NOVARTIS PHARMACEUTICALS CORPORATION, NOVARTIS AG, Plaintiffs-Appellees
WEST-WARD PHARMACEUTICALS INTERNATIONAL LIMITED, Defendant-Appellant
from the United States District Court for the District of
Delaware in No. 1:15-cv-00474-RGA, Judge Richard G. Andrews.
Christina A. L. Schwarz, Venable LLP, New York, NY, argued
for plaintiffs-appellees. Also represented by Nicholas N.
Kallas, Shannon Keough Clark, Laura Katherine Fishwick,
Susanne Flanders, Jared Levi Stringham.
Zimmer, Goodwin Procter LLP, Boston, MA, argued for
defendant-appellant. Also represented by Keith A. Zullow,
Cindy Chang, Steven J. Bernstein, Michael B. Cottler, New
York, NY; Natasha Elise Daughtrey, Los Angeles, CA; William
M. Jay, Washington, DC.
Stoll, Plager, and Clevenger, Circuit Judges.
Pharmaceuticals International Ltd
("West-Ward") appeals the decision of the United
States District Court for the District of Delaware holding
that claims 1-3 of U.S. Patent No. 8, 410, 131 would not have
been obvious in view of the prior art. We conclude that the
district court did not err in its nonobviousness
determination and affirm.
Pharmaceuticals Corp. and Novartis AG (collectively,
"Novartis") own the '131 patent, which claims
methods of using the compound everolimus to treat advanced
renal cell carcinoma ("RCC"). Everolimus is the
active ingredient in Novartis's Afinitor product.
West-Ward's predecessor in interest filed an Abbreviated
New Drug Application ("ANDA") seeking to
manufacture and sell generic versions of Afinitor, and
Novartis filed this patent infringement suit in response.
After a bench trial, the district court ruled that West-Ward
failed to prove by clear and convincing evidence that claims
1-3 of the '131 patent are invalid as obvious.
Novartis Pharm. Corp. v. West-Ward Pharm. Int'l
Ltd., 287 F.Supp.3d 505, 518 (D. Del. 2017)
("Decision"). West-Ward appeals the district
court's nonobvious-ness ruling.
Advanced RCC and the '131 Patent
RCC is a cancer of the kidneys that has spread to other parts
of the body. As of February 19, 2001-the priority date of the
'131 patent-advanced RCC carried a poor prognosis and was
known to be unpredictable and difficult to treat. At that
time, the only FDA-approved drug for treating advanced RCC
was the im-munostimulant interleukin-2, which was associated
with poor response rates and toxicity in patients. Interferon
alpha, another immunostimulant, was also administered to some
patients in practice and was likewise shown to have poor
response rates and toxicity. Numerous clinical trials
investigating a wide range of treatment strategies for
advanced RCC failed. Various chemotherapies, hormonal
therapies, and immunotherapies had been unsuccessful. The
prior art explained that "[a]dvanced RCC is
characterized by a high level of resistance to all treatment
modalities that have been studied." J.A. 2058. Cancer
drugs in general had high failure rates for treatment of
advanced RCC in clinical trials, with more than 70% of cancer
drugs failing during phase II, and a majority of cancer drugs
failing during phase III.
'131 patent covers methods of administering the compound
everolimus to inhibit the growth of advanced RCC tumors.
Claims 1-3 are at issue here. Everolimus is recited in claim
1 as formula I:
1. A method for inhibiting growth of solid excretory system
tumors in a subject, said method consisting of administering
to said subject a therapeutically effective amount of a
compound of formula I
R1 is CH3,
R2 is -CH2-CH2-OH, and X is
2.The method of claim 1 wherein the solid excretory system
tumor is an advanced solid excretory system tumor.
3. The method of claim 1 wherein the solid excretory system
tumor is a kidney tumor.
'131 patent col. 17 l. 43-col. 18 l. 29 (as amended by
Certificate of Correction).
belongs to a class of compounds called mTOR inhibitors. These
compounds bind intracellularly to and form a complex with the
FK506 binding protein ("FKBP-12"). This complex
then binds to and inhibits the activity of the mammalian
target of rapamycin (mTOR) enzyme. By February 2001, the
prior art disclosed that (1) compounds called mTOR inhibitors
produced effects, such as inhibition of hypoxia-inducible
factor 1 ("HIF-1"), that were hypothesized to
inhibit tumor growth; (2) evero-limus was an mTOR inhibitor;
and (3) temsirolimus, another mTOR inhibitor, had shown
responses in RCC patients in phase I clinical trials. There
was no data on the efficacy of everolimus to treat any type
of cancer, let alone to treat advanced RCC.
time of the priority date of the '131 patent, mTOR
inhibitors were known in the art to have a variety of
beneficial properties. Rapamycin, the first mTOR inhibitor,
was known to have antimicrobial, immunosuppres-sive, and
antitumor activities. Its poor solubility, however, precluded
its development as an anti-cancer agent. Temsirolimus,
another mTOR inhibitor and a derivative of rapamycin, was
also known to exhibit antitumor properties. Temsirolimus
showed improved solubility over ra-pamycin and demonstrated