ENDO PHARMACEUTICALS INC., MALLINCKRODT LLC, Plaintiffs-Appellees
ACTAVIS LLC, FKA ACTAVIS INC., ACTAVIS SOUTH ATLANTIC LLC, TEVA PHARMACEUTICALS USA, INC., Defendants-Appellants
from the United States District Court for the District of
Delaware in No. 1:14-cv-01381-RGA, Judge Richard G. Andrews.
Jay Black, Dechert LLP, Philadelphia, PA, argued for
plaintiffs-appellees. Also represented by Sharon K.
Gagliardi; Blake Greene, Austin, TX; Jonathan Loeb, Mountain
View, CA; Robert Rhoad, Princeton, NJ.
Jeffrey J. Toney, Kasowitz, Benson, Torres & Friedman
LLP, Atlanta, GA, for plaintiff-appellee Mallinckrodt LLC.
Also represented by Rodney R. Miller, Paul Gunter Williams.
C. O'Quinn, Kirkland & Ellis LLP, Washington, DC,
argued for defendants-appellants. Also represented by William
H. Burgess; Charles A. Weiss, Eric H. Yecies, Holland &
Knight, LLP, New York, NY.
Wallach, Clevenger, and Stoll, Circuit Judges.
WALLACH, CIRCUIT JUDGE.
Endo Pharmaceuticals Inc. ("Endo Pharmaceuticals")
and Mallinckrodt LLC ("Mallinckrodt")
(collectively, "Endo") sued Appellants Actavis LLC,
Actavis South Atlantic LLC, and Teva Pharmaceuticals USA,
Inc. (collectively, "Actavis") in the U.S. District
Court for the District of Delaware ("District
Court"), alleging that two Abbreviated New Drug
Applications filed by Actavis infringed claims 1-6 ("the
Asserted Claims") of Mallinckrodt's U.S. Patent No.
8, 871, 779 ("the '779 patent"), which Endo
Pharmaceuticals licenses. The District Court held that
Actavis failed to "prove by clear and convincing
evidence that any of the [A]sserted [C]laims . . . were
invalid" as obvious or anticipated, Endo Pharm. Inc.
v. Actavis Inc., No. 14-1381-RGA, 2017 WL 3731001, at *1
(D. Del. Aug. 30, 2017), and entered final judgment of
infringement, based on a stipulation by Actavis, J.A. 1.
appeals, challenging the invalidity determination. We have
jurisdiction pursuant to 28 U.S.C. § 1295(a)(1) (2012).
"Process for Preparing Morphinan-6-One Products with Low
Levels of α, β-Unsaturated Ketone Compounds,"
the '779 patent generally relates to compounds known as
"morphinan alkaloids," such as
"oxymorphone," which have "great medical
importance" and "are used extensively for pain
relief." '779 patent col. 1 ll. 24-30.
"Morphinan compounds and analogs thereof typically have
a ring structure . . . corresponding to Formula (1)”:
col. 1 ll.38-53. "[P]harmaceutically desirable morphinan
compounds" often "have a ketone group on the C-ring of
Formula (1) and a saturated bond[, i.e., single bond, ]
between the two carbon atoms positioned a and p to the ketone
on the C-ring." Id. col. 2 ll. 21-24.
"[T]hese compounds may be referred to as morphinan-6-one
compounds." Id. col. 2 ll. 28-29. "[T]he
ketone is present on the C(6) carbon atom, with the α
and β carbon atoms being the C(7) and C(8) positions . .
. ." Id. col. 2 ll. 25-26.
describing the prior art, the '779 patent explains that
"[v]arious processes for producing morphinan-6-one
compounds are known," and "many . . . involve some
form of catalytic hydrogenation of α, β-unsaturated ketone
intermediate compounds [('ABUKs')]," i.e.,
applying catalytic hydrogenation to compounds containing
ketone groups with double bonds between the α and
β carbon atoms to convert the double bonds to single
bonds. Id. col. 2 ll. 29- 32. However, "[ABUKs]
may persist as impurities in the final products."
Id. col. 2 ll. 43-45. These hydrogenation processes
also "may tend to undesirably reduce the ketone[, a key
functional part of morphinan-6-one compounds, ] as well as
reducing or removing the α, β-unsaturation."
Id. col. 2 ll. 47-48.
'779 patent discloses "processes for preparing
highly pure morphinan-6-one products" having a
relatively low concentration of ABUKs present as impurities,
which "involve treating a reaction mixture including a
morphinan-6-one compound and an [ABUK] with a
sulfur-containing compound." Id. col. 5 ll.
6-10. These processes can "effectively reduce the
concentration of undesirable [ABUKs] to acceptable
levels," id. col. 5 ll. 11-13, with the process
employing a sulfur-containing compound that can reduce ABUK
concentration "from levels of about 0.5% (by weight) or
more to levels of not more than about 0.1% . . ., or lower
(e.g., about 0.01% . . ., about 0.001% . . ., or lower), with
minimal side reactions, ketone reduction, and/or any other
undesirable effects," id. col. 5 ll. 17-22.
Asserted Claims recite:
1.A hydrochloride salt of oxymorphone comprising less than
0.001% of 14-hydroxymorphinone.
2.The hydrochloride salt of claim 1 comprising less than
0.0005% of 14-hydroxymorphinone.
3. A pharmaceutical acceptable form comprising the
oxymorphone hydrochloride according to claim 1.
4.A hydrochloride salt of a morphinan-6-one compound
corresponding to Formula (2):
comprising less than 0.001% measured by [high performance
liquid chromatography] of an [ABUK] corresponding to Formula
wherein the morphinan-6-one compound is oxymorphone and
wherein X is -N(R17)-;
R1 and R2 are hydrogen;
R3 is hydroxy;
R10 is ...