from the United States District Court for the District of
Delaware in Nos. 1:12-cv-01011-GMS, 1:12-cv-01490-GMS,
1:12-cv-01750-GMS, 1:13-cv-01874-GMS, 1:14-cv-01156-GMS,
1:15-cv-00040-GMS, 1:15-cv-00539-GMS, 1:15-cv-00540-GMS,
1:15-cv-00804-GMS, 1:16-cv-00034-GMS, Judge Gregory M. Sleet.
WILLIAM F. Lee, Wilmer Cutler Pickering Hale and Dorr LLP,
Boston, MA, argued for plaintiff-appellant. Also represented
by Mark Christopher Fleming, Lisa Jon Pirozzolo, Jason H.
Liss, Anna E. Lumelsky, Tasha Joy Bahal, Emily R. Whelan;
Robert M. Galvin, Palo Alto, CA.
J. Meloro, Willkie Farr & Gallagher LLP, New York, NY,
argued for all defendants-appellees. Defendant-appellee
Hospira, Inc. also represented by Michael Johnson.
C. Lombardi, Winston & Strawn LLP, Chicago, IL, for
defendant-appellee Sandoz Inc. Also represented by Kathleen
Bridget Barry, Maureen L. Rurka.
PaulBraier, Greenblum & Bernstein, P.L.C., Reston, VA,
for defendant-appellee Accord Healthcare, Inc. Also
represented by PETER Branko Pejic.
Edward Hood, Polsinelli PC, Chicago, IL, for
defendant-appellee Actavis LLC. Also represented by Mark
Thomas Deming, Khurram Naik; Robyn Ast-Gmoser, St. Louis, MO.
On Kong, Rhodes Attorneys at Law P.C., San Francisco, CA, for
defendants-appellees Mylan Laboratories Limited, Agila
Specialties Inc. Also represented by ELHAM FlROUZl Steiner,
Wilson, Sonsini, Goodrich & Rosati, PC, San Diego, CA.
Harry Weinstein, Budd Larner, P.C., Short Hills, NJ, for
defendants-appellees Dr. Reddy's Laboratories, Ltd., Dr.
Reddy's Laboratories, Inc. Also represented by Ellen
Tchorni Lowenthal, Stuart D. Sender.
C. Hughey, Merchant & Gould P.C., Minneapolis, MN, for
defendants-appellees Sun Pharmaceutical Industries Limited,
Sun Pharma Global FZE. Also represented by Aaron M. Johnson,
Christopher J. Sorenson.
William A. Rakoczy, Rakoczy Molino Mazzochi Siwik LLP,
Chicago, IL, for defendants-appellees Apotex Corp., Apotex
Inc. Also represented by PETER JAMES CURTIN, Thomas Ehrich,
Luke Timothy Shannon.
David Schuman, Carlson, Caspers, Vanden-burgh, Lindquist
& Schuman, P.A., Minneapolis, MN, for defendant-appellee
Teva Pharmaceuticals USA, Inc. Also represented by Jennell
Christine Bilek, Samuel T. Lockner, Alexandra Jane Olson,
Todd S. Werner.
Philip Lessler, Blank Rome LLP, New York, NY, for
defendants-appellees Glenmark Pharmaceuticals Ltd., Glenmark
Generics Ltd., Glenmark Generics Inc., USA. Also represented
by CHRISTOPHER K. Hu, Paul M. Zagar; David Anthony Dorey,
Michael Nelson, Duane Morris LLP, Chicago, IL, for
defendants-appellees Wockhardt Bio AG, Wock-hardt USA LLC.
Also represented by PATRICK Gallagher.
NEWMAN, MAYER, and O'Malley, Circuit Judges.
Newman, Circuit Judge.
Pharmaceuticals, Inc. is the exclusive licensee of U.S.
Patent No. 6, 713, 446 ("the '446 Patent"),
issued March 30, 2004 and assigned to the United States.
Millennium developed the patented product for treatment of
oncology disease, particularly multiple myeloma and mantle
cell lymphoma. The product has the brand name Velcade®.
Appellees in Appeal Nos. 15-2066, 16-1008, 16-1009, 16-1010,
16-1110, 16-1283, and 16-1762 (collectively,
"Sandoz") all filed abbreviated new drug
applications ("ANDAs"), admitting infringement and
seeking to invalidate various claims of the '446 Patent.
Based on the litigation that ensued, the district court held
that claims 20, 31, 49, and 53 of the '446 Patent were
invalid,  leading to this appeal.
filed a notice of appeal in Appeal No. 16-1109 after the
district court entered final judgment against Millennium in
separate cases arising from AN-DAs filed by Apotex and Teva,
based on collateral estoppel arising from the district
court's judgment of invalidity of claims 20, 31, 49, and
53 of the '446 Patent in the Sandoz-Millennium action. We
consolidated the appeals in the Sandoz, Apotex, and Teva
review of the record and the applicable law, we conclude that
the district court erred in the Sandoz litigation and that
invalidity was not established. We reverse and enter judgment
in favor of Millennium in the Sandoz litigation. We also
vacate the district court's judgment in the action
between Millennium, Teva, and Apotex based on our decision in
the Sandoz litigation and remand that action for further
'446 Patent describes the chemical compound D-mannitol
N-(2-pyrazine)carbonyl-L-phenylalanine-L- leucine boronate.
The compound is described as a boronate ester of bortezomib
(a boronic acid) and D-mannitol (a hydroxy compound) and has
the following chemical structure, with Millennium's
highlight of the bonds between the bortezomib moiety and the
Br. 13. The lyophilized compound is claimed in Claim 20:
20. The lyophilized compound D-mannitol N-(2-
asserted claims include the new compound as a lyophilized
cake, the method of preparation of the new compound, and its
reconstitution with a pharmaceutically acceptable carrier.
Dist. Ct. Op. *2.
and its properties as a proteasome inhibitor were previously
known and are described in United States Patent No. 5, 780,
454 ("the Adams Patent"). However, despite its
known efficacy against various cancers, bortezomib never
achieved FDA approval and market status because of its
instability, its rapid degradation in liquid formulations,
and its insolubility. The record states that these problems
remained unsolved despite extensive research effort by the
inventor Dr. Adams and others at Millennium and its
predecessor company. Dr. Adams' team attempted to develop
a stable liquid formulation of bortezomib, but after
evaluating approximately 20 different formulations, the team
failed to develop a formulation that was stable enough for
transportation, storage, and administration to patients under
conditions of clinical use and distribution.
inventor of the '446 Patent was associated with the
National Cancer Institute and the University of Kansas, and
was consulted by Dr. Adams after years of unsuccessful
attempts to solve formulation and stability problems with
bortezomib. Despite preparing approximately twenty-five
different liquid formulations, these efforts encountered the