Mylan Institutional LLC v. Aurobindo Pharma Ltd. , 857 F.3d 858 ( 2017 )

United States Court of Appeals
for the Federal Circuit
______________________
MYLAN INSTITUTIONAL LLC, APICORE US LLC,
Plaintiffs-Appellees
v.
AUROBINDO PHARMA LTD., AUROBINDO
PHARMA USA INC., AUROMEDICS PHARMA LLC,
Defendants-Appellants
______________________
2017-1645
______________________
Appeal from the United States District Court for the
Eastern District of Texas in No. 2:16-cv-00491-RWS-RSP,
Judge Robert Schroeder, III.
______________________
Decided: May 19, 2017
______________________
NICOLE W. STAFFORD, Wilson, Sonsini, Goodrich &
Rosati, PC, Austin, TX, argued for plaintiffs-appellees.
Plaintiff-appellee Mylan Institutional LLC also repre-
sented by DAVID S. STEUER, Palo Alto, CA; SAMI
SEDGHANI, San Francisco, CA.
JOANNA GARELICK GOLDSTEIN, Sharma & DeYoung
LLP, New York, NY, for Apicore US LLC. Also represent-
ed by ALLEN GARDNER, Gillam, Smith & Gardner, Tyler,
TX.
2 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
SAILESH K. PATEL, Schiff Hardin LLP, Chicago, IL,
argued for defendants-appellants. Also represented by
CINDY AHN; GEORGE CHIH-LUN YU, San Francisco, CA.
______________________
Before LOURIE, MOORE, and REYNA, Circuit Judges.
LOURIE, Circuit Judge.
Aurobindo Pharma Ltd., Aurobindo Pharma USA Inc.,
and Auromedics Pharma LLC (together, “Aurobindo”)
appeal from a decision of the United States District Court
for the Eastern District of Texas granting Mylan Institu-
tional LLC’s (“Mylan Inst.”) and Apicore US LLC’s
(“Apicore”) (together, “Mylan”) motion for a preliminary
injunction precluding Aurobindo from making, using,
selling, offering to sell, and importing the accused isosul-
fan blue (“ISB”) product that allegedly infringes three of
Apicore’s patents—U.S. Patent 7,622,992 (“the ’992 pa-
tent”), U.S. Patent 8,969,616 (“the ’616 patent”), and U.S.
Patent 9,353,050 (“the ’050 patent”). See Mylan Institu-
tional LLC v. Aurobindo Pharma Ltd., No. 2:16-cv-00491,
2017 WL 497593 (E.D. Tex. Feb. 7, 2017) (“Order Adopt-
ing R&R”). Because the district court did not err in its
grant of the preliminary injunction under the ’050 patent,
although it did err in granting the injunction under the
’992 and ’616 patents, we affirm.
BACKGROUND
Apicore owns, and Mylan Inst. is the exclusive licen-
see of, the ’992, ’616, and ’050 patents, which relate to
ISB, a triarylmethane dye used to map lymph nodes. The
’992 and ’616 patents (together, “the process patents”) are
directed to a process for preparing ISB by reacting iso-
leuco acid with silver oxide in a polar solvent, followed by
reaction with a sodium solution. See, e.g., ’992 patent col.
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 3
7 ll. 21–44. 1 The ’992 patent further requires 2.0–3.0
equivalents of silver oxide. See id. col. 9 l. 65. Claim 1 of
the ’616 patent is representative of the process patents
and reads as follows:
A process of preparing N-[4-[[4-(diethyl-
amino)phenyl] (2,5-disulfophenyl)methylene]-2,5-
cyclohexadien-1-ylidene]-N-ethylethanaminium,
sodium salt comprising combining a suspension of
isoleuco acid of the formula
in a polar solvent with silver oxide, recovering
isosulfan blue acid, and treating the isosulfan blue
acid with a sodium solution.
’616 patent col. 9 ll. 38–64 (emphasis added). Claim 1 of
the ’992 patent adds the limitation that 2.0–3.0 equiva-
lents of silver oxide are employed in the process, but
otherwise resembles the claim shown above. See ’992
patent col. 9 ll. 41–67.
1 Because the ’992, ’616, and ’050 patents have the
same written description, when referring to the written
description of any of the patents, we will cite only the ’992
patent for simplicity.
4 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
The ’050 patent (which the parties refer to as “the pu-
rity patent”) is directed to an ISB compound having a
purity greater than 99.0%, as measured by high perfor-
mance liquid chromatography (“HPLC”). See ’050 patent
col. 9 ll. 54–58. Claim 1 is illustrative and reads as fol-
lows:
A compound N-[4-[[4-(diethylamino)phenyl] (2,5-
disulfophenyl)methylene]-2,5-cyclohexadien-1-
ylidene]-N-ethylethanaminium, sodium salt hav-
ing a purity of at least 99.0% by HPLC.
Id. col. 9 ll. 55–58 (emphasis added).
Around 1981, Hirsch Industries (“Hirsch”) developed
a 1% injectable solution of ISB, which it commercialized
under the trade name Lymphazurin®. Covidien Ltd.
(“Covidien”), the successor-in-interest to Hirsch, held the
original new drug application (“NDA”) and was the sole
supplier of Lymphazurin® for 30 years. From its incep-
tion, Lymphazurin®’s production had been plagued by
difficulties in synthesizing and purifying ISB. Hirsch’s
original clinical trials described the mixture as containing
94.5% ISB as determined by HPLC, with the remaining
5.5% consisting of “closely related isomers” produced
during synthesis. Mylan Institutional LLC v. Aurobindo
Pharma Ltd., No. 2:16-cv-00491, 2016 WL 7587325, at *2
(E.D. Tex. Nov. 21, 2016) (“Report and Recommendation”)
(internal quotation marks omitted).
For 26 years following the Food and Drug Administra-
tion’s (“FDA”) approval of ISB, Sigma-Aldrich Corp.
(“Sigma”) supplied Hirsch and its successors with ISB
that was manufactured by Allied Chemical Corp. (“Al-
lied”). Allied’s manufacturing process was unknown, but
analysis of its ISB indicated the presence of lead, which
suggested the use of a lead compound in synthesis. Sigma
developed an isolation process to remove the unwanted
lead, but the ultimate purity of the ISB it sold was un-
known. In 2000, Allied stopped supplying Sigma with
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 5
ISB and, while Sigma was looking for a new supplier,
Covidien was forced to notify its customers that it was
“completely out of” Lymphazurin® until it could find a
new supplier for ISB. Id. at *2 (internal quotation marks
omitted). By 2008, Sigma had a new supplier, Inno-
vassynth, which synthesized ISB using ammonium di-
chromate, resulting in residual chromium impurities.
Sigma reported numerous problems with the purity of
Innovassynth’s product and eventually developed its own
manufacturing process for ISB sometime around 2010.
Apicore was founded in 2003 and began developing an
improved process for synthesizing ISB. In 2004, Apicore
partnered with Synerx Pharma LLC (“Synerx”), Mylan
Inst.’s predecessor, to develop and market a generic
version of Lymphazurin®. In 2007, Apicore filed a patent
application that ultimately led to the process and ’050
patents. Based on the claimed process, Synerx (acquired
by Mylan Inst. in 2012) filed an abbreviated new drug
application (“ANDA”) seeking FDA approval to market a
generic Lymphazurin®; the FDA approved the ANDA in
2010. By 2011, ISB sales were a significant portion of
Apicore’s revenue and in 2012, Covidien withdrew Lym-
phazurin® from the market for “reasons other than safety
or effectiveness.” Id. at *3 (internal quotation marks
omitted). Mylan Inst. became the sole supplier of the 1%
ISB drug product until 2016, when Aurobindo entered the
market.
Aurobindo sought FDA approval for a generic Lym-
phazurin®, informing the FDA that it had studied a
“number of patents” describing ISB manufacture and
selected, inter alia, Apicore’s ’992 patent, and that it
“considered the process described [therein] for the initial
sample preparation and further, the optimization of the
process.” Id. (internal quotation marks omitted). Auro-
bindo acknowledged to the FDA that it was looking for a
reagent “other than silver oxide.” Id. (internal quotation
marks omitted). It eventually selected manganese diox-
6 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
ide, and its process resulted in ISB with a 5–10% impuri-
ty which could not be removed by recrystallization.
Instead, it used preparatory HPLC to achieve an ISB
purity of greater than 99.5%. Mylan sued Aurobindo for
infringement and sought a preliminary injunction, which
the district court granted.
First, the district court 2 evaluated the likelihood of
success on the merits and found that Aurobindo likely
infringed the process patents under the doctrine of equiv-
alents. Id. at *10–12. The court found that the difference
in oxidation strength between silver oxide and manganese
dioxide is “irrelevant” under both the “function-way-
result” (“FWR”) and “insubstantial differences” tests for
equivalence, as applied to the “face of the claims,” because
the claims do not specify a requirement of oxidation
strength. Id. at *11. Further, the court explained that,
even if oxidation strength were relevant, it “finds manga-
nese dioxide to be a mild oxidant equivalent to silver
oxide in the context of the [process patents].” Id. The
court credited Dr. Sessler’s (Mylan’s expert) testimony in
light of record evidence that the silver oxide and manga-
nese dioxide processes produce crude ISB in similar
yields. The court explained that if manganese dioxide
were a substantially stronger oxidizing agent than silver
oxide, a skilled artisan “would expect different results.”
Id. at *12.
The district court found that Aurobindo did not raise
a substantial question of validity of the ’050 patent based
on its arguments that the process patent is invalid:
(1) under § 112 because the “by HPLC” limitation renders
2 Because the district court adopted the magistrate
judge’s report and recommendation, see Order Adopting
R&R, 2017 WL 497593, at *1, we shall refer to both the
district court judge’s and magistrate judge’s findings and
conclusions as those of the district court.
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 7
the claims indefinite; (2) under § 103 because the claims
would have been obvious over various combinations of art;
and (3) under § 102 because the claims are anticipated by
Sigma’s manufacture and sale of ISB.
On the issue of indefiniteness, the district court cred-
ited Sessler’s testimony and found that “by HPLC” was a
common and well-understood way of designating or de-
termining purity, as seen in “numerous sources,” includ-
ing other patents and the scientific literature. Id. at *8–9.
Thus, the court concluded that Aurobindo had not raised
a substantial question of validity of the ’050 patent under
§ 112. Id.
The district court also rejected Aurobindo’s obvious-
ness argument, finding that Aurobindo did not raise a
substantial question regarding motivation to combine the
references or a reasonable expectation of success. See id.
at *22. The court noted that “a purified compound is not
always prima facie obvious over the [prior art] mixture” if
the process to arrive at the purified compound is itself of
patentable weight. Id. at *18 (citing Aventis Pharma
Deutschland GmbH v. Lupin, Ltd., 499 F.3d 1293, 1301
(Fed. Cir. 2007)) (internal quotation marks omitted). The
court concluded that Apicore’s process leading to the
purified compound claimed in the ’050 patent constituted
“an invention of patentable weight itself” and thus the
purity claims would not necessarily have been prima facie
obvious over the prior art mixture of (less pure) ISB and
“closely related isomer[]” by-products. Id. at *18, *19
(internal quotation marks omitted).
The district court credited Mylan’s evidence of sec-
ondary considerations—specifically, long-felt but unmet
need, commercial success, copying/praise of others, and
unexpected results. Id. at *20–22. The court pointed to
the failure of Allied, Sigma, Innovassynth, and others in
the art to “reliably” produce “high-purity” ISB for 30
years. Id. at *20. And the court emphasized that Auro-
8 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
bindo “admitted to the FDA” that it had copied the ’992
patent. Id. at *21. Thus, the court concluded that Auro-
bindo had not raised a substantial question that the ’050
patent is invalid as obvious. Id.
The district court also concluded that Aurobindo had
not raised a substantial question that the ’050 patent
claims were anticipated under § 102(b) and § 102(g)(2) by
Sigma’s manufacture and sale of ISB. See id. at *13.
Aurobindo argued that Sigma had made and sold ISB
having a purity of greater than 99.0% six years before the
’050 patent priority date. See id. Aurobindo supported its
position by citing a Sigma Certificate of Analysis, which
indicated that a compound named “Patent Violet Blue,”
with a certain product number and Lot number, possessed
a purity that was 100% by HPLC. Id. The court rejected
Aurobindo’s argument, finding that: (1) it is not clear
that, at the time of the Certificate, Sigma’s use of the
term “Patent Violet Blue” referred to ISB because other
Sigma documents indicate that “Patent Violet Blue”
referred to several blue dye compounds with different
structures; and (2) the record established that the Certifi-
cate is inaccurate because it “contradicts numerous other
Sigma[] documents” that report a different purity for
samples from the same Lot. Id. at *14. Thus, the court
concluded that Aurobindo had not raised a substantial
question that the ’050 patent is invalid as anticipated. Id.
Second, the district court found that Apicore 3 would
be irreparably harmed without a preliminary injunction
and identified four “hallmark examples” of irreparable
harm that are demonstrated by the record: lost sales; lost
R&D; price erosion; and that Apicore must now directly
compete with an infringer. Id. at *23; Order Adopting
R&R, 2017 WL 497593, at *1.
3 The court only analyzed “irreparable harm” as to
Apicore, a fact that neither party challenges on appeal.
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 9
The district court found a “causal nexus” between Au-
robindo’s infringement and Apicore’s harm in that Auro-
bindo’s product “would not be on the market if [it] had not
obtained [FDA] approval for a product that will likely be
found to be covered by the patents.” Order Adopting
R&R, 2017 WL 497593, at *1. The court noted that
“[w]ithout infringing the ’992, ’616, and ’050 patents,
Aurobindo would not be able to make the [ISB] product
described in its ANDA” because Aurobindo’s ANDA
application touted greater than 99.0% purity for ISB.
Report and Recommendation, 2016 WL 7587325, at *24.
Third, the district court found that the balance of eq-
uities weighed in favor of granting the injunction. Id.
The court emphasized that Apicore “stands to lose its
entire [ISB] business, . . . which it relies on to fund ongo-
ing research and development,” and that Aurobindo was
aware of Apicore’s patented process and copied it. Id.
Thus, the court found that the balance of equities favored
Apicore. Id. (citing Windsurfing Int’l Inc. v. AMF, Inc.,
782 F.2d 995, 1003 (Fed. Cir. 1986) (“One who elects to
build a business on a product found [likely] to infringe
cannot be heard to complain if an injunction against
continuing infringement destroys the business so elect-
ed.”)).
Finally, the district court found that the public inter-
est factor also favored granting the preliminary injunc-
tion. The court observed that Apicore satisfied its end of
the patent bargain by disclosing its method for preparing
ISB and that it would likely not have done so if it had
known that a competitor would use that method to de-
stroy its ISB business before it “could make it to trial.”
Id. The court emphasized that the public interest in
obtaining lower-priced pharmaceutical compounds cannot
justify “entirely eliminating the exclusionary rights
covered by pharmaceutical patents.” Id. (internal quota-
tion marks omitted).
10 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
Aurobindo appeals the district court’s grant of a pre-
liminary injunction. We have jurisdiction pursuant to 28
U.S.C. § 1292(a)(1) and (c)(1).
DISCUSSION
The grant or denial of a preliminary injunction is
within the sound discretion of a district court, and we will
not reverse its judgment absent an abuse of that discre-
tion. Amazon.com, Inc. v. Barnesandnoble.com, Inc., 239
F.3d 1343, 1350 (Fed. Cir. 2001). Accordingly, we will
only overturn a decision granting a preliminary injunction
on appeal if “the court made a clear error of judgment in
weighing relevant factors or exercised its discretion based
upon an error of law or clearly erroneous factual find-
ings.” Sanofi–Synthelabo v. Apotex, Inc., 470 F.3d 1368,
1374 (Fed. Cir. 2006) (quoting Genentech, Inc. v. Novo
Nordisk A/S, 108 F.3d 1361, 1364 (Fed. Cir. 1997)). We
review the district court’s conclusions of law de novo.
Nat’l Steel Car, Ltd. v. Canadian Pac. Ry., Ltd., 357 F.3d
1319, 1325 (Fed. Cir. 2004).
“A plaintiff seeking a preliminary injunction must es-
tablish that he is likely to succeed on the merits, that he
is likely to suffer irreparable harm in the absence of
preliminary relief, that the balance of equities tips in his
favor, and that an injunction is in the public interest.”
Winter v. Nat. Res. Def. Council, Inc., 555 U.S. 7, 20
(2008).
On appeal, Aurobindo disputes the court’s findings
that Aurobindo “more likely than not” infringes the pro-
cess patents under the doctrine of equivalents, Report and
Recommendation, 2016 WL 7587325, at *12; Aurobindo
did not raise a substantial question as to validity of the
’050 patent; and there was irreparable harm to Apicore.
We discuss each issue in turn.
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 11
I. Process Patents
We first consider whether the district court erred in
finding that Mylan is likely to succeed on the merits
because Aurobindo “more likely than not” infringes the
process patents under the doctrine of equivalents. Report
and Recommendation, 2016 WL 7587325, at *12. To
establish a likelihood of success on the merits, a patentee
must show that it will likely prove infringement of the
asserted claims and that its infringement claim will likely
withstand the alleged infringer’s challenges to patent
validity and enforceability. Sciele Pharma, Inc. v. Lupin
Ltd., 684 F.3d 1253, 1259 (Fed. Cir. 2012) (citing Ama-
zon.com, 239 F.3d at 1350). A preliminary injunction
should not issue if the accused infringer “raises a substan-
tial question concerning either infringement or validity.”
Amazon.com, 239 F.3d at 1350.
Aurobindo argues that it had raised a substantial
question of infringement of the process patents under the
doctrine of equivalents because manganese dioxide oxi-
dizes isoleuco acid in a different way than silver oxide in
that manganese dioxide is a strong oxidizing agent,
whereas silver oxide is a weak oxidizing agent. Addition-
ally, Aurobindo continues, manganese dioxide oxidation
requires the use of an acid and the patents specifically
report the use of silver oxide as not requiring an acid.
Mylan responds that the district court correctly found
a likelihood of success on the merits of infringement
under the doctrine of equivalents because the court
properly found that manganese dioxide and silver oxide
are equivalent in the context of the process patents.
Specifically, the court credited Sessler’s testimony in light
of record evidence that the silver oxide and manganese
dioxide processes produce crude ISB in similar yields.
The court explained that if manganese dioxide was a
substantially stronger oxidizing agent than silver oxide, a
skilled artisan “would expect different results.” Report
12 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
and Recommendation, 2016 WL 7587325, at *12. That
finding, Mylan argues, was not clearly erroneous.
As set forth below, we conclude that the district
court’s analysis of equivalence in this case was flawed, no
doubt because of the sparse and confusing case law con-
cerning equivalents, particularly the paucity of chemical
equivalence case law, and the difficulty of applying the
legal concepts to the facts. We will attempt to provide
more clarity on these subjects.
This appeal is unusual in a first sense in that it arises
from the grant of a preliminary injunction based on the
doctrine of equivalents. There are few such reported
decisions, but see, e.g., Pfizer, Inc. v. Teva Pharm., USA,
Inc., 429 F.3d 1364, 1378 (Fed. Cir. 2005), owing to the
fact that equivalents cases are “highly factual inquir[ies]
[that] rarely come[] clear on a premature record.” Jener-
ic/Pentron, Inc. v. Dillon Co., Inc., 205 F.3d 1377, 1384
(Fed. Cir. 2000). Moreover, the law on the doctrine of
equivalents as applied to chemical materials is not clear,
and its misapplication can lead to unsound results. This
appears to be such a case.
In Graver Tank, the Supreme Court set out two
frameworks for evaluating equivalence—the familiar
FWR test (viz., whether the accused product performs
“substantially the same function in substantially the
same way to obtain the same result”) and the insubstan-
tial differences test (whether the accused product or
process is substantially different from what is patented).
Graver Tank & Mfg. Co. v. Linde Air Prod. Co., 339 U.S.
605, 608, 609 (1950). The Supreme Court’s most recent
visit with this branch of the law was in Warner-
Jenkinson, which dealt with whether a process of purifica-
tion performed at a pH of 5 was equivalent to one per-
formed at a pH of 6–9. Warner-Jenkinson Co. v. Hilton
Davis Chem. Co., 520 U.S. 17, 39 (1997). The Court noted
that equivalence is not a “prisoner of formula,” id. at 39,
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 13
but also observed that non-mechanical cases may not be
well-suited to consideration under the FWR test, see id. at
39–40 (“There seems to be substantial agreement that,
while the [FWR] test may be suitable for analyzing me-
chanical devices, it often provides a poor framework for
analyzing other products or processes.”).
The Supreme Court was surely correct in stating that
non-mechanical cases may not be well-suited to considera-
tion under the FWR test. That seems to be particularly
true in the chemical arts. Although in Graver Tank, the
Supreme Court recognized the use of FWR generally in
chemical cases, 339 U.S. at 608 (“Today the doctrine [of
equivalents] is applied to mechanical or chemical equiva-
lents in compositions or devices.”), the Court later
acknowledged in Warner-Jenkinson that the suitability of
the two tests may vary, depending on the circumstances
of the case, 520 U.S. at 40 (“Different linguistic frame-
works may be more suitable to different cases, depending
on their particular facts.”). Thus, the Court seemingly
blessed two equivalents tests, leaving to the lower courts
in future cases the choice of which to apply.
The district court here applied the FWR test in evalu-
ating the equivalence issue. 4 We will therefore review its
decision first in that light. In doing so, we conclude that
4 We note that the district court recognized that the
FWR test “may inform whether insubstantial differences
exist between a claim element and an accused element.”
Report and Recommendation, 2016 WL 7587325, at *11.
Under that analysis, the district court concluded that “the
oxidation strength of manganese dioxide is irrelevant
under the insubstantial difference test,” dismissing any
consideration of oxidation strength on claim construction
grounds, as will be discussed further below. Id. Thus, the
district court did not evaluate whether silver oxide and
manganese dioxide are insubstantially different.
14 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
the district court’s analysis of the process claims under
FWR was flawed by being unduly truncated and hence
incomplete.
Especially when evaluating an equivalents dispute
dealing with chemical compositions having many compo-
nents, chemical compounds with many substituents
(which are usually claimed as separate limitations), and
those having a medical or biological use, it is often not
clear what the “function” or “way” is for each claim limita-
tion. How a particular component of a composition, or
substituent of a compound, functions in a human or
animal body, or in what way, may not be known or even
knowable (although, as technology evolves, that may
change). And precedent requires that, for infringement
under the doctrine of equivalents, each limitation must
satisfy an equivalence test. See Warner-Jenkinson, 520
U.S. at 40.
The “result” of using a claimed compound may be
more easily evaluated, as the structure and uses of one
compound may be directly compared with those of anoth-
er. But, as indicated above, that is not how infringement
under FWR is determined. It must be determined on a
limitation-by-limitation basis. See id. Similarly, in the
case of a chemical process claim, as in this case, the
“result” of a process producing a chemical compound may
be clear5—why else would a claim for infringement of a
process claim be brought if the claimed result is not
obtained? But the “function” and “way” of a particular
5 In this case, the parties did not dispute the “re-
sult” prong before the magistrate judge, but did do so
before the district court judge, who did not address those
arguments. Thus, the court never made a finding on the
“result” prong. However, we need not decide whether that
constituted reversible error because we modify the prelim-
inary injunction for other reasons set forth herein below.
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 15
limitation of a chemical process claim may remain vague
and often overlap. In some cases, “way” and “function”
may be synonymous.
Aurobindo argued before the district court that the
“function” prong of the FWR test was not met because of
the difference in oxidation strength between silver oxide
and manganese dioxide. But the court did not seem to
address that argument, which in actuality related to the
“way” component of the FWR test. The court stated that
“[c]onverting the isoleuco acid to isosulfan blue acid is the
function of the silver oxide,” and then dismissed Aurobin-
do’s oxidation strength argument as “irrelevant” to the
FWR and “insubstantial difference” tests. Report and
Recommendation, 2016 WL 7587325, at *11 (emphasis
added). Nevertheless, the court made a finding that silver
oxide and manganese dioxide are “equivalent” in the
context of the process patents, without considering the
“way” prong of the FWR test. Id. In fact, the court ap-
peared to consider the relative oxidation strengths of
silver oxide and manganese dioxide as a consideration for
claim construction, rather than its equivalents analysis.
Id. at *10–12 (stating that the relative oxidation
strengths are “irrelevant” for both the FWR and insub-
stantial differences tests and that Aurobindo had not
argued for a “narrow[er]” claim construction that would
read an oxidation strength limitation into the claims, but
noting that a “more fully-developed factual record and
claim construction proceeding could change things” (em-
phases added)).
Thus, either the district court did not address the
“way” prong of the FWR analysis—having considered the
relative oxidation strengths to be an issue for claim
construction, and rejecting Aurobindo’s arguments about
oxidation strength because it had not argued for a narrow
claim construction—or it performed a “way” analysis
without considering critical factors under that prong,
namely, the relative oxidation strengths of silver oxide
16 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
and manganese dioxide, as well as the use of an acid in
the accused process. Either characterization constitutes
error in the court’s equivalents analysis.
The district court correctly evaluated the “function”
aspect of the FWR test—deciding, in effect, that the
function of the silver oxide was to oxidize the precursor
isoleuco compound to ISB acid. 6 But that is not consider-
ing the “way” the oxidation works. Manganese dioxide
and silver oxide may have the same function, but the
question is whether they operate in the same way. Criti-
cal facts that might be considered in an equivalents
analysis include the relative oxidation strengths of the
two oxidizing agents, as argued by Aurobindo, and the
fact that manganese dioxide requires the use of an acid
for oxidation, but silver dioxide does not, and results in a
different yield. All of this in fact may at trial indicate a
different “way.” Thus, there is room for sufficient doubt
as to whether silver oxide and manganese dioxide oxidize
isoleuco acid in the same way so as to satisfy the “way”
prong of the FWR test.
Accordingly, the district court erred in its equivalents
analysis under FWR and we reverse its determination.
When the case goes back to the district court for a full
trial on the merits, the court may wish to consider wheth-
er the substantiality of the differences test may be more
applicable in this case. Even if evaluating the “function”
6 We note that the court seemed to make a finding
as to the “function” prong, without stating it as such. It
acknowledged that Aurobindo only disputed the “function”
of the oxidizing agents, but then stated that “[c]onverting
the isoleuco acid to isosulfan blue acid is the function of
the silver oxide,” while rejecting Aurobindo’s arguments
on claim construction grounds. Id. at *11 (emphasis
added). We will treat that part of the court’s analysis as
its finding under the “function” prong of the FWR test.
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 17
and “way” prongs is feasible, the FWR test may be less
appropriate for evaluating equivalence in chemical com-
pounds if it cannot capture substantial differences be-
tween a claimed and accused compound.
For example, consider the well-known compounds as-
pirin and ibuprofen, which chemists would not usually
consider to be structural equivalents under the insubstan-
tial differences test. Chemical compounds are character-
ized by their structures, and these two compounds differ
substantially in structure (see appendix). However, the
two compounds would seem to be substantial equivalents
under the FWR test. They each provide analgesia and
anti-inflammatory activity (“function”) by inhibiting
prostaglandin synthesis (“way”) in order to alleviate pain,
reduce fevers, and lessen inflammation (“result”). See,
e.g., Hilton Davis Chem. Co. v. Warner-Jenkinson Co., 62
F.3d 1512, 1546 (Fed. Cir. 1995) (Lourie, J., dissenting).
Thus, a compound may appear to be equivalent under the
FWR test, but not under the substantiality of the differ-
ences test. Hence, the substantial differences test may be
more suitable than FWR for determining equivalence in
the chemical arts. Warner-Jenkinson, 520 U.S. at 40
(“Different linguistic frameworks may be more suitable to
different cases, depending on their particular facts.”).
In this case, the district court conducted an incom-
plete FWR analysis while essentially bypassing the
substantial differences test, in a situation where the
latter test might seemingly be more appropriate. The
claims in the process patents recite a method for prepar-
ing a specifically named compound by combining another
specifically depicted compound with a third specific
compound, viz., silver oxide. Each of these compounds is
expressly named, and an infringement analysis must not
take lightly the specific recitation of these materials. The
district court found that the accused process using man-
ganese dioxide was equivalent to the claimed process
using silver oxide. But the court failed to consider wheth-
18 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
er the key reagent in the process, manganese dioxide, was
substantially different from the claimed reagent, silver
oxide, and hence whether the substitution for, and omis-
sion of, silver oxide left the accused infringer outside of
the bounds of the claims.
Manganese dioxide and silver oxide are substantially
different in many respects. For example, manganese and
silver are in different groups of the Periodic Table. In
oxide form, manganese has an oxidation state of +4, while
silver is +1. Those differences may well be relevant to
equivalence at trial. Thus, the choice of test under the
doctrine of equivalents may matter in this case.
When the case returns to the district court for a full
trial on the merits, the court should, in addition to provid-
ing further analysis regarding fulfillment of the FWR test,
if it determines that it should still utilize that test, also
consider whether an evaluation of equivalence under the
substantial differences test may be better suited to the
particular facts of this case.
In sum, we conclude that the court’s equivalents anal-
ysis was deficient in its FWR analysis. Because, on the
record, there remains a substantial question concerning
infringement, we conclude that the court’s grant of a
preliminary injunction based on the process patents
constituted an abuse of discretion. Thus, we modify 7 the
court’s grant of the preliminary injunction to premise it
7 Ordinarily a failure by the district court to proper-
ly apply the doctrine of equivalents would warrant a
remand. However, because the injunction will stand
under the ’050 patent, as will be discussed infra, we see
no need to expend judicial resources and litigation ex-
penses on a remand. Thus, we will modify the district
court’s decision by affirming the grant of a preliminary
injunction premised only on the ’050 patent.
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 19
only on its evaluation of the ’050 patent, as will be dis-
cussed infra.
II. ’050 Patent
We next consider whether the district court erred in
finding that Aurobindo did not raise a substantial ques-
tion as to validity of the ’050 patent. Id. at *14,
*23. Aurobindo does not appeal the court’s finding that it
“more likely than not” infringes the ’050 patent. Id. at
*12. Thus, the preliminary injunction premised on the
’050 patent will stand unless Aurobindo raised a substan-
tial question concerning the validity of the patent, or
unless the court erroneously found irreparable harm. We
find that the court did not err in either respect.
Aurobindo argues that the claims of the ’050 patent
are anticipated by Sigma’s ISB product because a Sigma
Certificate of Analysis shows that Sigma made and sold
ISB with a purity of 100% six years before the relevant
date of the ’050 patent. Furthermore, Aurobindo argues
that the ’050 patent would have been obvious over Lym-
phazurin® itself because the prior art taught the use of
HPLC and other conventional purification techniques for
purifying ISB. Finally, Aurobindo argues that the ’050
patent is invalid because the limitation “having a purity
of at least 99.0% by HPLC” is indefinite. Aurobindo
contends that different HPLC parameters will produce
different results in a purity analysis and thus, because
the claims do not specify HPLC parameters, they are
indefinite.
Mylan responds that the district court’s findings re-
garding a lack of a substantial question of validity due to
anticipation, obviousness, and indefiniteness were not
clearly erroneous.
We agree with Mylan. Aurobindo points to no legal er-
ror in the district court’s analysis of the record evidence;
rather, it argues only that the court erred in “misreading
20 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
the factual content of the prior art.” Appellant’s Br. 43.
However, what the prior art teaches is a question of fact
that we review with deference, especially at the prelimi-
nary injunction stage. Amazon.com, 239 F.3d at 1358.
We do not “reweigh evidence on appeal.” In re NTP, Inc.,
654 F.3d 1279, 1292 (Fed. Cir. 2011).
The district court rejected Aurobindo’s argument that
the ’050 patent claims are anticipated by Sigma’s manu-
facture and sale of ISB because it found that the Sigma
Certificate of Analysis related to a compound named
“Patent Violet Blue” and it was not clear that, at the time
of the issuance of the Certificate, Sigma used that term to
refer to ISB. Additionally, the Certificate contradicts
other Sigma documents that report different purity levels
for samples from the same Lot. Report and Recommenda-
tion, 2016 WL 7587325, at *14. We discern no clear error
in those findings.
The district court also rejected Aurobindo’s obvious-
ness argument, finding that Aurobindo did not raise a
substantial question regarding motivation to combine the
references or a reasonable expectation of success. See id.
at *22. The court found that Apicore’s process leading to
the claimed ISB product with a purity of greater than
99.0% constituted “an invention of patentable weight
itself” and thus that the ’050 patent claims would not
necessarily have been prima facie obvious over the prior
art mixture of (less pure) ISB and “closely related iso-
mer[]” by-products. Id. at *18, *19 (internal quotation
marks omitted).
Finally, the district court rejected Aurobindo’s argu-
ment that the ’050 patent claims are invalid as indefinite.
The court found that the phrase “by HPLC” was a “com-
mon and well understood way of designating purity in
publications and patents that are relied upon by the
scientific and technical community.” Id. at *8 (quoting
Sessler’s testimony). The court found that “numerous
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 21
sources” support that determination, including patents
filed before the relevant date of the ’050 patent.
We see no error in the district court’s analysis. We
have previously acknowledged that “a purified compound
is not always prima facie obvious over the [prior art]
mixture” if the process to arrive at the purified compound
is itself of patentable weight. Aventis, 499 F.3d at 1301.
Moreover, if the prior art teaches a mixture containing a
compound but does not enable its purification, then the
purified form of the compound may not have been obvious
over the prior art mixture. See, e.g., Spectrum Pharm.,
Inc. v. Sandoz Inc., 802 F.3d 1326, 1335–36 (Fed. Cir.
2015) (concluding that a purified compound would have
been obvious over the prior art mixture where, inter alia,
“the whole spectrum of prior art available before the
invention was made would have enabled one of skill in the
art to make and use the claimed substantially pure
. . . compound” (emphasis added)). The court expressly
relied on the Aventis proposition in making its determina-
tion. Report and Recommendation, 2016 WL 7587325, at
*17–18 (quoting Aventis, 499 F.3d at 1301). We see no
error in its analysis. It is clear from the record here that,
although ISB was known in the prior art, the path to
arrive at ISB with a purity of greater than 99.0% was not
known before the relevant date of the ’050 patent.
Furthermore, the district court credited Mylan’s evi-
dence of secondary considerations—specifically, long-felt
but unmet need, commercial success, copying/praise of
others, and unexpected results. Id. at *20–22. The court
relied on record evidence showing the failure of Allied,
Sigma, Innovassynth, and others in the art to “reliably”
produce “high-purity” ISB for 30 years, id. at *20,
and that Aurobindo “admitted to the FDA” that it had
copied the ’992 patent, id. at *21. There is no clear error
in the court’s findings. In fact, the record demonstrates
that, prior to the ’050 patent’s relevant date, a reliable
source of high-purity ISB was so scarce that, at one point,
22 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
Covidien was forced to notify its customers that it was
“completely out of” Lymphazurin® until it could find a
new supplier for ISB. Id. at *2 (internal quotation marks
omitted).
Finally, there is no error in the court’s determination
that the ’050 patent is likely not invalid as indefinite.
The court’s finding was supported by substantial record
evidence, including the scientific literature and other
patents reporting purity using the same “by HPLC”
designation without providing specific HPLC parameters.
Id. at *8. The court found that even Dr. Brown’s testimo-
ny (Aurobindo’s expert) admitted that “purity by HPLC”
is typically used in FDA submissions for describing purity
levels. Id. at *9. Thus, the court determined that a
skilled artisan “would readily understand” the phrase and
would be able to “elucidate HPLC conditions” for deter-
mining ISB purity. Id. We see no error in that finding.
Thus, we see no error in the court’s legal analysis or
its factual findings pertaining to validity of the ’050
patent, particularly at the preliminary injunction stage of
the litigation.
III. Irreparable Harm
Finally, we consider whether the district court erred
in finding a likelihood that Apicore will sustain “substan-
tial and immediate irreparable injury” without prelimi-
nary relief. Id. at *22 (citing Apple, Inc. v. Samsung
Elects. Co., 678 F.3d 1314, 1325 (Fed. Cir. 2012)) (internal
quotation marks omitted).
Aurobindo argues that the district court erred in find-
ing a causal nexus between Apicore’s alleged harm and
the patented features of the process and ’050 patents.
Aurobindo contends that the patented features are the
use of silver oxide to oxidize isoleuco acid, and that the
ISB employed in the finished drug product is at least
99.0% pure by HPLC. However, Aurobindo argues, there
MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD. 23
is no evidence that the consumer demand for Mylan’s
product arises from the fact that the ISB it contained was
synthesized using silver oxide or that the ISB is at least
99.0% pure; in fact, argues Aurobindo, that information is
not available anywhere on Mylan’s marketing materials
for its ISB drug product. Rather, Aurobindo continues,
the record shows that there was no consumer demand for
the patented product because Lymphazurin® was com-
mercially successful until Mylan Inst.’s product drove it
out of the market due to pricing—not due to the difference
in the manufacturing process or purity of the ISB it
contains.
Mylan responds that Aurobindo’s causal nexus argu-
ment is flawed because it improperly focuses on a subset
of the relevant customers (physicians) and ignores all
others (active pharmaceutical ingredient (“API”) suppli-
ers, pharma companies, hospitals, the FDA, etc.). Mylan
maintains that Apicore’s harm is directly caused by
Aurobindo’s infringement because ample evidence shows
Sigma’s difficulty in finding an acceptable ISB supplier
and that, by admittedly copying Apicore’s patented pro-
cess, Aurobindo gained a competitive advantage.
We agree with Mylan that the district court’s deter-
minations were not clearly erroneous. On the record
evidence, the court found that: (1) due to Aurobindo’s
infringement, Apicore has, and will continue to, suffer
from lost sales, lost research and development, price
erosion, and having to directly compete with an infringer,
id. at *23; (2) there was a causal nexus between Aurobin-
do’s infringement and Apicore’s harm because Aurobindo’s
product “would not be on the market if [it] had not ob-
tained [FDA] approval for a product that will likely be
found to be covered by the patents,” Order Adopting R&R,
2017 WL 497593, at *1; and (3) “[w]ithout infringing the
[process and purity] patents, Aurobindo would not be able
to make the [ISB] product described in its ANDA,” Report
and Recommendation, 2016 WL 7587325, at *24.
24 MYLAN INSTITUTIONAL LLC v. AUROBINDO PHARMA LTD.
Those findings do not constitute clear error. Aurobin-
do argues that the court could not rely on the FDA’s
approval of Aurobindo’s ANDA application to automatical-
ly find a causal nexus between Apicore’s harm and Auro-
bindo’s infringement. But that is not what the court
found or how the court used that evidence. The record
evidence shows Aurobindo’s admitted copying of Apicore’s
’992 patent, id. at *4, Aurobindo’s ANDA promising an
ISB purity of greater than 99.0%, id. at *24, and the
failure of all others in the art to obtain an ISB purity of
greater than 94.5% until the invention of the ’050 patent,
id. at *20. Thus, the district court reasonably found that,
“[w]ithout infringing the [process and ’050] patents,
Aurobindo would not be able to make the [ISB] product
described in its ANDA.” Id. at *24. In making that
determination, the court did not rely on regulatory ap-
proval to automatically confer a causal nexus, as Auro-
bindo argues. Rather, it made a reasoned factual
determination, supported by substantial record evidence.
We see no legal error in the court’s analysis and no clear
error in its factual findings.
Aurobindo does not challenge the district court’s find-
ings that the balance of equity and public interest factors
weigh in favor of granting the preliminary injunction.
Thus, because we find no error in the court’s determina-
tion that Aurobindo has not raised a substantial question
of validity of the ’050 patent and that Apicore will be
irreparably harmed without preliminary relief, we affirm
the district court’s grant of the preliminary injunction
premised on the ’050 patent.
CONCLUSION
We have considered the parties’ remaining argu-
ments, but find them to be unpersuasive. For the reasons
set forth above, we modify the court’s grant of a prelimi-
nary injunction by premising it only on the ’050 patent.
AFFIRMED