asserted claims.
[d] said amount of edetate being no more than 0.1% by weight of said composition.
Claim 1 has been subdivided into four subsections for ease of reference.
"Edetate" EDTA as well as compounds structurally related to EDTA regardless of how they are synthesized, and which can prevent a no more than 10-fold increase in growth of each of ATCC 6538, ATCC 8739, ATCC 9027 and ATCC 10231 for at least 24 hours. "Propofol" 2, 6-diisopropylphenol. "an amount of edetate. . ." An amount of edetate, greater than 0% but less than or equal to 0.1% by weight of the pharmaceutical composition, which is sufficient to meet the microbiological test recited in the claim phrase. AstraZeneca, 352 F. Supp. 2d at 419.
As discussed below, Mayne's generic propofol emulsion includes each limitation recited in Claims 1, 3-14 of each asserted patent and Claim 38 of the '520 patent.
Limitation [a] of Claim 1 calls for "a sterile pharmaceutical composition for parenteral administration." Likewise, Mayne's generic propofol emulsion is also a sterile pharmaceutical composition for parenteral administration. (JPTO ¶¶ VI.B.8, 10;see also PX 21 at FPC221394, FPC221418.) Thus, the accused formulation meets this limitation.
Limitation [b] is "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." As stipulated by the parties, Mayne's generic propofol emulsion is also an oil-in-water emulsion, which includes propofol at a concentration of 10 mg/ml (or 1% by weight) and soybean oil at a concentration of 100 mg/ml (or 10% by weight). The propofol is dissolved in soybean oil, which is emulsified with water and stabilized by a surfactant, egg lecithin. (JPTO ¶¶ VI.B.9, 11-13; see also PX 21 at FPC221292, FPC221394, FPC221418.) Thus, the accused formulation meets this limitation.
Limitation [c] is "an amount of edetate sufficient to [pass the recited microbiological test]." Mayne's formulation contains 0.0008% by weight of calcium trisodium DTPA. (JPTO ¶¶ VI.B.21-23.) As noted above, the calcium trisodium DTPA in Mayne's generic propofol emulsion passes the microbiological test recited in Claim 1. (JPTO ¶ VI.B.22.) Thus, the key question is whether the calcium trisodium DTPA in Mayne's formulation is structurally related to EDTA (i.e., whether it is an edetate).
(Tr. at 1072; see also Tr. at 1381-82; PX 281 at FPC255811.) DTPA cannot "easily" be synthesized from EDTA in a laboratory (Tr. at 292-93); however, it can theoretically be synthesized from EDTA (Tr. at 284-86), because both DTPA and EDTA are members of a class of structurally analogous compounds known as polyaminopolycarboxylic acids (Tr. at 1363-65).
AstraZeneca's expert, Dr. Jack Norton, testified on the topic of whether DTPA and EDTA are structurally related. (Tr. at 281-86.) Dr. Norton concluded that, based on his knowledge of the "chemical literature," DTPA and EDTA were structurally related. (Tr. at 285-88.) AstraZeneca's other expert, Thomas Foster, also testified that DTPA and EDTA are structurally related. (Tr. at 156-59, 1297-98.) Similarly, Mayne's expert, Dr. Norman Weiner, testified that "DTPA is a structural analog of EDTA." (Tr. at 869.) Although Mayne's other expert, Dr. Harold Hopfenberg, resisted conceding that DTPA was structurally related to EDTA, he acknowledged that the two are structural analogs and belong to the same structurally analogous polyaminopolycarboxylic acid family of compounds. (Tr. at 1363-64.) Thus, as compounds in the same family of chemical structures, this Court finds that DTPA is a structural analog of EDTA. Further, as this Court stated in its Markman ruling, "the proper definition of edetate includes EDTA as well as . . . structural analogs of EDTA." AstraZeneca, 352 F. Supp. 2d at 417. That is, as EDTA's structural analog, DTPA is structurally related to EDTA and is an edetate as that term is used in Claim 1. See AstraZeneca, 352 F.Supp. 2d at 417. That does not end the inquiry, however, because the compound in Mayne's formulation is calcium trisodium DTPA not DTPA.
Finally, because calcium trisodium DTPA is structurally related to DTPA (i.e., calcium trisodium DTPA is a derivative of DTPA), it is structurally related to EDTA. (Tr. at 156-59 (discussing the calcium trisodium DTPA additive in Mayne's generic propofol emulsion, although imprecisely referring to it simply as DTPA); JX 4 (noting that calcium trisodium DTPA is "structurally similar to edetate"); PX 437-2; see Tr. at 944, 1297-1302; PX 21 at FPC221291-96 (Mayne's ANDA submission discussing the similarities between calcium trisodium DTPA and EDTA).) In fact, calcium trisodium DTPA is a member of the polyaminocarboxylic family, like EDTA and DTPA. (Tr. at 1300-01; PX 437-2; see Tr. at 856-66, 1299-1301, 1359-61; PX 281 at FPC255811; PX 437-1; PX 437-2.) As members of the same family, calcium trisodium DTPA and EDTA are structurally related (i.e., calcium trisodium DTPA is a derivative of EDTA). (See Tr. at 1363-64). See AstraZeneca, 352 F. Supp. 2d at 417. Thus, this Court finds that the accused formulation meets limitation [c].
Claims 3-14 of the '520 patent depend on Claim 1, thereby incorporating all the limitations of Claim 1. Claims 3-14 add further limitations relating to various attributes of the components of the claimed compositions other than the disputed "edetate" limitation. Because Mayne's formulation includes these additional limitations (JPTO ¶¶ VI.B. 11-13, 15-19; see Tr. at 160-64; PX 433-4 — 433-15), the accused formulation meets all the limitations in Claims 3-14 of the '520 patent.
Independent Claim 38 of the '520 patent is identical to Claim 1, but adds that "the edetate does not physically destabilise [the] emulsion." Similarly, calcium trisodium DTPA does not destabilize Mayne's generic propofol formulation. (Tr. 164-66; PXs 433-16, 433-17, 433-18; see Tr. 952-53; JX 12 at FPC205490; PX 21 at FPC221415-16, FPC221418-19.) Thus, Mayne's formulation meets all the limitations in Claim 38 of the '520 patent.
As discussed below, Mayne's generic propofol emulsion includes each limitation recited in Claims 1-14, 16-32 and 34 of each asserted patent as well as Claims 38 and 39 of the '520 patent when viewed under the rubric of the doctrine of equivalents. In particular, calcium trisodium DTPA and EDTA salts perform the same function in substantially the same way to achieve the same result.
EDTA salts are derivatives of EDTA and, therefore, are edetates.
The edetate in the asserted claims retards microbial growth in propofol oil-in-water emulsions. As already noted, calcium trisodium DTPA in Mayne's generic propofol formulation has the same function. (JPTO ¶¶ VI.B.21-23; see also PX 21 at FPC221296 (noting that the DTPA in Mayne's generic propofol formulation is "considered to behave in a similar manner to EDTA, the microbial inhibitor contained in the brand product Diprivan at 0.005%"); DX 152, Col. 1, line 60 — Col. 2, line 5.) Thus, this Court finds that calcium trisodium DTPA performs the same function as the edetate in the asserted claims.
At trial, AstraZeneca's expert, Dr. Joseph E. Knapp, testified that the microorganisms that thrive in propofol oil-in-water emulsions all require metal ions to grow. (Tr. at 308-12, 320-27; JX 29 at AZ100715-16, AZ100722, AZ100730; see Tr. at 1209-13; DX 65 at FPC252691-92.) Indeed, in July 2003, the FDA sent Mayne a "deficiency letter" in connection with its ANDA, requesting information about the safety of calcium trisodium DTPA in Mayne's generic propofol formulation. In response, Mayne submitted an expert report by Dr. John W. Kille. The Kille report explains that calcium trisodium DTPA "is effective [as a microbial inhibitor] as a result of its ability to chelate divalent metal ions that are essential for many biological processes." (PX 281 at FPC255829.) In light of Dr. Knapp's testimony, Dr. George's memorandum (JX 4) and Mayne's statements to the FDA (PX 281 at FPC255829), this Court finds that calcium trisodium DTPA performs in the same manner as EDTA salts, i.e., the edetate in the asserted claims.
A deficiency letter is a request for additional information from the FDA.
Mayne objects to the Kille report as a statement by "an independent contractor, not affiliated with Mayne." (Mayne's Response to AstraZeneca's Proposed Findings of Fact and Conclusions of Law, dated Apr. 18, 2005 ("Mayne Opp.") at 6-7.) This objection is overruled. By submitting the Kille report to the FDA as part of its response, Mayne adopted that report's contents as its own. Therefore, the Kille report is admissible as Mayne's admission against interest.
Finally, the edetate in the asserted claims retards microbial growth to the extent required by the microbiological test set forth in the claims. Mayne's calcium trisodium DTPA achieves the same result. (JPTO ¶¶ VI.B.21-23; Tr. at 473, 1205-06.) Thus, this Court finds that calcium trisodium DTPA achieves the same result as the edetate in the asserted claims, and is equivalent to the edetate in the asserted claims. Further, as discussed above, Mayne's generic propofol formulation includes the other limitations of Claims 1 and 3-14 of the asserted patents and Claim 38 of the '520 patent.
Claims 16-19 of the asserted patents and Claim 39 of the '520 patent describe the amount of edetate present in the claimed composition. The claims specify molar concentrations of edetate of 3×10-5 to 9×10-4, 3×10-5 to 7.5×10-4, 1.5×10-4, to 3×10-4 and 1.5×10-4, respectively. Because calcium trisodium DTPA is 0.0008% by weight in Mayne's generic propofol formulation, that constitutes a molar concentration of 2×10-5. (JPTO ¶¶ VI.B.21-23.) This Court finds that a molar concentration of 2×10-5 is equivalent to the molar concentrations of edetate recited in these claims. Additionally, as discussed above, the calcium trisodium DTPA in Mayne's formulation acts as an antimicrobial agent to perform the same function in the same way (i.e., chelation) and achieves the same result (i.e., passing the microbiological test) as the edetate in the asserted claims. (see JPTO ¶¶ VI.B.21-23.) Finally, as noted above, Mayne's generic propofol formulation includes the other limitations of Claims 16-19 of the asserted patents and Claim 39 of the '520 patent.
Indeed, the Glen UK patent does not discuss microbial contamination or suggest adding edetate to an oil-in-water emulsion to retard microbial growth. In this regard, the Glen UK patent does not suggest any test to determine whether growth had been sufficiently retarded as claimed in the '520 patent, or the methods of the '355 and '356 patents. Indeed, in issuing the asserted patents, the USPTO concluded that the Glen UK patent did not teach the inventions of the asserted patents.
During the prosecution of the '520 patent, the applicants made five separate Information Disclosure Statement ("IDS") submissions to the USPTO (Tr. at 569-76; DX 177 at AZ033245-52, AZ033415-17, AZ033446-48, AZ033523-25; DX 178 at AZ033578-81), citing, what Jules Goldberg testified was, a "huge amount of art." (Tr. at 538.) Goldberg concluded that "the patentees . . . had dug up just about [every prior art] they could." (Tr. at 538.) The cited art includes the Glen UK patent, the Glen '635 patent and the Original Diprivan formulation, all of which appear in the '520 patent's specification.
Mr. Goldberg, a partner at Reed Smith LLP, has been a patent attorney for over thirty years in the chemical and pharmaceutical arts. (Tr. at 520-26.) He is Mayne's litigation counsel in this action.
The patent specification states that propofol is a phenol. The prior art cited by the inventors discloses that phenols have antimicrobial properties. In particular, the Hart articles and an article by Jon J. Kabara disclose that phenols are antimicrobial agents and that EDTA was known to potentiate the antimicrobial properties of such phenols. (Tr. at 778-80, 840-45; PX 178 at AZ027032, AZ027037; DX 178 at AZ033668-69, AZ033677-85; see Tr. at 1149-54; JX 18 at FPC217835-837; JX 22 at FPC254665-67.) Indeed, after her review of the '520 patent, ESI's Dr. George acknowledged the antimicrobial properties of propofol. (Tr. at 939-40; PX 99 at FPC067907 ("Since propofol itself is a phenol, its antibacterial action is potentiated by the addition of a chelating agent, such as EDTA.").) Mayne contends that the antimicrobial properties of propofol were not known "by anyone outside of AstraZeneca at the time of the prosecution of the patents in suit." (See Mayne's Proposed Findings of Fact and Conclusions of Law, dated Apr. 8, 2005 ("Mayne Mem.") at 35 ("AstraZeneca failed to produce any evidence to show that information regarding propofol's antimicrobial properties . . . was published or otherwise known by anyone outside of AstraZeneca at the time of the prosecution of the Patents in Suit.").) However, the prior art references demonstrate that the patentees did not conceal propofol's antimicrobial properties.
Mr. Heller was a patent attorney for over thirty years, concentrating primarily in the chemical and pharmaceutical fields. (Tr. at 1108-09.) He died of injuries sustained in a bicycle accident.
Filing an ANDA to "obtain approval . . . to engage in the commercial manufacture, use, or sale of a drug . . . claimed in a patent or the use of which is claimed in a patent before [its] expiration" constitutes patent infringement. Teva Pharms. USA, Inc. v. Pfizer Inc., 395 F.3d 1324, 1328 (Fed. Cir. 2005). Indeed, " 35 U.S.C. § 271(e)(2)(A) simply provides an `artificial' act of infringement that creates case-or-controversy jurisdiction to enable the resolution of an infringement dispute before the ANDA applicant has actually made or marketed the proposed product." Warner-Lambert Co. v. Apotex Corp., 316 F.3d 1348, 1365 (Fed. Cir. 2003) (citing Glaxo Inc. v. Novopharm Ltd., 110 F.3d 1562, 1569 (Fed. Cir. 1997)).
"Once jurisdiction is established, however, the substantive determination whether actual infringement or inducement will take place is determined by traditional patent infringement analysis, just the same as it is in other infringement suits, including those in a non-ANDA context, the only difference being that the inquiries now are hypothetical because the allegedly infringing product has not yet been marketed." Warner-Lambert, 316 F.3d at 1365. "The plain language of 35 U.S.C. § 271(e)(2)(A) does not alter a patentee's burden of proving infringement." Warner-Lambert, 316 F.3d at 1366 (internal quotation and alterations omitted). "The proper inquiry under § 271(e)(2)(A) is `whether, if a particular drug were put on the market, it would infringe the relevant patent.'"Warner-Lambert, 316 F.3d at 1366 (quoting Bristol-Myers Squibb Co. v. Royce Labs., Inc., 69 F.3d 1130, 1135 (Fed. Cir. 1995). Thus, this Court's infringement inquiry must focus on Mayne's ANDA. See Glaxo, 110 F.3d at 1569.
Claim construction is an issue of law to be resolved by the Court. Markman v. Westview Instruments, Inc., 517 U.S. 370, 388-90 (1996). On December 28, 2004, the Court issued a Memorandum and Order construing three disputed claim terms of the patents in suit.
As already noted, this Court construed the claim term "edetate" as "EDTA as well as compounds structurally related to EDTA regardless of how they are synthesized, and which can prevent a no more than 10-fold increase in growth of each ofStaphylococcus aureus ATCC 6538, Escherichia coli ATCC 8739,Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231 for at least 24 hours." AstraZeneca, 352 F. Supp. 2d at 419. Mayne argues that this Court's definition is contrary to the holding of Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005), because it overemphasized the dictionary definition of edetate and minimized the weight accorded to the asserted patents' specification and prosecution history. (Letter to Court from Jules Goldberg, dated Aug. 4, 2005 at 1-3; Letter to Court from Jules Goldberg, dated July 15, 2005 at 1-2.) This Court disagrees.
The main problem with elevating the dictionary to such prominence is that it focuses the inquiry on the abstract meaning of words rather than on the meaning of claim terms within the context of the patent.
Dictionaries, by their nature, provide an expansive array of definitions. General dictionaries, in particular, strive to collect all uses of particular words, from the common to the obscure. By design, general dictionaries collect the definitions of a term as used not only in a particular art field, but in many different settings. In such circumstances, it is inevitable that the multiple dictionary definitions for a term will extend beyond the "construction of the patent [that] is confirmed by the avowed understanding of the patentee, expressed by him, or on his behalf, when his application for the original patent was pending." Goodyear Dental Vulcanite Co. v. Davis, 102 U.S. 222, 227 (1880). . . .
Even technical dictionaries or treatises, under certain circumstances, may suffer from some of these deficiencies. There is no guarantee that a term is used in the same way in a treatise as it would be by the patentee. In fact, discrepancies between the patent and treatises are apt to be common because the patent by its nature describes something novel. . . .
Moreover, different dictionaries may contain somewhat different sets of definitions for the same words. A claim should not rise or fall based upon the preferences of a particular dictionary editor, or the court's independent decision, uninformed by the specification, to rely on one dictionary rather than another. Finally, the authors of dictionaries or treatises may simplify ideas to communicate them most effectively to the public and may thus choose a meaning that is not pertinent to the understanding of particular claim language. . . . The resulting definitions therefore do not necessarily reflect the inventor's goal of distinctly setting forth his invention as a person of ordinary skill in that particular art would understand it.
Thus, while the Federal Circuit did not "preclude the appropriate use of dictionaries," Phillips, 415 F.3d at 1322, it noted that the analysis should begin by giving claim terms their ordinary and customary meaning as the terms would have been construed by "a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date of the patent application." Phillips, 415 F.3d at 1312-13. However, "[b]ecause the meaning of a claim term as understood by persons of skill in the art is often not immediately apparent, and because patentees frequently use terms idiosyncratically, the court looks to those sources available to the public that show what a person of skill in the art would have understood disputed claim language to mean." Phillips, 415 F.3d at 1314 (internal quotations omitted). "Those sources include the words of the claims themselves, the remainder of the specification, the prosecution history, and extrinsic evidence concerning relevant scientific principles, the meaning of technical terms, and the state of the art." Phillips, 415 F.3d at 1314 (internal quotations omitted).
Finally, the Federal Circuit noted that "there is no magic formula or catechism for conducting claim construction" and that "[t]he sequence of steps used by the judge in consulting various sources is not important; what matters is for the court to attach the appropriate weight to be assigned to those sources in light of the statutes and policies that inform patent law." Phillips, 415 F.3d at 1324. The Federal Circuit rejected the approach it previously suggested in Texas Digital Systems, Inc. v. Telegenix, Inc., 308 F.3d 1193 (Fed. Cir. 2002), which overemphasized the weight afforded to dictionary definitions and minimized the weight afforded to a patent's specification and prosecution history. Phillips, 415 F.3d at 1320-24. However, as noted, the court did not bar the use of general purpose or technical dictionaries. Phillips, 415 F.3d at 1322.
This Court's claim construction was consistent with the approach suggested in Phillips. In its Markman ruling, this Court started its inquiry by attempting to decipher the meaning the patentees accorded to the disputed terms because "[t]he parties [did] not dispute that the patentees manifested their intent to act as their own lexicographers in defining edetate." AstraZeneca, 352 F.Supp.2d at 412; see also Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996) ("Although words in a claim are generally given their ordinary and customary meaning, a patentee may choose to be his own lexicographer and use terms in a manner other than their ordinary meaning, as long as the special definition of the term is clearly stated in the patent specification or file history.").
This Court found that the patentees had defined "edetate" in the specification. AstraZeneca, 352 F. Supp. 2d at 412. However, the Court rejected limiting the term "edetate" to the examples provided in the specification because the specification's phraseology "ma[de] it clear that patentees were merely providing illustrations." AstraZeneca, 352 F. Supp. 2d at 414; see also Phillips, 415 F.3d at 1327 ("We have held that the fact that a patent asserts that an invention achieves several objectives does not require that each of the claims be construed as limited to structures that are capable of achieving all of the objectives." (internal quotations and alterations omitted)).
The '520 patent teaches that disodium edetate, trisodium edetate, tetrasodium edetate and disodium calcium edetate are appropriate EDTA derivatives. (Col. 4, lines 51-57.) However, the '520 patent notes that the exact type of edetate is not important, as long as the chosen edetate can prevent significant growth of microorganisms for at least twenty-four hours if there is adventitious extrinsic contamination. (Col. 4, lines 57-64.) Thus, the specification supports a broad definition of edetate: EDTA or an EDTA derivative that can prevent significant growth of microorganisms for at least twenty-four hours.
AstraZeneca, 352 F. Supp. 2d at 416. This Court rejected Mayne's proposal to narrow the definition to synthetic derivatives only because "the patentees did not disavow structural analogs from their definition of derivatives or criticize their usage. Instead, . . . the patentees' use of the word derivatives suggests that they intend their definition to incorporate compounds that are similar in structure to the parent compound." AstraZeneca, 352 F. Supp. 2d at 417; see also Phillips, 415 F.3d at 1325-27 (rejecting a limiting definition of "baffles").
As the above recitation illustrates, in construing the claim with respect to the term "edetate," this Court consulted various sources but gave primacy to the claims and the specification. Thus, this Court's analysis conformed to the rule announced inPhillips.
AstraZeneca, as the plaintiff in this action, bears the burden of proving infringement by a preponderance of the evidence.SmithKline Diagnostics, Inc. v. Helena Labs. Corp., 859 F.2d 878, 889 (Fed. Cir. 1988). Infringement analysis requires applying the asserted claims to the accused products and methods.Allen Eng'g Corp. v. Bartell Indus., Inc., 299 F.3d 1336, 1351 (Fed. Cir. 2002) ("Infringement is determined by comparing the accused devices not with products made by the patentee but with the claims of the patent as properly construed."). Where the filing of an ANDA triggers a patent infringement suit, the infringement analysis requires comparison of the asserted claims to the product that is likely to be sold following FDA approval. Abbott Labs. v. TorPharm, Inc., 300 F.3d 1367, 1373 (Fed. Cir. 2002).
"Literal infringement requires that each and every limitation set forth in a claim appear in an accused product." Franks Casing Crew Rental Tools, Inc. v. Weatherford Int'l, Inc., 389 F.3d 1370, 1378 (Fed. Cir. 2004) (internal citation omitted);Amhill Enters., Ltd. v. Wawa, 81 F.3d 1554, 1562 (Fed. Cir. 1996) ("Literal infringement of a claim exists when every limitation recited in the claim is found in the accused device, i.e., when the properly construed claim reads on the accused device exactly."); Baxter Healthcare Corp. v. Spectramed, Inc., 49 F.3d 1575, 1582 (Fed. Cir. 1995). "If even one limitation is missing or not met as claimed, there is no literal infringement."Mas-Hamilton Group v. LaGard, Inc., 156 F.3d 1206, 1211 (Fed. Cir. 1998) (citations omitted). Further, "[i]t is axiomatic that dependent claims cannot be found infringed unless the claims from which they depend have been found to have been infringed."Wahpeton Canvas Co. v. Frontier, Inc., 870 F.2d 1546, 1553 (Fed. Cir. 1989).
AstraZeneca, 352 F. Supp. 2d at 419. The claims require that edetate be present in an amount "greater than 0% but less than or equal to 0.1% by weight of the pharmaceutical composition, which is sufficient to meet the microbiological test recited in the claim phrase." AstraZeneca, 352 F. Supp. 2d at 419. Because, as discussed supra, Mayne's generic propofol formulation's calcium trisodium DTPA is an edetate, the accused product includes all the limitations in Claims 1, 3-14 and 38 of the '520 patent, Claims 1 and 3-14 of the '355 patent and Claims 1 and 3-14 of the '356 patent. Accordingly, this Court concludes that Mayne's generic propofol emulsion literally infringes Claims 1 and 3-14 of the asserted patents as well as Claim 38 of the '520 patent.See Baxter Healthcare, 49 F.3d at 1582 (holding that an accused product or method literally infringes when it includes every limitation of the asserted claim).
"The doctrine of equivalents, ubiquitous since its origin inWinans v. Denmead, 56 U.S. (15 How.) 330 (1853), exists solely for the equitable purpose of preventing an infringer from stealing the benefit of an invention." Texas Instruments, Inc. v. U.S. Int'l Trade Com'n, 805 F.2d 1558, 1572 (Fed. Cir. 1986) (internal quotations omitted); see Graver Tank Mfg. Co. v. Linde Air Prods. Co., 339 U.S. 605, 608 (1950) (noting that the doctrine of equivalents serves "`[t]o temper unsparing logic and prevent an infringer from stealing the benefit of the invention.'" (quoting Royal Typewriter Co. v. Remington Rand, Inc., 168 F.2d 691, 692 (2d Cir. 1948) (Hand, J.))). Where "one or more of the claim limitations are not literally present in the accused device, thus precluding a finding of literal infringement, the claim may still be held infringed if equivalents of those limitations are present."Allen Eng'g Corp. v. Bartell Indus., Inc., 299 F.3d 1336, 1345 (Fed. Cir. 2002) (citing Warner-Jenkinson Co. v. Hilton Davis Chem. Co., 520 U.S. 17, 24 (1997)). The doctrine strikes a balance between ensuring that the patentee enjoys the full benefit of his patent and that the claims give "fair notice" of the patent's scope. London v. Carson Pirie Scott Co., 946 F.2d 1534, 1538 (Fed. Cir. 1991).
Equivalents are assessed limitation-by-limitation.Warner-Jenkinson, 520 U.S. at 29, 40. For there to be infringement under the doctrine of equivalents, the differences between the absent claim limitations and accused product must be "insubstantial." Boehringer Ingelheim Vetmedica, Inc. v. Schering-Plough Corp., 320 F.3d 1339, 1351 (Fed. Cir. 2003). "While no particular linguistic framework controls the inquiry, the insubstantial differences inquiry may be guided by determining whether the element in the accused device `performs substantially the same function in substantially the same way to obtain the same result' as the claim limitation." Boehringer, 320 F.3d at 1351 (quoting Graver Tank, 339 U.S. at 608) (internal citation omitted); see Warner-Jenkinson, 520 U.S. at 39-40; Dawn Equip. Co. v. Kentucky Farms Inc., 140 F.3d 1009, 1016 (Fed. Cir. 1998); Corning Glass Works v. Sumitomo Elec. U.S.A., Inc., 868 F.2d 1251, 1258 (Fed. Cir. 1989). This standard has been referred to as the "function-way-result test."See Interactive Pictures Corp. v. Infinite Pictures, Inc., 274 F.3d 1371, 1376-77 (Fed. Cir. 2001).
The doctrine of equivalents may be limited by prosecution history estoppel. That is, claim amendments or arguments made during prosecution may give rise to a rebuttable presumption of a general disclaimer of the territory between the patentee's original claim and the amended or discussed claim. Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 740 (2002); Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 344 F.3d 1359, 1369 (Fed. Cir. 2003); Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1574 (Fed. Cir. 1997). Thus, if a narrowing claim amendment is related to patentability, prosecution history estoppel presumptively bars the assertion of the excluded range of equivalents for the amended claim element in subsequent litigation. Warner-Jenkins, 520 U.S. at 33. Further, embodiments of the claimed invention that are disclosed in the patent's specification but not claimed are dedicated to the public. See Johnson Johnston Assocs. v. R.E. Serv. Co., 285 F.3d 1046, 1054-55 (Fed. Cir. 2002). These principles limit the doctrine of equivalents because as between the patentee, who had the opportunity to obtain broader claims, and the public at large, it is the patentee who bears the cost of failing to seek protection for foreseeable embodiments of the claimed invention.See Sage Prods., Inc. v. Devon Indus., Inc., 126 F.3d 1420, 1425 (Fed. Cir. 1997).
Finally, even if an infringer obtains a patent covering the accused product, a finding of infringement under the doctrine of equivalents may still be warranted. See Fiskars, Inc. v. Hunt Mfg. Co., 221 F.3d 1318, 1324 (Fed. Cir. 2000); Bio-Technology Gen. Corp. v. Genentech, Inc., 80 F.3d 1553, 1559 (Fed. Cir. 1996).
As discussed supra, this Court finds that calcium trisodium DTPA is equivalent to the edetate in the asserted claims. Further, the amount of calcium trisodium DTPA in the accused product is equivalent to the amount of edetate recited in Claims 16-19 and 21-32 of the asserted patents and Claim 39 in the '520 patent. Finally, the calcium trisodium DTPA in Mayne's formulation is equivalent to the disodium edetate in Claims 2 and 20, and the amount of disodium edetate specified in Claim 34.
Mayne argues that AstraZeneca may not assert any range of equivalents for the asserted claims, because during prosecution it narrowed the claim term "edetate" to overcome the Patent Examiner's rejection in light of the Patel reference. Although prosecution history estoppel may limit the doctrine of equivalents, it does not limit the scope of the term edetate in this case. As this Court noted in its Markman ruling, AstraZeneca did not limit the meaning of edetate by argument or amendment. AstraZeneca, 352 F. Supp. 2d at 414. The amendments based on which Mayne argues for a narrow definition of "edetate" addressed the amount of edetate necessary and more precisely defined the microbiological test, but left the definition of edetate intact. AstraZeneca, 352 F. Supp. 2d at 414; see Interactive Pictures, 274 F.3d at 1376-77.
Further, this Court concludes that the antimicrobial activity of calcium trisodium DTPA was unforeseeable during prosecution and, therefore, the patentees' failure to expressly claim it was not fatal. See Festo, 344 F.3d at 1365 n. 2 ("[W]hen the narrowing amendment was made . . . is the relevant time for evaluating unforeseeability, for that is when the patentee presumptively surrendered the subject matter in question and it is at that time that foreseeability is relevant."). Moreover, as Mayne itself argued to the USPTO during prosecution of its '108 patent, the antimicrobial activity of DTPA was unforeseeable despite the '520 patent's disclosure of the properties of edetate. (Tr. at 953-54; DX 152, Col. 1, lines 9-43, 53-57; DX 153 at FPC207734, FPC207742-43, FPC207746.) Additionally, reliance on the '701 patent (issued to Furia) is improper in this context, because it relates to a different field from the asserted patents. See Festo, 344 F.3d at 1369.
This Court also concludes that claims to calcium trisodium DTPA were not dedicated to the public. (See Mayne Mem. at 50.) Under Federal Circuit law, disclosed but unclaimed embodiments of the claimed invention are dedicated to the public. See Johnson Johnston, 285 F.3d at 1054-55. In Johnson Johnston, the patentees had disclosed various alternative materials for the substrate recited in the claim. 285 F.3d at 1050. However, the claim only recited the alternative embodiment of aluminum. Id. at 1055. Here, the argument that the inventors should have claimed "the broad class of metal ion sequestering agents" (Mayne Mem. at 14-15) is misplaced, because the claims require edetate. Had the claims recited EDTA — instead of edetate — Mayne's argument might be more persuasive. Further, the passage in the asserted patents to which Mayne cites for its argument that calcium trisodium DTPA cannot be the edetate in the claims is a discussion of the Glen UK patent (PX 1, Col. 3, lines 33-41), not the claimed invention. Thus, this passage did not result in a disclaimer of calcium trisodium DTPA or any other equivalent of edetate.
Further, despite Mayne's patent covering its accused formulation, a finding of infringement under the doctrine of equivalents is not precluded. Fiskars, 221 F.3d at 1324;Bio-Technology, 80 F.3d at 1559. Although the existence of a patent covering Mayne's formulation may be one factor to consider in the equivalence analysis, see Fiskars, 221 F.3d at 1324;Hoechst Celanese Corp. v. BP Chem. Ltd., 78 F.3d 1575, 1582 (Fed. Cir. 1996), it does not outweigh the substantial evidence of equivalence between Mayne's calcium trisodium DTPA and the claimed edetate.
This Court concludes that the differences between calcium trisodium DTPA and the claimed edetate are insubstantial to one of ordinary skill in the art because calcium trisodium DTPA satisfies the "function-way-result" test. See Lighting World, Inc. v. Birchwood Lighting, Inc., 382 F.3d 1354, 1357 (Fed. Cir. 2004); Boehringer Ingelheim, 320 F.3d at 1351 ("Under the doctrine of equivalents, a claim limitation not literally met may be satisfied by an element of the accused product if the differences between the two are `insubstantial' to one of ordinary skill in the art."). Thus, the calcium trisodium DTPA in Mayne's generic propofol emulsion is equivalent to edetate in the asserted claims.
Accordingly, this Court concludes that Mayne's generic propofol formulation infringes Claims 1-14, 16-32 and 34 of the asserted patents as well as Claims 38 and 39 of the '520 patent under the doctrine of equivalents.
An issued patent is presumed valid. 35 U.S.C. § 282. Thus, the accused infringer bears the burden of proving invalidity by clear and convincing evidence. 35 U.S.C. § 282;Glaxo Group Ltd. v. Apotex, Inc., 376 F.3d 1339, 1348 (Fed. Cir. 2004); Oakley, Inc. v. Sunglass Hut Int'l, 316 F.3d 1331, 1339 (Fed. Cir. 2003). The burden of proving invalidity "is `especially difficult' when, as is the present case, the infringer attempts to rely on prior art that was before the patent examiner during prosecution." Glaxo, 376 F.3d at 1348 (quoting Al-Site Corp. v. VSI Int'l Inc., 174 F.3d 1308, 1323 (Fed. Cir. 1999)); Hewlett-Packard Co. v. Bausch Lomb Inc., 909 F.2d 1464, 1467 (Fed. Cir. 1990); see Am. Hoist Derrick Co. v. Sowa Sons, Inc., 725 F.2d 1350, 1359 (Fed. Cir. 1984).
This Court concludes that the asserted patents comply with 35 U.S.C. § 112. See also AstraZeneca, 352 F. Supp. 2d at 414.
A patent claim is invalid if the invention is anticipated by a public use or prior art reference — that is, if each limitation of that claim is found, either expressly or inherently, in a single public use or prior art reference. 35 U.S.C. § 102(a);Akamai Techs., Inc. v. Cable Wireless Internet Servs., Inc., 344 F.3d 1186, 1192-93 (Fed. Cir. 2003); Scripps Clinic Research Found. v. Genentech, Inc., 927 F.2d 1565, 1576-77 (Fed. Cir. 1991). "[T]he dispositive question regarding anticipation is whether one skilled in the art would reasonably understand or infer from the prior art reference's teaching that every claim [limitation] was disclosed in that single reference." Dayco Prods., Inc. v. Total Containment, Inc., 329 F.3d 1358, 1368 (Fed. Cir. 2003) (internal quotation marks and alterations omitted).
"[A] prior art reference may anticipate when the claim limitation or limitations not expressly found in the reference are nonetheless inherent in it." MEHL/Biophile Int'l Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999). "Under the principles of inherency, if the prior art necessarily functions in accordance with, or includes, the claimed limitations, it anticipates." Atlas Powder Co. v. Ireco, Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999). It is irrelevant that those of ordinary skill in the art failed to recognize the inherent characteristics. In re Cruciferous Sprouts Litig., 301 F.3d 1343, 1350 (Fed. Cir. 2002); Atlas Powder, 190 F.3d at 1347. Rather, "the discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." Atlas Powder, 190 F.3d at 1347 (citations omitted). Further, a claim element reciting a numerical range is anticipated by a reference that discloses any portion of that range. Scaltech, Inc. v. Retec/Tetra, LLC, 269 F.3d 1321, 1330 (Fed. Cir. 2001); Titanium Metals Corp. of Am. v. Banner, 778 F.2d 775, 782 (Fed. Cir. 1985) ("It is also an elementary principle of patent law that when, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is `anticipated' if one of them is in the prior art.").
Anticipation is a question of fact, Elan Pharm., Inc. v. Mayo Found. for Med. Educ. Research, 346 F.3d 1051, 1054 (Fed. Cir. 2003), as is the question of whether a prior art reference inherently discloses a patent claim limitation, Atlas Powder, 190 F.3d at 1346.
The USPTO considered the Glen UK patent on which Mayne relies for its anticipation argument, and concluded that it did not teach the claimed invention. As already noted, the Glen UK patent does not address the problem of microbial contamination or suggest adding a small amount of edetate to an oil-in-water emulsion to retard microbial growth. There is no mention in the Glen UK patent of the claimed test to determine whether growth had been sufficiently retarded or of the methods claimed in the '355 and '356 patents. Thus, because there is no evidence that the Glen UK patent's compositions control microbial growth, they do not practice the methods claimed in the '355 and '356 patents.See Merck Co. v. Teva Pharmaceuticals USA, Inc., 347 F.3d 1367, 1372 (Fed. Cir. 2003).
Moreover, Examples 2 and 3 in the Glen UK patent do not disclose propofol dissolved in a water-immiscible solvent, a requirement of each of the asserted claims. Further, those exemplary formulations in the Glen UK patent do not involve an oil-in-water emulsion, but instead a micro-emulsion. In view of the substantial differences between the disclosure in the Glen UK patent and the claimed propofol formulation, this Court concludes that the principle of inherency is inapplicable. See Trintec Indus., Inc. v. Top-U.S.A. Corp., 295 F.3d 1292, 1295 (Fed. Cir. 2002) (noting that inherency applies when the missing element is "necessarily present" in the prior art). Because the Glen UK patent, at best, provides "a place to start for formulators" (Tr. at 694-95, 830-32), it does not anticipate. Dewey Almy Chem. Co. v. Mimex Co., 124 F.2d 986, 989 (2d Cir. 1942) (L. Hand, J.) ("If the earlier disclosure offers no more than a starting point for further experiments, if its teaching will sometimes succeed and sometimes fail, it does not inform the art without more how to practice the new invention . . . and it is not an anticipation."); Akzo N.V. v. United States, Int'l Trade Comm'n, 808 F.2d 1471, 1479 (Fed. Cir. 1986); see In re Arkley, 455 F.2d 586, 587-88 (C.C.P.A. 1972).
Accordingly, this Court concludes that the Glen UK patent does not anticipate the claimed invention.
A patent claim is invalid if "the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains." 35 U.S.C. § 103(a); Merck v. Teva, 395 F.3d 1364, 1372-78 (Fed. Cir. 2005);Ryko Mfg. Co. v. Nu-Star, Inc., 950 F.2d 714, 716 (Fed. Cir. 1991). Unlike anticipation, an obviousness inquiry involves examining the combination of elements in multiple prior art references. The ultimate determination of obviousness is a question of law that turns on the underlying facts. Sandt Tech. Ltd. v. Resco Metal Plastics Corp., 264 F.3d 1344, 1354 (Fed. Cir. 2001). The fact finder must consider "1) the scope and content of the prior art; 2) the differences between the prior art devices and the claimed invention; 3) the level of ordinary skill in the art; and 4) objective considerations, such as commercial success, long felt need, failure of others, and copying." Sandt, 264 F.3d at 1354 (citing Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966)); Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc., 231 F.3d 1339, 1343 (Fed. Cir. 2000);Ecolochem, Inc. v. S. Cal. Edison Co., 227 F.3d 1361, 1371 (Fed. Cir. 2000).
For a patent to be invalid for obviousness based "on a combination of prior art references, there must be some teaching, suggestion, or motivation to combine the references." In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998) (citing In re Geiger, 815 F.2d 686, 688 (Fed. Cir. 1987)); ACS Hosp. Sys., Inc. v. Montefiore Hosp., 732 F.2d 1572, 1577 (Fed. Cir. 1984). Such motivation must be established by clear and convincing evidence. In re Dembiczak, 175 F.3d 994, 999 (Fed. Cir. 1999);In re Rouffet, 149 F.3d at 1357-58. The suggestion to combine references may flow from the problem itself, see Pro-Mold Tool Co. v. Great Lakes Plastics, Inc., 75 F.3d 1568, 1573 (Fed. Cir. 1996), or from "teachings of the prior art, and the knowledge of persons of ordinary skill in the art." In re Rouffet, 149 F.3d at 1357. Thus, "[w]hen determining the patentability of a claimed invention which combines two known elements, `the question is whether there is something in the prior art as a whole to suggest the desirability, and thus the obviousness, of making the combination.'" In re Beattie, 974 F.2d 1309, 1311-12 (Fed. Cir. 1992) (quoting Lindemann Maschinenfabrik GMBH v. American Hoist Derrick Co., 730 F.2d 1452, 1462 (Fed. Cir. 1984)).
35 U.S.C. § 102, as limited by 35 U.S.C. § 103(c), defines prior art for purposes of an obviousness analysis. Only "analogous art" may be considered. See Wang Labs., Inc. v. Toshiba Corp., 993 F.2d 858, 864 (Fed. Cir. 1993); In re Clay, 966 F.2d 656, 658-59 (Fed. Cir. 1992). To constitute analogous art, a prior art reference must (1) be "from the same field of endeavor [as the invention], regardless of the problem addressed," and (2) if the reference is not from the same field, it must be "reasonably pertinent to the particular problem with which the inventor is involved." In re Clay, 966 F.2d at 658-59. A reference is reasonably pertinent if it "`logically would have commended itself to an inventor's attention in considering his problem.'" Wang, 993 F.2d at 864 (quoting In re Clay, 966 F.2d at 659).
Thus, the '701 patent and its file history, which is not analogous art, need not be considered.
The claimed invention as a whole must be compared to the prior art as a whole, Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1383 (Fed. Cir. 1986); Hodosh v. Block Drug Co., 786 F.2d 1136, 1143 n. 5 (Fed. Cir. 1986), and courts must avoid aggregating pieces of prior art through hindsight which would not have been combined absent the inventors' insight. See Monarch Knitting Mach. Corp. v. Sulzer Morat GmbH, 139 F.3d 877, 880 (Fed. Cir. 1998); W.L. Gore Assocs., Inc. v. Garlock, Inc., 721 F.2d 1540, 1552-53 (Fed. Cir. 1983) ("To imbue one of ordinary skill in the art with knowledge of the invention in suit, when no prior art reference or references of record convey or suggest that knowledge, is to fall victim to the insidious effect of a hindsight syndrome wherein that which only the inventor taught is used against its teacher."). As a further check against hindsight analysis, the Court must consider "secondary considerations" of nonobviousness. Ruiz v. A.B. Chance Co., 234 F.3d 654, 662-63, 667 (Fed. Cir. 2000). These considerations include evidence of commercial success, long-felt but unsolved need for the invention, unexpected results and copying by the infringer. Dann v. Johnston, 425 U.S. 219, 230 n. 4 (1976); Graham, 383 U.S. at 17; Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1378 (Fed. Cir. 2005); Ruiz, 234 F.3d at 667.
Based on the evidence, this Court concludes that Mayne has not established by clear and convincing evidence that there is a suggestion in the art to combine any prior art reference with the Glen UK patent, or that one of ordinary skill in the art would be motivated to make such a combination. While Mayne proffered evidence to show that the individual elements of the claimed invention were known in the art, the prior art does not suggest the addition of edetate to an oil-in-water emulsion for injection in human patients. It is irrelevant that the individual elements of a claim are known, unless there is a suggestion to combine them. Life Techs., Inc. v. Clontech Labs., Inc., 224 F.3d 1320, 1326 (Fed. Cir. 2000) ("It is axiomatic that a claimed invention is not obvious solely because it is composed of elements that are all individually found in the prior art. . . . For the Johnson article to render the claimed invention obvious, there must have been, at the time the invention was made, a reasonable expectation of success in applying Johnson's teachings."); Jones v. Hardy, 727 F.2d 1524, 1529-30 (Fed. Cir. 1984).
The pertinent prior art on which Mayne relies was before the Patent Examiner. As Goldberg opined prior to this litigation, the patentees "legitimate[ly]" distinguished [the prior art] from the claimed inventions," and, as a result, "a properly informed Court would find this cited art insufficient to invalidate the claims." (Tr. at 537-39; JX 25 at FPC251527-29; JX 26 at FPC252294.) Finally, evidence of Modified Diprivan's commercial success and ESI's configuring its formulation by using the claimed invention as a blueprint further establish nonobviousness. Dann, 425 U.S. at 230 n. 4; Graham, 383 U.S. at 17; Syntex (U.S.A.), 407 F.3d at 1378; Ruiz, 234 F.3d at 667.
Accordingly, this Court concludes that the asserted claims would not have been obvious at the time those inventions were made.
A patent may be unenforceable if it is the product of inequitable conduct. "Inequitable conduct occurs when a patent applicant breaches his or her `duty of candor and good faith' to the PTO." Novo Nordisk Pharms., Inc. v. Bio-Technology Gen. Corp., ___ F.3d ___, 2005 WL 2443857, at *10 (Fed. Cir. Oct. 05, 2005) (quoting 37 C.F.R. § 1.56(a)); see Bruno Indep. Living Aids, Inc. v. Acorn Mobility Servs., Ltd., 394 F.3d 1348, 1351 (Fed. Cir. 2005). "Inequitable conduct requires proof that a patent applicant did not disclose material information to the PTO with intent to deceive." CFMT, Inc. v. YieldUp Int'l Corp., 349 F.3d 1333, 1340 (Fed. Cir. 2003) (citing Kingsdown Med. Consultants, Ltd. v. Hollister Inc., 863 F.2d 867, 872 (Fed. Cir. 1988)). Inequitable conduct may include an "affirmative misrepresentation of a material fact, failure to disclose material information, or submission of false material information, coupled with an intent to deceive." Molins PLC v. Textron, Inc., 48 F.3d 1172, 1178 (Fed. Cir. 1995); see also CFMT, 349 F.3d at 1340. "Both intent and materiality are questions of fact that must be proven by clear and convincing evidence." Dayco Prods., 329 F.3d at 1362; see CFMT, 349 F.3d at 1340.
The inequitable conduct analysis is performed in two steps: "first, a determination of whether the [conduct] meets a threshold level of materiality and intent to mislead, and second, a weighing of the materiality and intent in light of all the circumstances to determine whether the applicant's conduct is so culpable that the patent should be held unenforceable." Purdue Pharma L.P. v. Boehringer Ingelheim GMBH, 237 F.3d 1359, 1366 (Fed. Cir. 2001) (internal quotations and alterations omitted);Dayco Prods., 329 F.3d at 1363. If one claim of a patent is found unenforceable on grounds of inequitable conduct, the entire patent is unenforceable. J.P. Stevens Co. v. Lex Tex Ltd., 747 F.2d 1553, 1561 (Fed. Cir. 1984).
Under 37 C.F.R. § 1.56(b), information is material if it is "not cumulative to information already of record" and (1) establishes a prima facie case of unpatentability of a claim or (2) refutes or is inconsistent with a position taken by the applicant (i) in response to an argument of unpatentability by the PTO or (ii) in asserting patentability. See Purdue Pharma L.P. v. Endo Pharms. Inc., 410 F.3d 690, 696 (Fed. Cir. 2005); Bruno Indep., 394 F.3d at 1352-53; Dayco Prods., 329 F.3d at 1363-64. A withheld prior art reference may be highly material when it discloses a more complete combination of relevant features, even if those features are before the patent examiner in other references. Molins, 48 F.3d at 1180. However, information that does not affect patentability is not material.See Frazier v. Roessel Cine Photo Tech, Inc., 417 F.3d 1230, 1237-39 (Fed. Cir. 2005) (holding that because an advertisement did not affect patentability, the patentees' failure to disclose it was not material); Northern Telecom, Inc. v. Datapoint Corp., 908 F.2d 931, 940 (Fed. Cir. 1990) ("Since the Viatron 21 device was not prior art, it was not material to patentability."); Envtl. Designs, Ltd. v. Union Oil Co. of Cal., 713 F.2d 693, 698 (Fed. Cir. 1983) ("There was no duty . . . to bring to the attention of the [USPTO] the Riesenfeld disclosure because it was a mere `conception' and was admittedly not prior art."). "An applicant can not be guilty of inequitable conduct if the reference was cited to the examiner, whether or not it was a ground of rejection by the examiner." Fiskars, Inc. v. Hunt Mfg. Co., 221 F.3d 1318, 1327 (Fed. Cir. 2000); see 37 C.F.R. § 1.56(a). The Patent Examiner is presumed to have read and understood the art cited during the prosecution of a patent.Am. Hoist, 725 F.2d at 1359. Arguments by patentees advocating a particular interpretation of the prior art, "which the [Patent] Examiner [is] free to accept or reject," do not rise to the level of a material misrepresentation. See Life Techs., 224 F.3d at 1326.
"According to the [USPTO's] notice of final rulemaking, the rule change applied to all applications pending or filed after March 16, 1992." Bruno Indep., 394 F.3d at 1352 (citing Duty of Disclosure, 57 Fed. Reg. 2021 (Jan. 17, 1992)).
"Intent need not, and rarely can, be proven by direct evidence." Merck Co. v. Danbury Pharmacal, Inc., 873 F.2d 1418, 1422 (Fed. Cir. 1989). "Rather, in the absence of a credible explanation, intent to deceive is generally inferred from the facts and circumstances surrounding a knowing failure to disclose material information." Bruno Indep., 394 F.3d at 1354 (citing Paragon Podiatry Lab., Inc. v. KLM Labs. Inc., 984 F.2d 1182, 1193 (Fed. Cir. 1993)). An inference of intent to deceive is based on the totality of the circumstances, including the nature of the conduct and evidence of the presence or absence of good faith. Li Second Family L.P. v. Toshiba Corp., 231 F.3d 1373, 1379-80 (Fed. Cir. 2000); Perseptive Biosys., Inc. v. Pharmacia Biotech., Inc., 225 F.3d 1315, 1321-22 (Fed. Cir. 2000). Gross negligence alone is insufficient to establish intent. Kingsdown, 863 F.2d at 876; see Baxter Int'l, Inc. v. McGaw, Inc., 149 F.3d 1321, 1329 (Fed. Cir. 1998).
"As a general principle, materiality and intent are balanced — a lesser quantum of evidence of intent is necessary when the omission or misrepresentation is highly material, and vice versa." Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1358 (Fed. Cir. 2003); see Li Second Family, 231 F.3d at 1378 ("The more material the information misrepresented or withheld by the applicant, the less evidence of intent will be required in order to find that inequitable conduct has occurred."). "At the same time, however, there must be some threshold showing of intent to be balanced; [courts] will not find inequitable conduct on an evidentiary record that is completely devoid of evidence of the patentee's intent to deceive the [USPTO]." Amgen, 314 F.3d at 1358.
Finally, "[w]hen both materiality and deceptive intent have been established by clear and convincing evidence, decision of the ultimate issue of inequitable conduct is within the discretion of the district court." Norian Corp. v. Stryker Corp., 363 F.3d 1321, 1331 (Fed. Cir. 2004); Monsanto Co. v. Bayer Bioscience N.V., 363 F.3d 1235, 1239 (Fed. Cir. 2004) ("Once the challenger has shown the requisite levels of materiality and intent, the district court must balance the equities to determine whether the patentee has committed inequitable conduct that warrants holding the patent unenforceable.").
This Court concludes that information relating to AstraZeneca's internal unpublished work on formulations that retarded microbial growth without the use of edetate was not material to the prosecution of the asserted patents. First, these works were not prior art under 35 U.S.C. § 102. Second, even if AstraZeneca's internal unpublished work was prior art, it would be irrelevant to the claims of the patents, since the claimed formulations require edetate. Mayne's suggestion that AstraZeneca should have informed the Patent Examiner of propofol's antimicrobial properties misses the mark because that information was part of the record before the USPTO. Moreover, even if the information was not before the USPTO, it is irrelevant to the claims which relate to the antimicrobial properties of edetate — not propofol.
With respect to Mayne's contention that AstraZeneca made improper arguments to the USPTO to distinguish the Glen UK patent and the Patel reference, Rule 56(a) states that the duty of disclosure "is deemed to be satisfied" if all material information is cited in an Information Disclosure Statement or Form 1449. Fiskars, 221 F.3d at 1327. There is no dispute that the Glen UK patent and the Patel reference were both disclosed to the USPTO. The patentees' interpretation regarding the prior art references do not constitute material misrepresentations because the Patent Examiner was free to accept or reject those arguments and draw his own conclusions from the prior art before him. See Life Techs., 224 F.3d at 1326.
In any event, there is no evidence of the patentees' intent to deceive the USPTO. Even if this Court were to conclude that AstraZeneca withheld material information, this Court cannot infer a bad faith intent from such a failure to disclose without some additional evidence. Amgen, 314 F.3d at 1358. Accordingly, because this Court concludes that the patentees are not guilty of inequitable conduct, the asserted patents are enforceable.
This Court declines Mayne's invitation to infer intent to deceive from Mr. Platt's failure to testify at trial. Prior to the trial, this Court denied Mayne's motion to compel Mr. Platt's attendance because he lives in Great Britain — beyond the subpoena power of the Court, and because Mr. Platt is not a current AstraZeneca employee. See Fed.R.Civ.P. 45(c)(3);Price Waterhouse LLP v. First Am. Corp., 182 F.R.D. 56, 61 (S.D.N.Y. 1998); Zeeck v. Melina Taxi Co., 177 A.D.2d 692, 694, 576 N.Y.S.2d 878 (2d Dep't 1991). Because Mayne was allowed to use Mr. Platt's video deposition at trial, there was no prejudice to Mayne.
In exceptional cases, the Court may award reasonable attorney fees to the party prevailing in a patent infringement action. 35 U.S.C. § 285. The determination of whether a case is exceptional is a factual determination for which the patentee bears the burden of proof by clear and convincing evidence. Crystal Semiconductor Corp. v. TriTech Microelectronics Int'l, Inc., 246 F.3d 1336, 1351 (Fed. Cir. 2001); Yamanouchi Pharm., 231 F.3d at 1346-47. To determine whether a case is exceptional, a trial court must look at the totality of the circumstances.Yamanouchi, 231 F.3d at 1347.
As discussed above, 35 U.S.C. § 271(e)(2) creates an artificial act of infringement for purposes of establishing jurisdiction in the federal courts. Thus, the mere filing of "an ANDA application or certification cannot support a finding of willful infringement for purposes of awarding attorney's fees." Glaxo Group Ltd. v. Apotex, Inc., 376 F.3d 1339, 1350-51 (Fed. Cir. 2004). Similarly, the making of Paragraph IV Certifications cannot support a finding of willful infringement. See Aventis Pharm. v. Cobalt Pharm., Inc., 355 F. Supp. 2d 586, 590-93 (D. Mass. 2005). However, the filing of an ANDA along with other misconduct may support a finding that a case is exceptional for purposes of 35 U.S.C. § 285. See Yamanouchi, 231 F.3d at 1346-47. Such misconduct may "include willful infringement, . . . offensive litigation tactics, vexatious or unjustified litigation, or frivolous filings." Yamanouchi, 231 F.3d at 1346-47; see also Phonometrics, Inc. v. Westin Hotel Co., 350 F.3d 1242, 1246-48 (Fed. Cir. 2003).
Even if a court finds a case "exceptional" under the statute, it must exercise discretion in determining whether an award of attorney fees is warranted. See Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362, 1370 (Fed. Cir. 1999); see also Graco, Inc. v. Binks Mfg. Co., 60 F.3d 785, 794-95 (Fed. Cir. 1995) ("A finding by a court that a case is exceptional is a factual determination . . . whereas the decision to award fees is discretionary."). A number of factors determine whether attorney's fees are appropriate, including the "closeness of the case, tactics of counsel, the conduct of the parties and any other factors that may contribute to a fairer allocation of the burdens of litigation as between winner and loser." J.P. Stevens Co. v. Lex Tex Ltd., 822 F.2d 1047, 1051 (Fed. Cir. 1987). Thus, "[a]ttorney fees are not to be routinely assessed against a losing party in litigation in order to avoid penalizing a party `for merely defending or prosecuting a lawsuit,' and are awarded to avoid a gross injustice." Revlon, Inc. v. Carson Prods. Co., 803 F.2d 676, 679 (Fed. Cir. 1986) (quoting Fleischmann Distilling Corp. v. Maier Brewing Co., 386 U.S. 714, 718 (1967)).
Mayne's filing of the ANDA was not improper merely because two attorneys disagreed on one legal issue (i.e., validity of the asserted patents), especially when all involved attorneys uniformly concluded that the product of the ANDA would not infringe the asserted patents. See American Med. Sys., Inc. v. Med. Eng'g Corp., 6 F.3d 1523, 1530 (Fed. Cir. 1993) ("A finding of willfulness requires the fact-finder to find that clear and convincing evidence shows `that the infringer acted in disregard of the patent . . . [and] had no reasonable basis for believing it had a right to do the acts.'" (quoting Stickle v. Heublein, Inc., 716 F.2d 1550, 1565 (Fed. Cir. 1983))); Hall v. Aqua Queen Mfg., Inc., 93 F.3d 1548, 1555 (Fed. Cir. 1996) ("The test of willful infringement is `whether, under all the circumstances, a reasonable person would prudently conduct himself with any confidence that a court might hold the patent invalid or not infringed.'" (quoting State Indus., Inc. v. Mor-Flo Indus., Inc., 883 F.2d 1573, 1581 (Fed. Cir. 1989) (emphasis added)).
In light of Mayne's reliance on its counsels' opinion letters, AstraZeneca has not provided clear and convincing evidence that Mayne's ANDA was improper. See Comark Commc'ns, Inc. v. Harris Corp., 156 F.3d 1182, 1191 (Fed. Cir. 1998) ("It is well settled that an important factor in determining whether willful infringement has been shown is whether or not the infringer obtained the opinion of counsel."); In re Mahurkar Patent Litig., 831 F. Supp. 1354, 1395 (N.D. Ill. 1993), aff'd, 71 F.3d 1573 (Fed. Cir. 1995) ("[I]t [is] particularly difficult to infer willfulness when a layman receives and acts on legal advice."). Indeed, "cases where willful infringement is found despite the presence of an opinion of counsel generally involve situations where the opinion of counsel was either ignored or found to be incompetent." Read Corp. v. Portec, Inc., 970 F.2d 816, 829 (Fed. Cir. 1992). Here, Mayne did not ignore its counsels' opinions and AstraZeneca has not provided clear and convincing evidence that the Heller, Meloro and Goldberg opinion letters were incompetent.
Finally, Mayne's litigation conduct has not been baseless. While Mayne defended itself vigorously against charges of infringement and challenged the validity of the asserted patents, it did so with a good faith basis for each legal position advanced. See, e.g., Knorr-Bremse Systeme Fuer Nutzfahrzeuge GmbH v. Dana Corp., 372 F. Supp. 2d 833, 851-52 (E.D. Va. 2005);Mosinee Paper Corp. v. James River Corp. of Virginia, 22 U.S.P.Q.2d 1657, 1664 (E.D. Wis. 1992) (noting that the case was "not tried according to the usual patent case Marquis of Queensberry rules"); Morgan Adhesives Co. v. Chemtrol Adhesives, Inc., 574 F. Supp. 832, 836 (N.D. Ohio 1983), aff'd, 765 F.2d 158 (Fed. Cir. 1985); Leinoff v. Louis Milona Sons, Inc., 556 F. Supp. 280, 284 (S.D.N.Y. 1983), rev'd on other grounds, 726 F.2d 734 (Fed. Cir. 1984) ("There may well be some merit to plaintiff's assertion that defendant was not justified in challenging this court's prior finding of the validity of plaintiff's patent. However, there is no evidence of bad faith, and this court is not willing to discourage attorneys from that vigorous representation of clients which their Code of Professional Responsibility demands of them.").
Therefore, this case is not exceptional under 35 U.S.C. § 285 and an award of attorney fees is not warranted.
Accordingly, this Court concludes that (1) Mayne's generic propofol formulation literally infringes Claims 1 and 3-14 of the asserted patents as well as Claim 38 of the '520 patent; (2) Mayne's generic propofol formulation infringes Claims 1-14, 16-32 and 34 of the asserted patents as well as Claims 38 and 39 of the '520 patent under the doctrine of equivalents; (3) the asserted claims are valid; (4) the asserted patents are enforceable; and (5) this case is not exceptional under 35 U.S.C. § 285.
The foregoing constitutes this Court's findings of fact and conclusions of law as required by Rule 52 of the Federal Rules of Civil Procedure.
The parties are directed to submit a final judgment consistent with this Opinion and Order within seven (7) business days.

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