Endo Pharmaceuticals Inc. v. Mylan Pharmaceuticals Inc. et al
CLAIM CONSTRUCTION OPINION. Signed by Judge Joseph E. Irenas on 8/7/2013. (bkb)
UNITED STATES DISTRICT COURT
DISTRICT OF DELAWARE
ENDO PHARMACEUTICALS INC.,
HONORABLE JOSEPH E. IRENAS
CIVIL ACTION NO. 11-717
MYLAN PHARMACEUTICALS INC.,
and MYLAN INC.,
CLAIM CONSTRUCTION OPINION
MORRIS, NICHOLS, ARSHT & TUNNELL LLP
Jack B. Blumenfeld
1201 North Market Street
P.O. Box 1347
Wilmington, DE 19899
Counsel for Plaintiff
PATTERSON BELKNAP WEBB & TYLER LLP
Jeffrey I.D. Lewis
Edward R. Tempesta
1133 Avenue of the Americas
New York, NY 10036
Counsel for Plaintiff
POTTER ANDERSON & CORROON LLP
Richard L. Horwitz
David E. Moore
Bindu A. Palapura
Hercules Plaza, 6th Floor
1313 North Market Street
Wilmington, DE 19801
Counsel for Defendants
WILSON SONSINI GOODRICH & ROSATI PC
One Market Street
Spear Tower, Suite 3300
San Francisco, CA 94105
Katherine Van Gunst
Elham F. Steiner
Matthew J. Bresnahan
12235 El Camino Real, Suite 200
San Diego, CA 92130
Counsel for Defendants
IRENAS, Senior United States District Judge, sitting by
This is a patent infringement case brought under the HatchWaxman Act.
Plaintiff Endo Pharmaceuticals Inc. (“Endo”)
alleges that Defendants Mylan Pharmaceuticals Inc. and Mylan,
Inc. (collectively, “Mylan”) have infringed U.S. Patent Nos.
5,464,864 (filed Nov. 7, 1995) (the “’864 patent”), 5,637,611
(filed June 10, 1997) (the “’611 patent”), and 5,827,871 (filed
Oct. 27, 1998) (the “’871 patent”).
Presently before the Court
is the parties’ request for claim construction.
The Court held
a Markman hearing on July 18, 2013, and now construes the
disputed claim terms as set forth below.
Endo is the manufacturer of Frova, which is a drug
indicated for the acute treatment of migraine attacks with or
without aura in adults.
The active ingredient in Frova is
frovatriptan, which is the chemical 3-methylamino-6-carboxamido1,2,3,4-tetrahydrocarbazole.
Migraines are a type of headache. They typically last
anywhere from 4 to 72 hours.
Migraines are often preceded by
indicators, including an aura, nausea, vomiting, or sensitivity
Many migraine sufferers find that their migraines
occur after some kind of trigger, such as stress, certain foods,
or the menstrual cycle.
Frova is frequently prescribed off
label to treat menstrual migraines.
Although the causes of migraines are unknown, serotonin is
believed to affect migraines.
Serotonin works by binding to
various receptors, known as 5-HT receptors, and inducing
The receptor pertinent to this case is the
Frovatriptan is one of a class of drugs that
treats migraines by acting on the 5-HT1-B receptor.
Specifically, it acts as an agonist.
Agonists bind to cell
receptors and cause certain reactions to take place.
A critical element of frovatriptan’s effectiveness as a
migraine drug is its stereochemical properties.
refers to a molecule’s three-dimensional configuration.
compounds can have the same molecular formula but different
These molecules are called
A stereoisomer that is one of a pair of
stereoisomers that are nonsuperimposable images of each other is
called an enantiomer.
A well-known example of nonsuperimposable
images is the relationship between one’s right and left hand.
An enantiomer is identified as being either (R)- or (S)-,
depending on whether its substituents are oriented clockwise or
counterclockwise after they have been arranged according to
increasing atomic weight.
If the enantiomer rotates plane-
polarized light in either a clockwise or counterclockwise
direction, it may be identified by the symbols (+) or (-).
Where a compound does not have any of these designations, the
name refers to the compound without regard to its threedimensional orientation.
Compounds can also exist as a mixture of enantiomers.
a mixture contains an equal number of (R)- and (S)- enantiomers,
it is known as a racemic mixture or a racemate.
A compound that
is a racemic mixture is preceded by the symbol (±).
The chemical form that frovatriptan takes is also relevant.
Chemical compounds can exist in a variety of forms, including
free base forms, salts, solvates, hydrates, salt-hydrates, and
In its free base form, a compound can form a
salt in the presence of a suitable acid.
A salt is an ionic
compound that results from the neutralization reaction of an
acid and a base.
A solvate is a crystal that contains solvent
molecules at regular intervals in its structure.
When water is
the solvent, the resulting solvate is known as a hydrate.
salt-hydrate is a crystalline form of a salt that incorporates
discrete water molecules as part of its crystal lattice.
Frovatriptan is a salt-hydrate that is composed solely of (R)entantiomers.
The claims in the patents-in-suit cover both frovatriptan’s
chemical structure and its use in treating migraines. 1
filed an abbreviated new drug application (“ANDA”) seeking to
market a generic version of Frova before Endo’s patents expired.
In response, Endo commenced this action for patent infringement.
The parties have identified three claims that require
“compound of (general) formula (I)”; “or a salt,
solvate or hydrate thereof”; and “treatment of a condition
wherein a 5-HT1-like agonist is indicated.”
The Court construes
these claims below.
Claim construction is a matter of law for the Court to
Markman v. Westview Instruments, Inc., 517 U.S. 370,
“It is a ‘bedrock principle’ of patent law that
‘the claims of a patent define the invention to which the
patentee is entitled the right to exclude.’”
Phillips v. AWH
Corp., 415 F.3d 1303, 1319 (Fed. Cir. 2005) (en banc) (quoting
The three patents-in-suit are listed in the FDA’s Orange Book for Frova. In
addition to these patents, Endo has two other patents listed in the FDA’s
Orange Book for Frova. See U.S. Patent No. 5,616,603 (filed May 26, 1995);
U.S. Patent No. 5,962,501 (filed Dec. 23, 1996). Endo has granted Mylan a
covenant not to sue on these two patents.
Innova/Pure Water, Inc. v. Safari Water Filtration Sys., Inc.,
381 F.3d 1111, 1115 (Fed. Cir. 2004)).
The Court begins a claim construction analysis by examining
the intrinsic evidence, which includes the claims, the
specification, and the prosecution history. 2
Vitronics Corp. v.
Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996).
claim construction analysis must begin and remain centered on
the claim language itself.”
Innova, 381 F.3d at 1116.
a heavy presumption that a claim term conveys its ordinary and
customary meaning, which “is the meaning that the term would
have to a person of ordinary skill in the art in question at the
time of the invention.”
Phillips, 415 F.3d at 1313.
patentee may overcome this presumption and choose “to be his or
her own lexicographer by clearly setting forth an explicit
definition for a claim term.”
Johnson Worldwide Assocs., Inc.
v. Zebco Corp., 175 F.3d 985, 990 (Fed. Cir. 1999); see also
Schering Corp. v. Amgen Inc., 222 F.3d 1347, 1353 (Fed. Cir.
2000); Markman v. Westview Instruments, Inc., 52 F.3d 967, 979–
80 (Fed. Cir. 1995), aff’d 517 U.S. 370 (1996).
The claims themselves and the context in which a term is
used within the claims can “provide substantial guidance as to
the meaning of particular claim terms.”
Phillips, 415 F.3d at
The prosecution history “consists of the complete record of the proceedings
before the PTO and includes the prior art cited during the examination of the
patent.” Phillips, 415 F.3d at 1317.
In addition, other claims of the patent may be useful in
construing a claim term, as “claim terms are normally used
consistently throughout the patent.”
that differ from each other may provide insight into how a term
should be read.
Laitram Corp. v. Rexnord, Inc., 939 F.2d 1533,
1538 (Fed. Cir. 1991).
After examining the claims, “it is always necessary to
review the specification to determine whether the inventor has
used any terms in a manner inconsistent with their ordinary
Vitronics, 90 F.3d at 1582.
“For claim construction
purposes, the description may act as a sort of dictionary, which
explains the invention and may define terms used in the claims.”
Markman, 52 F.3d at 979.
For this reason, “the specification is
always highly relevant to the claim construction analysis.
Usually, it is dispositive; it is the single best guide to the
meaning of a disputed term.”
Vitronics, 90 F.3d at 1582.
Finally, the Court should also examine the prosecution
history, if it is in evidence.
Phillips, 415 F.3d at 1317.
“The prosecution history can often inform the meaning of the
claim language by demonstrating how the inventor understood the
invention and whether the inventor limited the invention in the
course of prosecution, making the claim scope narrower than it
would otherwise be.”
“[I]deally there should be no ‘ambiguity’ in claim language
to one of ordinary skill in the art that would require resort to
evidence outside the specification and prosecution history.”
Markman, 52 F.3d at 986.
But if the term remains unclear or
unambiguous after examining the intrinsic evidence, the Court
may turn to extrinsic evidence.
Pall Corp. v. Micron
Separations, Inc., 66 F.3d 1211, 1216 (Fed. Cir. 1995).
“Extrinsic evidence consists of all evidence external to the
patent and prosecution history, including expert and inventor
testimony, dictionaries, and learned treatises.”
F.3d at 980.
Although extrinsic evidence is useful in
determining how a person of ordinary skill in the art would
understand the term, it is less reliable for the purposes of
claim construction than the patent and its prosecution history.
Phillips, 415 F.3d at 1318-19.
Therefore, extrinsic evidence
must be viewed within the context of intrinsic evidence.
“compound of (general) formula (I)”
This term appears in claim 1 of the ‘864, ‘611, and ‘871
Endo urges the Court to give “compound” its plain and
ordinary meaning, while Mylan contends that “compound” means the
compound’s isolated enantiomers separately, as well as any
mixture of those enantiomers.
In essence, Endo would like
“compound” to mean any compound of formula (I) regardless of
Mylan, on the other hand, argues for a
construction that references the compound’s stereochemistry.
At oral argument, counsel for Endo represented that both
parties agree that “compound” includes “all R [enantiomers] and
no S to all S and no R, and every ratio in between.”
Mylan, therefore, argues that there is no
disagreement on the meaning of “compound” and that this
construction should be adopted to provide clarity.
Endo, on the
other hand, argues that such a construction necessarily imposes
limitations and that the applicants intended “compound” to be
without regard to stereochemistry.
The Court agrees with Endo.
The intrinsic language makes clear that “compound” does not
contemplate stereochemical structure.
First, the claim language
itself makes no reference to stereochemistry.
specifications indicate that the applicants intended “compound”
to be without stereochemical limitation.
Mylan argues that
“[a]ll three specifications disclose that compounds of formula
(I) will exist as ‘optical isomers (enantiomers)’ and ‘racemic
(Def.’s Br. 6)
However, the complete language of
the specifications to which Mylan refers reads, “It will be
appreciated that compounds of formula (I) may contain one or
more asymmetric centres, and such compounds will exist as
optical isomers (enantiomers).
The invention thus includes all
such enantiomers and mixtures, including racemic mixtures,
’864 Patent col.2 l.35-39; ’871 Patent col.2 l.35-39;
’611 Patent col.2 l.27-31 (emphasis added).
language clearly anticipates the compound as an enantiomer, a
mixture, or a racemic mixture, it does not place any limitations
on the compound’s stereochemistry.
Indeed, the fact that the
applicants stated that compound “may” exist as an enantiomer
indicates that they did not want to impose a stereochemical
See, e.g., Pfizer, Inc. v. Ranbaxy Labs. Ltd., 457
F.3d 1284, 1289 (Fed. Cir. 2006).
If a person of ordinary skill in the art had expected
“compound” to include “all such enantiomers and mixtures,
including racemic mixtures,” this statement would be redundant
See Ranbaxy, 457 F.3d at 1290.
As such, the
Court construes “compound of (general) formula (I)” to refer to
the formula without regard to stereochemistry.
See Pfizer Inc.
v. Teva Pharm. U.S.A., Inc., 882 F. Supp. 2d 643, 688 (D. Del.
2012) (construing the term “4-amino-3-(2-methylpropyl) butanoic
acid” as “the chemical compound 4-amino-3-(2-methylropyl)
butanoic acid,” meaning “the compound without limitation as to
“or a salt, solvate or hydrate thereof”
This term appears in claim 1 of the ’864 patent.
term, “or a physiologically acceptable salt, solvate or hydrate
thereof,” appears in claim 1 of the ’871 patent.
6 of the ’864 patent and claims 1, 8, and 9 of the ’611 patent
contain the term, “or a pharmaceutically acceptable salt
The parties agree that “salt” should be construed
consistently across these claims.
The crux of the parties’ disagreement over this term is
whether or not it encompasses a salt-hydrate.
Mylan asks the
Court to construe “or a salt, solvate or hydrate thereof” as
“the compound in free base form; or such compound as a salt; or
such compound as a solvate; or such compound as a hydrate.”
(Defs.’ Br. 7)
Endo asks the Court to give the term its plain
and ordinary meaning, which it argues means a compound that
meets the definition of one or more of salt, solvate, or
(Pl.’s Br. 15)
The evidence supports Endo’s
Endo argues that a person of ordinary skill in the art
would understand “salt” to include a hydrated salt, an anhydrous
salt, and the salt as a solvate.
(Id. at 16)
In other words, a
“salt” could be both a “salt” and a “hydrate” at the same time,
and either term would cover the resulting compound.
contends that the terms are exclusive and that a salt cannot
also be a hydrate and fall within the claim.
(Defs.’ Br. 8)
The Court sees no basis for finding that “salt” does not include
a salt that is also a hydrate or also a solvent.
construction, “salt” would be limited to anhydrous salts, and
nothing in the claim language or specifications indicates that
the inventors sought to limit “salt” in such a manner.
Mylan further argues that the fact that none of the thirtytwo examples in the ’864 and ’871 patents is a salt-hydrate
indicates that the applicants did not contemplate the compound
existing as a salt-hydrate.
But the law is clear that “even
when the specification describes only a single embodiment, the
claims of the patent will not be read restrictively unless the
patentee has demonstrated a clear intention to limit the claim
scope using ‘words or expressions of manifest exclusion or
Liebel-Flarsheim Co. v. Medrad, Inc., 385 F.3d
898, 906 (Fed. Cir. 2004) (quoting Teleflex, Inc. v. Ficosa N.
Am. Corp., 299 F3d 1313, 1327 (Fed. Cir. 2002)).
unequivocal intent is present here.
Finally, Mylan submits that “or a salt, solvate or hydrate
thereof” is a Markush group and thus must expressly indicate
that the members may be used in combination.
A Markush group is
a list of specified alternatives set forth in a claim and is
considered to be a closed group.
Gillette Co. v. Energizer
Holdings, Inc., 405 F.3d 1367, 1372 (Fed. Cir. 2005).
proper Markush group is limited by the closed language term
Abbott Labs. v. Baxter Pharm. Prods., Inc.,
334 F.3d 1274, 1281 (Fed. Cir. 2003).
“If a patentee desires
mixtures or combinations of the members of the Markush group,
the patentee would need to add qualifying language while
drafting the claim.”
According to Mylan, “[a] compound of general formula (I)
which is 3-methylamino-6-carboxamido-1,2,3,4tetrahydrocarbazole, or a salt, solvate or hydrate thereof” is a
Markush group because “which is” indicates a closed group. 3
(Oral Arg. Tr. 87:14-16; 88:9-89:3)
Mylan cites to Galderma
Laboratories, L.P. v. Tolmar Inc., No. 10-0045, 2012 WL 642450,
at *5-6 (D. Del. Feb. 13, 2012), in support of its position.
that case, this Court construed “pharmaceutical composition
which is a gel of” as “a pharmaceutical composition in the form
of a gel consisting of.”
Id. at *5.
But Galderma is
distinguishable from this case.
The Galderma Court based its construction on the patent’s
The applicants originally submitted claims
that used open-ended language:
Id. at *6.
the Examiner rejected those claims and suggested the partially
open language, “consisting essentially of,” the applicants
As Endo’s counsel noted at oral argument, this language appears only in
claim 1 of the ’864 patent.
“submitted claims using the closed language ‘which is a gel
Thus, because the applicants attempted to keep the
group of ingredients open, were offered the opportunity to
partially restrict the group, and chose to create a closed
group, the Court found that the group was closed.
absence of such prosecution history here, the Court is not
willing to depart from the practice of requiring a Markush group
to use the words “consisting of.”
The Federal Circuit has made clear that in an open group,
“a” means “one or more.”
See, e.g., KCJ Corp. v. Kinetic
Concepts, Inc., 223 F.3d 1351, 1356 (Fed. Cir. 2000).
Accordingly, the Court adopts the following construction for
claim 1 of the ’864 patent:
“or one or more of salt, solvate or
The Court adopts the following construction
for claim 1 of the ’871 patent:
“or one or more of a
physiologically acceptable salt, solvate or hydrate thereof.”
Finally, the Court adopts the following construction for claim 6
of the ’864 patent and claims 1, 8, and 9 of the ’611 patent:
“or one or more of a pharmaceutically acceptable salt thereof.”
“treatment of a condition wherein a 5-HT1-like agonist is
This term appears in claim 2 of the ’864 patent, claim 1 of
the ’871 patent, and claim 10 of the ’611 patent.
disagree as to whether “treatment” includes prophylaxis or is
limited to the treatment of a specific event.
Endo argues that
the Court should give “treatment” is ordinary and customary
(Pl.’s Br. 9)
Mylan, on the other hand, argues that
the Court should construe the term as “treatment or prophylaxis
of a condition.”
(Defs.’ Br. 10)
The Court will adopt Endo’s
To begin the analysis, the Court must determine what a
person of ordinary skill in the art would expect “treatment” to
Although extrinsic evidence is usually reserved for
resolving ambiguity in claim terms, the Court may consult
extrinsic evidence in the absence of ambiguity to understand how
a person of ordinary skill in the art would comprehend a term.
See Markman, 52 F.3d at 986 (“Extrinsic evidence . . . may be
necessary to inform the court about the language in which the
patent is written.
But this evidence is not for the purpose of
clarifying ambiguity in claim terminology.
It is not ambiguity
in the document that creates the need for extrinsic evidence but
rather unfamiliarity of the court with the terminology of the
art to which the patent is addressed.”).
The Court is not
“barred from considering any particular sources or required to
analyze sources in any specific sequence, as long as those
sources are not used to contradict claim meaning that is
unambiguous in light of the intrinsic evidence.”
F.3d at 1324.
In this case, the Court finds it useful to
consult the parties’ expert reports to determine the plain and
ordinary meaning of “treatment.”
According to the expert report of Endo’s expert, Dr.
Vincent P. Rocco,
The “treatment” term . . . would be understood by
one skilled in the art to mean the administration of a
compound for the purpose of providing relief from a
condition at the time at which that condition has
presented or is expected to present. . . .
. . . No one of ordinary skill in the art would
understand the term “method of treatment” to mean
“method of treatment and prevention.” Prevention is
distinct from treatment and the two should not be
confused. Treatment, for instance, refers to
alleviating the results of a specific event whereas
prevention has a broader connotation dealing with
avoiding a medical event from occurring without
necessarily identifying the source of such an event
(in the nature of a vaccine).
(Defs.’ Ex. 4 (“Rocco Report”) ¶¶ 69-70)
Mylan’s expert, Dr. Stephen J. Peroutka, describes
prophylactic treatment as follows:
“Prophylactic treatment of
migraine means routinely administering the claimed compounds
regardless of the presence of headache pain—in other words,
treating migraine by preventing its onset.”
(Pl.’s Ex. U
(“Peroutka Report”) ¶ 36)
Both of these descriptions demonstrate that a person of
ordinary skill in the art would understand treatment to be
separate from prophylaxis.
Dr. Rocco clearly says that
“prevention is distinct from treatment.”
(Rocco Report ¶ 70)
Although Mylan makes much of the fact that Dr. Rocco stated that
treatment would provide relief from a condition that “is
expected to present” (id. ¶ 69), the Court does not view this
language as referring to prophylaxis.
For example, as both
parties have noted, migraines are often preceded by any number
of symptoms, such as an aura or nausea.
Thus, when a migraine
sufferer experiences such a symptom, she can expect that a
migraine will occur and thus take medication to treat the
Or in the case of menstrual migraines, the
patient could take the medication around the time each month
that she would expect the migraines to present.
Prophylaxis, by contrast, would entail taking the
medication in the absence of any symptoms or expectation that a
migraine would occur.
Dr. Petrouka’s definition of prophylactic
treatment is consistent with this interpretation.
that prophylactic treatment “means routinely administering the
claimed compounds regardless of the presence of headache pain.”
(Petrouka Report ¶ 36)
This language demonstrates that
prophylaxis is understood to be fundamentally different than
With these definitions in mind, the Court turns to
the parties’ arguments.
Mylan contends that the applicants acted as their own
lexicographers here and defined treatment in the specifications.
It points to the following language to support its contention:
“The present invention therefore provides the use of compounds
of general formula (I) . . . for the treatment of a condition
where a 5-HT1-like agonist is indicated, in particular the
treatment or prophylaxis of migraine.”
’865 Patent, col.1 l.65-
col.2 l.26; ’871 Patent, col.1 l.65-col.2 l.25; ’611 Patent,
col.1 l.59-col.2 l.17.
A patentee may use the specifications to give a term a
definition “that differs from the meaning it would otherwise
Phillips, 415 F.3d at 1316.
To give a term a
distinctive meaning, the patentee must show an express intent to
Renishaw PLC v. Marposs Societa’ per Azioni, 158 F.3d
1243, 1249 (Fed. Cir. 1998).
“[T]he written description in such
a case must clearly redefine a claim term ‘so as to put a
reasonable competitor or one reasonably skilled in the art on
notice that the patentee intended to so redefine that claim
Elekta Instrument S.A. v. O.U.R. Scientific Int’l,
Inc., 214 F.3d 1302, 1307 (Fed. Cir. 2000) (quoting Process
Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357 (Fed.
The applicants have not done so here.
language Mylan quotes does not show any intent – let alone an
express intent – to define “treatment,” and the Court will not
construe “treatment” as “treatment or prophylaxis” on this
Absent an express definition, the Court looks to the other
As Endo points out, the specifications
clearly refer to “treatment” and “prophylaxis” separately.
example, the ’864 patent states, “Currently, the most widely
used treatment for migraine involves administration of
ergtamine, dihydroergotamine, or methysergide, which are also
’864 Patent, col.1 l.14-18 (emphasis
Another portion says, “Compounds of formula (I) . . .
are expected to have utility in the treatment and/or prophylaxis
of migraine . . . .”
Id. col.6 l.41-44 (emphasis added).
contends that construing treatment as “treatment or prophylaxis”
would render these specifications redundant and nonsensical.
Mylan, on the other hand, argues that the specifications
actually describe using the compound in a prophylactic manner
and that as such the applicants must have intended treatment to
To support this argument, Mylan points
to the following portion of the ’864 patent:
The physiologically acceptable compounds of the
invention will normally be administered in a daily
dosage regimen . . . of the compound of the formula
(I) . . . , the compound being administered 1 to 4
times per day. Suitably the compounds will be
administered for a period of continuous therapy, for
example for a week or more.
’864 Patent, col.7 l.56-67 (emphasis added).
typically last only 4 to 72 hours, Mylan argues that this
language indicates that the applicants intended the invention to
be used for prophylaxis as well as acute treatment.
interpretation runs contrary to the meaning of treatment
This paragraph gives no indication that the
invention is meant to be used absent any symptoms at all.
Rather, it suggests that when used to treat a migraine or to
prevent one that is expected to present, the medication should
be taken for an extended period of time for effective treatment.
Because the Court can find no basis for departing from the
plain and ordinary meaning, the Court construes “treatment” as
treatment without prophylaxis.
For the reasons set forth above, the disputed claim terms
will be construed as indicated.
An appropriate Order
accompanies this Opinion.
August 7th, 2013
/s/ Joseph E. Irenas ______
Joseph E. Irenas, S.U.S.D.J.
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