NOTE: This disposition is nonprecedential.
United States Court of Appeals for the Federal Circuit
IN RE OMEPRAZOLE PATENT LITIGATION
----------------------------------------------------------------
2007-1476, -1477, -1478
ASTRAZENECA AB, AKTIEBOLAGET HASSLE,
KBI-E, INC., KBI, INC., and ASTRAZENECA LP,
Plaintiffs-Appellants,
v.
MYLAN LABORATORIES, INC., MYLAN PHARMACEUTICALS, INCORPORATED,
ESTEVE QUIMICA, S.A., and LABORATORIOS DR. ESTEVE, S.A.,
Defendants-Appellees.
Errol B. Taylor, Milbank, Tweed, Hadley & McCloy, LLP, of New York, New York,
argued for plaintiffs-appellants. With him on the brief were Fredrick M. Zullow, John M.
Griem, Jr., Lawrence T. Kass, Claire A. Gilmartin, and Emily J. Kunz.
James H. Wallace, Jr., Wiley Rein LLP, of Washington, DC, argued for
defendants-appellees. With him on the brief was Mark A. Pacella.
Appealed from: United States District Court for the Southern District of New York
Judge Barbara S. Jones.
NOTE: This disposition is nonprecedential.
United States Court of Appeals for the Federal Circuit
IN RE OMEPRAZOLE PATENT LITIGATION
---------------------------------------------------------------
2007-1476, -1477, -1478
ASTRAZENECA AB, AKTIEBOLAGET HASSLE,
KBI-E, INC., KBI, INC., and ASTRAZENECA LP,
Plaintiffs-Appellants,
v.
MYLAN LABORATORIES, INC., MYLAN PHARMACEUTICALS, INCORPORATED,
ESTEVE QUIMICA, S.A., and LABORATORIOS DR. ESTEVE, S.A.,
Defendants-Appellees.
Appeals from the United States District Court for the Southern District of
New York in Cases No. 00-CV-6749, 03-CV-6057, and M21-81, Judge
Barbara S. Jones.
_____________________
DECIDED: June 10, 2008
_____________________
Before LOURIE, BRYSON, and GAJARSA, Circuit Judges.
LOURIE, Circuit Judge.
Astrazeneca, AB, Aktiebolaget Hassle, KBI-E, Inc., KBI, Inc., and Astrazeneca
LP (collectively “Astra”) appeal from the decision of the U.S. District Court for the
Southern District of New York, following a bench trial, finding noninfringement of U.S.
Patents 4,786,505 (“the ’505 patent”) and 4,853,230 (“the ’230 patent”) by Mylan
Laboratories, Inc., Mylan Pharmaceuticals, Incorporated (collectively “Mylan”), Esteve
Quimica, S.A., and Laboratorios Dr. Esteve, S.A. (collectively “Esteve”). Because Astra
fails to identify any reversible error, we affirm.
BACKGROUND
Astra is the owner of the ’505 and ’230 patents, both of which relate to oral
pharmaceutical preparations for omeprazole. Omeprazole is the active ingredient in
Prilosec®, a widely prescribed drug marketed by Astra that can be used to treat gastric
and duodenal ulcers by inhibiting the production of gastric acid. Omeprazole is difficult
to formulate, however, because it is acid-labile; i.e., it is susceptible to degradation in
acid-reacting and neutral media. In order to prevent degradation in the stomach,
omeprazole must be protected from acidic gastric juices. In addition, omeprazole
suffers from other formulation problems, including sensitivity to heat, organic solvents,
moisture, and light.
Astra scientists developed an oral dosage form of omeprazole that overcomes
those formulation problems. They developed an oral formulation that includes, inter
alia, a core containing omeprazole and an alkaline reacting compound (“ARC”), a water
soluble subcoat, and an enteric coating. Astra’s formulation led to the patents in suit.
Claim 1 of the ’505 patent, a representative claim, reads as follows:
1. An oral pharmaceutical preparation comprising
(a) a core region comprising an effective amount of a material selected
from the group consisting of omeprazole plus an alkaline reacting
compound, an alkaline omeprazole salt plus an alkaline reacting
compound and an alkaline omeprazole salt alone;
2007-1476, -1477, -1478 2
(b) an inert subcoating which is soluble or rapidly disintegrating in water
disposed on said core region, said subcoating comprising one or more
layers of materials selected from among tablet excipients and polymeric
film-forming compounds; and
(c) an outer layer disposed on said subcoating comprising an enteric
coating.
’505 patent claim 1 (emphasis added). The ’230 patent claims a broader selection of
active ingredients. Claim 1 of the ’230 patent reads as follows:
1. A pharmaceutical preparation comprising:
(a) an alkaline reacting core comprising an acid-labile pharmaceutically
active substance and an alkaline reacting compound different from said
active substance, an alkaline salt of an acid labile pharmaceutically active
substance, or an alkaline salt of an acid labile pharmaceutically active
substance and an alkaline reacting compound different from said active
substance;
(b) an inert subcoating which rapidly dissolves or disintegrates in water
disposed on said core region, said subcoating comprising one or more
layers comprising materials selected from the group consisting of tablet
excipients, film-forming compounds and alkaline compounds; and
(c) an enteric coating layer surrounding said subcoating layer, wherein the
subcoating layer isolates the alkaline reacting core from the enteric
coating layer such that the stability of the preparation is enhanced.
’230 patent claim 1 (emphasis added).
Mylan filed an Abbreviated New Drug Application on May 17, 2000, seeking
approval from the Food and Drug Administration (“FDA”) to market its 10 mg, 20 mg,
and 40 mg generic versions of Prilosec® (collectively “Mylan’s products”). Astra brought
suit against Mylan and Esteve (collectively “Mylan/Esteve”), along with several other
generic defendants, in the United States District Court for the Southern District of New
York, alleging infringement under the Hatch-Waxman Act. Those suits were
2007-1476, -1477, -1478 3
consolidated in a multi-district litigation for discovery and ultimately tried in two waves. 1
Astra’s case against Mylan/Esteve was tried during the second wave litigation.
During the course of litigation, the FDA granted approval of Mylan’s 10 mg and
20 mg formulations and tentative approval of the 40 mg formulation on June 2, 2003.
Mylan began selling its 10 mg and 20 mg formulations in the United States in August
2003. Mylan’s products consist of “(1) an inert sugar/starch sphere; (2) an active
coating of omeprazole, talc, and hydroxypropyl methylcellulose (“HPMC”) (“Film Coating
No. 1” or “active drug layer”); (3) a subcoating of HPMC, talc, and titanium dioxide (“Film
Coating No. 2”); (4) a second subcoating of HPMC and ethylcellulose (“Film Coating No.
3”); and (5) an enteric coating of methacrylic acid copolymer, triethylcitrate, and talc (the
“enteric coating”).” In re Omeprazole Patent Litig., 490 F. Supp. 2d 381, 425 (S.D.N.Y.
2007) (emphasis added). At issue in this appeal is the talc that is used in the active
drug layer of Mylan’s products.
After a forty-two day bench trial, the district court determined, inter alia, that
Mylan/Esteve did not infringe either of the asserted patents. Id. In reaching its
conclusion, the court held that Astra failed to show that Mylan/Esteve’s omeprazole
products met the limitations of paragraph (a) of claim 1 of the patents in suit. In
particular, the court found that Astra failed to prove by a preponderance of the evidence
that Mylan/Esteve’s products contained an ARC. The court rejected Astra’s assertion
1
The district court held a trial of the first wave defendants from December 2002
through June 2003 and found the patents in suit not invalid and infringed by three of the
four defendants. In 2003, we affirmed the court’s decision. In re Omeprazole Patent
Litigation, Nos. 03-1101 to 03-1106, 03-1131, 03-1132, to 03-1136, 03-1171, 03-1172,
03-1173, slip op. (Fed. Cir. Dec. 11, 2003) (Omeprazole I).
2007-1476, -1477, -1478 4
that carbonates in either the talc or the HPMC, or the triethylamine in the omeprazole,
satisfied the ARC and “effective amount” requirements of the asserted claims.
Astra timely appealed the court’s decision. We have jurisdiction pursuant to 28
U.S.C. § 1295(a)(1).
DISCUSSION
We review “the judgment of a district court following a bench trial ‘for errors of
law and clearly erroneous findings of fact.’” Dow Chem. Co. v. Mee Indus., Inc., 341
F.3d 1370, 1374 (Fed. Cir. 2003) (quoting Allen Eng’g Corp. v. Bartell Indus., Inc., 299
F.3d 1336, 1343-44 (Fed. Cir. 2002)). 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).
The issue on appeal is whether the district court erred in concluding that Astra
failed to prove the presence of an ARC in Mylan’s products. Astra raises several
2007-1476, -1477, -1478 5
arguments, not all of which need to be addressed in light of the conclusions we reach.
Astra primarily argues that the court erred by applying the wrong burden of proof for
infringement, by misapprehending the trial evidence, and by failing to apply the proper
claim construction to Mylan’s products. In response, Mylan/Esteve asserts that the
district court properly applied the correct legal standard, made proper findings of fact
that were not clearly erroneous, and applied the correct claim construction, which we
have previously affirmed on appeal.
We agree with Mylan/Esteve that it does not infringe the two patents. In order to
infringe the patents in suit, the accused products must contain an ARC in the active
core region. Previously, in Omeprazole I, we affirmed the district court’s construction of
an ARC, which was construed as:
(1) a pharmaceutically acceptable alkaline, or basic, substance having a
pH greater than 7 that (2) stabilizes the omeprazole or other acid labile
compound by (3) reacting to create a micro-pH of not less than 7 around
the particles of omeprazole or other acid labile compound.
Id. (quoting Astra Aktiebolag v. Andrx Pharms., Inc., 222 F. Supp. 2d 423, 453
(S.D.N.Y. 2002)).
At trial, Astra argued that the talc used in the active drug layer of Mylan’s
products, viz., Microace® talc, was alkaline and that the source of alkalinity was
carbonates. More specifically, Astra argued that carbonates that are introduced into the
active drug layer through the talc, and not the talc itself, are ARCs as that term is used
in the patents in suit. Indeed, in its briefs on appeal and during oral argument, Astra
repeatedly took the position that Mylan’s products satisfy the ARC requirement based
on the presence of carbonates that are introduced into Mylan’s formulation, rather than
the talc itself. See Astra Reply Br. at 4 (“The issue is not whether talc is an ARC, but
2007-1476, -1477, -1478 6
whether the carbonates that are introduced into Mylan/Esteve’s formulation through
Mylan/Esteve’s particular talc are ARCs.”); see also id. at 14 (“Again the ARC is the
carbonates – not the talc itself.”); id. at 27 (“[I]t is not the talc, but carbonates in
Mylan/Esteve’s Microace talc, that is the ARC.”).
The district court considered and rejected Astra’s assertion. The court primarily
rested its conclusion on its finding that Astra failed to prove the presence of carbonates
in Mylan’s products. In doing so, the court considered the evidence proffered by both
parties relating to the presence or absence of carbonates in the talc. The court first
considered tests that Astra’s expert, Dr. Davies, performed on Mylan’s talc. Those
tests, referred to as attenuated total reflectance Fourier spectroscopy (“ATR-FTIR”) and
energy dispersive x-ray analysis, indicated that carbonates were present in Mylan’s talc
and were the source of the alkalinity of the talc. The court, however, then considered
evidence proffered by Mylan/Esteve, which included tests that were performed by both
Esteve and Nippon, the supplier of Microace® talc, on batches of Mylan’s talc for the
presence of carbonates. The court found that those tests indicated that Mylan’s talc
contained no detectable amount of carbonates. After weighing the competing evidence,
the court found that Astra failed to prove the presence of carbonates in the talc of the
accused products. Omeprazole, 490 F. Supp. 2d at 430 (“Thus, the Court finds that the
empirical evidence of the presence of carbonates in the talc used in Mylan/Esteve’s
product is inconclusive.”). Such a determination is based on the district court’s
factfindings and cannot be overturned unless we find them to be clearly erroneous, and
we do not.
2007-1476, -1477, -1478 7
Astra argues that that finding is flawed because the district court applied the
wrong legal standard. According to Astra, the court misapplied the legal standard by
requiring “conclusive evidence” that carbonates were present in the talc, rather than
preponderant evidence. In addition, Astra asserts that the court applied an incorrect
legal standard a second time during its analysis of another claim limitation by requiring
Astra to dispel any “modicum of doubt” that the micro-pH in the accused omeprazole
containing region is not less than seven. Id. at 441-42. Astra likens the court’s
purported standards to those applied in criminal matters—i.e., proof beyond a
reasonable doubt.
A plain reading of the district court’s decision, however, reveals that the district
judge knew, understood, and applied the proper standard of proof. Indeed, the court
stated:
Plaintiffs bear the burden to prove their claims of infringement by a
preponderance of the evidence. A preponderance of the evidence means
such evidence which, when considered and compared with that opposed
to it, produces a belief that what is sought to be proved is more likely true
than not. The fact that section 271(e)(2) creates an artificial act of
infringement does not lessen that burden.
Id. at 414 (emphasis added); see also id. at 422 (“Demonstration that every limitation of
the claim is . . . met by the accused device [or product] must be shown by a
preponderance of the evidence.”) (quoting Enercon GmbH v. Int’l Trade Comm’n, 151
F.3d 1376, 1384 (Fed. Cir. 1998) (emphasis added)); see also id. at 442 (“Accordingly,
Plaintiffs have failed to show by a preponderance of the evidence that Mylan/Esteve's
product literally contains an ARC.”) (emphasis added). Astra’s focus on the isolated
phrases of “inconclusive” and “modicum of doubt” is insufficient to establish reversible
2007-1476, -1477, -1478 8
error. Given the court’s clear understanding and repeated recitation of the applicable
burden of proof, Astra’s argument is wholly inapt.
Astra argues, in the alternative, that even if the law required conclusive evidence,
it met that burden. Astra asserts that the district court ignored vast amounts of evidence
that showed the presence of carbonates in the talc. Astra’s argument amounts to mere
disagreement with the court’s factual findings, which cannot serve as a basis for
reversing the court. Because we find no clear error with respect to those findings,
Astra’s argument fails.
After concluding that Astra failed to prove the presence of carbonates in the
accused products, the district court made additional findings that served as alternative
grounds for concluding that the ARC limitation was not met. Shifting its focus from
carbonates to the talc itself, the court analyzed whether talc could satisfy the ARC
requirement of the claim. Based on the teachings of the specifications, which indicated
that talc is not an ARC but rather an ordinary additive, and statements that Astra made
during the prosecution of the European counterpart to the ’505 patent, the court found
that it could not. The court pointed out that the patent specifications, which are nearly
identical in this respect, list a number of compounds that can serve as ARCs, not
including talc. Omeprazole, 490 F. Supp. 2d at 430; see also ’505 patent col.3 ll.47-59;
’230 patent col.8 ll.43-55. In contrast, the specifications also list a number of ordinary
excipients, among which is talc. Omeprazole, 490 F. Supp. 2d at 430; see e.g., ’505
patent col.4 ll.54-56, col.5 ll.16-18; ’230 patent col.9 ll.48-50, col.10 ll.10-12. Thus, the
specifications themselves indicate that ARCs do not include talc.
2007-1476, -1477, -1478 9
In addition, during the prosecution of the European counterpart to the ’505
patent, Astra’s patent attorney referred to formulations 1 and 7 of Table 1 of the ’505
patent—formulations that clearly include talc. The attorney argued that those
formulations are “without alkaline compound in the core.” Omeprazole, 490 F. Supp. 2d
at 430. Once again, talc was not considered to be an ARC. Moreover, the court
determined that even if talc could function as an ARC, Astra failed to prove that Mylan’s
products satisfied other limitations of the claim, viz., that the accused products contain
an “effective amount” of talc to stabilize the omeprazole by creating a micro-pH of not
less than seven.
Astra’s remaining arguments raised in its briefs relate to those alternative
grounds offered by the district court in support of its decision. Having determined that
the district court did not clearly err in concluding that Astra failed to prove the threshold
requirement that the accused products contain non-negligible amounts of carbonates,
which, according to Astra, are the ARCs in Mylan’s products, and thus having failed
otherwise to show the presence of an ARC, we need not address Astra’s remaining
arguments as they relate to the court’s alternative grounds for its decision.
CONCLUSION
For the foregoing reasons, we affirm the decision of the district court.
AFFIRMED
2007-1476, -1477, -1478 10
In Re Omeprazole Patent Litigation
Combined Opinion