from the United States District Court for the Northern
District of Illinois in No. 1:12-cv-03846, Judge Rebecca R.
Pollard Masurovsky, Finnegan, Henderson, Farabow, Garrett
& Dunner, LLP, Washington, DC, argued for
plaintiff-appellee. Also represented by Danielle Andrea
Duszczyszyn, Mark J. Feldstein, Jason Lee Romrell.
W. Stafford, Wilson, Sonsini, Goodrich & Rosati, PC,
Austin, TX, argued for defendants-appellants. Also
represented by Robert Delafield; Adam William BURROWBRIDGE,
Washington, DC; Elham FlROUZl STEINER, San Diego, CA; NANCY
L. ZHANG, Palo Alto, CA.
MOORE, Reyna, and TARANTO, Circuit Judges.
TARANTO, CIRCUIT JUDGE.
Pharmaceuticals, Inc. owns U.S. Patent No. 8, 399, 445, which
describes and claims acetylcysteine compositions
substantially free of chelating agents. It is listed in the
Food and Drug Administration's Approved Drug Products
with Therapeutic Equivalence Evaluations (the Orange
Book) as covering Cumberland's chelating-agent-free
formulation of Acetadote®, an intravenous antidote for
overdoses of acetaminophen. When Mylan Institutional LLC
filed an abbreviated new drug application to market its own
chelating-agent-free acetylcysteine formulation, Cumberland
brought this patent-infringement action in the Northern
District of Illinois against Mylan Institutional LLC and
Mylan Inc. (hereafter "Mylan, " individually or
jointly). Mylan stipulated to infringement but asserted
invalidity on two grounds: derivation of the claimed
invention from someone at the FDA and obviousness. The
district court rejected both challenges after a bench trial.
In particular, the court found that Mylan proved neither (1)
that anyone at the FDA conceived of the claimed invention
before the patent-named inventor nor (2) that there was a
reasonable expectation that the claimed formulations, without
any chelating agents, would succeed. Cumberland Pharm.,
Inc. v. Mylan Institutional LLC, 137 F.Supp.3d 1108,
1121-22, 1127 (N.D. 111. 2015). We affirm.
priority date relevant here (August 24, 2005), acetylcysteine
was known in the art as an antidote for acetaminophen
overdoses. '445 patent, col. 1, lines 20-34. It also was
known to have a stability problem: heavy metal ions, whether
inherent in the formulation or found as contaminants,
catalyze the oxidation of acetylcysteine in solution, causing
it to degrade. Id., col. 1, lines 39-40; see
Cumberland, 137 F.Supp.3d at 1112 n.2. A prior-art
response to the stability problem was to include edetate
disodium (EDTA or edetate) in an acetylcysteine formulation.
'445 patent, col. 1, line 45, through col. 2, line 4.
EDTA, a chelating agent, surrounds and binds to heavy metal
ions, preventing them from acting as catalysts that oxidize
acetylcysteine. Id. Such EDTA-containing
formulations of acetylcysteine were considered safe, despite
potential negative side effects. Id., col. 2, lines
'445 patent declares: "It has been surprisingly
found that an aqueous composition containing acetylcysteine,
sterilized water, and a pH-adjusting agent, is stable without
the addition of a chelating agent." Id., col.
2, lines 48-50. The patent claims such compositions. Every
claim in the patent requires a "stable" composition
that is "free of chelating agents, " id.,
col. 9, line 16, through col. 10, line 53, and the district
court construed the term to mean "[T]acking one or more
chelating agents, " Cumberland, 137 F.Supp.3d
facts central to the dispute over the '445 patent's
validity date from 2002, when the FDA was considering
Cumberland's application for permission to market the
original EDTA-containing formulation of Acetadote®, a
formulation previously approved in other countries. On
December 10, 2002, the FDA sent Cumberland a letter, in which
the FDA gave Cumberland the following instructions (among
others): "[2c] Provide scientific and regulatory
justification for the inclusion of Edetate as a component in
the drug product. In addition, provide a description of the
pharmacological properties for Edetate in this drug
product." J.A. 12837. Six days later, representatives of
the FDA and Cumberland spoke by telephone. Notes of the call
state: "Regarding item 2(c), the Division explained that
data should be provided to support any justification for the
inclusion of Edetate, since a non-trivial amount is included
in the formulation." J.A. 12899.
December 20, 2002, Cumberland formally responded to the FDA
in a letter written by Leo Pavliv, who was the Cumberland
official responsible for Acetadote® and who is the named
inventor on the '445 patent. The letter explained that
EDTA was included to stabilize the formulation and stated:
"If no or lower concentrations of edetate are capable of
ensuring product stability, lowering or removing edetate
would raise questions of how the safety and efficacy of the
product would be effected." J.A. 14783. Mr. Pavliv
ultimately testified at trial that, shortly after writing
this letter, he had the idea of testing the stability of an
acetylcysteine formulation without EDTA.
March 5, 2003, Cumberland asked the FDA to schedule a call
for further discussion of its December 20, 2002 response.
With respect to question 2c, Cumberland proposed to discuss
the following: "Cumberland believes the use of Edetate
as a component in the drug product is justified both from a
scientific as well as a regulatory point of view. Does FDA
agree?" J.A. 11343. There is no written record of the
occurrence or content of the requested call. At trial,
however, Mr. Pavliv testified that the call took place; that
FDA representatives indicated on the call that they were not
prepared to say whether they considered EDTAs inclusion
justified; and that Mr. Pavliv then stated his idea to
perform a stability study. Accord- ing to Mr. Pavliv, at
least one FDA representative on the call approved of his idea
to do a study and asked him to put the proposal in writing.
did so in a July 21, 2003 letter, stating: "As requested
by FDA, upon product approval [i.e., upon FDA
approval of the EDTA-containing formulation], Cumberland
Pharmaceuticals intends to initiate studies to determine the
impact on product stability of both decreasing and completely
removing edetate disodium from the formulation." J.A.
14916. The FDA issued its Chemistry Review of the
EDTA-containing formulation on January 9, 2004. That document
states: "The sponsor reported that, as requested by the
FDA upon drug approval, an independent study will be
initiated to determine the impact on drug product stability
of both decreasing and completely removing the amount of
edetate sodium." J.A. 12968; see id. at 12969
(referring twice more to Cumberland's commitment to a
post-approval study). The FDA approved the EDTA-containing
product on January 23, 2004, J.A. 11334-37, with the approval
letter reminding Cumberland of its commitment to
"evaluate the potential benefit of Edetate disodium on
the stability of the drug product, " the study to
"include a comparison of the current concentration of
Edetate to a formulation with a lower concentration and no
concentration of Edetate." Id. at 11336.
then arranged by contract for testing to be done by Bioniche
Pharma Group, "Mylan's predecessor company."
Cumberland, 137 F.Supp.3d at 1116. The protocol,
proposed by Mr. Pavliv and approved by the FDA without
change, included testing a formulation that turned out to be
the claimed invention, i.e., a formulation
containing neither EDTA nor any other chelating
agent.On November 18, 2004, three months into the
study, Mr. Pavliv received encouraging stability data. On
August 24, 2005, having received further encouraging
stability data ...