The Medicines Company v. Mylan, Inc. , 853 F.3d 1296 ( 2017 )

United States Court of Appeals
for the Federal Circuit
______________________
THE MEDICINES COMPANY,
Plaintiff-Cross-Appellant
v.
MYLAN, INC., MYLAN PHARMACEUTICALS INC.,
BIONICHE PHARMA USA, LLC,
Defendants-Appellants
______________________
2015-1113, 2015-1151, 2015-1181
______________________
Appeals from the United States District Court for the
Northern District of Illinois in No. 1:11-cv-01285, Judge
Amy J. St. Eve.
______________________
Decided: April 6, 2017
______________________
PORTER F. FLEMING, Haug Partners LLP, New York,
NY, argued for plaintiff-cross-appellant. Also represented
by EDGAR HAUG, ANGUS CHEN.
SHANNON BLOODWORTH, Perkins Coie, LLP, Washing-
ton, DC, argued for defendants-appellants. Also repre-
sented by DAN L. BAGATELL, Hanover, NH; DAVID LEE
ANSTAETT, AUTUMN N. NERO, DAVID R. PEKAREK KROHN,
Madison, WI.
______________________
2 THE MEDICINES COMPANY v. MYLAN, INC.
Before DYK, WALLACH, and HUGHES, Circuit Judges.
DYK, Circuit Judge.
The Medicines Company (“Medicines”) is the owner of
U.S. Patent Nos. 7,582,727 (“the ’727 patent”) and
7,598,343 (“the ’343 patent”). In response to an Abbreviat-
ed New Drug Application (“ANDA”) submitted by Mylan,
Inc. (“Mylan”), Medicines filed suit in the United States
District Court for the Northern District of Illinois alleging
that Mylan’s ANDA infringed claims 1–3, 7–10, and 17 of
the ’727 patent, and claims 1–3 and 7–11 of the ’343
patent. Mylan counterclaimed seeking a declaration that
the asserted claims were invalid.
The district court held on summary judgment that the
asserted claims of the ’343 patent were not infringed
because Mylan did not satisfy the “efficient mixing”
limitation of those claims. After conducting a bench trial,
the court held that the asserted claims of the ’727 patent
were infringed because those claims did not include an
“efficient mixing” limitation.
We hold that both the ’727 and ’343 patents include a
“batches” limitation that requires batch consistency,
which, according to the patents in suit, is achieved
through efficient mixing. Efficient mixing is therefore
required by the asserted claims of both patents. We
further construe efficient mixing as defined by Example 5
of the patents’ specification. We therefore reverse the
district court’s judgment of infringement with respect to
the ’727 patent, and affirm its summary judgment of
noninfringement with respect to the ’343 patent. We do
not address the validity of the patents in suit.
BACKGROUND
I
The ’727 and ’343 patents are directed to pharmaceu-
tical formulations—or “batches”—of the drug bivalirudin
THE MEDICINES COMPANY v. MYLAN, INC. 3
produced through a process that consistently minimizes
impurities. Bivalirudin is a synthetic peptide used to
prevent blood clotting in patients undergoing cardiac
catheterization. This clinical application arises from the
drug’s ability to act as a reversible inhibitor of thrombin,
a key enzyme in the cascade of biochemical reactions
responsible for the formation of blood clots. Bivalirudin’s
pharmacological properties were known in the art, well
before the filing of the patents in suit, and were covered
by a patent owned by Medicines that expired in 2015, U.S.
Patent No. 5,196,404.
The claimed inventions of the ’727 and ’343 patents
are directed to minimizing impurities in batches of bival-
irudin that have been compounded with a base. See ’727
patent, col. 2 ll. 19–22; ’343 patent, col. 2 ll. 19–22. Bival-
irudin as an active ingredient is typically distributed or
sold as a dry powder that must be compounded with a
base, before being reconstituted in a clinical setting and
administered to a patient as an intravenous injection.
Reconstitution involves dissolving the drug (in dry powder
form) in an aqueous solvent such as water or saline.
Because dissolving bivalirudin by itself (without a base)
results in an acidic solution not suitable for injection,
commercial forms of bivalirudin compound bivalirudin
with a base, which increases the pH of the reconstituted
drug to a clinically acceptable level.
II
Medicines received approval from the Food & Drug
Administration (“FDA”) to market a base-compounded
bivalirudin drug product in 2000, and has sold the ap-
proved product since 2001 under the tradename
ANGIOMAX®, well before the critical date of the patents
in suit. In approving ANGIOMAX®, the FDA required
Medicines to limit the level of “Asp9-bivalirudin”—an
impurity generated during the compounding process that
shortens bivalirudin’s shelf life—to less than 1.5 percent.
4 THE MEDICINES COMPANY v. MYLAN, INC.
Asp9-bivalirudin is formed when the ninth amino acid of
bivalirudin’s peptide chain converts from asparagine to
aspartic acid. Consequently, Medicines was required to
reject any ANGIOMAX® batch determined to have an
Asp9 level higher than 1.5 percent. See United States v.
Barr Labs., Inc., 812 F. Supp. 458, 471–72 (D.N.J. 1993);
21 C.F.R. § 211.165(f).
Between 2001 and 2005, Medicines and its contract
manufacturer, Ben Venue Laboratories (“BVL”), produced
and sold numerous batches of compounded bivalirudin
having Asp9 levels of less than 1.5 percent. Although the
“old compounding process,” Medicines Co. v. Mylan Inc.,
72 F. Supp. 3d 837, 850 (N.D. Ill. 2014), used by Medi-
cines and BVL to produce ANGIOMAX® “resulted in
variable and sometimes high levels of Asp9 impurities,”
id. at 847, the overriding majority of these batches in fact
had Asp9 levels below 0.6 percent (the level specified in
the asserted claims). As the district court observed, “79 of
87 prior art ANGIOMAX® batches had Asp9 levels at or
below about 0.6% and [Medicines] sold dozens of these
batches prior to the critical date.” Id. at 864.
In 2005 and 2006, however, Medicines produced two
batches of ANGIOMAX® with Asp9 levels above the 1.5
percent limit specified by the FDA. After failing to solve
the problem of inconsistent batches internally, Medicines
retained a consultant, Dr. Gary Musso, who together with
Dr. Gopal Krishna, an employee of Medicines at the time,
identified the compounding process used by BVL as the
source of the problem. Drs. Krishna and Musso are the
named co-inventors of the ’727 and ’343 patents.
The process of compounding bivalirudin generally in-
volves three steps: (1) forming a bivalirudin solution by
dissolving the drug in an aqueous solution; (2) mixing the
bivalirudin solution with a pH-adjusting solution contain-
ing a base; and (3) removing solvents to yield the final
compounded drug product. See Medicines, 72 F. Supp. 3d
THE MEDICINES COMPANY v. MYLAN, INC. 5
at 843. The ’727 and ’343 patents explain that in mixing
the pH-adjusting solution into the bivalirudin solution,
“concentrated sites in the compounding solution that have
much higher pH levels” are formed. See, e.g., ’727 patent,
col. 9 ll. 20–22. These localized “hot spots” catalyzed the
degradation of bivalirudin to Asp9-bivalirudin, resulting
in undesirable high levels of the impurity in some in-
stances. See, e.g., id. col. 9 l. 19.
Based on this principle, Drs. Krishna and Musso de-
veloped an improved, “efficient mixing” process for mixing
the pH-adjusting solution with the bivalirudin solution
that minimized the formation of these hotspots. See
Medicines, 72 F. Supp. 3d at 848. This improved “efficient
mixing” process resulted in batches that consistently
satisfied the FDA’s 1.5 percent limit on the level of Asp9-
bivalirudin. Moreover, based on Drs. Krishna and Musso’s
experiments, Medicines discovered that the Asp9 level of
batches compounded using the improved “efficient mix-
ing” process never exceeded 0.6 percent. See id. at 848–49.
This batch consistency of bivalirudin drug products
compounded using “efficient mixing” is the invention
disclosed and claimed by the patents in suit, which were
filed on the same day and share nearly identical specifica-
tions. See Medicines Co. v. Mylan Inc., 2012 WL 3234282,
at *2 (N.D. Ill. Aug. 6, 2012).
Representative claim 1 of the ’727 patent provides:
1. Pharmaceutical batches of a drug product
comprising bivalirudin . . . wherein the batches
have a pH adjusted by a base, said pH is about 5-6
when reconstituted in an aqueous solution for in-
jection, and wherein the batches have a maximum
impurity level of Asp9-bivalirudin that does not ex-
ceed about 0.6% as measured by HPLC.
’727 patent, col. 25 ll. 56–64 (emphasis added).
6 THE MEDICINES COMPANY v. MYLAN, INC.
Representative claim 1 of the ’343 patent provides:
1. Pharmaceutical batches of a drug product
comprising bivalirudin . . . prepared by a com-
pounding process comprising:
(i) dissolving bivalirudin in a solvent to
form a first solution;
(ii) efficiently mixing a pH-adjusting solu-
tion with the first solution to form a sec-
ond solution, wherein the pH-adjusting
solution comprises a pH-adjusting solution
solvent; and
(iii) removing the solvent and pH-
adjusting solution solvent from the second
solution;
wherein the batches have a pH adjusted by a
base, said pH is about 5-6 when reconstituted in
an aqueous solution for injection, and wherein the
batches have a maximum impurity level of Asp9-
bivalirudin that does not exceed about 0.6% as
measured by HPLC.
’343 patent, col. 27 ll. 13–31 (emphasis added).
The emphasized claim limitation is common to both
patents, and we refer to this shared limitation as the
“batches limitation.” The term “pharmaceutical batches”
is defined by the patents as follows:
As used here, “batch” or “pharmaceutical batch”
refers to material produced by a single execution
of a compounding process of various embodiments
of the present invention. “Batches” or “pharma-
ceutical batches” as defined herein may include a
single batch, wherein the single batch is repre-
sentative of all commercial batches (see generally,
Manual of Policies and Procedures, Center for
Drug Evaluation and Research, MAPP 5225.1,
THE MEDICINES COMPANY v. MYLAN, INC. 7
Guidance on the Packaging of Test Batches at 1),
and wherein the levels of, for example, Asp9-
bivalirudin, total impurities, and largest unknown
impurity, and the reconstitution time represent
levels for all potential batches made by said pro-
cess. “Batches” may also include all batches pre-
pared by a same compounding process.”
’727 patent, col. 5 ll. 24–36; ’343 patent, col. 5 ll. 24–36.
III
Seeking to market a generic version of ANGIOMAX®,
Mylan submitted an ANDA to the FDA in 2010. In its
ANDA, Mylan stated that it would limit the Asp9 level of
its generic product to less than 2.0 percent. See Medicines,
72 F. Supp. 3d at 846. Mylan also made a paragraph IV
certification under the provisions of the Hatch-Waxman
Act, 21 U.S.C. § 355(j)(2)(A)(vii)(IV), asserting that its
product would not infringe the ’727 and ’343 patents
(listed in the FDA’s Orange Book), or that these patents
were invalid. In response, Medicines filed suit in the
district court alleging infringement of the ’727 and ’343
patents under 35 U.S.C. § 271(e)(2). Mylan filed counter-
claims seeking declaratory judgments of invalidity.
The parties disputed the meaning of two claim terms:
“pharmaceutical batches” and “efficiently mixing.” With
respect to “pharmaceutical batches,” the district court
construed the term consistent with the definition set forth
in the patents’ specification to refer to either: (1) “a single
batch, wherein the single batch is representative of all
commercial batches . . . made by a compounding process,
and wherein the levels of, for example, Asp9-bivalirudin,
total impurities, and largest unknown impurity, and the
reconstitution time represent levels for all potential
batches made by said process”; or (2) “all batches pre-
pared by a same compounding process.” Medicines, 2012
WL 3234282, at *3–5 (emphasis added). The district
court’s construction—to which both parties ultimately
8 THE MEDICINES COMPANY v. MYLAN, INC.
consented—adds the emphasized language to the specifi-
cation’s definition of “batches,” thereby clarifying that the
definition requires a particular process. See id. at *5.
With respect to “efficiently mixing,” the district court
relied on two examples set forth in the patents’ specifica-
tions comparing Medicines’ “old compounding process”
using “inefficient mixing conditions” (Example 4) with the
improved “efficient mixing” process developed by Drs.
Krishna and Musso (Example 5). See id. at *14–15; see
also ’727 patent, col. 21 l. 44–col. 24 l. 35; ’343 patent, col.
22 l. 21–col. 25 l. 3. The court ultimately agreed that
Medicines had disclaimed the “inefficient mixing condi-
tions” of Example 4 and adopted Mylan’s proposed con-
struction of “efficiently mixing” to require “not using
inefficient mixing conditions such as described in Exam-
ple 4.” Medicines, 2012 WL 3234282, at *15.
Based on these claim constructions, the district court
held on summary judgment that Mylan’s ANDA did not
infringe the ’343 patent because the material facts con-
cerning Mylan’s compounding process were not in dispute
and these “undisputed facts show[ed] that Mylan’s com-
pounding process is more inefficient than the ‘inefficient
mixing’ process” of Example 4. See Medicines Co. v Mylan
Inc., 2013 WL 6633085, at *10 (N.D. Ill. Dec. 16, 2013).
With respect to the ’727 patent, however, the court held
that “efficiently mixing” was not a claim limitation and
determined that factual disputes concerning the Asp9
level of Mylan’s ANDA product precluded summary
judgment. See id. at *20.
The district court conducted a six-day bench trial with
respect to infringement and validity of the ’727 patent. In
its post-trial opinion, the court rejected Mylan’s invalidity
contentions and held that Mylan’s ANDA infringed the
’727 patent as a matter of law. In so holding, the district
court appeared to assume that any batch with an Asp9
level below 0.6 percent would infringe the claims, even
THE MEDICINES COMPANY v. MYLAN, INC. 9
though the court had earlier determined that the prior art
disclosed such batches. The court reasoned that “Mylan’s
ANDA specification [would] allow[] it to market a drug
product with Asp9 . . . levels from 0.0%–2.0%, a range that
includes the ’727 patent’s claimed ranges of 0.0–0.6%,”
and “[w]hat a generic applicant asks for and receives
approval to market, if within the scope of a valid claim, is
an infringement.” See Medicines, 72 F. Supp. 3d at 883–85
(quoting Sunovion Pharms., Inc. v. Teva Pharms. USA,
Inc., 731 F.3d 1271, 1279 (Fed. Cir. 2013)). The court
again rejected Mylan’s argument that the claims of the
’727 patent required “efficient mixing” and entered final
judgment in favor of Medicines on all claims and counter-
claims with respect to the ’727 patent. Id. at 886–88.
Mylan has appealed the district court’s judgment of
infringement and no invalidity of the ’727 patent, and
Medicines has cross-appealed the district court’s sum-
mary judgment of noninfringement of the ’343 patent. We
have jurisdiction pursuant to 28 U.S.C. § 1295(a)(1).
IV
Shortly after the completion of briefing in this case,
the panel issued an opinion holding the ’727 and ’343
patents invalid under the on-sale bar of 35 U.S.C. § 102(b)
based on pre-critical date batches of ANGIOMAX® pro-
duced by BVL for Medicines. See Medicines Co. v. Hospi-
ra, Inc., 791 F.3d 1368, 1372 (Fed. Cir. 2015). Accordingly,
in this case, we reversed the district court’s judgment
with respect to the ’727 patent and dismissed Medicines’
cross-appeal regarding the ’343 patent as moot.
The full court subsequently granted Medicines’ peti-
tion for rehearing en banc in Hospira, and on rehearing
held that Medicines’ relationship with BVL did not give
rise to an invalidating “commercial offer for sale” under
Pfaff v. Wells Electronics, Inc., 525 U.S. 55, 57–68 (1998).
See Medicines Co. v. Hospira, Inc., 827 F.3d 1363, 1373–
74 (Fed. Cir. 2016) (en banc). We reopened and stayed
10 THE MEDICINES COMPANY v. MYLAN, INC.
this appeal when the court granted rehearing in Hospira.
Following the court’s en banc decision, we requested the
parties submit supplemental briefs. We now decide this
appeal on the merits. 1
DISCUSSION
Our review of the district court’s summary judgment
is plenary. See, e.g., Glaxo Grp. Ltd. v. TorPharm, Inc.,
153 F.3d 1366, 1370 (Fed. Cir. 1998). We review the
district court’s factual findings after a bench trial for clear
error and the court’s legal conclusions de novo. See, e.g.,
Braintree Labs., Inc. v. Novel Labs., Inc., 749 F.3d 1349,
1358 (Fed. Cir. 2014). The district court’s claim construc-
tions present pure questions of law subject to de novo
review because the court made no factual findings con-
cerning extrinsic evidence in construing the disputed
claim terms. See, e.g., In re Papst Licensing Dig. Camera
Patent Litig., 778 F.3d 1255, 1261 (Fed. Cir. 2015).
1 Although Mylan’s appeal calls into question the
validity of the patents in suit, Mylan’s counsel agreed that
a finding of noninfringement would render it unnecessary
for the court to reach this issue. See Oral Argument at
1:14, Medicines Co. v. Mylan, Inc., No. 15-1113 (Fed. Cir.
Dec. 6, 2016). Under Cardinal Chemical Co. v. Morton
Int’l, Inc., 508 U.S. 83, 99 (1993), a finding of nonin-
fringement cannot moot a counterclaim of invalidity, but
we retain the discretion to limit the grounds upon which
appeals are decided. Here, because Mylan has agreed that
a judgment of noninfringement with respect to both
patents in suit “would be tantamount to the relief sought
on the merits” and that we need not reach the invalidity
issues, we decline to reach the merits of Mylan’s invalidi-
ty contentions. See Old Town Canoe Co. v. Confluence
Holdings Corp., 448 F.3d 1309, 1318 n.2 (Fed. Cir. 2006).
THE MEDICINES COMPANY v. MYLAN, INC. 11
I
Mylan argues on appeal that the district court erred
by declining to interpret the claims of the ’727 patent to
require “efficient mixing” as part of the batches limita-
tion. We agree with Mylan that “efficient mixing” is
required by the batches limitation and is therefore a
limitation of both the ’727 and ’343 patents.
The batches limitation restricts the claims of the ’727
patent (as well as the ’343 patent) to “batches hav[ing] a
maximum impurity level of Asp9-bivalirudin that does not
exceed about 0.6%.” At the outset, we note that the batch-
es limitation cannot be literally construed to cover indi-
vidual batches of base-compounded bivalirudin having
Asp9 levels that “do[] not exceed about 0.6%.” Such a
construction would render the claims of the ’727 patent
invalid in light of Medicines’ numerous pre-critical-date
sales of ANGIOMAX® batches having Asp9 levels below
0.6 percent. See Medicines, 72 F. Supp. 3d at 864.
Rather, properly construed, what the batches limita-
tion requires is the use of a process that achieves batch
consistency. This requirement follows from simply read-
ing the batches limitation against the specification’s
definition of the term “batches,” as slightly revised by the
district court with the agreement of the parties to clarify
that the “batches” must be made by a particular com-
pounding process. See Medicines, 2012 WL 3234282, at *5.
That definition limits the “batches” claimed by the pa-
tents in suit to either “all batches prepared by a same
compounding process,” or “a single batch . . . wherein the
levels of [Asp9-bivalirudin] represent levels for all poten-
tial batches made by said process.” ’727 patent, col. 5 ll.
24–36 (emphasis added); ’343 patent, col. 5 ll. 24–36. The
batches limitation therefore requires a process that
achieves consistency between batches produced from the
“same compounding process”—i.e., batch consistency.
12 THE MEDICINES COMPANY v. MYLAN, INC.
There is no real dispute that the claims require batch
consistency vis-à-vis the batches limitation. Indeed, to the
extent that Medicines’ “old compounding process” resulted
in ANGIOMAX® batches having inconsistent Asp9 levels,
see Medicines, 72 F. Supp. 3d at 850, Medicines agrees
that batch consistency is the “result of following the
patent[s in suit]” and is what “distin[guishes] [them] from
the prior art.” See Oral Argument at 1:44, Medicines Co.
v. Hospira, Inc., No. 14-1469 (Fed. Cir. Dec. 6, 2016); id.
at 3:17 (“Q. The point six limitation is not enough to
distinguish the prior art . . . it’s the consistency limita-
tion, right? A. Yes.”).
The patentee, however, takes the position that the
batches limitation is not necessarily limited to a com-
pounding process that achieves batch consistency. In-
stead, according to Medicines, the batches limitation is
satisfied whenever an accused infringer consistently
produces batches having Asp9 levels below 0.6 percent,
and that the claims do not require the use of a particular
process that achieves batch consistency.
We disagree, for several reasons. First, adopting Med-
icines’ interpretation of the batches limitation would yield
an unworkable claim construction. Under Medicines’
interpretation, proof of infringement would necessitate
forward-looking assessments of whether an accused
infringer’s production of future or “potential” batches
would be likely to generate Asp9 levels greater than
“about 0.6%.” To illustrate, if a defendant using the same
compounding process produced fifty batches each having
an Asp9 level below 0.6 percent, each of those fifty batches
would infringe. But the defendant would not know wheth-
er any of the batches infringed until all fifty batches had
been produced because if even one of those batches was
determined to have an Asp9 level higher than 0.6 percent,
none of the batches would infringe. See Oral Argument at
17:00–19:06, Medicines Co. v. Mylan, Inc., No. 15-1113
(Fed. Cir. Dec. 6, 2016). For an ongoing commercial com-
THE MEDICINES COMPANY v. MYLAN, INC. 13
pounding process, this approach cannot provide “reasona-
ble certainty” regarding the scope of the asserted claims.
Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120,
2129 (2014); Geneva Pharms., Inc. v. GlaxoSmithKline
PLC, 349 F.3d 1373, 1384 (Fed. Cir. 2003) (“A claim is
indefinite if its legal scope is not clear enough that a
person of ordinary skill in the art could determine wheth-
er a particular composition infringes or not.”); Morton
Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed.
Cir. 1993) (“[C]laims. . . [must be] sufficiently precise to
permit a potential competitor to determine whether or not
he is infringing.”).
Medicines’ interpretation also fails to consider the
specification and prosecution history of the patents in
suit, both of which demonstrate that the invention dis-
closed by the ’727 and ’343 patents is a compounding
process that achieves batch consistency. The specification,
for example, states that “development of a compounding
process for formulating bivalirudin that consistently
generates formulations having low levels of impurities is
desirable,” ’727 patent, col. 2 ll. 19–21 (emphasis added),
and that “the compounding process . . . of the invention
described herein may consistently generate pharmaceuti-
cal batches . . . having the same characteristics, id. col. 13
ll. 10–13 (emphasis added).
During prosecution of the ’727 patent (as well as the
’343 patent), Medicines further represented that “[i]n the
present invention, various embodiments relate to a less
subjective and more consistent process for the mixing of
the pH-adjusting solution with the bivalirudin solution.”
J.A. 20122 (emphasis added). Medicines also took pains to
distinguish its pre-critical date sales of ANGIOMAX® in
observing that “[p]harmaceutical batches . . . as described
[by the patents in suit], and as prepared by the new pro-
cess of the present invention . . . have not been on
sale/marketed/or offered for sale for more than one (1)
year as of the [patents’] filing date.” Id. (emphasis added).
14 THE MEDICINES COMPANY v. MYLAN, INC.
Finally, any remaining doubt that the batches limita-
tion requires a compounding process is dispelled by Medi-
cines’ admission to the district court that “[w]hen viewed
in the context of the specification, it is readily apparent
that the [definition of ‘pharmaceutical batches’] refers to
the compounding processes described in the patents-in-
suit.” Medicines, 2013 WL 6633085, at *15.
Thus, we reject Medicines’ interpretation and con-
clude that the batches limitation requires the use of a
compounding process that achieves batch consistency. In
doing so, we note that our decision does not impermissibly
add a process limitation to a product claim that does not
require a process because the specification’s definition of
“batches” by itself injects a compounding process as a
limitation in the asserted claims. 2
The question remains as to what that compounding
process entails. Based on the intrinsic evidence of the
patents in suit, the answer is that the compounding
process must use efficient mixing.
The patents’ specification unequivocally states that
the “pH-adjusting solution will be efficiently mixed,” and
that “[e]fficient mixing of the pH-adjusting solution . . .
will minimize levels of Asp9-bivalirudin.” See ’727 patent,
col. 8 ll. 54–58 (emphasis added); ’343 patent, col. 8 ll. 54–
58. Indeed, apart from efficient mixing, no part of the
patents’ disclosure teaches another method capable of
producing consistent batches. In comparing the batches
resulting from the “inefficient mixing conditions” of Ex-
ample 4 with those from the “efficient mixing conditions”
of Example 5, the specification teaches that “the charac-
2 See, e.g., Baldwin Graphic Sys., Inc. v. Siebert,
Inc., 512 F.3d 1338, 1344 (Fed. Cir. 2008); Vanguard
Prods. Corp. v. Parker Hannifin Corp., 234 F.3d 1370,
1372 (Fed. Cir. 2001).
THE MEDICINES COMPANY v. MYLAN, INC. 15
teristics of the batches generated by [Example 4] may be
variable,” and that “the [efficient mixing] process demon-
strated in Example 5 produced batches generally and
consistently having lower levels of impurities than the
[inefficient mixing] process of Example 4.” ’727 patent,
col. 22, ll. 25–28, col. 23 ll. 24–26 (emphasis added); ’343
patent, col. 23 ll. 1–4, col. 23 ll. 62–65. Finally, the specifi-
cation teaches that consistent “batch(es) may be prepared
by a compounding process comprising dissolving bivaliru-
din in a solvent to form a bivalirudin solution, efficiently
mixing a pH-adjusting solution with the bivalirudin
solution to form a compounding solution, and removing
solvents from the compounding solution. This compound-
ing process includes all of the embodiments as described.”
’727 patent, col. 15 ll. 14–20 (emphasis added); ’343 pa-
tent, col. 15 ll. 14–20. The specification therefore teaches
efficient mixing as a necessary and sufficient condition for
achieving batch consistency.
The prosecution history confirms that achieving batch
consistency requires efficient mixing. Medicines expedited
the examination of the applications giving rise to the ’727
and ’343 patents by filing substantially the same Petition
to Make Special in both applications. 3 See Medicines, 2013
3 Under regulations in force at the time, an appli-
cant seeking accelerated examination in the U.S. Patent
& Trademark Office (“PTO”) through a Petition to Make
Special was required to conduct a “pre-examination
search” of the prior art and to file an Information Disclo-
sure Statement citing “references deemed most closely
related to the subject matter encompassed by the claims.”
See Manual of Patent Examining Procedure (“MPEP”) ch.
708.02(a) (8th ed. Sept. 2007); see also 71 Fed. Reg.
36,323, 36,325 (June 26, 2006). The regulations further
required the filing of an “accelerated examination support
document” requiring petitioners to provide “a detailed
16 THE MEDICINES COMPANY v. MYLAN, INC.
WL 6633085, at *5. In these petitions, Medicines ex-
plained the problem of high Asp9 levels of batches from its
“old compounding process” and stated that “various
embodiments” of the “present invention . . . relate to a less
subjective and more consistent process for the mixing of
the pH-adjusting solution with the bivalirudin solution.
This process involves efficiently mixing the pH-adjusting
solution and the dissolved bivalirudin solution, which is
not performed in the Applicants’ prior compounding
process.” J.A. 20122 (emphasis added).
After considering the same intrinsic evidence we have
just summarized, the district court concluded that Medi-
cines had disclaimed inefficient mixing. See Medicines,
2012 WL 3234282, at *12–14; see also Southwall Techs.,
Inc. v. Cardinal IG Co., 54 F.3d 1570, 1576 (Fed. Cir.
1995). Whether we view the patentee as having dis-
claimed inefficient mixing or construe “batches” to require
efficient mixing, see Trustees of Columbia Univ. v. Syman-
tec Corp., 811 F.3d 1359, 1363–64 (Fed. Cir. 2016), at
bottom, the compounding process must be one that uses
efficient mixing.
Medicines urges that reading the batches limitation to
require “efficient mixing” would render the asserted
claims of the ’343 patent—which already recite an “effi-
ciently mixing” step—superfluous, and that the batches
limitation extends to compounding processes that do not
use efficient mixing. This is not correct. The recitation of
other product-by-process limitations in the claims of the
’343 patent—“dissolving bivalirudin in a solvent to form a
first solution” and “removing the solvent and pH-
adjusting solution solvent”—means that the claims of the
patents in suit would merely overlap, and “overlapping
explanation of how each of the claims are patentable over
the references cited.” These requirements appear to be
applicable to current patent applications as well. See
MPEP 708.02(a) (9th ed. Nov. 2015).
THE MEDICINES COMPANY v. MYLAN, INC. 17
patent claims are not unusual.” Andersen Corp. v. Fiber
Composites, LLC, 474 F.3d 1361, 1370 (Fed. Cir. 2007).
Divorcing efficient mixing from the batches limitation
would also have the impermissible result of “extend[ing]
[Medicines’] monopoly beyond the invention” disclosed,
and potentially to the prior art. 4 Gen. Elec. Co. v. Wabash
Appliance Corp., 304 U.S. 364, 371 (1938); Plummer v.
Sargent, 120 U.S. 442, 449 (1887); Cochrane v. Badische
Anilin & Soda Fabrik, 111 U.S. 293, 309–11 (1884).
For all these reasons, the reading of the batches limi-
tation that “most naturally aligns with the patent’s de-
scription of the invention” is one that requires “efficient
mixing.” Phillips, 415 F.3d at 1316. And “[a]lthough [the
’727 patent’s] claim language does not expressly recite
[efficient mixing], that is what they mean . . . The situa-
tion here involves specifications that in all respects tell us
what the claims mean, buttressed by statements made
during prosecution . . . Accordingly, to attribute to the
claims a meaning broader than any indicated in the
patents and their prosecution history would be to ignore
the totality of the facts of the case and exalt slogans over
real meaning.” Ormco Corp. v. Align Tech., Inc., 498 F.3d
1307, 1316 (Fed. Cir. 2007).
II
The next question is what is meant by “efficient mix-
ing.” Medicines argues that the patents’ common specifi-
cation defines “efficient mixing” as “mixing [that] is
characterized by minimizing levels of Asp9-bivalirudin in
the compounding solution,” i.e., below 0.6 percent Asp9-
4 As practiced by Medicines in the prior art, batch
consistency was achieved pursuant to FDA regulations by
rejecting batches having higher-than-acceptable Asp9
levels. See 21 C.F.R. § 211.165(f).
18 THE MEDICINES COMPANY v. MYLAN, INC.
bivalirudin in the intermediate solution. 5 Medicines
argues that this definition is controlling. We disagree.
Although this statement is taken verbatim from the
specification, e.g., ’727 patent, col. 9 ll. 34–35, it does not
purport to be definitional because it does not accord with
the linguistic formula used by the patentee to signal the
designation of other defined terms—including “batches.”
See ’727 patent, col. 5 ll. 24–36; see also, e.g., id. col. 5 ll.
37–38 (defining “drug product”); id. col. 5, ll. 46–53 (defin-
ing “carrier”). As the district court observed, in defining
terms, “the patentees use[d] a similar format: the defined
term in quotation marks, followed by the terms ‘refers to’
or ‘as defined herein.’” Medicines, 2012 WL 3234282, at
*9; see also ’343 patent, col. 5 ll. 24–53. Because it departs
from this format, the statement Medicines relies on lacks
the clear expression of intent necessary for a patentee to
act as its own lexicographer. See, e.g., Merck & Co. v. Teva
Pharms. USA, Inc., 395 F.3d 1364, 1370 (Fed. Cir. 2005).
More importantly, Medicines’ construction is prob-
lematic because it amounts to a mere recitation of the
results obtained from “efficient mixing” rather than a
definition of what the efficient mixing process is. Before
the district court, Medicines “conced[ed] that its proposed
definition . . . construes that term functionally—i.e., by its
intended result.” Medicines, 2012 WL 3234282, at *11.
Although functional limitations in patent claims are
not per se objectionable even when the means-plus-
5 The patents’ specification provides that the term
“‘[m]inimize’ as used herein refers to the generation of a
level of Asp9-bivalirudin in the compounding solution that
is less than about 0.6%.” ’727 patent, col. 8 ll. 58–60; ’343
patent, col. 8 ll. 58–60.
THE MEDICINES COMPANY v. MYLAN, INC. 19
function format is not invoked, 6 they cannot be “so broad
that [they] cause[] the claim to have a potential scope of
protection beyond that which is justified by the specifica-
tion disclosure.” In re Swinehart, 439 F.2d 210, 213
(C.C.P.A. 1971). Here, Medicines’ construction would
expand the scope of “efficient mixing” to cover any way of
mixing that achieves a compounding solution having an
Asp9 level of less than 0.6 percent. The patentee’s con-
struction of “efficient mixing” thus attempts to claim all
solutions to the identified “impurities” problem, without
describing the entire range of solutions to that problem.
Medicines’ construction is therefore not permissible. See
Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336,
1352–53 (Fed. Cir. 2010) (en banc) (“Such claims merely
recite a description of the problem to be solved while
claiming all solutions to it and . . . cover any [solution]
later actually invented and determined to fall within the
claim’s functional boundaries—leaving it to [others] to
complete an unfinished invention.”); see also Bayer Crop-
Science AG v. Dow AgroSciences LLC, 728 F.3d 1324,
1330–31 (Fed. Cir. 2013). Rather, efficient mixing must be
defined in terms of the particular process or processes
identified in the specification.
There is no contention that “efficient mixing” carries
an accepted meaning to one of ordinary skill in the art.
We therefore turn to the remainder of the specification,
“the single best guide to the meaning of a disputed term”
and “a concordance for the claims” to determine the
process of efficient mixing. Phillips, 415 F.3d at 1315. The
specification’s detailed description teaches that “[e]fficient
mixing . . . may be achieved through various methods.
One such method may be to add . . . the pH-adjusting
6There is no contention here that that claims are
means-plus-function claims governed by 35 U.S.C. § 112(f)
(formerly 35 U.S.C. § 112 ¶ 6).
20 THE MEDICINES COMPANY v. MYLAN, INC.
solution and bivalirudin solution portion-wise.” ’727
patent, col. 9 ll. 34–38; ’343 patent, col. 9, ll. 34–38. “Effi-
cient mixing may also be achieved by adding the pH-
adjusting solution to the bivalirudin solution at a constant
rate . . . [or] at [a] variable rate . . . .” ’727 patent, col. 10
ll. 17–32; ’343 patent, col. 10 ll. 17–32. “Furthermore,
efficient mixing may be achieved through the use of one or
more mixing devices . . . [such as] a paddle mixer, mag-
netic stirrer, shaker, re-circulating pump, homogenizer,
and any combination thereof. The mixing rate of . . . a
paddle mixer may be between about 100 rpm and 1000
rpm . . . The mixing rate for . . . a homogenizer (i.e., high
shear mixing) may be between about 300 and about 6000
rpm . . . The mixing device may mix continuously . . . or at
specific periods of time.” ’727 patent, col. 10 ll. 42–61; ’343
patent, col. 10 ll. 42–61. “Moreover, efficient mixing may
be achieved through adding the pH-adjusting solution to
specific sites within the bivalirudin solution . . . In cases
wherein a mixing device is used, the pH-adjusting solu-
tion may be added to the site of the mixing device . . . .”
’727 patent, col. 11 ll. 10–16; ’343 patent, col. 11 ll. 10–16.
In our view, these portions of the specification’s de-
tailed description of efficient mixing are “vague and
unhelpful.” Finnigan Corp. v. ITC, 180 F.3d 1354, 1364
(Fed. Cir. 1999). Rather than teaching what efficiently
mixing is, the detailed description provides a laundry list
of mixing techniques that individually (or in combination)
may (or may not) constitute efficient mixing. Thus, un-
surprisingly, neither the district court nor the parties
relied on this portion of the specification to ascertain the
meaning of “efficient mixing.” See Medicines, 2012 WL
3234282, at *8–14. We similarly decline to do so.
Apart from the detailed description, two embodiments
disclosed by the specification—Examples 4 and 5—clearly
state what efficient mixing is and is not.
THE MEDICINES COMPANY v. MYLAN, INC. 21
Example 4 describes “inefficient mixing”:
Example 4: Effects of Rapidly Adding pH Adjust-
ing Solution to the Bivalirudin Solution Under In-
efficient Mixing Conditions—Large Scale Study
The pH-adjusting solution was added to the bival-
irudin solution either all at once, or rapidly in
multiple portions, while the bivalirudin solution
was mixed by two paddle mixers located at the top
and bottom of the bivalirudin solution. Both pad-
dle mixers operated at a rate of between about
400 and about 800 rpm.
’727 patent, col. 21 ll. 44–64; ’343 patent, col. 22 ll. 23–42.
Example 5 describes “efficient mixing”:
Example 5: Effects of Adding pH Adjusting Solu-
tion at a Constant Rate and Under Efficient Mix-
ing Conditions—Large Scale Study
The pH-adjusting solution was added to the bival-
irudin solution at a controlled rate of 2 L/min us-
ing a peristaltic pump. A homogenizer was used to
provide a high shear mixing environment (be-
tween about 1000 rpm and 1300 rpm) within the
bivalirudin solution as the pH-adjusting solution
was added[.] A feed tube extended from the peri-
staltic pump to an inlet in the homogenizer, so
that the pH-adjusting solution was added to the
bivalirudin solution at a site adjacent to the
blades of the homogenizer. Simultaneously, a
paddle mixer was used for mixing (mixing rate of
between about 300 rpm and 700 rpm) near the
surface of the bivalirudin solution.
’727 patent, col. 22 ll. 30–58; ’343 patent, col. 23 ll. 6–31.
The district court relied on the “inefficient mixing
conditions” of Example 4 to construe “efficient mixing” as
“not using inefficient mixing conditions such as described
22 THE MEDICINES COMPANY v. MYLAN, INC.
in Example 4.” Medicines, 2012 WL 3234282, at *15. On
appeal, Medicines repeatedly criticizes the court’s nega-
tive construction as failing to define what “efficient mix-
ing” is, as opposed to what it is not. 7 Although there is no
per se rule against negative constructions, see Amgen Inc.
v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1329 (Fed.
Cir. 2003), Medicines’ argument carries some force. The
logic of the argument suggests that that we should look to
the specification’s only clear delineation of what “efficient
mixing” is—Example 5.
Critically, Medicines relied on the mixing parameters
of Example 5 to overcome prior art cited during prosecu-
tion and did not cite any other examples of efficient
mixing—including the generic teachings of the detailed
description. In response to an anticipation rejection based
on inherency, Medicines argued that the properties of the
batches obtained from the mixing conditions of Example 5
were not “inherent . . . but rather [were] influenced by the
process used to generate the product.” J.A. 20182. Medi-
cines emphasized that although Example 4 used “two
paddle mixers located at the top and bottom of the bival-
irudin solution” and “added . . . the bivalirudin solution
either all at once, or rapidly in multiple portions,” “the
batches of Example 5 were prepared by a different proto-
7 See Medicines, 2012 WL 3234282, at *15; see also,
e.g., Medicines Revised Principal and Response Brief 30
(“This construction is flawed because it only defines
[‘efficient mixing’] in a negative manner, by what it is
not—without describing what ‘efficient mixing’ is.” (em-
phasis in original)); id. at 61 (“The district court’s effi-
ciently mixing construction is erroneous because it only
defines the term in a negative manner, by what it is not,
instead of what it is.”); Medicines Revised Reply Brief 13
(“[A] proper construction of ‘efficient mixing’ should focus
on what ‘efficient mixing’ is . . . .”).
THE MEDICINES COMPANY v. MYLAN, INC. 23
col” in which “the pH-adjusting solution was added to the
bivalirudin solution at a controlled rate of 2L/min using a
peristaltic pump,” and that “[a] homogenizer was used to
provide a high shear mixing environment (between about
1000 rpm and 1300 rpm) within the bivalirudin solution
as the pH-adjusting solution was added.” Id.
We conclude that one of ordinary skill in the art
would rely on Example 5 to ascertain the metes and
bounds of “efficiently mixing.” As the only embodiment of
efficient mixing, Example 5 is “highly indicative of the
scope of the claims.” Johns Hopkins Univ. v. CellPro, Inc.,
152 F.3d 1342, 1355 (Fed. Cir. 1998). 8 Example 5, howev-
er, is not merely the only disclosed embodiment of efficient
mixing—it is the only description of efficient mixing in the
patents in suit that casts light on what efficient mixing is
and that enables one of ordinary skill in the art to achieve
the objects of the claimed invention. Although the specifi-
cation provides that Example 5 is “non-limiting,” e.g., ’727
patent, col. 16 l. 6, no other part of the patents’ written
description sufficiently teaches the affirmative steps that
constitute efficient mixing. In this circumstance, we think
it entirely appropriate to limit the term “efficiently mix-
ing” to the sole portion of the specification that adequately
discloses “efficient mixing” to the public. See Alloc, Inc. v.
ITC, 342 F.3d 1361, 1370 (Fed. Cir. 2003); SciMed Life
Sys., Inc. v. Advanced Cardiovascular Sys., Inc., 242 F.3d
1337, 1344–45 (Fed. Cir. 2001).
When held against the detailed description’s open-
ended and vague teachings regarding “efficient mixing,”
8 See also, e.g., Fenner Invs., Ltd. v. Cellco P’ship,
778 F.3d 1320, 1323 (Fed. Cir. 2015) (“Any explanation,
elaboration, or qualification presented by the inventor
during patent examination is relevant, for the role of
claim construction is to ‘capture the scope of the actual
invention’ that is disclosed, described, and patented.”).
24 THE MEDICINES COMPANY v. MYLAN, INC.
Example 5 provides a clear “objective standard by which
to measure the scope of the term.” Sonix Tech. Co. v.
Publications Int’l, Ltd., 844 F.3d 1370, 1375 (Fed. Cir.
2017). 9 Accordingly, construing “efficiently mixing” to
incorporate the efficient mixing conditions of Example 5 is
necessary to “tether the claims to what the specification[]
indicate[s] the inventor actually invented.” Retractable
Techs., Inc. v. Becton, Dickinson & Co., 653 F.3d 1296,
1305 (Fed. Cir. 2011). In doing so, we adopt “[t]he con-
struction that stays true to the claim language and most
naturally aligns with the patent’s description of the
invention . . . [which] in the end, [is] the correct construc-
tion.” Phillips, 415 F.3d at 1312.
We therefore construe the “efficient mixing” required
by the patents in suit to require using the efficient mixing
conditions of Example 5.
III
The net effect of our claim construction is that to in-
fringe either the ’727 patent or the ’343 patent, infringing
batches must be compounded using a process that em-
ploys the efficient mixing conditions of Example 5. See
Abbott Labs. v. Sandoz, Inc., 566 F.3d 1282, 1291–95
(Fed. Cir. 2009) (en banc). Under this claim construction,
Mylan’s ANDA does not infringe the asserted claims since
is undisputed that, for example, Mylan does not use
multiple mixing devices as required by Example 5.
For completeness, we note the inapplicability under
our claim construction of the district court’s holding under
Sunovion. The district court relied on the fact that
Mylan’s ANDA specifies an Asp9 level of up to 2.0 percent,
9 See also Columbia University, 811 F.3d at 1366
(“The patentee cannot rely on its own use of inconsistent
and confusing language in the specification to support a
broad claim construction which is otherwise foreclosed”).
THE MEDICINES COMPANY v. MYLAN, INC. 25
a specification that, if approved, would “allow[] [Mylan] to
produce all batches having less than 0.6% Asp9 impuri-
ties.” Medicines, 72 F. Supp. 3d at 886. The district court
reasoned that, like the infringing ANDA in Sunovion,
“Mylan’s ANDA specification seeks approval for a bival-
irudin drug product made from pharmaceutical batches
allowed to have . . . [an] Asp9 within the scope of the ’727
patent’s issued claims.” Id. at 885–86. The court therefore
held that “Mylan infringes as a matter of law.” Id. at 886.
This holding rests on an incorrect claim construction
of the ’727 patent that does not require “efficient mix-
ing.” 10 See id. at 887. Under the correct claim construc-
tion, Sunovion is inapplicable because that decision “only
applies when an ANDA specification defines a compound
such that it meets the limitations of an asserted claim.”
Ferring B.V. v. Watson Labs., Inc.-Fla., 764 F.3d 1382,
1387 (Fed. Cir. 2014) (internal quotation marks omitted).
Mylan’s ANDA does not on its face establish that Mylan’s
compounding process uses efficient mixing since, for
example, nothing in the ANDA speaks to whether Mylan
uses high-shear mixing as required by Example 5.
Instead, “[w]hen an ANDA is silent with respect to in-
fringement . . . the correct analysis is . . . [whether] the
ANDA applicant would likely sell an infringing composi-
tion pursuant to an approved ANDA.” Id. at 1387–88
(internal quotation marks omitted) (quoting Glaxo, Inc. v.
Novopharm, Ltd., 110 F.3d 1562, 1570 (Fed. Cir. 1997)).
In this case, the undisputed facts before the district court
10 While we also disagree with the district court’s
construction of “efficient mixing” as “not using inefficient
mixing conditions such as described in Example 4,” the
district court correctly concluded that Mylan did not
infringe the ’343 patent under this construction because
Mylan’s compounding process was “more inefficient” than
Example 4. Medicines, 2013 WL 6633085, at *9.
26 THE MEDICINES COMPANY v. MYLAN, INC.
on summary judgment foreclose the possibility that
Mylan “would likely sell an infringing” product. There is
no genuine dispute that Mylan’s compounding process
“adds the pH-adjusting solution all at once” and “uses one
paddle mixer” operating at 200 rpm. Medicines, 2013 WL
6633085, at *10 (internal quotation marks omitted).
Example 5, however, requires multiple mixers and adds
the pH-adjusting solution at a continuous rate using a
peristaltic pump. See ’727 patent, col. 22 ll. 46–64; ’343
patent, col. 23 ll. 21–36. Accordingly, Mylan’s ANDA
cannot infringe the asserted claims of the ’727 patent and
the ’343 patent. 11
CONCLUSION
We reverse the district court’s judgment of infringe-
ment with respect to the ’727 patent and affirm the
court’s summary judgment of noninfringement with
11 Medicines argues that Mylan achieves efficient
mixing by mixing a smaller solution volume than de-
scribed in Example 5, using a pH-adjusting solution
having a higher concentration of base, and using a higher
mannitol concentration in the bivalirudin solution and no
mannitol in the pH-adjusting solution. We disagree with
Medicines that these differences create a genuine dispute
of material fact regarding infringement. The detailed
description of “efficient mixing” set forth in the patents’
specification does not teach achieving efficient mixing by
adjusting volume or concentration—to the contrary, the
patent teaches “once the compounding solution is formed,”
adjusting the “final volume” is “[o]ptional,” and that the
“methods” for doing so are “known in the art.” ’727 pa-
tent, col. 11 ll. 25–30; ’343 patent, col. 11, 25–30. Exam-
ples 4 and 5 use the same volumes and concentrations,
which confirms that these parameters are irrelevant to
“efficient mixing.”
THE MEDICINES COMPANY v. MYLAN, INC. 27
respect to the ’343 patent. Accordingly, the judgment of
the district court is
REVERSED IN PART AND AFFIRMED IN PART